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Extended transduodenal sphincteroplasty for bile duct stones associated with a periampullary diverticulum.
Extended transduodenal sphincteroplasty has been suggested as an alternative to choledochoduodenostomy for the surgical management of bile duct stones associated with a periampullary diverticulum but its value has not previously been investigated. Over a 3 year period, nine patients underwent extended transduodenal sphincteroplasty for common bile duct calculi associated with a periampullary diverticulum with no operative or post-operative mortality and minimal morbidity. Follow-up ranging from 20 to 60 months has shown remission of pain in all but one patient, who has had a normal endoscopic cholangiogram and no further episodes of jaundice or cholangitis. Extended transduodenal sphincteroplasty is a safe and effective alternative to choledochoduodenostomy for the surgical management of choledocholithiasis associated with a periampullary diverticulum. | en | apollo | train |
Several studies have demonstrated that insulin/IGF-I signaling inhibits autophagy via activation of the mammalian target of rapamycin (mTOR) and thus enhances the aging process [22,23].glucose metabolism, protein synthesis, and cellular proliferation.The insulin/IGF-I signaling system regulates many crucial functions e.g.FIGURE 27.1 A schematic presentation on the key players regulating autophagy and NF-κB signaling in the generation of inflammaging phenotype. Possible drug treatments and their targets controlling autophagy and inflammation are depicted. Arrows indicate activating and blockers' inhibiting effects. AICAR, 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide; NMN, nicotinamide mononucleotide; NSAID, nonsteroidal anti-inflammatory drug; SAID, steroidal anti-inflammatory drug. ### Insulin/IGF-I-FOXO Pathway
Studies on age-related mutants of _Caenorhabditis elegans_ revealed that loss-of-function mutations in genes of the DAF-2 pathway could lead to a doubling of the life span [5,20,21] _._ Lifespan extension was associated with increased stress resistance and a clear delay in the onset of age-related tissue pathology. These early studies demonstrated that the life span extension induced by the inhibition of the DAF-2 pathway is dependent on activation of the DAF-16 protein. DAF-16 is a transcription factor that controls the expression of several metabolic regulators and host defense genes, e.g. antioxidants and heat shock proteins. Genes of the DAF-2/DAF-16 pathway have been conserved during evolution, e.g. DAF-2 is the ortholog of the mammalian insulin/ insulin-like growth factor 1 (IGF-I) receptor and DAF-16 corresponds to proteins of the FOXO family in mammals (Fig. 27.1). This was the first indication that cellular metabolism is linked to regulation of the aging process. The insulin/IGF-I signaling system regulates many crucial functions e.g. glucose metabolism, protein synthesis, and cellular proliferation. Several studies have demonstrated that insulin/IGF-I signaling inhibits autophagy via activation of the mammalian target of rapamycin (mTOR) and thus enhances the aging process [22,23].As a proof of concept, several genetic studies have revealed that these endocrine mutants, which express reduced levels of IGF-I or growth hormone (an inducer of IGF-I expression in liver), are dwarfs but they live longer than their wild type counterparts.The extension of life span varies by 20–70% in different dwarf models [24,25]. | en | apollo | train |
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Approximately 80% of cervical cancers are squamous cell carcinoma, and 15% are adenocarcinomas.**What is the relative frequency of the two major histologic subtypes of cervical cancer?**
Approximately 20%.**If high-grade squamous intraepithelial lesions are left untreated over a period of several years, what percentage will progress to invasive cancer?**
The FDA approved the vaccine for administration to girls and women between 9 and 26 years of age. **The quadrivalent HPV vaccine should be given to males in what age group? **
The FDA did not approve the vaccine for administration to boys and men in any age group. **The HPV vaccine is effective against the oncogenic types 16 and 18. What percentage of cervical cancers is caused by these two types of HPV? **
HPV types 16 and 18 are responsible for about 70% of all cervical cancers. **What is the most common presenting symptom for patients with cervical cancer? **
The classic symptoms are intermittent painless metrorrhagia or spotting. Up to 80% of patients present with abnormal vaginal bleeding, most commonly postmenopausal. Only 10% note postcoital bleeding. Less frequent symptoms include vaginal discharge and pain. Late symptoms or indicative for more advanced disease are pain referred to flank or leg, dysuria, hematuria, and rectal bleeding. **What is the most appropriate management for a gross cervical lesion discovered during a routine examination? **
Biopsy. Specimens from ulcerated lesions should be obtained from their center. **What is the next appropriate step in management of an ASCUS Pap test in a patient whose reflex HPV testing is positive for high-risk HPV subtypes? **
Colposcopy including cervical biopsy and endocervical curettage. **If high-grade squamous intraepithelial lesions are left untreated over a period of several years, what percentage will progress to invasive cancer? **
Approximately 20%. **What is the relative frequency of the two major histologic subtypes of cervical cancer? **
Approximately 80% of cervical cancers are squamous cell carcinoma, and 15% are adenocarcinomas.**
Approximately half of patients with cervical cancer present with stage I disease.**What epidemiologic risk factors have been identified for the development of cervical cancer?**
Women in lower socioeconomic status, young age at first intercourse, multiple sexual partners, high parity, HIV infection, and history of other sexually transmitted infections. | en | apollo | train |
Comparing performance of multinomial logistic regression and discriminant analysis for monitoring access to care for acute myocardial infarction.
One way to monitor patient access to emergent health care services is to use patient characteristics to predict arrival time at the hospital after onset of symptoms. This predicted arrival time can then be compared with actual arrival time to allow monitoring of access to services. Predicted arrival time could also be used to estimate potential effects of changes in health care service availability, such as closure of an emergency department or an acute care hospital. Our goal was to determine the best statistical method for prediction of arrival intervals for patients with acute myocardial infarction (AMI) symptoms. We compared the performance of multinomial logistic regression (MLR) and discriminant analysis (DA) models. Models for MLR and DA were developed using a dataset of 3,566 male veterans hospitalized with AMI in 81 VA Medical Centers in 1994-1995 throughout the United States. The dataset was randomly divided into a training set (n = 1,846) and a test set (n = 1,720). Arrival times were grouped into three intervals on the basis of treatment considerations: <6 hours, 6-12 hours, and >12 hours. One model for MLR and two models for DA were developed using the training dataset. One DA model had equal prior probabilities, and one DA model had proportional prior probabilities. Predictive performance of the models was compared using the test (n = 1,720) dataset. Using the test dataset, the proportions of patients in the three arrival time groups were 60.9% for <6 hours, 10.3% for 6-12 hours, and 28.8% for >12 hours after symptom onset. Whereas the overall predictive performance by MLR and DA with proportional priors was higher, the DA models with equal priors performed much better in the smaller groups. Correct classifications were 62.6% by MLR, 62.4% by DA using proportional prior probabilities, and 48.1% using equal prior probabilities of the groups. The misclassifications by MLR for the three groups were 9.5%, 100.0%, 74.2% for each time interval, respectively. Misclassifications by DA models were 9.8%, 100.0%, and 74.4% for the model with proportional priors and 47.6%, 79.5%, and 51.0% for the model with equal priors. The choice of MLR or DA with proportional priors, or DA with equal priors for monitoring time intervals of predicted hospital arrival time for a population should depend on the consequences of misclassification errors. | en | apollo | train |
Immunorecognition of long double-stranded RNA by endothelial cells may be an important mechanism involved in endothelial cell activation and development of endothelial dysfunction. | en | apollo | train |
The committee heard from the ERG that the company's model did not capture the progressive nature of idiopathic pulmonary fibrosis. The committee noted that the company, in choosing the model structure, made several clinically implausible assumptions. For example:
No relationship between time on treatment, time to disease progression (defined as a 10% decline in predicted FVC, a decline in 6‑minute walking distance of 50 metres or more, or death) and mortality. The committee agreed that these were likely to be linked, so it was not appropriate to model them independently.
Acute exacerbations were not explicitly connected to disease progression and mortality. Clinical experts advised that exacerbations had a substantial effect on quality of life and mortality. The committee agreed that the model may not fully represent the impact of idiopathic pulmonary fibrosis on patients.The committee had serious concerns about the company's model and understood that the ERG could address only some of the issues in its exploratory analyses. The committee noted that, in its response to the appraisal consultation document, the company did not provide new clinical evidence but did provide revised analyses with:
New parametric survival curves for mortality (see section 4.13 for discussion about the survival curves).
New assumptions around how long the benefits of treatment last (see section 4.14 for discussion about the time the benefits of treatment last).
A new subgroup with an FVC between 50% and 90% predicted. | en | apollo | train |
Transient cerebral circulatory arrest coincides with fainting in cough syncope.
During prolonged coughing, intrathoracic and intra-abdominal pressures are transmitted via the great veins to the intracranial compartment, causing transient elevated intracranial pressure. The resulting reduction of cerebral perfusion pressure may cause a critical impairment of cerebral blood flow (CBF). Obstructive airway disease seems to be a prerequisite to build up the intrathoracic and intracranial pressures to a degree sufficient to compromise CBF and cause cough syncope. Using transcranial Doppler sonography (TCD) monitoring of middle cerebral artery flow velocities, we studied three patients with cough syncope. During coughing, they showed a transient cerebral circulatory arrest, which coincided with loss of consciousness in the two patients who fainted during TCD monitoring. EEG showed slowing, heart rate increased, and systemic arterial BP in one patient was preserved during the syncope. Our findings support the hypothesis that a critical reduction of CBF causes cough syncope. | en | apollo | train |
2,268, from June 30, 1997, a diagnosis of brain death should be confirmed by at least two doctors, one of whom is a specialist in neurology (D).The order of examination is irrelevant, i.e., it does not matter whether the neurologist performs the first or the second examination. A later CFM ruling established that a diagnosis of brain death may be performed by a neurosurgeon or a pediatric neurologist instead of a specialist in neurology.
The minimum interval between the two clinical assessments required for the determination of brain death varies according to the age of the individual as follows (D):48 hours for infants aged 7 days to under 2 months old; 24 hours for infants aged 2 months to under 1 year old; 12 hours for infants aged 1 to under 2 years old; and 6 hours for individuals over 2 years old.
The interval between clinical assessments varies considerably at the global level (D). [bib_ref] Brain death worldwide: accepted fact but no global consensus in diagnostic criteria, Wijdicks [/bib_ref] [bib_ref] Brain death documentation: analysis and issues, Wang [/bib_ref] Although CFM resolution no. 1,480 regulates the duration of this interval, the time interval defined for the diagnosis of brain death per age range is arbitrary (D). | en | apollo | train |
beta-Naphthoflavone and 3'-methoxy-4'-nitroflavone exert ambiguous effects on Ah receptor-dependent cell proliferation and gene expression in rat liver 'stem-like' cells.
Both natural and synthetic flavonoids are known to interact with the aryl hydrocarbon receptor (AhR); however, their agonist/antagonist properties in vitro have been so far studied mostly in the context of cytochrome P450 1A1 gene (Cyp1a1) regulation. We investigated effects of two synthetic flavones known either as AhR agonist (beta-naphthoflavone; BNF) or antagonist (3'-methoxy-4'-nitroflavone; 3M4NF), using an in vitro model of liver 'stem-like' cells, on expression of various AhR target genes and AhR-dependent cell proliferation. We found that the presumed antagonist 3M4NF induces a partial nuclear translocation and activation of AhR. Although inhibiting the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced Cyp1a1 expression, 3M4NF alone induced a minor increase of CYP1A1 mRNA and protein. However, 3M4NF did not induce AhR binding to synthetic dioxin response elements (DRE). In contrast to Cyp1a1, 3M4NF induced a marked expression of other AhR-regulated genes, such as Cyp1b1 and Nqo1, as well as transcriptional repression of Cdh13 gene, confirming that its effects may be promoter-context specific. Like BNF, 3M4NF induced AhR-dependent cell proliferation of contact-inhibited rat liver 'stem-like' WB-F344 cells, associated with a marked upregulation of Cyclin A, as well as the downregulation of proteins involved in formation of cell-cell contacts. Based on these experimental findings, we conclude that partial agonists/antagonists of AhR can increase cell proliferation rate and AhR-dependent genes expression in both cell type- and gene-specific manner. The specificity of effects of flavones on diverse AhR targets should be taken into account, when studying AhR signaling using presumed AhR antagonists. | en | apollo | train |
A dehiscent, prolapsed facial nerve protruding over the footplate is prone to injury.Facial paralysis: resulting from injury to the facial nerve.4.Care should be taken not to injure the chorda tympani when removing the posterosuperior bony canal rim,
4.13. 13. The EAC is packed with gelatin sponge and iodoform gauze, suture the first incision. ### Special Comments
1. 1. Expose the oval window, long process of the incus, and facial canal adequately. 2. 2. The mobility of all three ossicles should be assessed. 3. 3. Pay attention to the integrity of the facial canal and its relationship with the oval window. 4. 4. Avoid applying epinephrine cotton ball for hemostasis in tympanic cavity after opening of the oval window. 5. 5. Avoid using suction directly over the opening of the oval window. 6. 6. The mucosa of the oval window niche should be removed before sealing the oval window with fat. 7. 7. The length of the prosthesis should be long enough for its medial end to enter the perilymph fluid without contacting the membranous labyrinth. 8. 8. The crook of the prosthesis should be crimped on the long process of the incus adequately to avoid incus erosion. 9. 9. Bed rest for 3 days after operation, avoiding straining and nose blowing. 10. 10. Avoid air travel for at least 1 month to reduce the risk of significant changes in middle ear pressure and displacement of the tympanic membrane and prosthesis. ### Complications
1. 1. Sensorineural hearing loss: It is usually irreversible. Trauma to the inner ear should be avoided during operation. 2. 2. Vertigo or dizziness: This symptom is not common after surgery, but may be due to loss of perilymph fluid, surgical trauma, protrusion of prosthesis to the utricle, or serous labyrinthitis. 3. 3. Loss or distortion of taste affecting the tongue on the side of the operation: This symptom is caused by severance of or trauma to the chorda tympani nerve. Care should be taken not to injure the chorda tympani when removing the posterosuperior bony canal rim,
4. 4. Facial paralysis: resulting from injury to the facial nerve. A dehiscent, prolapsed facial nerve protruding over the footplate is prone to injury.5.5.Perilymph fistula: resulting from failure to seal the oval window.The mucosa of the oval window niche should be removed before sealing the window with fat or fascia.6.6.Tympanic membrane perforation: due to failure to effectively repair a torn tympanic membrane.Special care should be take not to tear the tympanic membrane when elevating the annulus. | en | apollo | train |
Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity.
When prototrophic yeast cells are cultured under nutrient-limited conditions that mimic growth in the wild, rather than in the high-glucose solutions used in most laboratory studies, they exhibit a robustly periodic metabolic cycle. Over a cycle of 4 to 5 hours, yeast cells rhythmically alternate between glycolysis and respiration. The cell division cycle is tightly constrained to the reductive phase of this yeast metabolic cycle, with DNA replication taking place only during the glycolytic phase. We show that cell cycle mutants impeded in metabolic cycle-directed restriction of cell division exhibit substantial increases in spontaneous mutation rate. In addition, disruption of the gene encoding a DNA checkpoint kinase that couples the cell division cycle to the circadian cycle abolishes synchrony of the metabolic and cell cycles. Thus, circadian, metabolic, and cell division cycles may be coordinated similarly as an evolutionarily conserved means of preserving genome integrity. | en | apollo | train |
(A) The experimental setup showing recording of thalamocortical neurons with stimulation of mechanoreceptor. (B) Histology image showing location of the recording electrodes in somatosensory thalamus (VPM). (C) Thalamic neuron fires in a tonic manner to 100 Hz stimulation at 0.6% isoflurane. Increasing the isoflurane dose to 1.0% causes the neuron to fire primarily only to the onset of the stimulation. Increasing the isoflurane dose to 1.2% causes the neuron to fire essentially only an initial burst of activity with the simulation onset. Recovery of the tonic firing ability occurs when the isoflurane dose is once again set to 0.6%. Thus, somatosensory throughput through the thalamus is reduced with increasing dose of isoflurane in a repeatable and reversible manner. The cellular mechanism or mechanisms through which a thalamic consciousness switch might work remain unknown. Nevertheless, two facts converge to suggest that neuronal nicotinic acetylcholine receptors (nAChRs) are a plausible anaesthetic target. First, neuronal nAChRs are potently inhibited by many anaesthetics at subanaesthetic doses [67, 68]. This fact suggests that nAChRs are inhibited in significant proportions at the concentration of anaesthesia associated with a loss of consciousness. Second, the α4β2 subtype of the nAChR has its highest density of expression in the thalamus [69], suggesting that the localized decrease in regional thalamic activity seen in anaesthesia brain imaging studies might be due to a regionally localized antagonism of nAChRs and might really be a reflection of a localized direct action of anaesthetics on the thalamus and not just a secondary reduction caused by decreased corticothalamic activity.This idea was tested in sevoflurane anaesthetized rats that were given enough sevoflurane to induce a loss of the righting reflex (LORR – a correlate for unconsciousness).With rats rendered unconscious, minuscule amounts of nicotine were microinfused into the thalamus of each rat through a previously implanted cannula that was aimed at the central medial (CM) nucleus of the thalamus. | en | apollo | train |
Stimulant psychosis is a mental disorder characterized by psychotic symptoms (e.g., hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or several day 'binge' on psychostimulants; however, it has also been reported to occur in approximately 0.1% of individuals, or 1 out of every 1,000 people, within the first several weeks after starting amphetamine or methylphenidate therapy. Methamphetamine psychosis, or long-term effects of stimulant use in the brain (at the molecular level), depend upon genetics and may persist for some time.
The most common causative agents are substituted amphetamines, including substituted cathinones, as well as certain dopamine reuptake inhibitors such as cocaine and phenidates.
Signs and symptoms
The symptoms of stimulant psychosis vary depending on the drug ingested, but generally involve the symptoms of organic psychosis such as hallucinations, delusions, or paranoia. Other symptoms may include mania, erratic behavior, agitation and/or aggression.
Cause
Substituted amphetamines
Drugs in the class of amphetamines, or substituted amphetamines, are known to induce "amphetamine psychosis" typically when chronically abused or used in high doses. In an Australian study of 309 active methamphetamine users, 18% had experienced a clinical level psychosis in the past year. Commonly abused amphetamines include methamphetamine, MDMA, 4-FA, as well as substituted cathinones like a-PVP, MDPV, and mephedrone, though a large number of other closely related compounds have been recently synthesized. Methylphenidate is sometimes incorrectly included in this class, although it is nonetheless still capable of producing stimulant psychosis.
The symptoms of amphetamine psychosis include auditory and visual hallucinations, grandiosity, delusions of persecution, and delusions of reference concurrent with both clear consciousness and prominent extreme agitation. A Japanese study of recovery from methamphetamine psychosis reported a 64% recovery rate within 10 days rising to an 82% recovery rate at 30 days after methamphetamine cessation. However it has been suggested that around 5–15% of users fail to make a complete recovery in the long term. Furthermore, even at a small dose, the psychosis can be quickly reestablished. Psychosocial stress has been found to be an independent risk factor for psychosis relapse even without further substituted amphetamine use in certain cases.
The symptoms of acute amphetamine psychosis are very similar to those of the acute phase of schizophrenia although in amphetamine psychosis visual hallucinations are more common and thought disorder is rare. Amphetamine psychosis may be purely related to high drug usage, or high drug usage may trigger an underlying vulnerability to schizophrenia. There is some evidence that vulnerability to amphetamine psychosis and schizophrenia may be genetically related. Relatives of methamphetamine users with a history of amphetamine psychosis are five times more likely to have been diagnosed with schizophrenia than relatives of methamphetamine users without a history of amphetamine psychosis. The disorders are often distinguished by a rapid resolution of symptoms in amphetamine psychosis, while schizophrenia is more likely to follow a chronic course.
Although rare and not formally recognized, a condition known as Amphetamine Withdrawal Psychosis (AWP) may occur upon cessation of substituted amphetamine use and, as the name implies, involves psychosis that appears on withdrawal from substituted amphetamines. However, unlike similar disorders, in AWP, substituted amphetamines reduce rather than increase symptoms, and the psychosis or mania resolves with resumption of the previous dosing schedule.
Cocaine
Cocaine has a similar potential to induce temporary psychosis with more than half of cocaine abusers reporting at least some psychotic symptoms at some point. Typical symptoms of sufferers include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom.
Cocaine-induced psychosis shows sensitization toward the psychotic effects of the drug. This means that psychosis becomes more severe with repeated intermittent use.
Phenidates
Methylphenidate and its analogues (e.g., ethylphenidate, 4F-MPH, and isopropylphenidate) share similar pharmacological profiles as other norepinephrine-dopamine reuptake inhibitors. Chronic abuse of methylphenidate has the potential to lead to psychosis. Similar psychiatric side effects have been reported in a study of ethylphenidate. No studies regarding psychosis and 4F-MPH or isopropylphenidate have been conducted, but given their high DAT binding and cellular uptake activity, the possibility of stimulant psychosis remains.
Caffeine
There is limited evidence that caffeine, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.
Diagnosis
Differential diagnosis
Though less common than stimulant psychosis, stimulants such as cocaine and amphetamines as well as the dissociative drug phencyclidine (PCP, angel dust) may also cause a theorized severe and life-threatening condition known as excited delirium. This condition manifests as a combination of delirium, psychomotor agitation, anxiety, delusions, hallucinations, speech disturbances, disorientation, violent and bizarre behavior, insensitivity to pain, elevated body temperature, and hysterical strength. Despite some superficial similarities in presentation excited delirium is a distinct (and more serious) condition than stimulant psychosis. The existence of excited delirium is currently debated.
Transition to schizophrenia
A 2019 systematic review and meta-analysis by Murrie et al found that the pooled proportion of transition from amphetamine-induced psychosis to schizophrenia was 22% (5 studies, CI 14%–34%). This was lower than cannabis (34%) and hallucinogens (26%), but higher than opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were slightly lower in older cohorts but were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up.
Treatment
Treatment consists of supportive care during the acute intoxication phase: maintaining hydration, body temperature, blood pressure, and heart rate at acceptable levels until the drug is sufficiently metabolized to allow vital signs to return to baseline. Typical and atypical antipsychotics have been shown to be helpful in the early stages of treatment. In the instance of persistent psychosis after repeated use of stimulants, there are cases in which electroconvulsive therapy has been beneficial. This is followed by abstinence from psychostimulants supported with counseling or medication designed to assist the individual preventing a relapse and the resumption of a psychotic state.
See also
Amphetamine
Delusional parasitosis
Dopamine hypothesis of psychosis
Excited delirium
Psychosis
Substance-induced psychosis
Neuroleptic malignant syndrome
References
External links
Psychosis
Biology of bipolar disorder
Amphetamine | en | apollo | train |
Nitric oxide-mediated posttranslational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability.
Nitric oxide (NO) regulates neuronal function and thus is critical for tuning neuronal communication. Mechanisms by which NO modulates protein function and interaction include posttranslational modifications (PTMs) such as S-nitrosylation. Importantly, cross signaling between S-nitrosylation and prenylation can have major regulatory potential. However, the exact protein targets and resulting changes in function remain elusive. Here, we interrogated the role of NO-dependent PTMs and farnesylation in synaptic transmission. We found that NO compromises synaptic function at the Drosophila neuromuscular junction (NMJ) in a cGMP-independent manner. NO suppressed release and reduced the size of available vesicle pools, which was reversed by glutathione (GSH) and occluded by genetic up-regulation of GSH-generating and de-nitrosylating glutamate-cysteine-ligase and S-nitroso-glutathione reductase activities. Enhanced nitrergic activity led to S-nitrosylation of the fusion-clamp protein complexin (cpx) and altered its membrane association and interactions with active zone (AZ) and soluble N-ethyl-maleimide-sensitive fusion protein Attachment Protein Receptor (SNARE) proteins. Furthermore, genetic and pharmacological suppression of farnesylation and a nitrosylation mimetic mutant of cpx induced identical physiological and localization phenotypes as caused by NO. Together, our data provide evidence for a novel physiological nitrergic molecular switch involving S-nitrosylation, which reversibly suppresses farnesylation and thereby enhances the net-clamping function of cpx. These data illustrate a new mechanistic signaling pathway by which regulation of farnesylation can fine-tune synaptic release. | en | apollo | train |
In more advanced cases (5–6 mm; degree II involvements), the initial cause-related treatment is frequently supplemented with surgery involving contouring of the inter-radicular bone (osteoplasty) or reduction of the tooth prominence at the furcation entrance by grinding (odontoplasty), in order to reduce the horizontal extension of the furcation involvement.43-31** Intrabony defect on the mesial aspect of a left maxillary premolar treated with a bioabsorbable barrier membrane. (a) Clinical attachment loss was 12 mm. (b) Radiograph showing the presence of a deep interproximal intrabony defect approaching the apex of the tooth. (c) A 7-mm interproximal intrabony defect was measured after flap elevation, defect debridement, and root planing. (d) A bioabsorbable barrier membrane has been placed and sutured to cover the defect. (e) At 1 year, a 4-mm pocket depth and 5-mm clinical gain of attachment were recorded. (f) The 1-year radiograph shows that the intrabony defect is almost resolved. ## Membranes for furcation involvement
The invasion of the furcation area of multi-rooted teeth by periodontitis represents a serious complication in periodontal therapy. The furcation area is often inaccessible to adequate instrumentation, and the roots frequently present concavities and furrows which make proper cleaning of the area impossible (see Chapter 39). As long as the pathologic process only extends a small distance (<5 mm; degree I and II involvements) into the furcation area, further progress of the disease can usually be prevented by scaling and root planing, provided a proper oral hygiene program is established after treatment. In more advanced cases (5–6 mm; degree II involvements), the initial cause-related treatment is frequently supplemented with surgery involving contouring of the inter-radicular bone (osteoplasty) or reduction of the tooth prominence at the furcation entrance by grinding (odontoplasty), in order to reduce the horizontal extension of the furcation involvement.However, both of these latter treatments involve a risk of complications on a long-term basis.Following tunnel preparation, caries frequently develops in the furcation area and root-resected teeth often present complications of non-periodontal nature, although controversial reports exist regarding the long-term results of these treatment modalities (Hamp _et al_.1975; Langer _et al_. | en | apollo | train |
In Vivo Study of Nasal Bone Reconstruction with Collagen, Elastin and Chitosan Membranes in Abstainer and Alcoholic Rats.
The aim of the present study was to evaluate the use of collagen, elastin, or chitosan biomaterial for bone reconstruction in rats submitted or not to experimental alcoholism. Wistar male rats were divided into eight groups, submitted to chronic alcohol ingestion (G5 to G8) or not (G1 to G4). Nasal bone defects were filled with clot in animals of G1 and G5 and with collagen, elastin, and chitosan grafts in G2/G6, G3/G7, and G4/G8, respectively. Six weeks after, all specimens underwent radiographic, tomographic, and microscopic evaluations. Bone mineral density was lower in the defect area in alcoholic animals compared to the abstainer animals. Bone neoformation was greater in the abstainer groups receiving the elastin membrane and in abstainer and alcoholic rats receiving the chitosan membrane (15.78 ± 1.19, 27.81 ± 0.91, 47.29 ± 0.97, 42.69 ± 1.52, 13.81 ± 1.60, 18.59 ± 1.37, 16.54 ± 0.89, and 37.06 ± 1.17 in G1 to G8, respectively). In conclusion, osteogenesis and bone density were more expressive after the application of the elastin matrix in abstainer animals and of the chitosan matrix in both abstainer and alcoholic animals. Chronic alcohol ingestion resulted in lower bone formation and greater formation of fibrous connective tissue. | en | apollo | train |
HIV-1 infection and HIV-1 Tat protein permit the survival and replication of a non-pathogenic trypanosomatid in macrophages through TGF-beta1 production.
Monoxenic trypanosomatids, which usually are non-pathogenic in humans, have been detected in AIDS patients, but the mechanisms underlying the establishment of these protozoa in HIV-1-infected individuals are poorly understood. Here we addressed the role of HIV-1 and the HIV-1 Tat protein in the replication of the monoxenic trypanosomatid Blastocrithidia culicis in HIV-1-infected primary human macrophages. We found that HIV-1 and B. culicis replication augmented almost three times in co-infected macrophages, and that Tat antiserum significantly reduced the exacerbated protozoan growth. Exposure of B. culicis only infected macrophages to Tat protein also resulted in enhanced protozoan proliferation, reaching a twofold increase at 100 ng/mL. Electron microscopy analysis revealed that B. culicis and HIV-1 co-habit the same cells, and showed protozoan dividing forms inside macrophages. Protozoan replication diminished when B. culicis only infected macrophages were treated with Tat protein in the presence of anti-TGF-beta1 antibodies, suggesting a participation of this cytokine in the augmentation of protozoan multiplication. In fact, exogenous TGF-beta1 promoted the trypanosomatid replication in macrophages. Overall, our results suggest that HIV-1 infection deactivates the macrophage microbicidal activity, permitting the survival and multiplication of an otherwise non-pathogenic protozoan in these cells, a process partially mediated by Tat protein, via TGF-beta1 secretion. | en | apollo | train |
May require nasogastric tube
3 Flushing of nasolacrimal ducts and antibiosis.Critical Care (Oxbow) or Recovery diet (Supreme Petfoods).Check blood glucose levels (normal range 6.0-8.9 mmol/L)
2 Syringe feeding with commercial feed suspensions, e.g.## Management
1 Chronic cases often cachexic - may need parenteral fluid support.2.11 Fluorescein can be used to check nasolacrimal duct patency.Calcium levels are readily responsive to dietary levels and calcium status is monitored with ionized calcium (total calcium 3.0-4.0 mmol/L; ionized 1.57-1.83 mmol/L)
5 Culture and sensitivity
a Aerobic and anaerobic culture of abscesses
6 Endoscopy
7 Examination of oral cavity under GA
8 Biopsy (osteosarcoma). Fig. 2.8 Buccal tilting and overgrowth of the upper first premolar. Fig. 2.9 Right lateral oblique skull showing osteolysis around the root of the left first mandibular premolar associated with a tooth root abscess; there is also overgrowth of the second premolar, first molar and incisor roots. Fig. 2.10 Explanatory diagram of Figure 2.9. Fig. 2.11 Fluorescein can be used to check nasolacrimal duct patency. ## Management
1 Chronic cases often cachexic - may need parenteral fluid support. Check blood glucose levels (normal range 6.0-8.9 mmol/L)
2 Syringe feeding with commercial feed suspensions, e.g. Critical Care (Oxbow) or Recovery diet (Supreme Petfoods). May require nasogastric tube
3 Flushing of nasolacrimal ducts and antibiosis.p.o.or co-trimoxazole at 30 mg/kg b.i.d.p.o._plus_
• anaerobic antibiosis, e.g.metronidazole at 10-20 mg/kg p.o.s.i.d.or procaine G benzylpenicillin at 20 000-60 000 IU/kg s.i.d.i.m., s.c.
• Drilling out of tooth root apices to initiate tooth root death where extraction is not viable
• Analgesia, e.g.meloxicam at 0.3 mg/kg p.o.s.i.d. | en | apollo | train |
Detecting Virus-Like Particles from the Umgeni River, South Africa.
It is important to consider viruses in water quality because of their incidence as causal agents for diarrhoeal disease, and due to their characteristics, which allow them to survive in changing environmental conditions indefinitely. This study assessed the viral quality of the Umgeni River in South Africa seasonally. A two-step tangential flow filtration process was setup to remove the bacteria and to concentrate the virus populations from large volume water samples. The concentrated water samples contained up to 659 and 550 pfu/mL of somatic and F-RNA coliphages, respectively. Several virus families including <i>Adenoviridae</i>, <i>Herpesviridae</i>, <i>Orthomyxoviridae</i>, <i>Picornaviridae</i>, <i>Poxviridae</i> and <i>Reoviridae</i> were found in the river based on the morphologies examined under transmission electron microscopy. All concentrated water samples produced substantial cytopathic effects on the Vero, HEK 293, Hela and A549 cell lines. These results indicate the potential of viruses in the water samples especially from the lower catchment areas of the Umgeni River to infect human hosts throughout the year. The present study highlights the importance of routine environmental surveillance of human enteric viruses in water sources. This can contribute to a better understanding of the actual burden of disease on those who might be using the water directly without treatment. | en | apollo | train |
Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia-reperfusion injury?
Ischaemia-reperfusion (I/R) injury is a common feature of several diseases associated with high morbidity and mortality, such as stroke and myocardial infarction. The damaged tissue displays cardinal signs of inflammation and microvascular injury that, unless resolved, lead to long-term tissue damage with associated dysfunction. Current therapies are limited and are often associated with many side effects. Increasing evidence suggests that members of the formyl peptide receptor (FPR) family, in particular human FPR2/ALX, might have an important role in the pathophysiology of I/R injury. It was recently demonstrated that several peptides and non-peptidyl small-molecule compounds have anti-inflammatory and pro-resolving properties via their action on members of the FPR family. Here I review this evidence and suggest that FPR ligands, particularly in the brain, could be novel and exciting anti-inflammatory therapeutics for the treatment of a variety of clinical conditions, including stroke. | en | apollo | train |
Nearly all patients with chronic critical illness leave the hospital with profound impairments of physical function, cognitive status or both, and most therefore require institutional care.The prognosis of patients with CCI is generally poor, surprisingly the hospital survival is about 50 % with a 1 year survival of approximately 25 %.The placement of a tracheostomy for long term ventilation is used by many to identify CCI patients [2]. Although prolonged dependence on mechanical ventilation is a hallmark of CCI, CCI is not simply an extended period of acute critical illness but a discreet syndrome including profound weakness attributed to myopathy, neuropathy, alteration in body composition, anasarca, neuroendocrine changes, brain dysfunction manifesting as coma or delirium, increased vulnerability to infections and skin breakdown leading to decubital ulceration [3–6]. Depending on the setting, CCI patients account for between 5 and 10 % of adult ICU admissions. It is estimated that there are currently approximately 100,000 CCI in the United States [2, 6]. This increasing number of CCI patients led to an 8.8 % increase in the number of long term acute care (LTAC) hospital beds between 1997 and 2006 [2]. Mechanically ventilated patients with a history of prior pulmonary disease and who require renal replacement therapy are at the greatest risk of CCI [3, 7–9]. These patients are usually elderly with a slight male predominance. Patients suffering postoperative complications make up a large percentage of CCI patients. These are usually patients with underlying cardio—pulmonary disease who have undergone cardiac or abdominal surgery. Trauma and burn patients as well as those with acute lung injury (ARDS) and patients with chronic respiratory failure (usually COPD) make up the majority of the remaining patients. CCI occurs in the setting of multiple episodes of sepsis with SIRS, multiorgan dysfunction syndrome (MODS) and respiratory failure. The prognosis of patients with CCI is generally poor, surprisingly the hospital survival is about 50 % with a 1 year survival of approximately 25 %. Nearly all patients with chronic critical illness leave the hospital with profound impairments of physical function, cognitive status or both, and most therefore require institutional care.Only about 10 % of CCI patients are alive at home and functionally independent at 1 year [2].In addition to the CCI patients who remain ventilator dependent and are managed in long term acute care facilities (LTAC) is an even larger group of patients who recover from their acute illness but suffer from long term disabilities, most notably neuromuscular dysfunction. | en | apollo | train |
Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state.
High intrahepatic expression levels of interferon stimulated genes (ISGs) in chronic hepatitis C patients are associated with poor response to interferon plus ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA, ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB, IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3, Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2. Expression levels of genes promoting antiviral state were positively correlated with each other but were not correlated with those that suppress antiviral state. Expression levels of some ISGs were inversely associated with common polymorphisms within the IL28B locus. Genes promoting antiviral state were expressed lower (e.g., ISG15, P = 1.42E-12 and MxA, P = 6.40E-11) in individuals with the protective rs12979860 CC genotype, and genes suppressing antiviral state were expressed higher (A20, P = 0.00107 and Zc3h12a, P = 0.00129, respectively), although some ISGs were not significant after the Bonferroni correction. The expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were independent predictors for non-response. These results suggest that rs12979860 genotype may be associated with response to combination therapy through an inverse relationship between antiviral and suppressor ISGs in the liver. | en | apollo | train |
Research led by scientists at The University of Melbourne, published in the International Journal of Cancer, could eventually improve treatments with the identification of a protein that appears to help tumour cells become more aggressive.
Scientists, led by Associate Professor Mehrdad Nikfarjam, have identified a protein called p21-activated kinase 1 (PAK1), in the tumor environment of pancreatic cancer. It was previously found that PAK1 was in pancreatic tumor cells and targeting this protein, in combination with current chemotherapies, resulted in decreased tumor growth and spread in a model of pancreatic cancer in mice.
Now, the team has determined that PAK1 is also involved in the tumor environment of pancreatic cancer and specifically in a cell type called the stellate cells. Stellate cells are responsible for the fibrosis (scarring) observed surrounding the pancreatic tumour cells, that reduces the effectiveness of chemotherapy.
The current study investigated the role of PAK1 in these stellate cells and how they communicate with the tumor cells. PAK1 was found to be involved in the fibrotic production, proliferation and death of these cells and could assist tumor cells to a become more aggressive. Targeting PAK1 in the tumor environment in mice resulted in decreased fibrosis (scar tissue formation), reduced tumour growth, increased tumour sensitivity to chemotherapy and increased survival of mice with pancreatic cancer. Although further testing is needed, an inhibitor could potentially increase survival of patients with pancreatic cancer.
“Communication between stellate cells and tumor cells is important, leading to the aggressiveness of pancreatic tumors” Lead author Dannel Yeo said. “Targeting PAK1 could reduce the fibrosis surrounding pancreatic tumors and allow conventional chemotherapies to have greater effects on the tumours”. | en | apollo | train |
Then, labor accelerated much faster in multiparas.Rates for multiparas were similar from 4 to 6 cm.They found that normal labor may take more than 6 hours to progress from 4 to 5 cm and more than 3 hours to progress from 5 to 6 cm dilation.But, the standard deviation of 3.4 hours is large, hence, the active phase was reported to have a statistical maximum of 11.7 hours. Indeed, rates of cervical dilation ranged from a minimum of 1.2 up to 6.8 cm/hr. Friedman (1972) also found that multiparas progress somewhat faster in active-phase labor, with a minimum normal rate of 1.5 cm/hr. His analysis of active-phase labor concomitantly describes rates of fetal descent and cervical dilation (see Fig. 22-18). Descent begins in the later stage of active dilation, commencing at 7 to 8 cm in nulliparas and becoming most rapid after 8 cm. Hendricks and coworkers (1970) challenged Friedman's conclusions about the course of normal human labor. Their principal diferences included: (1) absence of a latent phase, (2) no deceleration phase, (3) brevity ofilabor, and (4) dilation at similar rates for nulliparas and multiparas after 4 cm. They disputed the concept of a latent phase because they observed that the cervix dilated and efaced slowly during the 4 weeks preceding labor. They contended that the latent phase actually progressed over several weeks. hey also reported that labor was relatively rapid. Specifically, the average time from admission to complete dilation was 4.8 hours for nulliparas and 3.2 hours for multiparas. Others have reassessed the Friedman labor curves. Zhang and associates (2010) studied electronic labor records from 62,415 parturients with spontaneous labor at term and vaginal birth. For nulliparas, the median time to progress from 4 to 5 cm was 1.3 hours, from 5 to 6 cm 0.8 hours, and thereafter, additional centimeters were gained approximately each 0.5 hours. They found that normal labor may take more than 6 hours to progress from 4 to 5 cm and more than 3 hours to progress from 5 to 6 cm dilation. Rates for multiparas were similar from 4 to 6 cm. Then, labor accelerated much faster in multiparas.In a study performed at Parkland Hospital, epidural analgesia was found to lengthen the active phase of the Friedman labor curve by 1 hour (lexander, 2002).his increase was the result of a slight but significant decline in the rate of cervical dilation-1.4 cm/hr in women given epidural analgesia compared with 1.6 cm/hr in those without such analgesia. | en | apollo | train |
(40, 64, 67).The study of progressive stages of malignant neoplastic growth by numerous investigators has clearly demonstrated that tumor progression leads to the selection of more aggressive, malignant tumor cells as progression ensues.Westin EH, Wong-Staal F, Gelmann EP, et al: Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci USA 79:2490-2494, 1982
66. Wolman SR: Karyotypic progression in human tumors. Cancer Met Rev 2:257-293, 1983
67. Yuasa Y, Srivastava SK, Dunn CY, et al: Acquisition of transforming properties by alternative point mutations with c-bas/has human proto-oncogene. Nature 303:775-779, 1983. # 15
Oncogene Products as Potential therapeutic Targets for Control of Established Metastatic Disease
Ronald H. Goldfarb and Kenneth W. Brunson
## INTRODUCTION
An explosive pace of research has developed in the last several years exploring the role of oncogenes and their products (see preceding Chapters, -, this volume). The potential of elucidating the molecular mechanisms operative in neoplastic transformation has generated widespread excitement and research interest within the scientific community, particularly among cancer biologists. A large component of research performed in this area has been directed towards understanding the biochemical and molecular basis of the initiation and promotion of the transformed phenotype of cells that have undergone oncogenic transfection in cell culture (4, 26, 46, 47, 51, 89, 90). A variety of studies have also indicated that oncogenes and their products may also contribute to additional aspects of tumor progression (5, 46, 47, 62, 87). Most recently, a number of research groups have carried out investigations to ascertain whether oncogenes and their encoded gene products contribute to the progressive stages of malignant neoplastic growth resulting in tumor invasion in tumor invasion and metastatic spread (1, 6, 7, 19, 20, 21, 22, 49, 68, 80, 85). The study of progressive stages of malignant neoplastic growth by numerous investigators has clearly demonstrated that tumor progression leads to the selection of more aggressive, malignant tumor cells as progression ensues. (40, 64, 67).It has been suggested that this biological and clinical progression might reflect, at least in part, the sequential appearance within the tumor of increasingly genetically altered heterogeneous tumor cell subpopulations with new characteristics (64).The occurrence of tumor progression transcends academic interest or curiosity. | en | apollo | train |
A case presenting concurrence of Marfan syndrome, Basedow's disease and Arg353Gln polymorphism-related factor VII deficiency.
We report the case of a 48-year-old Japanese man who suffered from Marfan syndrome with severe aortic regurgitation, mitral regurgitation and rapid atrial fibrillation, which were aggravated by hyperdynamic circulatory conditions associated with coexistent Basedow's disease. Furthermore, concurrence of Arg353Gln polymorphism-related factor VII deficiency was discovered at the preoperative assessments. Both of his two brothers suffered from Marfan syndrome; however they had no findings of Arg353Glu polymorphism-related factor VII deficiency or Basedow's disease. After normalization of thyroid function, he had successfully the operations of Bentall procedure: a composite prosthetic graft: replacement of both the ascending aorta and aortic valve, and mitral valve annuloplasty. No specific therapy such as fresh frozen plasma or factor VII replacement therapy was required. He completely returned to his business work 6 weeks after the operation. Concurrence of Marfan syndrome and factor VII deficiency induced by two-hit genomic abnormalities and furthermore Basedow's disease, which significantly compromised the pathophysiological condition of Marfan syndrome, is extremely rare. | en | apollo | train |
Because FLT3-ITD can be targeted with emerging novel inhibitors, patients with this molecular abnormality should be considered for clinical trials with these agents whenever possible.Indeed, postremission therapy is also a setting for introduction of new agents (Table 132-5).If a suitable HLA donor does not exist, investigational therapeutic approaches are considered.The toxicity is relatively low with
Class of Drugs Examples of Agents in Class
Inhibitors of Mutant proteins
Tyrosine kinase inhibitors Dasatinib, midostaurin, quizartinib, sorafenib IDH2 mutation inhibitor AG-221
Inhibitors of Cell Proliferation
Inhibitors of Protein Synthesis and Degradation
HSP-90 antagonists 17-Allylaminogeldanamycin (17-AAG), DMAG, or derivatives
Nucleoside analogues Clofarabine, troxacitabine, elacytarabine, sapacitabine
Compounds with Immuno-Mediated Mechanisms
Antibodies CSL362 (anti-CD123), anti-CD33 (SGN33), anti-KIR
Immunomodulatory Lenalidomide, interleukin 2, histamine dihydrochloride autologous HSCT (5% mortality rate), but the relapse rate is higher than with allogeneic HSCT, due to the absence of the graft-versusleukemia (GVL) effect seen with allogeneic HSCT and possible contamination of the autologous stem cells with residual tumor cells. Prognostic factors may ultimately help to select the appropriate postremission therapy in patients in first CR. Our approach includes allogeneic HSCT in first CR for patients without favorable cytogenetics or genotype (e.g., patients who do not have CEBPA biallelic mutations or NPM1 mutations without FLT3-ITD) and/or with other poor risk factors (e.g., an antecedent hematologic disorder or failure to attain remission with a single induction course). If a suitable HLA donor does not exist, investigational therapeutic approaches are considered. Indeed, postremission therapy is also a setting for introduction of new agents (Table 132-5). Because FLT3-ITD can be targeted with emerging novel inhibitors, patients with this molecular abnormality should be considered for clinical trials with these agents whenever possible.Among AML patients with t(8;21) and inv(16), those with KIT mutations, who have a worse prognosis, may be considered for novel investigational studies, including tyrosine kinase inhibitors.The inclusion of gemtuzumab ozogamicin in induction and consolidation chemotherapy-based treatment has been reported to be beneficial in this subset of patients. | en | apollo | train |
Feline acne is a problem seen in cats primarily involving the formation of blackheads accompanied by inflammation on the cat's chin and surrounding areas that can cause lesions, alopecia, and crusty sores. In many cases symptoms are mild and the disease does not require treatment. Mild cases will resemble dirt on the cat's chin, but the "dirt" will not brush off. More severe cases, however, may respond slowly to treatment and seriously detract from the health and appearance of the cat. Feline acne can affect cats of any age, sex or breed, although Persian cats are also likely to develop acne on the face and in the skin folds. This problem can happen once, be reoccurring, or even persistent throughout the cat's life.
Sebaceous glands are skin glands that produce oil and are mostly found in the skin of the chin, at the base of the tail, and in the eyelids, lips, prepuce, and scrotum. They are connected to hair follicles. In acne, the follicles become clogged with black sebaceous material, forming comedones (also known as blackheads). Comedones can become irritated, swollen, infected, and ultimately pustules. These may elicit itching and discomfort due to swelling and bacterial growth inside infected glands. Bacterial folliculitis occurs when follicules become infected with Staphylococcus aureus, and commonly associated with moderate-to-severe feline acne. Secondary fungal infections by Malassezia may also occur.
Other conditions that can cause similar-appearing conditions include skin mites, ringworm, yeast infection, or autoimmune diseases such as eosinophilic granuloma complex ("rodent ulcers"). These can be ruled out by a simple biopsy of affected cells.
Feline acne is one of the top five most common skin conditions that veterinarians treat.
Causes
Although the exact cause of feline acne is unknown, some causes include:
Hyperactive sebaceous glands
Poor hygiene
Stress
Developing secondary to fungal, viral, and bacterial infections
Reaction to medication
Eating or drinking from plastic containers. While it has commonly been suggested that cats are "allergic" to these containers, recent research suggests that plastic containers harbour bacteria due to irregular surfaces.
Demodicosis or mange, causing itchiness and hair loss
Suppressed immune system
Hair follicles that don't function properly
Rubbing the chin (to display affection or mark territory) on non-sanitized household items
Hormonal imbalance
Contracting the infection from other cats in the same household
Obese cats which have difficulty grooming themselves are predisposed to dry, flaky skin and feline acne.
Treatment
Topical treatments such as warm compresses to the chin area may be sufficient for mild cases. Veterinary intervention may be required for treatment if secondary infection occurs. In this case, treatment may begin with clinical drainage of the pustules and a course of oral antibiotics.
Clearing the acne can be accomplished using an extra-soft bristled toothbrush or flea comb (one designated for this purpose) to brush the cat's chin. This will loosen debris and remove dried scabs. Epsom-salt compresses applied twice daily dry the affected area to relieve the inflammation and itchiness.
Prevention
Placing the cat's water in a shallow dish may prevent the chin from absorbing the bacteria in the water while the cat is drinking. If the cat is allergic to plastics or dyes, using a stainless-steel or glass dish is recommended . Cats may also have food allergies that make the development of acne more likely, so that switching kibble, or changing to a hydrolysed diet may be effective. Maintaining good hygiene and grooming habits make the development of feline acne less likely. Washing and exfoliating the chin with a gentle benzoyl-peroxide solution also may be preventive of further outbreaks.
References
External links
Cat diseases
Acneiform eruptions | en | apollo | train |
The present data strongly suggest that LUTS are associated with chronic ischaemia of the prostate and urinary bladder. alpha-blockers increase perfusion in the LUT and C(max). These results might explain the therapeutic effects of alpha-blockers on LUTS. | en | apollo | train |
Recent research that questioned the potential of antioxidants to fight against aging has elicited a number of reactions from the industry, questioning the relevance of the findings to human skin.
Earlier this month researchers, led by Dr. David Gems at the University of London published work that questioned the role of oxidative damage in the aging of C. elegans (nematode worm) by knocking out the genes for superoxide dismutase, an important antioxidant enzyme. Although the research only focused on this one organism, the scientists concluded that when the study’s results are taken in conjunction with similar research, the universal acceptance of the oxidative theory of aging is undermined.
The theory that aging is caused by an accumulation of molecular damage resulting from oxidative damage has, according to Dr. Gems, filled a knowledge gap for more than fifty years. But in his opinion it doesn’t stand up to the evidence. “But there is no clear evidence that dietary antioxidants can slow or prevent aging. There is even less evidence to support the claims of most anti-aging products,” he said.
Industry insiders and dermatologists, however, have taken issue with these conclusions highlighting a body of evidence that supports the use of both dietary and topically applied antioxidants.
An industry insider, who requested to remain nameless, referred to this body of evidence as the ‘elephant in the room.’ “A large body of quality peer-reviewed studies show vitamin C and other antioxidants reduce the appearance of fine lines and wrinkles by protecting cells from free radical damage and by stimulating the production of collagen,” he said.
Palmer and Kitchin explain that free radicals can promote the oxidation of nucleic acids, proteins and lipids and can damage intracellular structures, including DNA. “In addition, free radicals cause an increase in the production of transcription factors such as activator protein 1, which produces metalloproteinases that can break down collagen, causing wrinkling of the skin,” they added. They also noted the body of evidence that supports the ability of antioxidants to prevent the immunosuppressant action of UV light that can promote skin cancer formation.
Furthermore, Kitchin and Palmer note that superoxide dismutase (the gene knocked out in the C. elegans research) is not the only defense an organism can employ against reactive oxygen species.
Therefore, for the two dermatologists, as for much of the industry, topical antioxidant application remains an exciting and promising area of anti-aging study and treatment. | en | apollo | train |
Real Time Ultrasound Imaging is an essential tool and service used and provided for by physical therapists in Australia and across Europe. It is rapidly gaining popularity in the US and all over the globe.
RTUS is now being used to improve outcomes of hip, neck, and shoulder pain, and is being popularised by its implications for the rehabilitation of back pain and spinal stability retraining (Hides, Jill, Richardson, and Hodges).
Real-time ultrasound imaging, in conjunction with physiotherapy techniques, facilitates recovery and aids in the prevention of many musculoskeletal conditions of the back, pelvis and hips. The technology is used to assess the function and monitor the retraining and strengthening of the core stabilizing muscles, including the pelvic floor musculature, transversus abdominus and multifidus.
Real-time Ultrasound Imaging provides a moving image of the muscles, allowing the physiotherapist to point out which muscles should be working and when you are activating them correctly. This feedback is a very valuable tool when learning to recruit these muscles correctly. With training, these muscles can return to more normal functioning, activating automatically when required.
The equipment used in real-time ultrasound imaging is non-invasive and does not use radiation. A real-time ultrasound imaging appointment usually takes up to an hour to complete, depending on the number of areas requiring imaging. Your physiotherapist will determine whether a real-time ultrasound session would be of benefit to you. When attending a real-time ultrasound appointment, please ensure you have a full bladder as this greatly enhances the image clarity. The sessions are claimable on private health insurance with extras.
Functional core stability is essential in our daily activities. It allows us to maintain an upright posture and fix our trunk in position so we can move our limbs with accuracy and strength. Without sufficient strength and endurance in our core stabilizing muscles, our body is vulnerable to injury, and this can also lead to back pain, poor posture and lethargy. | en | apollo | train |
Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in combination with pseudoephedrine, a decongestant, known as loratadine/pseudoephedrine. It is taken by mouth.
Common side effects include sleepiness, dry mouth, and headache. Serious side effects are rare and include allergic reactions, seizures, and liver problems. Use during pregnancy appears to be safe but has not been well studied. It is not recommended in children less than two years old. It is in the second-generation antihistamine family of medication.
Loratadine was patented in 1980 and came to market in 1988. It is on the World Health Organization's List of Essential Medicines. Loratadine is available as a generic medication. In the United States, it is available over the counter. In 2019, it was the 66th most commonly prescribed medication in the United States, with more than 11million prescriptions.
Medical uses
Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria, and other skin allergies. For allergic rhinitis, loratadine is indicated for both nasal and eye symptoms - sneezing, runny nose, and itchy or burning eyes.
Similarly to cetirizine, loratadine attenuates the itching associated with Kimura's disease.
Forms
The drug is available in many different forms, including tablets, oral suspension, and syrup, and in combination with pseudoephedrine. Also available are quick-dissolving tablets.
Contraindications
Patients with severe hepatic (liver) disorders may need to start with a lower dose. No dose adaptation is necessary for elderly or renally (kidney) impaired patients.
Loratadine is usually compatible with breastfeeding (classified category L-2 - probably compatible, by the American Academy of Pediatrics). In the U.S., it is classified as category B in pregnancy, meaning animal reproduction studies have failed to demonstrate a risk to the fetus, but no adequate and well-controlled studies in pregnant women have been conducted.
Adverse effects
As a "non-sedating" antihistamine, loratadine causes less (but still significant, in some cases) sedation and psychomotor retardation than the older antihistamines because it penetrates the blood/brain barrier to a smaller extent.
Other possible side effects include headache and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal problems.
Interactions
Substances that act as inhibitors of the CYP3A4 enzyme such as ketoconazole, erythromycin, cimetidine, and furanocoumarin derivatives (found in grapefruit) lead to increased plasma levels of loratadine — that is, more of the drug was present in the bloodstream than typical for a dose. This had clinically significant effects in controlled trials of 10 mg loratadine treatment
Antihistamines should be discontinued 48 hours prior to skin allergy tests, since these drugs may prevent or diminish otherwise-positive reactions to dermal activity indicators.
Pharmacology
Pharmacodynamics
Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H1 receptors. The potency of second generation histamine antagonists is (from strongest to weakest) desloratadine (Ki 0.4 nM) > levocetirizine (Ki 3 nM) > cetirizine (Ki 6 nM) > fexofenadine (Ki 10 nM) > terfenadine > loratadine. However, the onset of action varies significantly and clinical efficacy is not always directly related to only the H1 receptor potency, as concentration of free drug at the receptor must also be considered. Loratadine also shows anti-inflammatory properties independent of H1 receptors. The effect is exhibited through suppression of the NF-κB pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells.
Pharmacokinetics
Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism; it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others. Loratadine is almost totally (97–99%) bound to plasma proteins. Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.
Loratadine's peak effect occurs after 1–2 hours, and its biological half life is on average eight hours (range 3 to 20 hours) with desloratadine's half-life being 27 hours (range 9 to 92 hours), accounting for its long-lasting effect. About 40% is excreted as conjugated metabolites into the urine, and a similar amount is excreted into the feces. Traces of unmetabolised loratadine can be found in the urine.
In structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.
History
Schering-Plough developed loratadine as part of a quest for a potential blockbuster drug: a nonsedating antihistamine. By the time Schering submitted the drug to the U.S. Food and Drug Administration (FDA) for approval, the agency had already approved a competitor's nonsedating antihistamine, terfenadine (trade name Seldane), and, therefore, put loratadine on a lower priority. However, terfenadine had to be removed from the U.S. market by the manufacturer in late 1997 after reports of serious ventricular arrhythmias among those taking the drug.
Loratadine was approved by the FDA in 1993. The drug continued to be available only by prescription in the U.S. until it went off patent in 2002. It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.
Schering also developed desloratadine (Clarinex/Aerius), which is an active metabolite of loratadine.
Society and culture
Over-the-counter
In 1998, in an unprecedented action, the American insurance company Anthem petitioned the FDA to allow loratadine and two other antihistamines to be made available over the counter (OTC) while it was still under patent; the FDA granted the request, which was not binding on manufacturers. In the US, Schering-Plough made loratadine available OTC in 2002. As of 2015 loratadine was available in many countries OTC.
Brands
As of 2017, loratadine was available under many brand names and forms worldwide, including several combination drug formulations with pseudoephedrine, paracetamol, betamethasone, ambroxol, salbutamol, phenylephrine, and dexamethasone.
brands included: Actalor, Actidin, Aerotina, Alaspan, Alavert, Albatrina, Alerdina, Alerfast, Alergan, Alergiano, Alergiatadina, Alergin Ariston, Alergipan, Alergit, Alergitrat L, Aleric Lora, Alermuc, Alernitis, Alerpriv, Alertadin, Alertine, Aleze, Algac, Algecare, Algistop, Alledryl, Aller-Tab, Allerfre, Allerget, Allergex Non Drowsy, Allergyx, Allerhis, Allernon, Allerta, Allertyn, Allohex, Allor, Allorat, Alloris, Alor, Analor, Anhissen, Anti-Sneeze, Antial, Antil, Antimin, Ao Hui Feng, Ao Mi Xin, Ao Shu, Ardin, Atinac, Avotyne, Axcel Loratadine, Bai Wei Le, Bang Nuo, Bedix, Belodin, Benadryl, Besumin, Bi Sai Ning, Bi Yan Tong, Biliranin, Biloina, Biolorat, Bollinol, Boots Hayfever Relief, Boots Hooikoortstabletten, Boots Once-a-Day Allergy Relief, Carin, Carinose, Chang Ke, Civeran, Clara, Claratyne, Clarid, Clarihis, Clarihist, Clarilerg, Clarinese, Claritin, Claritine, Clarityne, Clarityne SP, Clarotadine, Clatatin, Clatine, Clear-Atadine, Clear-Atadine Children's, Clistin, Contral, Cronitin, Da Sheng Rui Li, Dao Min Qi, Dayhist, Debimin, Desa, Devedryl, Dexitis, Dimegan, Dimens, Dimetapp Children's ND Non-Drowsy Allergy, Doliallérgie Loratadine, Effectine, Eladin, Elo, Emilora, Encilor, Eradex, Erolin, Ezede, Fei Ge Man, Finska, Flonidan, Flonidan Control, Florgan, Folerin, Frenaler, Fristamin, Fu Lai Xi, Fucole Minlife, Genadine, Glodin, Gradine, Halodin, Helporigin, Hisplex, Histaclar, Histafax, Histalor, Horestyl, Hua Chang, Hysticlar, Igir, Immunix, Immunex, Inclarin, Inversyn, Jin Su Rui, Jing Wei, Ke Mi, Klarihist, Klinset, Klodin, Kui Yin, Lallergy, Larotin, Latoren, Laura, LD, Lei Ning, Lesidas, Liberec, Lisaler, Logadine, Logista, Lohist, Lolergi, Lolergy, Lomidine, Lomilan, Loptame, Lora, Lora-Lich, Lora-Mepha Allergie, Loracare, Loracil, Loraclear, Loradad, Loraderm, Loradin, Loradine, Lorado Pollen, Loradon, Lorafix, Lorahexal, Lorahist, Lorakids, Loralab-D, Loralerg, Loralivio, Loramax, Loramin, Loramine, Loran, Lorange, Loranil, Lorano, Loranox, Lorantis, LoraPaed, Lorastad, Lorastamin, Lorastine, Lorastyne, Lorat, Loratab, Loratadim, Loratadin, Loratadina, Loratadine, Loratadinum, Loratadyna, Loratan, Loratin, Loraton, Loratrim, Loratyne, Lorchimin, Lordamin, Lordinex, Loremex, Loremix, Lorfast, Lorid, Loridin, Lorihis, Lorimox, Lorin, Lorine, Loristal, Lorita, Loritex, Loritin, Lorly, Lormeg, Lorsedin, Lortadine, Losta, Lostop, Lotadin, Lotadine, Lotarin, Lotin, Megalorat, Mildin, Min Li Ke, Minlife, Mintapp, Mosedin, Mudantil L, Nasaler, Neoday, Niltro, Non-Drowsy Allergy Relief, Nosedin, Noseling, Novacloxab, NT-Alergi, Nufalora, Nularef, Numark Allergy, Omega, Oradin, Oradine, Oramine, Orin, Orinil, Pollentyme, Pressing, Pretin, Primorix, Profadine, Pulmosan Aller, Pylor, Rahistin, Ralinet, Ramitin, Refenax, Restamine, Rhinigine, Rihest, Rinalor, Rinconad, Rinityn, Rinolan, Riprazo, Rityne, Roletra, Rotadin, Rui Fu, Run Lai, Rupton, Sensibit, She Tai, Shi Nuo Min, Shi Tai Shu, Shu Rui, Shun Ta Xin, Silora, Sinaler, Sohotin, Soneryl, Sunadine, Symphoral, Tabcin, Tai Ming Ke, Ticevis, Tidilor, Tinnic, Tirlor, Toral, Triaminic, Tricel, Tuulix, Urtilar, Utel, Vagran, Winatin, Xanidine, Xepalodin, Xian Ning, Xin Da Yue, Xing Yuan Jia, XSM, Xue Fei, Yi Fei, Yi Shu Chang, Yibang, Zhengshu, Zhi Min, Zifar, Zoratadine, and Zylohist.
, in a combination drug with pseudoephedrine, it was available under the brands: Airet, Alavert D-12, Aldisa SR, Alerfast D, Alergical LP, Alergin Plus Ariston, Alerpriv D, Alledryl-D, Allerpid, Aseptobron Descongestivo, Bai Wei Qing, Benadryl 24 D, Ciprocort D, Claridex, Claridon, Clarinase, Clarinase Repetab, Claritine Active, Claritin Allergy + Sinus, Clarityne, Clarityne D, Clarityne-D, Clear-Atadine, Coderin, Cronase, De-Cold, Decidex Plus, Decongess I, Defonase, Demazin NS, Dimegan-D, Effectine D, Ephedrol, Fedyclar, Finska-LP, Frenaler-D, Hui Fei Shun, Ke Shuai, Claritin-D, Larotin D, Lertamine, Lohist-Extra, Lora Plus, Loralerg D, Loranil-D, Loratin D, Loratin Plus, Lordinex D, Loremix D, Lorexin-D, Lorfast-D, Loridin-D, Lorinase, Minlife -P, Mosedin plus sr, Narine Repetabs, Nasaler Plus, Nularef-D, Oradin Plus, Pretin-D, Primorix-D, Rhinos SR, QiKe, Rinomex, Sinaler D, Sudamin, Sudolor, Tricel-D, Zhuang Qi, Zoman-D, and Zoratadine-P.
, in a combination drug with paracetamol, it was available as Sensibit D and in combination with paracetamol and pseudoephedrine, it was available as: Atshi, Clariflu, and Trimed Flu.
, in a combination drug with betamethasone, it was available as Celestamincort, Celestamine NF, Celestamine NS, Celestamine* L, Ciprocort L, Claricort, Clarityne cort, Corticas L, Cortistamin-L, Histafax Compuesto, Histamino Corteroid L, Labsalerg-B, Lisaler Beta, and Sinaler B, and in combination with betamethadol with available as Nularef Cort.
, in a combination drug with ambroxol, it was available as Aliviatos, Ambroclar, Antitusivo L Labsa, Bronar, Broncovital, Broquixol, Clarixol, Ideobron, Lorabrox, Lorfast-AM, Sensibit XP, and Toraxan, and in a combination drug with ambroxol and salbutamol as Sibilex.
, in a combination drug with phenylephrine, it was available as Bramin-Flu, Clarityne D, Clarityne Plus, Clarityne-D, Histafax D, Brafelix, Loramine R, Loraped, Maxiclear Cold & Nasal, Maxiclear Hayfever & Sinus Relief, and Rinavent, and in combination with phenylephrine and paracetamol it was available as Sensibit D NF.
, in a combination drug with dexamethasone it was available as Alerfast Forte and Frenaler Forte.
Marketing
The marketing of the Claritin brand is important in the history of direct-to-consumer advertising of drugs.
The first television commercial for a drug was aired in the US in 1983, by Boots, and sparked controversy. The FDA responded with strong regulation requiring disclosure of side effects and other information. These rules made pharmaceutical manufacturers balk at spending money on ads that had to highlight negative aspects.
In the mid-1990s, the marketing team for Claritin at Schering-Plough found a way around these rules. They created brand awareness commercials that never actually said what the drug was for, but instead showed sunny images, and the voiceover said things like "At last, a clear day is here" and "It's time for Claritin" and repeatedly told viewers to "ask your doctor" about Claritin. The first ads succeeded in making people aware of the brand and increased prescriptions, which led Schering-Plough and others to aggressively pursue the advertising strategy.
In 1998, a 12-page one shot comic based in the Batman: The Animated Series was given away to advertise Claritin. The book, written by PRIEST, penciled by Joe Staton, and inked by Mike DeCarlo, sees Tim Drake unable to perform his crime fighting duties due to the combination of hay fever and other antihistamines making him drowsy. After being given a prescription for Claritin he is able to arrive and save Batman from Poison Ivy.
This trend, along with advice from its attorneys that it could not win a First Amendment case on the issue, led the FDA to issue new rules for TV commercials in 1997. Instead of including the "brief summary" that took up a full page in magazine ads and would take too long to explain in a TV commercial, drug makers were allowed to refer viewers to print ads, 1-800 numbers, or websites, and urge people to talk to their doctor if they wanted additional information.
Schering-Plough invested million in Claritin direct-to-consumer advertising in 1998 and 1999, far more than any other brand. Overall, spending on direct-to-consumer advertising by the pharmaceutical industry rose from million in 1995 to billion in 1998, and by 2006, was billion.
See also
Benzocycloheptenes
Azatadine (loratidine minus chlorine atom and ester)
References
External links
1988 introductions
Bayer brands
Benzocycloheptapyridines
Carbamates
Chloroarenes
H1 receptor antagonists
Merck & Co. brands
Peripherally selective drugs
Pfizer brands
Piperidines
Schering-Plough brands
World Health Organization essential medicines
Wyeth brands
Wikipedia medicine articles ready to translate | en | apollo | train |
Nucleoside/nucleotide combination is an effective alternative to HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT. | en | apollo | train |
[Febrile cytolysis disclosing hemorrhagic fever with renal syndrome].
We report the case of a 40-year-old-man who developed febrile cytolysis as the presenting sign of hemorragic fever with renal syndrome (HFRS). On admission, he had fever (40 degrees C) and epigastric pain. The AST level was at 2N, the ALT at 3N. There was a thrombocytopenia (61 000/mm(3)) without anemia or hyperleukocytosis. Three days after admission, the platelet count decreased to 40 000/mm(3), serum urea and creatinine increased from normal rate to 10.8mmol/l, 204.0 micromol/l, respectively. The HIV, HBV, HCV, leptospirosis antibodies were negative. The Hantavirus serology was positive (Ig G: 1/512). This case suggests that HFRS should be entertained as a possible cause of cytolysis with thrombocytopenia in patients with fever and no initial sign of renal involvement in North-Eastern France. | en | apollo | train |
Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced colorectal oncogenesis in C57BL/6J mice.
This study compared the effects of three anti-mutagenic lichen extracts on colorectal oncogenesis in azoxymethane (AOM)-treated mice and determined whether the extracts also regulated the homeostatic response to genotoxic damage. C57BL/6J mice (n = 12 per group) were treated with the lichen extracts Antimutagen-He (AMH): AMH-C, AMH-D, or AMH-E dimethyl sulfoxide (DMSO, control) for 2 weeks. At the end of the treatment, mice were given a single AOM injection to induce DNA damage and killed 6 h later for measuring apoptosis and proliferation. Apoptotic and proliferation indexes in mice treated with AMH-C, AMH-D, and AMH-E were 0.61%, 1.41%, and 0.77%; and 30.62%, 21.93%, and 27.27%, respectively, which were significantly lower than those of control mice (5.88% and 38.69%) (p < 0.05). To examine the effects of lichen extracts on colorectal cancer, separate groups of mice (n = 25 per group) treated with AMH-C, AMH-D, AMH-E, or DMSO were given 4-weekly AOM injections to induce oncogenesis. Mice were killed 24 weeks after the last AOM injection for assessing colon tumor formation. Colonic tumor incidences were 47.3%, 13%, and 20%; the tumor volumes were 18.47, 2.75, and 10.78 mm(3), respectively, in mice treated with AMH-C (p < 0.05), AMH-D (p < 0.05), and AMH-E (p > 0.05), compared to 24% and 13.28 mm(3) in mice of control correspondingly. No lichen extract showed evident toxic effects on mice. No usnic acid was found in these lichen extracts. The regulation of acute apoptosis and cell proliferation in colonic epithelial cells and the anti-mutagenesis do not seem directly related to the cancer protective effect. | en | apollo | train |
This study was performed to determine whether injury induced by cerebral ischemia could be further improved by transplantation with bone marrow-derived mesenchymal stem cells (MSCs) modified by Survivin (SVV).
MSCs derived from bone marrow of male Sprague-Dawley rats were infected by the self-inactive lentiviral vector GCFU carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected in infected MSCs supernatants under hypoxic conditions by ELSIA. In vivo, experiments consisted of three groups, one receiving intravenous injection of 500 μl of phosphate-buffered saline (PBS) without cells (control group) and two groups administered the same volume solution with either three million GFP-MSCs (group GFP) or SVV/GFP-MSCs (group SVV). All animals were submitted to 2-hour middle cerebral artery occlusion (MCAO) and then reperfusion. Differentiation and survival of the transplanted MSCs were determined by confocal microscope. Western blot was used to detect the expression of VEGF and bFGF in ischemic tissue. A 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to assess the infarct volume. Evaluation of neurological function was performed using a modified Neurological Severity Score (mNSS).
In vitro, modification with SVV further increased secretion of VEGF and bFGF under hypoxic condition. In vivo, only very few transplantated cells co-expressed GFP and NeuN. The survival transplanted cells in the group SVV was 1.3-fold at 4 days after transplantation and 3.4-fold higher at 14 days after transplantation, respectively, when compared with group GFP. Expression of VEGF and bFGF in the ischemic tissue were further up-regulated by modification with SVV. Moreover, modification with SVV further reduced the cerebral infarct volume by 5.2% at 4 days after stroke and improved post-stroke neurological function at 14 days after transplantation.
Modification with SVV could further enhance the therapeutic effects of MSCs possibly through improving the MSCs survival capacity and up-regulating the expression of protective cytokines in the ischemic tissue.
Despite the advances in medical, thrombolytic and surgical treatment, the treatment of cerebral infarction still lacks an ideal method. Previous studies have shown that MSCs could differentiate into potential neuron-like cells both in vivo and in vitro [1, 2], suggesting that MSCs transplantation could improve neurological function after cerebral ischemia, and the efficacy is closely related to the number of MSCs grafted . However, the survival rate of simple transplantation of MSCs in ischemic tissue is very low . Recent research has demonstrated that the combining of apoptosis inhibitors with MSCs or anti-apoptosis gene-modified MSCs for transplantation promoted better recovery of neurological function after cerebral ischemia [5–7], which suggests that anti-apoptosis strategies for the MSCs transplantation might break through the limitation of current MSCs strategies for the treatment of cerebral infarction. Survivin (SVV) is a special new member of the inhibitor of apoptosis protein family (IAP). A study by Fan et al. has demonstrated that transplantation with survivin-engineered MSCs can further improve the cardiac performance of rats after myocardial infarction by enhancing survival of the transplanted cells . However, it is unclear whether such MSCs could result in better therapeutic effects for stroke in rats. In this paper, we try to investigate the effects of transplantation with MSCs modified by SVV on an experimental stroke model performed in rats.
The investigation conformed to the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health (NIH Publication, No. 86-23, revised 1985). The investigators responsible for molecular, histological and functional studies were blinded to the treatment groups.
MSCs were prepared from rat bone marrow as described by Friedenstein et al . In brief, we euthanized Sprague Dawley (SD) rats weighted 80-100 g and harvested bone marrow. Bone marrow cells were introduced into 100-mm dishes and cultured in complete medium, consisting of Dulbecco's Modified Eagle's Medium (DMEM; Sigma) containing 10% fetal bovine serum and antibiotics: 100 U/ml penicillin G, 100 mg/mg streptomycin, and 0.25 mg amphotericin B. Culture medium was replaced every three days and floating cells were discarded. Following two passes, the attached cells were divided into three new flasks and cultured until the cell density of the colonies grew to approximately 90% confluence. These cells were analyzed by fluorescence-activated cell sorting (FACS) as described previously . After blocking for nonspecific binding with buffer containing 1% bovine serum albumin, the cells were incubated for 20 minutes at 4°C with the following antibodies: anti-CD29, Phycoerythrin (PE), anti-CD106, PE, (Biolegend). anti-CD44, luorescein isothiocyanate (FITC), anti-CD14, FITC and anti-CD45, FITC (AbD Serotec). The matched isotype controls were purchased from AbD Serotec or Biolegend. At least 1 × 104 cells per sample were acquired and analyzed.
The differentiation of MSCs in vitro towards the adipogenic and the osteogenic lineage as previously described [11, 12]. Briefly, for adipocyte differentiation, MSCs was cultured 3 weeks with adipogenic medium, containing 10-6M dexamethasone, 10 μg/ml insulin and 100 μg/ml 3-isobutyl-1-methylxantine (Sigma). For Osteoblast differentiation, MSCs was cultured 3 weeks with osteogenic medium, containing 10-7M dexamethasone, 50 μg/ml ascorbic acid and 10 mM β-glycerophosphate (Sigma). Oil-red-O and von kossa dyes were employed to identify adipocytes, osteoblasts respectively.
Human SVV recombinant lentiviral vector was constructed using previous method . Briefly, the full-length human SVV cDNA without termination codon was amplified by polymerase chain reaction (PCR) from pUC18-SVV and inserted into the Age I site of the GCFU plasmid to form a GFP/SVV fusion gene. The identity of SVV cDNA obtained in this manner was confirmed by sequencing and comparing it with the Gene Bank sequence NM_001168.2. The primer sequence was forward, 5'-GATGATGACGACAAACCGGTCATGGGTGCCCCGACGTTG-3' and reverse, 5'-TCACCATGGTGGCGACCGGTTTATCCATGGCAGCCAGCTG-3'. The SVV recombinant lentiviral vector was prepared using Lipofectmaine 2000 transfection technology.
For passage 1 MSCs were infected by lentivirus with a multiplicity of infection (MOI) of 8 . The MSCs infected with SVV recombinant lentivirus were defined as SVV/GFP-MSCs and the MSCs infected with mock lentivirus were defined as GFP-MSCs. To achieve the optimal gene transfer, polybrene (a final concentration of 8 μg/ml) was used. All MSCs were expanded to 3 passes, and then used for transplantation. The efficiency of gene transduction was assessed with FACS.
The survivin expression was detected by immunofluorescence staining. In brief, the 3rd passage transfected MSCs were plated onto fibronectin-coated chamber slides, fixed with 4% paraformaldehyde (Sigma) for 10 minutes at room temperature, and washed twice in 0.01 M phosphate-buffered saline (PBS, GIBCO). Slides were blocked with goat serum for 20 minutes and incubated overnight with mouse anti-human Survivin antibody (AbCam) at 4°C. After that, the slides were incubated with Texas-Red fluorescent anti-mouse secondary antibody (Santa Cruz) for 30 minutes at 4°C. Between steps the slides were washed with PBS. A 1:500 dilution of primary antibody against human SVV and a 1:500 dilution of secondary antibody were used, respectively. Cells were examined by fluorescencemicroscopy (Leica Co, Germany).
After the 3rd passage infected MSCs completed adherence, they were incubated for 24 hours at 37°C in a humidified modular hypoxia chamber (Billups Rothenberg) containing 95% nitrogen and 5% carbon dioxide (n = 4 in each group). Subsequently, the supernatants were collected for analysis. Commercial VEGF or bFGF ELISA (enzyme-linked immunosorbent assay) kits (R&D Systems Inc. Minneapolis, USA) was used to quantify the concentration of VEGF and bFGF in each of the samples. The supernatant from MSCs cultured in normal condition was used for control. Any experiment was repeated for three times.
Adult male Sprague-Dawley rats weighing 220-250 g were used in this study. A middle cerebral artery occlusion (MCAO) was established with the modified Longa method . Rats were initially anesthetized with 10% chloral hydrate. Rectal temperature was controlled at 37°C with a feedback-regulated water heating system. The right common carotid artery, external carotid artery (ECA), and internal carotid artery were exposed. A 3.0 monofilament nylon suture (18.5 mm, determined by animal weight), with its tip rounded by heating near a flame, was advanced from the ECA into the lumen of the internal carotid artery until it blocked the origin of the middle cerebral artery (MCA). 2 hours after MCAO, animals were reanesthetized with halothane, and reperfusion was performed by withdrawal the suture until the tip cleared the lumen of the ECA.
MSCs transplantation was performed as a method reported in previous study . Briefly, after 2-hour middle cerebral artery occlusion (MCAO) and 24-hour reperfusion, Rats were grouped into three groups which received a 500 μl injection of either phosphate-buffered saline (PBS) without cells (group control, n = 18) or containing three million GFP-MSCs (group GFP, n = 30) or SVV/GFP-MSCs (group SVV, n = 30) via tail vein.
In order to identify survival and differentiate of the transplanted MSCs, a method of double immunofluorescent staining was used. Rats in the GFP and SVV groups were euthanized with 10% chloral hydrate at 4 days (n = 6 in each group) or 14 days (n = 6 in each group) after transplantation. For preparation of frozen sections, rats were perfused transcardially with normal saline and the brain samples were removed immediately. Blocks corresponding to coronal coordinates form bregma -1 to 1 mm were obtained and frozen rapidly in liquid nitrogen. A series of 6-um-thick sections was obtained. Thereafter, the frozen sections were rewarmed at room temperature for 45 minutes to 1 hour, and were concubated overnight at a dilution of 1:200 with FITC labeled goat anti-GFP (AbCam) and rabbit anti-rats Neuronal nuclei (NeuN, which is a marker of neuron.) (DAKO), and then incubated for 45 minutes using a secondary antibody of goat anti-rabbit/mouse IgG conjugated with TAXES (Santa Cruz) for detecting NeuN at 37°C. Between steps the slides were washed with 0.01M PBS. Finally, the sections were used to detect the survival and differentiation into neuron-like cells of the transplanted MSCs by a laser scanning confocal microscope (Zeiss Co., LSM510).
Rats were euthanized with 10% chloral hydrate at 4 days (n = 6 in each group) or 14 days (n = 6 in each group) after transplantation. The protein concentration from injured cerebral tissues was determined using the bicinchoninic acid (BCA) protein assay kits (Beyotime Biotechnology, P.R. China). Thirty micrograms protein were loaded on 10% acrylamide gel for electrophoresis and were electroblotted onto a polyvinylidene difluoride membrane (PVDF, Invitrogen). The membranes were then probed with mouse anti-VEGF (1:500) and anti-bFGF (1:500), respectively, followed by incubation with horseradish-peroxidase-conjugated sheep-anti-mouse IgG (Bio-Rad Laboratories). Protein expression was detected with an enhanced chemiluminescence detection system (Amersham Pharmacia Biotech Inc) and β-actin was used as a loading control. All bands from western blot were analyzed using Image J software (version 1.6 NIH) to verify the relative level of VEGF and bFGF defined as the optical density ration of VEGF or bFGF over β-actin.
At 14 days after MSCs transplantation, rats in each groups (n = 6) were used for evaluate cerebral infarction volume. The brain samples were removed carefully and dissected into five equally spaced coronal blocks using a vibratome. The fresh brain slices were immersed in a 2% solution of 2, 3, 5-triphenyltetrazolium chloride (TTC) (Sigma) in PBS (GIBCO) at 37°C for 30 minutes. The cross-sectional area of infarction and non infarction in each brain slice was measured using Image J analysis software (version 1.6 NIH). The infarct volume was indirectly determined by subtracting the volume of intact tissue in the ipsilateral hemisphere from that in the contralateral hemisphere.
Data were presented as mean values and standard deviation. A method of ANOVA (analysis of variance) with Scheffe's post hoc test was used to identify differences among all groups. A P value of less than 0.05 was considered as statistical significance.
Cells were scattered in a number of colony distributions 3 days after planted. At day 8 ~ 9, the bottle was covered with long-spindle cells. Passaged cells (mostly spindle cells) were uniformly distributed, and covered the bottom every 4 ~ 5 days. The 3rd Passage MSCs highly expressed the surface marker molecules CD29 (97.7%), CD90 (100%) and CD106 (100%), and lowly expressed the blood cell surface molecules CD14 (2.2%) and CD45 (2.6%) (Figure 1).
Phenotypic characterization and differentiation of cells: (A) The initial passage MSCs grew as a morphologically homogeneous population of fibroblast-like cells, (B) The Passage 3 MSCs grew as whorls of densely packed spindle-shaped (scale bar = 200 um in A and B). (C) Adipocyte differentiation of MSCs: Upon induction with adipocyte induction media cells showed adipocyte globules on oil red 'O' staining. (D) Osteogenic differentiation of MSCs: Upon induction with osteogenic induction media cells showed calcium deposits on von kossa staining. (scale bar = 100 um in C and D) (E-I): Flow cytometry analysis: MSCs expressed the markers molecules CD29, CD106, CD90 and negative for the blood cell surface molecules CD45, CD14. The percentage of positivity was mentioned in the brackets.
Cells were differentiated in vitro using adipogenic and oesteogenic induction media. Following 3 weeks of adipogenic induction, the cells stained Oil red 'O' positive showing lipid laden adipocyte phenotype. Similarly, when induced with oesteogenic induction medium for 3 weeks, these cells showed oesteogensis upon staining with von kossa for calcium deposits (Figure 1C, D).
After infection with SVV recombinant lentivirus and mock lentivirus, MSCs were over expressed GFP (Figure 2A, B), and the efficiency of gene transduction was similar to that of mock lentivirus (97.2% vs. 92.9%) (Figure 2F, G). The 3rd passage transfected MSCs were planted on fibronectin-coated chamber slides for immunofluorescence microscopy. Expression of the SVV gene was evident in SVV/GFP-MSCs (Figure 2D), but not in GFP-MSCs (Figure 2C).
Efficiency of gene transduction and SVV expression: (A): Expression of green fluorescent protein in GFP-MSCs. (B): Expression of green fluorescent protein in SVV/GFP-MSCs. (scale bar = 100 um). (E-G): The efficiency of gene transduction was analyzed by FACS: (E) Control MSCs, (F) GFP-MSCs, (G) SVV/GFP-MSCs. (C-D): SVV expression in gene modified MSCs, (C): no SVV expression in GFP-MSCs, (D): stronger SVV expression in SVV/GFP-MSCs (scale bar = 50 um in A, B, C and D).
The transplanted MSCs via tail vein were identified by GFP. In the group SVV and the group GFP, the transplanted MSCs were distributed throughout the damaged tissues, with the majority located close to the injured tissue. Quantitative analysis showed that number of the GFP-positive MSCs in the group SVV increased by about 1.3-fold (101.8 ± 10.3 per high-power magnification field [HPF] vs.76.8 ± 7.9 per HPF, P < 0.05) at 4 days after transplantation, and by 3.4-fold (61.3 ± 8.2 per HPF vs.17.8 ± 4.8 per HPF, P < 0.01) at 14 days after transplantation when compared with in the group GFP. There were very few GFP-positive cells coexpression NeuN in the cell transplantation groups (Figure 3).
Confocal images of brain sections from rats after MSCs transplantation.: (A)4 days in group SVV, (B)4 days in group GFP, (C)14 days in group SVV, (D)14 days in group GFP, (Column1) GFP-positive cells (write arrows), (Column2) neuronal marker NeuN-positive cells(green arrows). (Column3) GFP-positive MSCs (yellow arrows) expressed neuronal marker NeuN. (E) Quantitative analysis of the number of survival MSCs at 4 and 14 days after transplantation. Data are mean ± S.D. (n = 6), Scale bar = 100 um. *P < 0.05, # P < 0.01.
In vitro, there was no difference in VEGF and bFGF concentration between GFP-MSCs and uninfected MSCs (VEGF concentration: 760.7 ± 94.7 vs. 696.6 ± 79.1 P > 0.05, bFGF concentration: 678.6 ± 83.9 vs.607.9 ± 69.3 P > 0.05). However, MSCs over expression of SVV increased the secretion of VEGF (1093.9 ± 93.3 P < 0.01) and bFGF (868.9 ± 84.6 P < 0.01) when compared with GFP-MSCs under hypoxic conditions (Figure 4D, E). In vivo, The levels of VEGF and bFGF in the group GFP significantly increased at 4 days (the ratio of optical density of VEGF over β-actin: 0.66 ± 0.12 vs. 0.42 ± 0.09, P < 0.05, the ratio of optical density of bFGF over β-actin: 0.41 ± 0.09 vs. 0.35 ± 0.07, P < 0.05) but no obvious differences at 14 days (0.45 ± 0.15 vs.0.35 ± 0.07, P > 0.05; 0.32 ± 0.08 vs.0.27 ± 0.05, P > 0.05), when compared with the group control. However, modification with SVV further upregulated expression of VEGF and bFGF. The levels of VEGF (0.91 ± 0.18 at 4 days after transplantation, 0.83 ± 0.21 at 14 days after transplantation) and bFGF (0.82 ± 0.12 at 4 days after transplantation, 0.48 ± 0.10 at 14 days after transplantation) were significantly higher than those of in the group control and the group GFP (p < 0.05 or p < 0.01) (Figure 4A-C).
VEGF and bFGF expression in vitro and in vivo: (A) Western blot analysis was performed for VEGF and bFGF expression in injured cerebral tissues at 4 days and 14 days after MSCs transplantation in group control, group GFP and group SVV, β-actin served as a loading control. Quantitative analysis shows that the ratio of optical density for VEGF (B) or bFGF (C) in group SVV was significantly higher than those in the group control and the group GFP. (D-E) ELSIA analysis for VEGF (D) and bFGF (E) in MSCs supernatants under hypoxic conditions, the lever of VEGF and bFGF in MSCs modificated with SVV were higher than those in MSCs modificated with GFP and Control MSCs. *P < 0.05, # P < 0.01.
The pale stained area was determined to the infarct area (Figure 5A). The infarct volume in the group control (28.7% ± 3.8%) was significantly larger than that in the group GFP (24.5% ± 2.3%, P < 0.05) and in the group SVV (19.3% ± 2.8%, P < 0.01). When compared with the group GFP, transplantation with SVV/GFP-MSCs further reduced the infarct volume by 5.2% (P < 0.05) (Figure 5B).
Administration of SVV-MSCs decreases Infarct Volume: (A) Brain sections stained with TTC to visualize the ischemic lesions 14 days after MSCs transplantation in group Control, group GFP and group SVV. (B) Quantitative analysis of the Infarct Volume. Data are expressed as the mean ± SD (n = 6). Scale bar = 10 mm.
There were no difference in mNSS among the group SVV, group GFP and group control at 1 day after the transplantation (P = 0.77). Neurological deficits improved in all groups at 14 days after transplantation. Scores in group SVV (5.3 ± 0.81, P < 0.01) and group GFP (6.8 ± 0.98, P < 0.01) were lower than those in the control group (8.5 ± 0.83). When compared with the group GFP, transplantation with SVV/GFP-MSCs further reduced the scores (P < 0.01) (Figure 6).
Transplantation with SVV-MSCs improved neurological function: The score of mNSS on 1 and 14 days after MSCs transplantation in group Control, group GFP and group SVV. Data are expressed as the mean ± SD (n = 6). *P < 0.01.
Our study showed that modification with SVV enhanced survival of the transplanted MSCs, further upregulated expression of VEGF and bFGF in the cerebral ischemic tissues, reduced the infarct volume and finally further improved the neurological functional recovery in a rat model of stroke.
Previous studies have demonstrated that MSCs can improve the neurological function after stroke by promoting the nerve regeneration . Very few transplanted MSCs co-expression GFP and NeuN were found in our observation. This is consistent with the results of a study by Chen et al . Although so few cells with the neurons specific surface marker are detected, there is no electrophysiology or other evidences which can prove that these cells have the functions of the nerve cells. Furthermore, their morphous was not similar as the new neuron-like cells but as that before transplantation. Thus, we cannot provide a supportive evidence of differentiation of the transplanted MSCs into new neuron-like cells. On the other hand, we found that the amount of the survival MSCs in the group GFP was very few. Several factors may be involved in so low capacity of survival of the transplanted MSCs, such as the strong inflammatory and oxidative stress reaction, a large amount of pro-apoptosis factors and chemokines, and the lethal effect on the transplanted cells caused by ischemia-reperfusion injury for example. Inversely, the amount of survival MSCs in the group SVV was significantly more than that of the group GFP at 4 days and else 14 days after transplantation. It indicated that the SVV can improve the MSCs post-transplantation survival rate, which may be explained by powerful anti-apoptosis effect of SVV . As reported in previous studies, the high death rate of the transplanted MSCs in the ischemic tissue limited the therapeutic effects [4, 17]. In our study, we also found that transplantation with GFP-MSCs only improved neurological function marginally when compared with group control. However, the score of mNSS in the group SVV was significantly lower than that of group GFP. It indicated that MSCs modified with SVV can further improve the neurological function after MACO. However, considering the results of confocal observation, it is difficult to ascribe the improvement of neurological function to differentiation.
Thus, we further investigated the effect of modification for MSCs with SVV on neuroprotective factors such as VEGF and bFGF, which can promote vascular regeneration and anti-apoptosis after cerebral ischemia [15, 18, 19]. In vitro or in vivo, our results showed that MSCs modified by SVV could enhance secretion of VEGF and bFGF, uniformly. Previous studies have also demonstrated that treatment of stroke with MSCs enhancing VEGF and bFGF expression. So, the paracrine effect may be a major factor for the nerve repair in the cerebral ischemic rats. Moreover, in group SVV or group GFP, there was a similar trend between up-regulation of these neurotrophic factors and the transplanted MSCs survival in the cerebral ischemic tissue. This indicated that enhancement of paracrine effect of MSCs for these neuroprotective factors may be indirectly resulted from improvement of the transplanted MSCs survival due to modification with SVV.
Finally, we found that, although modification with SVV further reduced the infarct volume after MACO when compared with transplantation with GFP-MSCs, the extent of reduction was still relatively small, which only led to reduction of 5.2% in average. This may be explained by a method of transplantation via tail vein in our study. Notwithstanding, there are several potential mechanisms how MSC get through the blood brain barrier (BBB) after stroke. At first, one of potential mechanisms is passive translocation of MSCs to the brain parenchyma through a disrupted BBB after stoke. The second, active transendothelial migration of MSCs, similar as the recruitment of leukocytes and monocytes from the bloodstream to an inflammation site, is expected to be involved in the engraftment of MSCs transplanted via intravenous injection. After stroke, many inflammation cytokines and chemokines were released into peripheral blood including vascular cell adhesion molecule 1, p-selectin, CXCR4 and SDF-1, which promote the adhesion of MSCs to the endothelium or induce the migration of MSCs to the ischemic tissue in the brain [20–22]. However, in previous studies, it has been demonstrated that the transplanted cells may be detained by lung, spleen, sinus hepaticus, or other organs so that only parts of them could reach the damaged region to exert an action of reparation for ischemic cerebral tissue [3, 23]. Thus, further study aiming at an optimal method of transplantation should be required. Meanwhile, there were several limitations in our study: (1) whether SVV change property of stem cells which differentiate into neuronal lineage cells is still not determined; (2) how SVV up-regulates expression of VEGF and bFGF, and how these cytokines improve the neurological function were not investigated; (3) how other organs detain the transplanted MSCs was not determined. Even so, our study may be helpful to extend our understanding for transplantation with MSCs in stroke.
Modified with SVV could further enhance the therapeutic effects of MSCs possibly through improving the MSCs survival capacity and up-regulating the expression of protective cytokines in the ischemic tissue.
Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, for their technical assistance. This work was supported in part by the Natural Science Foundation of Fujian Province of China (2008J0282) and by the professorial academic Foundation of Fujian Medical University (JS06077).
All authors have read and approved the final manuscript. NL conceived the study and participated in its design, YZ and MZ participated in the design of the study, performed the immunohistochemistry, animal experiment, statistical analysis, and drafted the manuscript. LF carried out lentiviral vector construction, DL carried out the Western blot analysis, HD, RC, and FL participated in refinement of experiment protocol and coordination and helped in drafting the manuscript. | en | apollo | train |
SCFE is a Salter-Harris type 1 fracture through the proximal femoral physis. Stress around the hip causes a shear force to be applied at the growth plate. While trauma has a role in the manifestation of the fracture, an intrinsic weakness in the physeal cartilage also is present. The almost exclusive incidence of SCFE during the adolescent growth spurt indicates a hormonal role. Obesity is another key predisposing factor in the development of SCFE. The fracture occurs at the hypertrophic zone of the physeal cartilage. Stress on the hip causes the epiphysis to move posteriorly and medially. By convention, position and alignment in SCFE is described by referring to the relationship of the proximal fragment (capital femoral epiphysis) to the normal distal fragment (femoral neck). Because the physis has yet to close, the blood supply to the epiphysis still should be derived from the femoral neck; however, this late in childhood, the supply is tenuous and frequently lost after the fracture occurs. Manipulation of the fracture frequently results in osteonecrosis and the acute loss of articular cartilage (chondrolysis) because of the tenuous nature of the blood supply. | en | apollo | train |
Pregnancy Rating:
Lactation risk:
Renal Dosing
Adult: Contraindicated in severe impairment or anuria.
Pediatric: Contraindicated in severe impairment or anuria
Hepatic Dosing
Adult: Not defined
Pediatric: Not defined
Adult: Contraindicated in severe impairment or anuria.
Pediatric: Contraindicated in severe impairment or anuria
Adult: Not defined
Pediatric: Not defined | en | apollo | train |
Cruciferous vegetables, in particular those included into the Brassica genus, are good sources of a variety of nutrients and health-promoting phytochemicals. Phenolic compounds are the major antioxidants of Brassica; hence the contribution of Brassica vegetables to health improvement has largely been associated to their antioxidant capacity. This study aimed to assess anti-diabetic, antilipidemic, and antioxidant activity of phenolic rich extract of Brassica oleraceae var gongylodes (BOvG) in Wistar rats. The findings revealed that the administration of BOvG extract to diabetic rats significantly reduced fasting blood glucose by 64% within 7 days of treatment. Additionally, BOvG extract was also observed to normalize the diabetic rats’ lipid profile and HbA1c (Glycated hemoglobin). BOvG extract also showed protection of liver- kidney functions, which was evidenced by the significant decrease in Blood Urea Nitrogen (BUN), Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT). The treatment also improved the antioxidant status of the diabetic rats where the enzymatic activities of Catalase (CAT) and Super Oxide Dismutase (SOD) were significantly increased. Furthermore, RP-HPLC analysis detected chlorogenic acid, rutin, and sinapic acid against known standards in BOvG extract. Hence, the present investigation suggests that BOvG phenolic rich extract (as a multi-component therapy) exhibited anti-diabetic, antilipidemic and antioxidant properties in STZinduced diabetic rats. | en | apollo | train |
All medications should be taken when the patient is in an upright position, and the patient should remain upright for several minutes after medication ingestion.Patients should be instructed to drink at least 4 ounces of liquid with any pill.The best treatment for pill esophagitis is prevention.Symptoms may take up to 6 weeks to resolve.In patients unable to tolerate taking oral medication, fluconazole can be given IV.34
Herpes esophagitis is generally a self-limited process that resolves over about 7 days. Immunocompromised patients should be treated with antivirals, such as acyclovir (400 mg PO five times per day for 7-14 days or 5-10 mg/kg IV every 8 hours for 7-14 days), famciclovir (500 mg PO three times a day for 7-14 days), or valacyclovir (1 g three times a day for 7-14 days).35 For CMV, initial treatment can begin with ganciclovir (5 mg/kg IV every 12 hours for 2-3 weeks) or foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 2-3 weeks). If the causative organism cannot be adequately identified or if the patient is severely debilitated, admission to the hospital may be required. Patients discharged from the ED should receive appropriate follow-up with the relevant specialist (e.g., gastroenterology, infectious disease). In addition to therapy directed at the infecting organism, treatment with antacids, topical anesthetics, or sucralfate may provide symptomatic relief. #### Pill Esophagitis
If a patient with suspected pill esophagitis has persistent symptoms, endoscopy may be necessary. It also helps to determine alternative causes. No data exist supporting any specific treatment, although, intuitively, antacid medication may prevent further erosion of damaged mucosa. Symptoms may take up to 6 weeks to resolve. The best treatment for pill esophagitis is prevention. Patients should be instructed to drink at least 4 ounces of liquid with any pill. All medications should be taken when the patient is in an upright position, and the patient should remain upright for several minutes after medication ingestion.#### Eosinophilic Esophagitis
These patients usually are seen after standard antireflux measures have failed or after they have developed a food impaction.The treating physician should consider the possibility of food impaction, ensure that appropriate antacid therapy is used, and refer the patient to a gastroenterologist for further treatment. | en | apollo | train |
Asymmetrical ligand binding by abscisic acid 8'-hydroxylase.
Abscisic acid (ABA), a plant stress hormone, has a chiral center (C1') in its molecule, yielding the enantiomers (1'S)-(+)-ABA and (1'R)-(-)-ABA during chemical synthesis. ABA 8'-hydroxylase (CYP707A), which is the major and key P450 enzyme in ABA catabolism in plants, catalyzes naturally occurring (1'S)-(+)-enantiomer, whereas it does not recognize naturally not occurring (1'R)-(-)-enantiomer as either a substrate or an inhibitor. Here we report a structural ABA analogue (AHI1), whose both enantiomers bind to recombinant Arabidopsis CYP707A3, in spite of stereo-structural similarity to ABA. The difference of AHI1 from ABA is the absence of the side-chain methyl group (C6) and lack of the alpha,beta-unsaturated carbonyl (C2'C3'-C4'O) in the six-membered ring. To explore which moiety is responsible for asymmetrical binding by CYP707A3, we synthesized and tested ABA analogues that lacked each moiety. Competitive inhibition was observed for the (1'R) enantiomers of these analogues in the potency order of (1'R,2'R)-(-)-2',3'-dihydro-4'-deoxo-ABA (K(I)=0.45 microM)>(1'R)-(-)-4'-oxo-ABA (K(I)=27 microM)>(1'R)-(-)-6-nor-ABA and (1'R,2'R)-(-)-2',3'-dihydro-ABA (no inhibition). In contrast to the (1'R)-enantiomers, the inhibition potency of the (1'S)-analogues declined with the saturation of the C2',C3'-double bond or with the elimination of the C4'-oxo moiety. These findings suggest that the C4'-oxo moiety coupled with the C2',C3'-double bond is the significant key functional group by which ABA 8'-hydroxylase distinguishes (1'S)-(+)-ABA from (1'R)-(-)-ABA. | en | apollo | train |
Regulation of the biogenesis of OXPHOS complexes in cell transition from replicating to quiescent state: involvement of PKA and effect of hydroxytyrosol.
A study is presented on the expression of mitochondrial oxidative phosphorylation complexes in exponentially growing and serum-starved, quiescent human fibroblast cultures. The functional levels of respiratory complexes I and III and complex V (adenosine triphosphate (ATP) synthase) were found to be severely depressed in serum-starved fibroblasts. The depression of oxidative phosphorylation system (OXPHOS) complexes was associated with reduced levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the down-stream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factors (TFAM). In serum-starved fibroblasts decrease of the catalytic activity of AMP cyclic dependent protein kinase (PKA) and phosphorylation of cAMP response element-binding protein (CREB), the transcription coactivator of the PGC-1α gene, was found. Hydroxytyrosol prevented the decline in the expression of the PGC-1α transcription cascade of OXPHOS complexes in serum-starved fibroblast cultures. The positive effect of HT was associated with activation of PKA and CREB phosphorylation. These results show involvement of PKA, CREB and PGC-1α in the regulation of OXPHOS in cell transition from the replicating to the quiescent state. | en | apollo | train |
Endovascular treatment of posterior circulation aneurysms by electrothrombosis using electrically detachable coils.
In a multicenter study, 120 patients with intracranial aneurysms presenting a high surgical risk were treated using electrolytically detachable coils and electrothrombosis via an endovascular approach. The results of treatment in patients with posterior fossa aneurysms (42 patients with 43 aneurysms) are presented. The most frequent clinical presentation was subarachnoid hemorrhage (24 cases). The clinical follow-up periods ranged from 1 week to 18 months. Complete aneurysm occlusion was obtained in 13 of 16 aneurysms with a small neck and in four of 26 wide-necked aneurysms. A 70% to 98% thrombosis of the aneurysm was achieved in 22 of 26 aneurysms with a wide neck and in three of 16 small-necked aneurysms. One aneurysm could not be treated due to a technical complication. Two cases required postprocedural surgical clipping of a residual aneurysm. One patient (originally in Hunt and Hess Grade V) experienced procedural rupture of the aneurysm requiring an emergency parent artery occlusion. He eventually died 5 days later. Another patient (originally in Grade IV) had coil migration and posterior cerebral artery territory ischemia. A third patient developed a permanent neurological deficit (hemianopsia) after complete occlusion of a wide-necked basilar bifurcation aneurysm. One patient, harboring an inoperable giant basilar bifurcation aneurysm, died from aneurysm bleeding 18 months after partial occlusion. Overall morbidity and mortality rates related to treatment were 4.8% (two cases) and 2.4% (one case), respectively (2.6% and 0% if considering only patients in Hunt and Hess Grades I, II, and III). It is suggested that this technique is a viable alternative in the management of patients with posterior fossa aneurysms associated with high surgical risk. Longer angiographic and clinical follow-up study is necessary to determine the long-term efficacy of this recently developed endovascular occlusion technique. Close postoperative angiographic and clinical monitoring of patients with wide-necked subtotally occluded aneurysms is mandatory to check for potential aneurysmal recanalization, regrowth, and rupture. | en | apollo | train |
Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis.
The endothelial cell monolayer of cerebral vessels and its basement membrane (BM) are ensheathed by the astrocyte endfeet, the leptomeningeal cells, and their associated parenchymal BM, all of which contribute to establishment of the blood-brain barrier (BBB). As a consequence of this unique structure, leukocyte penetration of cerebral vessels is a multistep event. In mouse experimental autoimmune encephalomyelitis (EAE), a widely used central nervous system inflammatory model, leukocytes first penetrate the endothelial cell monolayer and underlying BM using integrin beta1-mediated processes, but mechanisms used to penetrate the second barrier defined by the parenchymal BM and glia limitans remain uninvestigated. We show here that macrophage-derived gelatinase (matrix metalloproteinase [MMP]-2 and MMP-9) activity is crucial for leukocyte penetration of the parenchymal BM. Dystroglycan, a transmembrane receptor that anchors astrocyte endfeet to the parenchymal BM via high affinity interactions with laminins 1 and 2, perlecan and agrin, is identified as a specific substrate of MMP-2 and MMP-9. Ablation of both MMP-2 and MMP-9 in double knockout mice confers resistance to EAE by inhibiting dystroglycan cleavage and preventing leukocyte infiltration. This is the first description of selective in situ proteolytic damage of a BBB-specific molecule at sites of leukocyte infiltration. | en | apollo | train |
Screening and Diagnosis of Chronic Pharyngitis Based on Deep Learning.
Chronic pharyngitis is a common disease, which has a long duration and a wide range of onset. It is easy to misdiagnose by mistaking it with other diseases, such as chronic tonsillitis, by using common diagnostic methods. In order to reduce costs and avoid misdiagnosis, the search for an affordable and rapid diagnostic method is becoming more and more important for chronic pharyngitis research. Speech disorder is one of the typical symptoms of patients with chronic pharyngitis. This paper introduces a convolutional neural network model for diagnosis based on the typical symptom of speech disorder. First of all, the voice data is converted into a speech spectrogram, which can better output the speech characteristic information and lay a foundation for computer diagnosis and discrimination. Second, we construct a deep convolutional neural network for the diagnosis of chronic pharyngitis through the design of the structure, the design of the network layer, and the description of the function. Finally, we perform a parameter optimization experiment on the convolutional neural network and judge the recognition efficiency of chronic pharyngitis. The results show that the convolutional neural network has a high recognition rate for patients with chronic pharyngitis and has a good diagnostic effect. | en | apollo | train |
Chronic exendin-4 treatment reduced body weight in both obese and lean Zucker rats by reducing food intake: metabolic rate was apparently suppressed. These effects did not require an intact leptin system. Neither does the absence of an intact leptin system sensitize animals to exendin-4. Partial tolerance to the anorectic effect of exendin-4 in lean rats may have been due to elevated plasma corticosterone and depressed plasma leptin levels, but other counter-regulatory mechanisms seem to play a role in obese Zucker rats. | en | apollo | train |
Genotypic and phenotypic characteristics of Yersinia enterocolitica isolated from the surface of chicken eggshells obtained in Argentina.
The prevalence of Yersinia enterocolitica on chicken eggshell surfaces in San Luis, Argentina, was investigated. The pathogenic potential of recovered isolates was assessed by means of phenotypic virulence tests and the presence of the 72-kb pYV plasmid. Antimicrobial susceptibility was determined by the agar diffusion method. DNA digested with XbaI was analyzed by pulsed-field gel electrophoresis (PFGE), and relationships between genomic DNA profiles were established. Eight Y. enterocolitica B2 O:9 strains were recovered after enrichment, for a prevalence of 2.27%. All strains harbored the virulence pYV plasmid, bound Congo red, grew in a low-calcium medium, and autoagglutinated at 37 degrees C. They lacked pyrazinamidase activity and did not hydrolyze esculin. These Y. enterocolitica strains were susceptible to amikacin, ciprofloxacin, chloramphenicol, and trimethoprim-sulfamethoxazole and were resistant to rifampin. According to the genomic DNA patterns obtained by PFGE, the isolates clustered into two groups, I and II. The highest similarity coefficient observed between Y. enterocolitica strains was 0.947. Microbiological controls on production stages of eggs and good culinary practices are necessary to reduce the risk of Y. enterocolitica infection for consumers. | en | apollo | train |
Genome Modification in Enterococcus faecalis OG1RF Assessed by Bisulfite Sequencing and Single-Molecule Real-Time Sequencing.
Enterococcus faecalis is a Gram-positive bacterium that natively colonizes the human gastrointestinal tract and opportunistically causes life-threatening infections. Multidrug-resistant (MDR) E. faecalis strains have emerged, reducing treatment options for these infections. MDR E. faecalis strains have large genomes containing mobile genetic elements (MGEs) that harbor genes for antibiotic resistance and virulence determinants. Bacteria commonly possess genome defense mechanisms to block MGE acquisition, and we hypothesize that these mechanisms have been compromised in MDR E. faecalis. In restriction-modification (R-M) defense, the bacterial genome is methylated at cytosine (C) or adenine (A) residues by a methyltransferase (MTase), such that nonself DNA can be distinguished from self DNA. A cognate restriction endonuclease digests improperly modified nonself DNA. Little is known about R-M in E. faecalis. Here, we use genome resequencing to identify DNA modifications occurring in the oral isolate OG1RF. OG1RF has one of the smallest E. faecalis genomes sequenced to date and possesses few MGEs. Single-molecule real-time (SMRT) and bisulfite sequencing revealed that OG1RF has global 5-methylcytosine (m5C) methylation at 5'-GCWGC-3' motifs. A type II R-M system confers the m5C modification, and disruption of this system impacts OG1RF electrotransformability and conjugative transfer of an antibiotic resistance plasmid. A second DNA MTase was poorly expressed under laboratory conditions but conferred global N(4)-methylcytosine (m4C) methylation at 5'-CCGG-3' motifs when expressed in Escherichia coli. Based on our results, we conclude that R-M can act as a barrier to MGE acquisition and likely influences antibiotic resistance gene dissemination in the E. faecalis species. | en | apollo | train |
### Directional Branches
Endovascular branched grafts used to maintain blood flow to critical aortic branches were not an independent innovation but rather a continued evolution of previous designs.The transition at the end of the distal end of the connecting stent in the target vessels remains a challenge with some of these procedures.All rights reserved
## Preservation of Normal Anatomy
Another key philosophy from surgery translated into endovascular techniques is the preservation of normal anatomy whenever possible. It is possible to restore blood flow to critical branches via surgical bypasses in combination with standard endovascular grafts that cover and occlude blood flow the native vessel ostia or via so-called parallel grafts . Although such "hybrid techniques" were a critical step in treating more patients by endovascular approaches, they most definitely do not preserve normal anatomy and hybrid techniques have the further downside of necessitating surgical intervention in combination with the endovascular repair. Fenestrations are the foremost example of preservation of normal anatomy in endovascular aortic repair that incorporate blood flow to branch vessels. In fenestrated repair, the structure of the combined endovascular graft and covered bridging stent placed in the branch vessel often replicates the native anatomy to within a millimeter or two. In some instances, blood flow may even be optimized as any stenosis in the orifice may be resolved by the stents. Angulation and tortuosity of branches may provide additional challenges to branch stent conformance to the anatomy leading to distortion at the junction of the stents with the arteries or kinking of the stents. In practice, additional self-expanding stents are often added to help address these transitions and to provide long-term branch patency. The transition at the end of the distal end of the connecting stent in the target vessels remains a challenge with some of these procedures. ### Directional Branches
Endovascular branched grafts used to maintain blood flow to critical aortic branches were not an independent innovation but rather a continued evolution of previous designs.This was followed by modular bifurcated branch devices with off-the-shelf components to accommodate a wide range of iliac artery anatomy and simplified the procedure by allowing implantation in a staged fashion. | en | apollo | train |
These results suggest adaptive mechanisms of capillary perfusion with increasing stenosis and development of collateral compensatory circulation in the vascular region of the human ICA. Conjunctival orthogonal polarized spectral imaging during unilateral ICA reconstruction enables continuous noninvasive analysis of bilateral conjunctival microcirculation in the terminal region of the ICA and enables monitoring for efficient carotid shunt perfusion during and after endarterectomy. | en | apollo | train |
Most significantly IL-6 and TGF-β together can induce the development of the inflammatory T-helper-17 (Th17) cell lineage.IL-6 also induces the proliferation of thymocytes and likely plays a role in the development of thymic T cells.In the presence of IL-2, IL-6 induces the differentiation of mature and immature T cells into cytotoxic T cells.In patients with CD, it has been demonstrated in many studies that IL-2 secretion from lamina propria cells is decreased as compared to normal patient samples. Daclizumab, a humanized monoclonal antibody to CD25, produced in an effort to block the binding of IL-2 to the IL-2R, was tested in patients with UC and initially appeared promising in a small open-label study [20], but upon testing in a placebo-controlled study, the therapy did not show efficacy [21]. This effect could be related to the fact that IL-2R (CD25) is also present on T regulatory cells. The inhibition of binding of IL-2 to its receptor present on Treg cells thereby inhibits the proliferation of these cells, which are important in downregulation of the immune response. This highlights a common problem in the targeting of the cytokine pathway for treatment of inflammatory diseases, in that cytokines frequently have multiple effects and can function in both a pro-inflammatory as well as an anti-inflammatory capacity. ### Interleukin-6
IL-6 is a pleiotropic cytokine considered to be a major player in inflammation, regulation of T-cell responses, and apoptosis. Many different cell types produce IL-6. The main sources in vivo are stimulated monocytes, fibroblasts, endothelial cells, macrophages, T cells, and B-lymphocytes. IL-6 is a B-cell differentiation factor in vivo and in vitro and an activation factor for T cells. In the presence of IL-2, IL-6 induces the differentiation of mature and immature T cells into cytotoxic T cells. IL-6 also induces the proliferation of thymocytes and likely plays a role in the development of thymic T cells. Most significantly IL-6 and TGF-β together can induce the development of the inflammatory T-helper-17 (Th17) cell lineage.Interestingly, IL-6 levels are increased in the serum of patients with active CD and UC compared to normal controls.A study looking at a known functional polymorphism of the IL-6 gene and the site of disease in CD patients did not demonstrate an association of IL-6 functional polymorphisms with CD or protection from CD. | en | apollo | train |
Involvement of MAPK, Akt/GSK-3β and AMPK/mTOR signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor.
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells. After axon transection, stretch receptors were isolated and incubated in saline in the presence or without specific inhibitors of various signaling proteins. Inhibition of MEK1/2, p38, Akt, GSK-3β and mTOR increased axotomy-induced apoptosis of remote glial cells, whereas inhibition of ERK1/2 and GSK-3β enhanced necrosis. This suggests the involvement of these signaling proteins in protective, antiapoptotic and antinecrotic processes in the remote satellite glia surrounding the axotomized mechanoreceptor neuron. | en | apollo | train |
If the initial loading dose is well tolerated, the subsequent doses can be administered as 30-minute infusions. As long as treatment is tolerated, it can be given until disease progression.
The net price of a 150-mg vial of trastuzumab is £407.40 (excluding VAT; 'British national formulary' edition 59). For a patient weighing 62 kg, four vials are required for the first loading dose and three vials for each subsequent dose. Assuming that excess trastuzumab is wasted, the drug cost of eight infusions of trastuzumab (the median number of infusions in the regulatory trial) is £10,185. Costs may vary in different settings because of negotiated procurement discounts.# The manufacturer's submission
The Appraisal Committee (appendix A) considered evidence submitted by the manufacturer of trastuzumab and a review of this submission by the Evidence Review Group (ERG; appendix B).
The manufacturer's decision problem compared trastuzumab plus cisplatin and either capecitabine or 5-fluorouracil with:
epirubicin plus cisplatin and either capecitabine or 5-fluorouracil and
epirubicin plus oxaliplatin and capecitabine. The choice of comparators was based on the results of a survey of commonly used treatments for gastric cancer in England and Wales. Outcomes were overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. In the economic evaluation, the incremental cost per quality-adjusted life year (QALY) was presented. | en | apollo | train |
Prothymosin alpha1 effects on IL-2-induced expression of LFA-1 on lymphocytes and their adhesion to human umbilical vein endothelial cells.
Prothymosin alpha1 (Pro alpha1) is known to stimulate in vitro and in vivo natural killer (NK) and lymphokine (IL-2)-activated killer (LAK) cells against tumor cells. In this process, LAK cells first adhere to endothelial cells in vivo, raising the question whether Pro alpha1 affects this interaction as well. The binding ability of peripheral blood lymphocytes (PBL) to human umbilical vein endothelial cells (HUVEC) was increased by incubation with IL-2 in a concentration-dependent manner, reaching a maximal value at 20U/ml IL-2. Although Pro alpha1 alone was without any stimulating effect, it significantly increased PBL binding to unstimulated HUVECs in combination with suboptimal IL-2 (5 and 10 U/ml). The combination of Pro alpha1 (1 microg/ml) and 5 U/ml or 10 U/ml IL-2 is as effective as 10 U/ml or 20 U/ml IL-2 alone. This Pro alpha1 effect on IL-2-activated lymphocytes was found to be augmented on IL-1 or tumor necrosis factor (TNF)-alpha-activated endothelial cells. Analyzing the effect of Pro alpha1 on IL-2-activated lymphocytes by flow cytometry revealed an increase of CD16, CD56, and CD18 surface marker expression, whereas CD3, CD11a/b, CD49d, and CD54 were not affected. In conclusion, Pro alpha1 functions as a mediator of the adhesion of IL-2-activated lymphocytes to HUVECs. | en | apollo | train |
Procainamide can be administered safely by intravenous and intramuscular routes and is well absorbed orally.Other adverse effects include nausea and diarrhea (in about 10% of cases), rash, fever, hepatitis (<5%), and agranulocytosis (approximately 0.2%).Approximately one third of patients receiving long-term procainamide therapy develop these reversible lupus-related symptoms.may be somewhat less effective than quinidine (see below) in sup-particularly with intravenous use. However, in therapeutic concenpressing abnormal ectopic pacemaker activity but more effective trations, its peripheral vascular effects are less prominent than those in blocking sodium channels in depolarized cells. of quinidine. Hypotension is usually associated with excessively rapid procainamide infusion or the presence of severe underlying left ventricular dysfunction. Procainamide’s cardiotoxic effects include excessive action poten-Procainamide has direct depressant actions on SA and AV tial prolongation, QT-interval prolongation, and induction of nodes, and these actions are only slightly counterbalanced by torsades de pointes arrhythmia and syncope. Excessive slowing of drug-induced vagal block. conduction can also occur. New arrhythmias can be precipitated. A troublesome adverse effect of long-term procainamide therapy is a syndrome resembling lupus erythematosus and usually consisting of arthralgia and arthritis. In some patients, pleuritis, Procainamide has ganglion-blocking properties. This action pericarditis, or parenchymal pulmonary disease also occurs. reduces peripheral vascular resistance and can cause hypotension, Renal lupus is rarely induced by procainamide. During long-term
TABLE 14–2 Membrane actions of antiarrhythmic drugs. 1Not available in the USA. na, data not available. therapy, serologic abnormalities (eg, increased antinuclear antibody titer) occur in nearly all patients, and in the absence of symptoms, these are not an indication to stop drug therapy. Approximately one third of patients receiving long-term procainamide therapy develop these reversible lupus-related symptoms. Other adverse effects include nausea and diarrhea (in about 10% of cases), rash, fever, hepatitis (<5%), and agranulocytosis (approximately 0.2%). Procainamide can be administered safely by intravenous and intramuscular routes and is well absorbed orally.Excessive accumulation of NAPA has been implicated in torsades de pointes during procainamide therapy, especially in patients with renal failure.Some individuals rapidly acetylate procainamide and develop high levels of NAPA.However, the lupus syndrome appears to be less common in these patients.Procainamide is eliminated by hepatic metabolism to NAPA and by renal elimination. | en | apollo | train |
## 25.7 MRI and Local Staging of Prostate Cancer
The use of a pelvic coil alone is not recommended for staging purposes with a 1.5 T [55].The advent of 3 T magnets might rekindle an interest in MRSI.At the moment, due to the technical limitations of MRSI, it seems that the most widely used protocol is a combination of DWI and DCE.Citrate ratio (From [29])
In a recent multicenter study, the value of the area under the ROC curve of MRSI was not more accurate than that of T2 weighted imaging to localize cancer with 1.5 T magnets [82]. Multiparametric functional MRI accuracy to localize PCa can be improved by combining different functional sequences [63]. Rationale: In a study [83], it was shown that the areas identified in the majority of the tumors on the ADC map and Ktrans maps covered slightly different regions of the PZ. Sensitivity of combined DWI and DCE-MRI was thus significantly improved over that of each technique alone, with a small decrease in specificity. The authors concluded that the areas of low ADC were associated with high cellular density and lower extracellular space, whereas high contrast enhancement could be attributed to areas with high microvessel density and leaky vasculature, characteristics of tumor tissue. Since both types of tissues are present within tumors, the combined ADC and DCE-MRI techniques are more likely to provide more accurate cancer detection. Using a combination of MRSI and DCE, a study showed [65] that some tumors were detected only by elevated Ktrans and not by the ratio of CC/Ci, which underlines the significance of combining the two parameters for cancer localization. For practical reasons, performing the three functional sequences on every patient is a time-consuming (60 min) examination, difficult to accept by the patient, the radiologist, and the technologist in routine practice. At the moment, due to the technical limitations of MRSI, it seems that the most widely used protocol is a combination of DWI and DCE. The advent of 3 T magnets might rekindle an interest in MRSI. ## 25.7 MRI and Local Staging of Prostate Cancer
The use of a pelvic coil alone is not recommended for staging purposes with a 1.5 T [55].### 25.7.1 Organ-Confined Tumors
Organ-confined tumors (Fig.25.10) show a normal signal of the prostate capsule, which is darker than that of the tumor and without abnormality on functional MRI.The fat of the subapical area is not infiltrated. | en | apollo | train |
Syndapin isoforms participate in receptor-mediated endocytosis and actin organization.
Syndapin I (SdpI) interacts with proteins involved in endocytosis and actin dynamics and was therefore proposed to be a molecular link between the machineries for synaptic vesicle recycling and cytoskeletal organization. We here report the identification and characterization of SdpII, a ubiquitously expressed isoform of the brain-specific SdpI. Certain splice variants of rat SdpII in other species were named FAP52 and PACSIN 2. SdpII binds dynamin I, synaptojanin, synapsin I, and the neural Wiskott-Aldrich syndrome protein (N-WASP), a stimulator of Arp2/3 induced actin filament nucleation. In neuroendocrine cells, SdpII colocalizes with dynamin, consistent with a role for syndapin in dynamin-mediated endocytic processes. The src homology 3 (SH3) domain of SdpI and -II inhibited receptor-mediated internalization of transferrin, demonstrating syndapin involvement in endocytosis in vivo. Overexpression of full-length syndapins, but not the NH(2)-terminal part or the SH3 domains alone, had a strong effect on cortical actin organization and induced filopodia. This syndapin overexpression phenotype appears to be mediated by the Arp2/3 complex at the cell periphery because it was completely suppressed by coexpression of a cytosolic COOH-terminal fragment of N-WASP. Consistent with a role in actin dynamics, syndapins localized to sites of high actin turnover, such as filopodia tips and lamellipodia. Our results strongly suggest that syndapins link endocytosis and actin dynamics. | en | apollo | train |
Large swings in blood pressure and heart rate as well as profuse diaphoresis are typical, mainly in response to the intense muscular contractions but they may also be related to the action of the toxin on the CNS.Fever and pneumonia are common complications.Spasms of the pharyngeal, laryngeal, or respiratory muscles carry the constant threat of apnea or suffocation.The incubation period varies greatly, from one or two days after exposure to a month or longer. Long incubation periods are associated with mild and localized types of the disease. There are several clinical types of tetanus, usually designated as local, cephalic, and generalized. Generalized tetanus This is the most common form. It may begin as local tetanus that becomes generalized after a few days, or it may be diffuse from the beginning. Trismus is frequently the first manifestation. In some cases this is preceded by a feeling of stiffness in the jaw or neck, slight fever, and other general symptoms of infection. The localized muscle stiffness and spasms spread quickly to other bulbar muscles as well as those of the neck, trunk, and limbs. A state of unremitting rigidity develops in all the involved muscles: the abdomen is board-like, the legs are rigidly extended, and the lips are pursed or retracted (risus sardonicus); the eyes are partially closed by contraction of the orbicularis oculi, or the eyebrows are elevated by spasm of the frontalis. Superimposed on this persistent state of enhanced muscle activity are paroxysms of tonic contraction or spasm of muscles (tetanic seizures or “convulsions”), which occur spontaneously or in response to the slightest external stimulus (see Weinstein for a review). They are agonizingly painful. Consciousness is not lost during these paroxysms. The tonic contraction of groups of muscles results in opisthotonos or in forward flexion of the trunk, flexion and adduction of the arms, clenching of the fists, and extension of the legs. Spasms of the pharyngeal, laryngeal, or respiratory muscles carry the constant threat of apnea or suffocation. Fever and pneumonia are common complications. Large swings in blood pressure and heart rate as well as profuse diaphoresis are typical, mainly in response to the intense muscular contractions but they may also be related to the action of the toxin on the CNS.Generalized spasms and rigidity of trunk and limbs developing in a neonate a few days after birth should always suggest the diagnosis of tetanus.This form of tetanus occurs when there has been inadequate sterile treatment of the umbilical cord stump in a neonate born to an unimmunized mother.Local tetanus This is the most benign form. | en | apollo | train |
OBJECTIVE: The study aimed to assess whether sub-endometrial contractility is reduced by the use of intramuscular (IM) progesterone. DESIGN: This is a randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo transfer (FET) were randomly allocated to "vaginal progesterone" or "IM progesterone": patients randomized to the vaginal arm were treated with 200 mg micronized progesterone 3 times daily while patients randomized into the IM progesterone arm were treated with a single daily injection of 50 mg progesterone in oil. The main outcome measure was the number of sub-endometrial contractions (waves) per minute 1 day before a blastocyst embryo transfer. RESULTS: Thirty-four patients were enrolled. The progesterone serum concentration was significantly higher in patients using the IM progesterone (85.2 ± 50.1 vs. 30.3 ± 11.2 nmol/L, respectively) but this did not translate into a lower sub-endometrial contractility (2.4 ± 4.8 vs. 1.4 ± 1.1 contraction/min, respectively). Clinical pregnancy rates were comparable between groups. The number of sub-endometrial waves was significantly lower among pregnant patients (p = 0.02). CONCLUSIONS: The use of IM progesterone in medicated FET cycles does not reduce the sub-endometrial activity compared to vaginal progesterone administration. Our data support a poor clinical pregnancy outcome with high wave activity, regardless of the progesterone mode. | en | apollo | train |
Liver and spleen
2.31.27B):
1.**_Alternatively_** , the organs can be palpated in the order given below (Fig.9 and .If a swelling is palpable, more time should be spent in examining the same, and follow the steps described in Chs.• **Local temperature**
By the dorsum of the hand, any area of raise in local temperature over the abdominal wall should be assessed. Increase in temperature may indicate local inflammation
• **Tenderness**
Tenderness is the pain felt by the patient when the examiner presses gently over the inflamed area. The examination for tenderness should start at the side opposite to the site of pain, and the area of pain should be examined last. This is mainly elicited by observing the patient's face; pain makes the patient wince the face
Some of the common areas of tenderness in chronic abdominal illnesses are:
• Tenderness at McBurney's point **—** recurrent appendicitis (Ref Figs. 30.52A and B)
**_In children_** , who are too young to cooperate, the child's right hand itself is used for palpation. The child's hand is taken over the abdomen by the examiner, and the child will withdraw and cry when tenderness is felt _(Grainger's method)_
###### Deep palpation
This is done when the abdominal muscles are relaxed fully, i.e. during expiration or in the pause between inspiration and expiration. ###### Intra-abdominal organs
• It is better to follow a sequence as a matter of routine, so that no area is left unexamined
• It is better to start the palpation in the left iliac fossa, and go anticlockwise to end in the genitalia (Fig. 31.27A):
• Next is to feel the left kidney, and spleen
• Next is to feel the liver, gallbladder, right kidney
• Next is to feel the right colon, urinary bladder and the left colon
• Next is to feel the aorta, para-aortic lymph nodes
• Next is to feel the groins
• Lastly, the external genitalia
FIGURE 31.27Paths for examination of intra-abdominal organs—(A) Path 1; (B) Path 2. If a swelling is palpable, more time should be spent in examining the same, and follow the steps described in Chs. 9 and . **_Alternatively_** , the organs can be palpated in the order given below (Fig. 31.27B):
1. Liver and spleen
2.Aorta and para-aortic nodes
4.Right iliac fossa
5.Left iliac fossa
6.Groins
7.Suprapubic region and
8.Genitalia
**In general, in adults, intra-abdominal organs are not palpable unless they are distended, dilated or enlarged._Pancreas is not palpable even when it is enlarged._**
1.**Stomach**
**_Normal stomach is not palpable._** The following pathologies can make the stomach palpable. | en | apollo | train |
Non-IgE-mediated allergic diseases.This response can evolve into chronic inflammation, which is characterized by the presence of effector T cells and eosinophils, and is most clearly seen in chronic allergic asthma.A further approach to the treatment of allergic disease may be to block the recruitment of eosinophils to sites of allergic inflammation. The eotaxin receptor CCR3 is a potential target in this context. In experimental animals, the production of eosinophils in bone marrow and their exit into the circulation is reduced by blocking IL-5 action. Anti-IL-5 antibody (mepolizumab) is of benefit in treating human patients with the hypereosinophilic syndrome, in which chronic overproduction of eosinophils causes severe organ damage. Clinical trials of anti-IL-5 treatment of asthma, however, show that, in practice, any beneficial effect is likely to be limited to a small subset of asthma patients with prednisone-dependent eosinophilic asthma; in these patients, IL-5 blockade seems to reduce the number of asthma attacks when the corticosteroid dose is reduced. Summary. The allergic response to innocuous antigens reflects the pathophysiological aspects of a defensive immune response whose physiological role is to protect against helminth parasites. It is triggered by the binding of antigen to IgE antibodies bound to the high-affinity IgE receptor FcεRI on mast cells and basophils. Mast cells are strategically distributed beneath the mucosal surfaces of the body and in connective tissue. Antigen cross-linking the IgE on the surface of mast cells causes them to release large amounts of inflammatory mediators. The resulting inflammation can be divided into early events that are characterized by short-lived mediators such as histamine, and later events that involve leukotrienes, cytokines, and chemokines, which recruit and activate eosinophils, basophils, and other leukocytes. This response can evolve into chronic inflammation, which is characterized by the presence of effector T cells and eosinophils, and is most clearly seen in chronic allergic asthma. Non-IgE-mediated allergic diseases.These effector arms of the immune response occasionally react with noninfectious antigens to produce acute or chronic allergic reactions.Although the mechanisms initiating the various forms of hypersensitivity are different, much of the pathology is due to the same immunological effector mechanisms.in susceptible individuals occur by binding of the drug to the surface of circulating blood cells. | en | apollo | train |
Novel Dental Poly (Methyl Methacrylate) Containing Phytoncide for Antifungal Effect and Inhibition of Oral Multispecies Biofilm.
Despite the many advantages of poly (methyl methacrylate) (PMMA) as a dental polymer, its antifungal and antibacterial effects remain limited. Here, phytoncide was incorporated into PMMA to inhibit fungal and biofilm accumulation without impairing the basic and biological properties of PMMA. A variable amount of phytoncide (0 wt % to 5 wt %) was incorporated into PMMA, and the basic material properties of microhardness, flexural strength and gloss were evaluated. In addition, cell viability was confirmed by MTT assay. This MTT assay measures cell viability via metabolic activity, and the color intensity of the formazan correlates viable cells. The fungal adhesion and viability on the PMMA surfaces were evaluated using <i>Candida albicans</i> (a pathogenic yeast). Finally, the thickness of saliva-derived biofilm was estimated. The flexural strength of PMMA decreased with increasing phytoncide contents, whereas there were no significant differences in the microhardness and gloss (<i>p</i> > 0.05) and the cell viability (<i>p</i> > 0.05) between the control and the phytoncide-incorporated PMMA samples. The amounts of adherent <i>Candida albicans</i> colony-forming unit (CFU) counts, and saliva-derived biofilm thickness were significantly lower in the phytoncide-incorporated PMMA compared to the control (<i>p</i> < 0.05). Hence, it was concluded that the incorporation of appropriate amounts of phytoncide in PMMA demonstrated antifungal effects while maintaining the properties, which could be a possible use in dentistry application such as denture base resin. | en | apollo | train |
Prospective cells of the loop of Henle are thought to be first positioned at the junctional region of the middle and upper limbs of the S-shaped body near the vascular pole of the glomerulus, where it will form the macula densa [181].Uniformity in proximal tubule length is achieved by 1 month of life, which subsequently lengthens at a uniform rate.(1) Wt1 and Wnt4 expression in a pretubular aggregate. (2) Wt1 in a pretubular aggregate (arrowhead) and the proximal portion of the renal vesicle (arrow). (3) Wt1 expression in the lower limb of the comma-shaped body. (4) Wt1 in the podocytes and parietal epithelium of the proximal segment of an early S-shape body. (5) Wt1 in podocyte and parietal epithelium of the proximal segment of an S-shape body (Used with permission of Springer Science + Business Media from Georgas et al. [177]); (c) Representative kidney phenotype of mice with a conditional mutation affecting nephron segmentation. Loss of Notch2 in the metanephric mesenchyme results in loss of proximal nephron elements (glomeruli, proximal tubules and S-shaped bodies). Red arrows glomeruli, green proximal tubule, yellow S-shaped bodies; turquoise, collecting duct (Used with permission from Cheng et al. [178])
All parts of the developing nephron increase in size as they become mature. However, the most striking changes consist of increased tortuosity of the proximal convoluted tubule, and elongation of the loop of Henle [2]. Cellular maturation of the proximal tubule involves transition from columnar to cuboidal epithelium, elaboration of apical and basal microvilli, and gradual increase in tubular diameter and length [179]. The human kidney at birth shows marked heterogeneity in proximal tubule length as one progresses from the outer cortex to the inner cortex [180]. Uniformity in proximal tubule length is achieved by 1 month of life, which subsequently lengthens at a uniform rate. Prospective cells of the loop of Henle are thought to be first positioned at the junctional region of the middle and upper limbs of the S-shaped body near the vascular pole of the glomerulus, where it will form the macula densa [181].Maturation of the primitive loop involves elongation of both ascending and descending limbs through the cortico-medullary boundary.Continued maturation involves differentiation of descending and ascending limb epithelia [183].Development of the presumptive distal tubule involves elongation of the connecting segment, which joins with the ureteric bud/collecting duct. | en | apollo | train |
6-Substituted sulfocoumarins are selective carbonic anhdydrase IX and XII inhibitors with significant cytotoxicity against colorectal cancer cells.
6-Substituted sulfocoumarins bearing the carboxamido, trimethylammonium as well as the cyano and methoxy moieties with interesting inhibitory activity/selectivity against the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII are reported. Moieties leading to the best inhibition were tert-butylcarboxamido, phenylcarboxamido, and 4-pyridylcarboxamido, with K(I) values of 2.1-8.1 nM. No inhibition of the off-target hCA II and I was observed. A number of these compounds were evaluated against HT-29 colon cancer cell lines ex vivo. Compounds 9c and 9e revealed effective cytotoxic effects after 72 h of incubation in both normoxic and hypoxic conditions, unlike sulfonamide CA inhibitors that show such effects only in hypoxia. These results may be of particular importance for the choice of future drug candidates targeting hypoxic tumors and metastases, considering the fact that a sulfonamide CA IX inhibitor (SLC-0111) is presently in phase I clinical trials. | en | apollo | train |
Charles Rob, Alfred Nobel and Aphrodite: the development of surgery for venous thromboembolism.
Charles Rob and the vascular surgeons at Strong Memorial Hospital have made significant contributions to the development of venology. Their impact on the surgical treatment of venous thromboembolism is emphasized. The technique for thrombectomy with temporary arteriovenous fistula is described. In a prospective randomized study from Sweden iliac vein patency was found in 76% of the operated group and 35% of the conservatively treated group after 6 months, and 77% versus 30%, respectively, after 5 years. A patent femoropopliteal vein with competent valves was found in 52% of the surgically treated patients compared with 26% of those treated conservatively after 6 months, and 36% versus 11%, respectively, after 5 years. Thrombectomy with temporary arteriovenous fistula is the author's method of choice to treat patients with acute iliofemoral venous thrombosis if the history of swelling of the thigh indicating iliac vein obstruction is less than 7 days' duration and the activity expectancy of the patient is more than 10 years. | en | apollo | train |
Discovery and characterization of small molecule Rac1 inhibitors.
Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1. Fluorescence polarization studies indicate that these compounds target the nucleotide-binding site of Rac1. In cells, both compounds blocked Rac1 binding to its effector PAK1 following EGF-induced Rac1 activation in a dose-dependent manner, while showing no inhibition of the closely related Cdc42 and RhoA activity. Furthermore, functional studies indicate that both compounds reduced cell proliferation and migration in a dose-dependent manner in multiple pancreatic cancer cell lines. Additionally, the two compounds suppressed the clonogenic survival of pancreatic cancer cells, while they had no effect on the survival of normal pancreatic ductal cells. These compounds do not share the core structure of the known Rac1 inhibitors and could serve as additional lead compounds to target pancreatic cancers with high Rac1 activity. | en | apollo | train |
Our data establish that both fat-loading and suboptimal selenium status enhance collagen and IL-8 production by C3A hepatocytes in response to TGFbeta1, possibly as part of an epithelial to mesenchymal transition. | en | apollo | train |
Sharp Grossmont Hospital is located in La Mesa, California, United States. It is the largest health care facility in East San Diego County with a service area covering 750 square miles. It is owned by Grossmont Healthcare District, who has leased it to Sharp HealthCare since 1991.
Overview
Sharp Grossmont Hospital, located in San Diego, is a 524-bed hospital that provides medical and surgical care, intensive care, sub-acute and long-term care, rehabilitation and emergency services.
Sharp Grossmont Hospital is the largest health care facility in East San Diego County with programs in emergency and critical care, cardiac care, orthopedics, rehabilitation, behavioral health, neurology, women's health, children's health and hospice care. Sharp Grossmont is a Magnet hospital for nursing excellence.
Sharp Grossmont Hospital's Emergency and Critical Care Center includes private rooms equipped with showers and TV, as well as either a couch or reclining chair that converts to a bed. More than two-thirds of the hospital's acute-care beds are private.
Services
Cardiovascular Services
David & Donna Long Cancer Center
Emergency and Critical Care Center
Endoscopy Services
Grossmont Plaza Surgery Center
Hospice
Hyperbaric Oxygen Therapy
Infusion Center
Limb Preservation Program
Massage and Healing Touch Therapies
Mental Health Services
Neonatal Intensive Care Unit
Nutrition Counseling
Orthopedic Services
Outpatient Imaging Center
Palliative Care Services
Pre-Anesthesia Evaluation Services (PAES)
Pulmonary Services
Radiology and Diagnostic Imaging
Rehabilitation Services
Robotic Surgery (da Vinci Surgical System)
Senior Services
Sharp Grossmont Hospital Care Clinic
Skilled Nursing Facilities
Sleep Disorders Center
Spiritual Care Services
Stroke Center
Thoracic (Lung) Surgery
Women's Health Center
Wound Healing Center and Hyperbaric Medicine
Medical firsts
The David & Donna Long Cancer Center is the first center in San Diego County to implement the TomoTherapy Hi-Art System, a radiation treatment device with a built-in computerized tomography (CT) scanner.
Sharp Grossmont opened the first hospice house in San Diego, known as the LakeView Home, offering in-home end-of-life care.
First in San Diego County to have a computerized tomography scanner with three-dimensional radiation treatment capabilities and dose calculations.
In 1993, the first East [San Diego County] outpatient cardiovascular diagnosis center opened at Sharp Grossmont Hospital as part of the Cardiovascular Institute.
In 1993, Sharp Grossmont opened the David and Donna Long Center for Cancer Treatment, San Diego County's first stand-alone cancer center offering diagnoses, treatment (chemotherapy), drug trials and radiation therapy in one location.
Awards to the hospital
In 2021, the hospital's emergency department was recognized with Gold Standard Level 1 accreditation as an "Accredited Senior-Friendly Emergency Department" by the American College of Emergency Physicians (ACEP)
In 2020, the hospital received an A grade in the Fall 2020 Leapfrog Hospital Safety Grade Survey
In 2020, the hospital was awarded the American Heart Association/American Stroke Association Get With The Guidelines Stroke Gold Plus Quality Achievement Award
In 2018, the hospital was honored with Planetree Gold Certification for Excellence in Person-Centered Care
In 2018, the hospital was recognized with The Joint Commission Three-Year Accreditation
In November 2007, Sharp HealthCare was awarded the Malcolm Baldrige National Quality Award by the United States National Institute of Standards and Technology. Sharp was one of five organizations to receive the award, which is the nation's highest Presidential honor for quality and organizational performance excellence. Sharp was the first health care provider in California and the eighth in the nation to receive this recognition. Sharp Grossmont Hospital is a part of Sharp HealthCare.
In 2006, it received the American Nurses Credentialing Center’s Magnet designation for excellence in nursing practices and patient care.
References
External links
Sharp HealthCare
Sharp Grossmont Hospital
Grossmont Healthcare District
This hospital in the CA Healthcare Atlas A project by OSHPD
Sharp documentary
Baldrige National Quality Program
Hospitals in San Diego County, California
Companies based in San Diego | en | apollo | train |
Evaluation of hematoma by MRI in follow-up of aorto-femoral bypass.
We selected a population of 20 patients with atherosclerotic disease, submitted to implantation of aorto-femoral bypass graft. These patients were studied by MRI with T1- and T2-weighted sequences (w.s.) using a 0.5 T superconductive magnet. Investigation was performed at 1 wk, 1, 3, and 6 mo after dacron implantation, to evaluate the normal evolution of hematoma and the potential development of complications. At the first week examination, hematoma presented medium signal intensity on T1 w.s. and high signal intensity on T2 w.s.; at 1 mo control the amount of hematoma was slightly reduced and we found persistence of high signal intensity on T2 w.s.; progressive reduction of size and signal intensity on T2 w.s. was noted at 3 mo control, in patients operated for peripheral vascular disease; on the other hand we found persistence of high signal intensity in T2 w.s. in patients treated for abdominal aortic aneurysms; only after 6 mo it was evident in all patients fibrotic evolution of the collection and low signal intensity in both T1 and T2 w.s. Thus, MRI study was useful in the evaluation of patency, morphology, and in detection of intraluminal thrombosis, but also in the characterization of periprosthetic hematoma. | en | apollo | train |
The McKittrick-Wheelock syndrome: a case of acute renal failure due to neoplastic cholera.
The McKittrick-Wheelock syndrome is characterized by severe electrolyte and fluid depletion as a result of rectal tumor hypersecretion. Typically, a metabolic acidosis ensues. We report the case of a 58-year-old man who presented with a mixed metabolic acidosis and alkalosis. He was hyponatremic, hypokalemic, and hypochloremic, with acute renal failure on blood testing. Following fluid resuscitation, a predominant alkalemia was observed. The patient was found to be passing 1.5 L of mucous per rectum per day, containing high concentrations of sodium and potassium, similar to that observed in cholera stool. A large rectal villous adenoma was discovered on sigmoidoscopy, and definitive management was achieved by removal of the tumor. This case provides a demonstration of the ranging metabolic disturbance associated with secretory diarrhea. Other endogenous and infective causes are discussed, and mechanisms compared with the case described. | en | apollo | train |
Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV.
Human respiratory syncytial virus (hRSV) is responsible for serious lower respiratory tract disease in infants and in older adults, and remains an important vaccine need. RSV fusion (F) glycoprotein is a key target for neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1 F) induces high neutralizing antibody titers in naïve animals, but it remains unknown to what extent pre-fusion F can boost pre-existing neutralizing responses in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV. A single immunization with non-adjuvanted DS-Cav1 F strongly boosts RSV neutralizing responses, directed towards pre-fusion F-specific epitopes, whereas a post-fusion F is unable to do so. Vaccination with pre-fusion F thus represents a promising strategy for maternal immunization and for other RSV vaccine target populations such as older adults. | en | apollo | train |
Having a new diagnosis skin cancer can be traumatizing, but there are plenty of available treatments that can be performed. At Swann Dermatology, we take great pride in our team offering comprehensive evaluation and management for skin cancer including cutting-edge methods of skin cancer removal. We offer preventative services including treatment of precancerous lesions with prescriptions and photodynamic therapy and offer a wide array of cosmeceuticals and sunscreens that Dr. Swann himself has found ideal to prevent skin cancers. Our team offers comprehensive skin cancer treatment unparalleled in Southwest Missouri.
We offer Mohs micrographic surgery, where Dr. Swann operates as the skin cancer surgeon and pathologist, using the microscope to identify and localize the tumor roots and extract them in a way that offers the absolute highest cure rate for skin cancers and also taking the least amount of healthy neighboring skin. Many skin cancers do not require Mohs surgery and we can treat these tumors by conventional excisions or other destructive modalities. We will help identify the best treatment option for you and put the diagnosis behind you. For more information about the most common types of skin cancer and how each are treated differently, we hope you find our skin cancer educational material useful.
Esteya Brachytherapy at Swann Dermatology for non-surgical treatment of non-melanoma skin cancers including squamous cell carcinoma and basal cell carcinoma.
We offer electronic brachytherapy with a radiation machine specifically designed to treat skin cancer without surgery. This is different than traditional external beam radiation therapy. With brachytherapy, the dose-curves are steep. This means that the radiation field is kept very tight and small. Cure rates are not as high as Mohs surgery, but approach 95-97% without surgery. Esteya is a patient-friendly, electronic brachytherapy solution for treating skin cancer. Specifically designed for non-melanoma skin cancer treatments, Esteya provides a non-surgical treatment that destroys cancer cells while sparing healthy surrounding tissue. There's minimal or no recovery period — which means there will be negligible impact on your daily activities. Depending on tumor characteristics including the histologic type, depth, tumor size and location, our team will develop a plan. Many plans require visiting our office twice weekly for 4-6 weeks.
We offer traditional excision, paraffin-embedded Mohs sections or "Slow Mohs", electrodessication and currettage as well as cryotherapy. Not all skin cancers should be treated equally and not all patients are candidates for every treatment. Our aim is to provide all the options available for ideal treatment of skin cancer and minimize your treatment time.
For information about non-melanoma skin cancers, read below. For information about melanoma, click here.
More than a million new cases of skin cancer are diagnosed every year in the United States, making it the most common of all cancers. Skin cancer can be an even greater concern for those with light skin or eye color and an active outdoor lifestyle. Prevention and early detection are the best defenses against skin cancers and routine screening is important. We specialize in skin cancer management with advanced treatment options.
In order to detect skin cancer early, you should examine your skin regularly to identify areas of skin changes in size, shape, color or diameter. Protecting your skin from the sun is also important as 90 percent of all basal and squamous cell carcinomas are thought to be caused by overexposure to ultraviolet light.
One in five Americans will develop skin cancer at some point in their lives. Skin cancers are generally curable if caught early. However, people who have had skin cancer are at a higher risk of developing a new skin cancer, which is why regular self-examination and doctor visits are imperative.
Mohs Micrographic Surgery — The preferred method for optimal management of complex tumors including those on the head and neck, large tumors, or tumors previously treated by other methods where recurrence of the cancer has detected. Mohs Micrographic Surgery combines removal of cancerous tissue with microscopic review while the surgery takes place. By mapping the diseased tissue layer by layer, less healthy skin is damaged when removing the tumor.
Mohs Micrographic Surgery — Because squamous cell carcinomas can be more aggressive than basal cell carcinomas, Mohs surgery is often the best choice for squamous cell carcinoma of the skin, because it is able to give the best cure rate. Mohs Micrographic Surgery combines removal of cancerous tissue with microscopic review while the surgery takes place. By mapping the diseased tissue layer by layer, less healthy skin is damaged when removing the tumor.
Surgical Excision — In this treatment the tumor is surgically removed and stitched up. The tissue is sent in a jar to a pathologist who sections the tissue and makes slides, then reads the slides to determine if the representative margins appear clear. It takes approximately 5 business days to determine if the margins are clear or if further surgery is warranted.
Radiation Therapy — Traditional radiation therapy is used for difficult-to-treat tumors, either because of their location, severity or persistence. Electronic brachytherapy can be utilized in-office to treat relatively early primary tumors with a high cure rate and no surgical scar.
The key to detecting skin cancers is to notice changes in your skin. | en | apollo | train |
Mechanical circulatory support after surgical repair of Bland-White-Garland syndrome. A study of three cases.
The anomalous origin of the left coronary artery arising from the pulmonary artery (ALCAPA), also known as Bland-White-Garland (BWG) syndrome, is a rare congenital heart disease. We present cases of three children in whom BWG syndrome was repaired surgically. In two of them, the left coronary artery was transplanted from the pulmonary trunk to the aorta, and in one, the Takeuchi procedure was performed. In both cases in which the left coronary artery was transplanted to the aorta, mechanical circulatory support was used after the surgery. This was due to a low ejection fraction (10%) while weaning from cardiopulmonary bypass. Although associated with numerous complications, mechanical circulatory support can be a lifesaving therapy in patients with a poor left ventricular function after the correction of BWG syndrome. | en | apollo | train |
Approximately 48% of patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) have circulating ANCA that is usually antimyeloperoxidase.The other laboratory findings reflect the organ systems involved.Evidence of inflammation as evidenced by elevated ESR, fibrinogen, or α2-globulins can be found in 81% of patients.Although the precise pathogenesis of this disease is uncertain, its strong association with asthma and its clinicopathologic manifestations, including eosinophilia, granuloma, and vasculitis, point to aberrant immunologic phenomena. Patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) often exhibit nonspecific manifestations such as fever, malaise, anorexia, and weight loss, which are characteristic of a multisystem disease. The pulmonary findings in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) clearly dominate the clinical picture with severe asthmatic attacks and the presence of pulmonary infiltrates. Mononeuritis multiplex is the second most common manifestation and occurs in up to 72% of patients. Allergic rhinitis and sinusitis develop in up to 61% of patients and are often observed early in the course of disease. Clinically recognizable heart disease occurs in ∼14% of patients and is an important cause of mortality. Skin lesions occur in ∼51% of patients and include purpura in addition to cutaneous and subcutaneous nodules. The renal disease in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is less common and generally less severe than that of granulomatosis with polyangiitis and microscopic polyangiitis. The characteristic laboratory finding in virtually all patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is a striking eosinophilia, which reaches levels >1000 cells/μL in >80% of patients. Evidence of inflammation as evidenced by elevated ESR, fibrinogen, or α2-globulins can be found in 81% of patients. The other laboratory findings reflect the organ systems involved. Approximately 48% of patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss) have circulating ANCA that is usually antimyeloperoxidase.In order to be diagnosed with eosinophilic granulomatosis with polyangiitis (Churg-Strauss), a patient should have evidence of asthma, peripheral blood eosinophilia, and clinical features consistent with vasculitis.The prognosis of untreated eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is poor, with a reported 5-year survival of 25%. | en | apollo | train |
PTH levels are undetectable or inappropriately low in severe hypomagnesemia despite the stimulus of severe hypocalcemia, and acute repletion of magnesium leads to a rapid increase in PTH level. Serum phosphate levels are often not elevated, in contrast to the situation with acquired or idiopathic hypoparathyroidism, probably because phosphate deficiency is often seen in hypomagnesmia (Chap. 393). Diminished peripheral responsiveness to PTH also occurs in some patients, as documented by subnormal response in urinary phosphorus and urinary cAMP excretion after administration of exogenous PTH to patients who are hypocalcemic and hypomagnesemic. Both blunted PTH secretion and lack of renal response to administered PTH can occur in the same patient. When acute magnesium repletion is undertaken, the restoration of PTH levels to normal or supra-normal may precede restoration of normal serum calcium by several days. Repletion of magnesium cures the condition. Repletion should be parenteral. Attention must be given to restoring the intracellular deficit, which may be considerable. After IV magnesium administration, serum magnesium may return transiently to the normal range, but unless replacement therapy is adequate, serum magnesium will again fall. If the cause of the hypomagnesemia is renal magnesium wasting, magnesium may have to be given long-term to prevent recurrence (Chap. 423). PTH is not sufficiently active to fully prevent hypocalcemia (although retaining phosphaturic activity, for example). This problem occurs when the PTH1R–signaling protein complex is defective (as in the different forms of pseudohypoparathyroidism [PHP], discussed below); when PTH action to promote calcium absorption from the diet via the synthesis of 1,25(OH)2D is insufficient because of vitamin D deficiency or because vitamin D is ineffective (defects in vitamin D receptor or vitamin D synthesis); or in CKD in which the calcium-elevating action of PTH is impaired.PHP, on the other hand, has a pathophysiology that is different from the other disorders of ineffective PTH action.PHP resembles hypoparathyroidism (in which PTH synthesis is deficient) and is manifested by hypocalcemia and hyperphosphatemia, yet elevated PTH levels. | en | apollo | train |
These structures are best visualized on coronal and axial sections (see Plates 13-2 and 13-5) and must be carefully evaluated when assessing a patient with facial trauma.The medial and lateral pterygoid plates lie immediately posterior to the maxilla.Disruptions of the integrity or symmetry of the arch may be associated with craniofacial developmental abnormalities or facial trauma.The shape and size of the incisive foramen is appreciated on axial sections (see Plates 13-2 and 13-3). There is considerable variation in the size of the nasopalatine canal and incisive foramen. It is important to differentiate between a large incisive foramen and an incisive canal cyst because the latter can cause localized dilation of the canal or widening of the incisive foramen and may cause displacement of teeth (see Chapter 21). FIGURE 13-6 **A** and **B,** Sagittal CBCT sections through the midsagittal plane showing the course of the nasopalatine canal _(yellow arrow)_ and the opening of the incisive foramen _(white arrow)_. Note the range of normal variation in the size of these structures. **C,** Axial section through the level of the incisive foramen _(arrow)_. The maxillary sinus occupies a major portion of the maxillary body. When evaluating the maxilla, the continuity of the sinus walls should be examined (see Plates 13-2, 13-4, 13-5, and 13-7). This examination includes the anterior wall, lateral wall (or infratemporal wall), medial wall (lateral wall of nasal fossa), and superior wall (orbital floor). Additionally, the symmetry of the right and left sinuses is evaluated. The zygomatic processes of the maxilla, which emanates from the junction of the anterior and lateral walls of the maxillary body, articulate posteriorly with the maxillary process of the zygoma. These two processes form the anterior segment of the zygomatic arch. The zygomaticomaxillary suture is visualized as a thin radiolucent, jagged line in this portion of the arch. Disruptions of the integrity or symmetry of the arch may be associated with craniofacial developmental abnormalities or facial trauma. The medial and lateral pterygoid plates lie immediately posterior to the maxilla. These structures are best visualized on coronal and axial sections (see Plates 13-2 and 13-5) and must be carefully evaluated when assessing a patient with facial trauma.## Nasal Cavity and Paranasal Sinuses
The nasal cavity and paranasal sinuses aerate the maxillary, sphenoid, ethmoid, and frontal bones.The paranasal sinuses communicate directly with, and drain into, the nasal cavity via **ostia**.The nasal cavity is divided by the nasal septum in the midline (see Plates 13-2, 13-4, and 13-5). | en | apollo | train |
## Cancer of the urethra
### Male urethra
This very rare tumour may arise in the prostatic, bulbar or penile urethra, and is thought to be commoner in patients with a history of chronic inflammation or stricture.Nonetheless, with early diagnosis and improving outcomes, survivorship figures are high – for example, there are now over 250 000 men alive post-diagnosis in the UK alone.This is an oral androgen-receptor-antagonist agent which appears to target several steps in the androgen-receptor–signalling pathway, thereby inhibiting the major driver of prostate-cancer growth. Indeed this study was closed early because at the point of interim analysis, the median survival was 18.4 months versus 13.6 months – a relative reduction of 37% in risk of death though admittedly at the cost of side-effects such as fatigue, diarrhoea and vasomotor symptoms. In the UK, about 15% of patients receive chemotherapy at any point in their cancer journey; in the USA the figure is somewhat higher. In patients with unresponsive widespread bone pain, treatment with radioactive phosphorus may be of value. Up to 75% of patients have been reported to benefit, though remissions tend to be short. 89Sr has recently been marketed as a superior radionuclide for use in this way [99], and may possibly be preferentially taken up in metastases rather than treating the whole bone marrow. Many other newer therapies (including radiopharmaceuticals such as radium-223) are emerging as promising agents for advanced prostate cancer – see, for example, Mitka [106] and Parker _et al_. [107]. Overall, it has been estimated that patients with carcinoma of the prostate lose, on average, almost a decade of life; the disease is now claiming around 10 000 lives annually in the UK. In the USA, about 240 000 cases were diagnosed in 2012, with 28 000 deaths from this disease – second only to lung cancer. Prostate cancer is responsible for about 26% of all deaths from malignant disease in men over the age of 85. Nonetheless, with early diagnosis and improving outcomes, survivorship figures are high – for example, there are now over 250 000 men alive post-diagnosis in the UK alone. ## Cancer of the urethra
### Male urethra
This very rare tumour may arise in the prostatic, bulbar or penile urethra, and is thought to be commoner in patients with a history of chronic inflammation or stricture.The tumour spreads by direct invasion into the perineum and penile tissues.The penile urethra drains to inguinal lymph nodes, and the prostatic urethra to pelvic nodes.Urethral carcinomas present with a urethral mass, obstruction, fistula, pain and haematuria.The age range is 50–80 years. | en | apollo | train |
Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension.
Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis. | en | apollo | train |
Chronic diseases develop over time and are considered incurable. Diabetes, heart disease, some forms of cancer and dental disease are examples that are common in Putnam County.
It is best to prevent them in the first place. If that is not possible, learning to manage your condition is second best. With good management, you can preserve the quality of your life. You can reduce your symptoms, slow down the progression of your illness and sometimes even reverse it.
To help you manage your health, a chronic disease self-management program (CDSMP) is offered by the Putnam County Department of Health, in partnership with the Putnam County Office for Senior Resources, the Visiting Nurse Association of Hudson Valley, and Putnam Hospital Center. This program is based on a research model developed at Stanford University. Peer leaders—individuals who have chronic disease themselves—are specially trained to lead these workshops. Decades of research has shown that these peer leaders are successful in engaging and empowering patients to feel better and take charge of their health.
For more information on the CDSMP series of workshops, click here.
The toll of chronic diseases is enormous—both in terms of human suffering and healthcare costs. In fact, 70 percent of all U.S. healthcare costs are attributable to chronic diseases, and worldwide the burden of chronic disease now surpasses communicable diseases.
Please browse below for information about specific programs and services provided.
The Live Healthy Putnam (LHP) initiative, launched in 2007 by the PCDOH, is the umbrella program for chronic disease prevention in the County. Initially formed to promote the voluntary ban on trans fats in Putnam County restaurants, the program has expanded and now embodies a 30-member coalition of community organizations interested and invested in promoting healthy lifestyles. The work of the coalition is not limited to one level of prevention, but instead covers all levels including primary prevention. Improving nutrition, increasing physical activity and reducing tobacco use are some of the overall goals.
For more information about the Live Healthy Putnam Coalition, click here.
The PCDOH connects eligible residents to free Healthy Living Partnership (HLP) screenings for breast, cervical and colorectal cancer. Further referrals for diagnosis and treatment are then made. The PCDOH and HLP provide free education regarding breast, cervical, colorectal and prostate cancer.
The PCDOH partners with POW’R Against Tobacco (Putnam, Orange, Westchester, Rockland) to implement strategies to decrease the social acceptability of tobacco use. Anti-smoking messages and activities are also promoted in conjunction with the youth-based “Reality Check” program. This New York State Department of Health tobacco education program is coordinated through the Youth Bureau of Putnam County.
The PCDOH also partners with the American Cancer Society to recruit participants for their longitudinal Cancer Prevention Study, a major research study seeking to better understand the lifestyle, environmental, and genetic factors that cause or prevent cancer.
Information and education about early recognition and warning signs of stroke is disseminated at workshops, health fairs, online and through social media networks.
Trained nutritionists at the PCDOH provide extensive nutrition education, both to residents and to major stakeholder groups, including school district administrators, health teachers, childcare staff, cardiac patients and parents. Weight management, the new My Plate guidelines, the DASH (dietary approaches to stop hypertension) diet and healthy lunch ideas are some of the topics presented. Interactive health-oriented games are developed to engage and teach youth in school health classes and at health fairs. The PCDOH additionally works with the Cornell Cooperative Extension to promote nutrition-related curriculum such as “Heart Healthy Gardens” and the “Garden to Table” programs.
Monthly meetings for the Putnam Chapter of the Mended Hearts Support Group through postings on Comcast’s and Cablevision’s local community bulletin board, and the Putnam County website.
Described above in the “Cancer” section, these initiatives can also significantly reduce risks of cardiovascular disease and stroke.
Tooth decay is the number-one chronic disease among children. The PCDOH launched a Dental Health Screening Initiative in 2010. Staff members work with the Putnam County school districts to provide free on-site dental screenings for 4th graders. The PCDOH also served as a referral source and provider of educational materials and resources on dental health to the community. Additionally WIC and MCH nursing staff providing individual counseling to mothers on the dangers of baby bottle syndrome and dental caries. | en | apollo | train |
The degree of visual loss depends upon the underlying cause.##### Optic atrophy
Optic atrophy is the end result of many processes that damage the nerve (see Optic nerve lesions, above).from a tumour, an abscess or meningitis
Retinal vein obstruction (thrombosis or compression)
Optic neuritis (inflammation of the optic nerve, often caused by demyelination)
Accelerated hypertension.ethambutol, quinine, tobacco and methyl alcohol. ##### Defects of the optic chiasm
The most common cause of bitemporal hemianopia (i.e. blindness in the outer half of each visual field) is a pituitary adenoma, which compresses the decussating fibres from the nasal half of each eye. Other causes are craniopharyngioma and secondary neoplasm. ##### Defects of the optic tract and radiation
Damage to the tracts or radiation, usually by tumour or a vascular accident, produces a homonymous hemianopia (blindness affecting either the right or the left half of each visual field) in one half of the visual field contralateral to the lesion. ##### Defects of the occipital cortex
Homonymous hemianopic defects are caused by unilateral posterior cerebral artery infarction. The macular region may be spared in ischaemic lesions as a result of the dual blood supply to this area from the middle and posterior cerebral arteries. In contrast, injury to one occipital pole produces a bilateral macular (central) field defect. #### Optic disc oedema (papilloedema) and optic atrophy
The principal pathological appearances of the visible part of the nerve, the disc, are:
Swelling (papilloedema)
Pallor (optic atrophy). ##### Papilloedema
Papilloedema produces few visual symptoms in the early stages. As disc oedema develops there is enlargement of the blind spot and blurring of vision. The exception is optic neuritis, in which there is early and severe visual loss. The common causes of papilloedema are:
Raised intracranial pressure, e.g. from a tumour, an abscess or meningitis
Retinal vein obstruction (thrombosis or compression)
Optic neuritis (inflammation of the optic nerve, often caused by demyelination)
Accelerated hypertension. ##### Optic atrophy
Optic atrophy is the end result of many processes that damage the nerve (see Optic nerve lesions, above). The degree of visual loss depends upon the underlying cause.The parasympathetic efferents that control the constrictor muscle of the pupil arise in the Edinger–Westphal nucleus in the midbrain, and run with the oculomotor (third) nerve to the eye.The Edinger–Westphal nucleus receives afferents from the optic nerve (for the light reflex) and from the convergence centre in the midbrain (Fig.17.6). | en | apollo | train |
Immune mechanisms play an important role in both male and female sterility. Even more frequent is the participation of immunity in autoimmune and alloimmune recurrent abortions. Immunopathologic reactions occur also in women suffering from preeclampsia and postclimacteric syndrome. To the important causes of female and male sterility belong chronic infections in the reproductive system.
Treatment of all above mentioned disorders involved methods of immunomodulation, mainly local and systemic glucocorticoids, repeated high doses of intravenous immunoglobulines, anticoagulants (aspirin, heparin) and recently also oral enzyme therapy. In infectious processes, the rational use of antibiotics is inevitable.
Immunomodulation ameliorates healing of male and female sterility, autoimmune as well as alloimmune recurrent abortions. Significant progress was also obtained in the treatment of adnexitis and prostatitis. Here, the clinical or subclinical immunological defect prompted us to use immunomodulators of chemical or biologic nature (among the latter, combination of oral animal and plant proteolytic enzymes). Their use in combination with antibiotics led to a more frequent and more effective healing not only in the infections evoked by "common" bacteria, but also in processes caused by chlamydia, mycoplasma, and ureaplasma.
Immunomodulation represents an important part of the complex therapy of male and female sterility, recurrent abortions and chronic infections of the reproductive system. | en | apollo | train |
This tube can become swollen because of allergic reactions, weakness in the tissues surrounding it, or infections.Most of these infections are a backup of noxious fluids and gases into the middle ear because of an obstructed connecting pipe, the eustachian tube.Ear infections are terribly painful for a child.Steuer MK, Hofstadter F, Probster L, Beuth J, Strutz J. Are ABH antigenic determinants on human outer ear canal epithelium responsible for Pseudomonas aeruginosa infections? _ORL J Otorhinolaryngol Relat Spec._ 1995;57:148-152. **EAR INFECTION, OTITIS MEDIA (CHILDHOOD EAR INFECTION)–** _An infection of the inner ear, most common in young children._
**Symptoms**
Symptoms of acute otitis media usually develop suddenly and can include the following:
■ Pain
■ Coughing
■ Nasal congestion
■ Fever
■ Irritability
■ Discharge from the ear
■ Loss of appetite
■ Vomiting
**About Otitis Media**
As many as two-thirds of all children under 6 years of age suffer from chronic ear infections, accounting for half of all visits to pediatricians. Most of these children have allergies to both environmental and food-based particles. Several studies have shown that the ear fluids of children with a history of chronic ear infections lack specific chemicals called complement, which are needed to attack and destroy the bacteria. Another study showed that a serum lectin called mannose binding protein is missing in the ear fluid of children with chronic infections. This lectin apparently binds to mannose sugars on the surface of the bacteria and agglutinates them, allowing for their faster removal. Both of these important immune factors eventually do develop in their proper amounts, which may help explain why the frequency of ear infections gradually lessens as the child ages. Ear infections are terribly painful for a child. Most of these infections are a backup of noxious fluids and gases into the middle ear because of an obstructed connecting pipe, the eustachian tube. This tube can become swollen because of allergic reactions, weakness in the tissues surrounding it, or infections.But there is growing worry that the overuse of antibiotics is making the bacteria that cause ear infections—and more serious ailments—resistant to the drugs.This has doctors and parents looking for new alternatives.Why do antibiotics stop working?A baby's first ear infection is typically treated with a mild antibiotic such as amoxicillin. | en | apollo | train |
In other cases, however, this will not be enough and will only bring temporary relief, because the structural imbalances within the teeth and jaw can repeatedly reinstate the systemic imbalance and consequent symptoms, and may need specific whole-person dental treatment to bring about lasting change.Maxillary compression, maxillary arch distortion, mandibular retrusion, mandibular protrusion, entrapment of the mandible, temporo-mandibular disc displacement, loss of vertical dimension, worn teeth, abnormal growth patterns in the teeth maxillae or mandible, open bite, excessive overbite or overjet, crossbite, injuries to the teeth or face, tooth extractions, braces, bridges – all of these primary dental sources can lead to severe symptoms, locally or systemically, and can restrict cranio-sacral mobility, vitality and healthy function. The consequent structural disturbances, deeply ingrained in the tissues and in the growth patterns, may be exerting a constant persistent imbalance which will maintain and perpetuate the disruption to health until the underlying structural cause in the dentition is resolved. In such cases, cranio-sacral treatment will improve balance and integrity and enable the system to adapt around the structural imbalance. Often this may be enough, because a well-balanced fluently functioning integrated system may often cope with minor structural disturbances perfectly well. In other cases, however, this will not be enough and will only bring temporary relief, because the structural imbalances within the teeth and jaw can repeatedly reinstate the systemic imbalance and consequent symptoms, and may need specific whole-person dental treatment to bring about lasting change.Cranio-sacral integration can still address the various other stresses and strains that may be contributing to the patient's discomfort, and rebalance the various repercussions of the unbalanced jaw.This will certainly enable the system to cope better and may perhaps eliminate symptoms completely.But cranio-sacral integration will not replace missing teeth or restore vertical dimension. | en | apollo | train |
It also predicts risk of cardiovascular disease and relates to both BMI and the waist: hip ratio.Cutoff points have also been defined for waist circumference, which is another simple measure for predicting excess visceral adipose tissue [37].World Health Organization, Geneva, Switzerland.Publication WHO/NUT/NCD/98.1.Because women have a higher percentage body fat for a comparable weight than men, this indicates that women can carry fat better than men. It has been suggested that they do so because their excess fat is mainly subcutaneous and peripherally distributed (thighs, buttocks, breasts) compared with men in whom fat is stored in the abdominal region [35]. The classification proposed by WHO [Table 1 [34]) is based on the relationship between BMI and mortality. BMIs between 18.5 and 24.9 kg/m2 are defined as normal, between 30 and 39 as obese, and >40 as severely obese [35]. A BMI >30 does not always correspond to excess adiposity. A muscle builder may have a BMI of 30 that is associated with a large muscle mass. Ethnic groups with deviating body proportions, such as being very tall and thin, have healthy BMIs ranging from 17 to 22 kg/m2 and have excessive fat mass at a BMI of 25 [36]. TABLE 1
Cutoff Points for Body Mass Index
BMI (kg/m2) | WHO classification of obesity
---|---
<18.5 | underweight
18.5–24.9 | normal range
25.0–29.9 | grade 1 overweight
30.0–39.9 | grade 2 overweight
≥40.0 | grade 3 overweight
_Source:_ World Health Organization (1997). Obesity: Preventing and managing the global epidemic. Report of a WHO Consultation presented at the World Health Organization, June 3–5, 1997. Publication WHO/NUT/NCD/98.1. World Health Organization, Geneva, Switzerland. Cutoff points have also been defined for waist circumference, which is another simple measure for predicting excess visceral adipose tissue [37]. It also predicts risk of cardiovascular disease and relates to both BMI and the waist: hip ratio.TABLE 2
Cutoff Points for Waist Circumferences
Waist circumference | Men | Women
---|---|---
Need for concern | ≥94cm | ≥80cm
Critical level | ≥102cm | ≥88cm
_Source:_ National Heart, Lung, and Blood Institute, Obesity Education Initiative Expert Panel (1998).Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. | en | apollo | train |
Elizabeth Louise Barrett-Connor (April 8, 1935 – June 10, 2019) was Chief of the Division of Epidemiology and Distinguished Professor at the University of California, San Diego. She investigated the role of hormones in pathogenesis of cardiovascular disease, diabetes and osteoporosis.
Early life and education
Barrett-Connor was born in Evanston, Illinois. She was the only child of Florence Hershey and William Barrett. Her father was a chemical engineer, and working in ammunition companies. She grew up in Lee, Massachusetts, and learned to read with her grandmother, who was a postal worker. As a child she saw Leonard Bernstein in orchestra and attended the Northfield Preparatory School. Barrett-Connor studied zoology at Mount Holyoke College and was a member of Phi Beta Kappa. She graduated in 1956. In 1960 she earned her medical degree at Cornell University, before completing her internal medicine residency at the University of Texas Southwestern Medical Center. Her early work studied the diarrhea of United States students in Mexico. Barrett-Connor was a National Institutes of Health postdoctoral researcher at the London School of Hygiene & Tropical Medicine. She earned a diploma in the Clinical Medicine of the Tropics at the London School of Hygiene & Tropical Medicine in 1965. She moved to the University of Miami as an infectious disease epidemiologist.
Research and career
Barrett-Connor specialised in healthy ageing and women's health. In particular, she championed studying cardiovascular disease in women as well as men. She was recruited to the faculty at the University of California, San Diego in 1972. In 1972 Barrett-Connor founded the Rancho Bernardo Heart and Chronic Disease Study (RBS), which involved over 6,000 people in Rancho Bernardo, San Diego. For the study, Barrett-Connor recruited people from Rancho Bernardo, and studied the connection between lipids and heart disease. She managed to recruit almost 70% of the Rancho Bernardo population. She selected the area as it was reported as having a healthy population. She has collected data for over forty years, including frozen blood samples, and transcends changes in lifestyle and cholesterol. She investigated how family history, fat distribution, cholesterol, physical activity and cigarette smoking impact chronic diseases. Barrett-Connor used the RBS to study sex differences in cardiovascular disease. As of 2011, one third of the participants still reported on their health, and half still have health tests at the Bernado Center Drive Clinic.
Barrett-Connor identified many aspects of women's health, including that women with diabetes have a high triglyceride and that diabetes eliminates women's protection against cardiovascular disease. It included innovative techniques to assess bone density, demonstrating that low calcium can result in hip fracture. She also showed that smoking during middle age can result in osteoporosis, and that drinking coffee can result in low bone mineral density.
Alongside RBS, Barrett-Connor led the Diabetes Prevention Program Outcomes Study. She was also interested in overlooked issues in men's health, including osteoporosis, and was involved with the Osteoporotic Fractures in Men Study and Testosterone Trials. In 1971 Barrett-Connor established the UCSD Epidemiology and Biostatistics Course.
Her approach to storing blood samples to investigate new hypotheses at a later date was adopted by the European Prospective Investigation into Cancer and Nutrition and the UK Biobank study.
Awards and honours
1986 American College of Preventive Medicine Boucot Sturgis Lecture
1987 American Diabetes Association Kelly West Memorial Lecture
1994 American College of Physicians James D. Bruce Memorial Award
1995 National Institutes of Health Florence Mahoney Lecture
1997 Society for Epidemiologic Research John C. Cassel Memorial Lecture
1998 American Epidemiological Society Harry S. Feldman Lecture
1999 National Institutes of Health Award for Outstanding Work
1999 London School of Hygiene & Tropical Medicine Heath Clark Lecture
2003 American Society for Preventive Cardiology Stokes Award
2003 Cornell University Medical College Alumni Association Award of Distinction
2003 Endocrine Society Clinical Investigator Award
2004 Awarded an honorary doctorate at the Norwegian University of Science and Technology (NTNU)
2009 National Osteoporosis Foundation Living Legacy Award
2009 American Heart Association Distinguished Scientist Award
2011 American Heart Association Population Research Prize
2012 Endocrine Society Mentoring Award
2013 International Academy of Cardiology Distinguished Fellowship Award
2013 Women in Epidemiology, Epidemiology and Prevention Mentoring Award
2018 Endocrine Society's Fred Conrad Koch Lifetime Achievement Award
The American Heart Association hold a series of Elizabeth Barrett-Connor research awards in her honour. She has previously served as the President of the American Public Health Association, the American Epidemiological Society, the American Heart Association Epidemiology Council and the Society for Epidemiologic Research.
Personal life
Barrett-Connor was married to James Connor, a paediatrician at the University of California, San Diego. She had three children, Jonathan, Caroline and Steven as well as two-step children, James-Davis and Susan. Barrett-Connor died on June 10, 2019.
References
1935 births
2019 deaths
American women epidemiologists
American epidemiologists
People from Evanston, Illinois
Mount Holyoke College alumni
Cornell University alumni
Alumni of the London School of Hygiene & Tropical Medicine
University of California, San Diego faculty
21st-century American women | en | apollo | train |
This is the first report to identify bacteremia following febrile episodes during neutropenia as a predictive factor for IFI in pediatric patients with hematologic or malignant disease. When bacteremia is detected in such patients, sufficient preventive measures against IFI, including intensive use of antifungal agents, are warranted. | en | apollo | train |
Maine Medical Center (MMC) Department of Radiology has a tradition of leadership in residency training. The MMC Diagnostic Radiology (DR) Residency Program was established in the early 1950s as one of the first graduate medical education programs in the hospital. The first interventional radiology (IR) resident clinic in the United States was founded at MMC in 2008. Established in 2016, the MMC Integrated Interventional Radiology Residency Program was among the first 12 such programs accredited by the Accreditation Council for Graduate Medical Education (ACGME). The MMC DR and IR programs remain the only radiology residencies in the state of Maine today.
Maine Medical Center has a long tradition of medical training. It is a 637-bed, non-profit, tertiary referral center, and it is the largest medical center in northern New England. It has been educating physicians since it was founded in 1874 as Maine General Hospital, the first general hospital in the state. Maine Medical Center remains Maine’s only Level I Trauma Center today. Maine Medical Center is also Maine’s only academic medical center, supporting over 240 residents and fellows in 15 residency and 9 fellowship programs. With a referral base of over 1.4 million people throughout Maine and eastern New Hampshire, there is incredible diversity in patients and pathology.
The MMC Integrated IR Residency Program faculty consists of 36 radiologists, nearly all fellowship-trained, including 8 interventional radiologists. There are 3 IR advanced practice providers. With only 1 IR resident per year, the program is small enough that the residents are intimately involved with procedures, and the clinical teaching is one-on-one with the faculty members. In addition, faculty and residents get to know each other quite well. The varied, practical clinical experience at MMC prepares residents well for their careers in IR.
The program is located in Portland, the largest city in the state of Maine. Portland is a historic seacoast town with a funky vibe, working waterfront, hundreds of galleries and unique shops, and award-winning restaurants. Portland has been ranked “America’s Foodiest Small Town” by Bon Appetit in 2009, “America’s Most Livable Cities” (No. 1) by Forbes in 2009, “The Coolest Small Cities in America” by GQ in 2010, “Best Cities for Young Professionals” (No. 6) by Forbes in 2011, “America’s Best Cities for Hipsters” (No. 5) in by Travel + Leisure in 2012, “The 15 Most Underrated Cities in the U.S.” (No. 8) by Complex in 2013, “16 Best Places to Live in the U.S.” (No. 13) by Outside in 2014, “The 10 Best Places to Live Now” (No. 3) by Men’s Journal in 2015, and “America’s Coolest Small Towns” (No. 5) by Jetsetter in 2015. Portland has been dubbed “The San Francisco of the East” for its cultural diversity and abundance of restaurants. Outside of Portland, Maine’s famous rocky coast, numerous islands, sandy beaches, unspoiled lakes, and majestic mountains offer limitless outdoor activities, such as swimming, surfing, hiking, camping, bicycling, kayaking, canoeing, snowmobiling, fishing, skiing, and so much more. Come do your residency in Vacationland!
Graduates of an integrated IR residency qualify to take the IR/DR examination offered by the American Board of Radiology (ABR). The IR/DR certificate recognizes competency in both diagnostic radiology and interventional radiology, and certificate holders can practice in either or both domains.
The Interventional Radiology (IR) specialty was founded in the early 1960s by Charles Dotter, MD, who invented angioplasty and the catheter-delivered stent, which were first used to treat peripheral artery disease. However, the procedural domain of IR has increased dramatically since then. Furthermore, clinical care has become an integral and essential part of interventional care. Therefore, the traditional one-year fellowship in Vascular and Interventional Radiology (VIR) following one year of clinical internship and four years of DR residency was deemed no longer adequate. Fortunately, in February 2012 the American Board of Medical Specialties (ABMS) recognized IR as a distinctive specialty in medicine, noting that IR practitioners have unique expertise in three areas that mark the domain of IR – diagnostic imaging, image-guided procedures, and patient care. The ACGME sanctioned the formation of a new IR residency program in 2013, and subsequently approved the program requirements on September 28, 2014. Three pathways were endorsed: (1) integrated IR residency, which entails one year of clinical internship followed by five years of IR residency; (2) independent IR residency, which involves two years of IR residency after one year of clinical internship and four years of DR residency; and (3) Early Specialization in Interventional Radiology (ESIR), which consists of one year of clinical internship followed by four years of DR residency with an emphasis on IR during PGY-5, followed by one year of independent IR residency. During an integrated IR residency, the first three years highlight DR, and the last two years feature IR. The integrated IR residency is the desired dominant training pathway for IR according to the ABMS, ACGME, American Board of Radiology (ABR), and Society of Interventional Radiology. The first eight integrated IR residency programs were accredited by the ACGME in the fall of 2015, and initially participated in the 2016 National Residency Matching Program (NRMP) match for a 2017-22 residency. The MMC Integrated IR Residency Program was accredited in the spring of 2016 as one of the first 12 such programs, and initially participated in the 2017 match for a 2018-23 residency. The first match for independent IR residencies will be in 2019 for a 2020-22 residency. The last VIR fellowship match will be in 2018 for the final 2019-20 fellowship year.
Although MMC has had a Diagnostic Radiology residency for greater than 60 years, it never had a VIR fellowship. This has enabled MMC DR residents to be intimately involved with procedures, and has earned the residency a reputation as one of the top training programs in the country for preparation for VIR fellowship. Accordingly, greater than 25 percent of our graduates have chosen to pursue IR! With the approaching sunset of VIR fellowships, we chose to develop an integrated IR residency at MMC in order to continue our long tradition of robust IR training in the new paradigm.
Welcome to the MMC Integrated Interventional Radiology Residency Program website! If you wish not to define yourself by organ system or pathology, desire to work with physicians from all specialties, enjoy caring for patients who are too sick for other any other therapy, and like to rely upon your innovative problem-solving skills, IR may be the right specialty for you!
When I interviewed for my first job here after completing VIR fellowship, I had never been to Maine or even New England before. The only Portland that I had heard of was in Oregon (which actually is named after Portland, Maine). However, I was so impressed by the IR group at MMC, the city of Portland, and the state of Maine, that I declined several competing job offers at esteemed academic institutions in large urban centers in order to move here all the way from my hometown of Chicago. Maine Medical Center is truly unique, filling a dual role as both a community hospital and a tertiary referral center. It is also Maine’s only academic medical center and Level I Trauma Center. The large referral base, which includes not only all of Maine but eastern New Hampshire as well, presents an incredibly diverse patient population in addition to a comprehensive array of IR procedures that rivals the major academic institutions. Yet, the camaraderie and attention to work-life balance are more commonly seen at much smaller community hospitals. The combination of a strong IR program and outstanding quality of life makes the MMC Integrated IR Residency Program the ideal place to train.
Portland was a hidden gem when I moved here in 2007. It was a quintessential quaint New England seacoast town with the urban sophistication of a large city. Since then, as the sampling of “Best of” lists above attests, everyone from hipsters to retirees has discovered that Portland is a top destination. So make Portland your destination, and experience IR residency the way life should be. | en | apollo | train |
At the time of each donation, blood samples are collected for testing.
ABO Testing and Blood Group Resolution To aid in selection of compatible units for patient transfusion.
Red blood cell antibody screen To determine the presence of unexpected antibodies to red blood cell antigens. If detected, the red blood cell antibody identity is indicated on the component label.
Extended red blood cell phenotype (selected donations) To aid in selection of compatible units for patient transfusion a portion of donations are tested for extended red blood cell antigens. These antigens may include minor blood group systems such as Rhesus (C, E, c, e), Kell (K), Duffy (Fya, Fyb), Kidd (Jka, Jkb) MNSs (S, s). The phenotype results will appear in the lower right hand quadrant of the red blood cell component end label, or may appear on an attached tag. See our Labels and Tags section for more details.
To reduce the risk of disease transmission. See our Circular of Information, Warnings and Precautions section, for details. Before release for transfusion, a blood donation is tested and must be non-reactive for diseases known to be transmitted by transfusion (see left column).
** Performed when increased risk is present, see Customer Letter 2010-13.
Selected donations may be also tested for cytomegalovirus (CMV) antibody, or the presence of Immunoglobulin A (IgA) antibodies for at-risk patients that may require blood components tested for CMV or IgA antibodies. Donations for further manufacturing into plasma protein products are also tested for Parvovirus B19.
Our routine process is that all platelet components are cultured for bacteria 36 hours after collection, and then held for six hours after bacteria culture bottle inoculation. Platelet components are issued to hospitals for transfusion only if the culture results are negative at the time of issue. Cultures are incubated for six days, and hospitals are notified if the component bacteria culture becomes positive. For further information on bacteria testing, see Customer Letters 2007-03 and 2017-31. Bacterial detection of pooled platelets using the Bacti/ALERT detection system was implemented as part of the buffy coat component production method implementation (Edmonton site pilot 2005, Vancouver site pilot 2007, and national rollout 2008). Bacterial detection of apheresis platelets using the Bacti/ALERT detection system was implemented in May 2004.
Additional information can be found in the Clinical Guide to Transfusion. | en | apollo | train |
The ultrasonographic AMFT evaluation is strongly correlated to the presence of metabolic syndrome and could be a valuable tool to predict metabolic diseases and associated cardiovascular risks in men. | en | apollo | train |
Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II.
Left ventricular hypertrophy leads to heart failure and represents a high risk leading to premature death. Cyclic nucleotides (cAMP and cGMP) play a major role in heart contractility and cyclic nucleotide phosphodiesterases (PDEs) are involved in different stages of advanced cardiac diseases. We have investigated their contributions in the very initial stages of left ventricular hypertrophy development. Wistar male rats were treated over two weeks by chronic infusion of angiotensin II using osmotic mini-pumps. Left cardiac ventricles were used as total homogenates for analysis. PDE1 to PDE5 specific activities and protein and mRNA expressions were explored.Rats developed arterial hypertension associated with a slight cardiac hypertrophy (+24%). cAMP-PDE4 activity was specifically increased while cGMP-PDE activities were broadly increased (+130% for PDE1; +76% for PDE2; +113% for PDE5) and associated with increased expressions for PDE1A, PDE1C and PDE5A. The cGMP-PDE1 activation by Ca(2+)/CaM was reduced. BNP expression was increased by 3.5-fold, while NOX2 expression was reduced by 66% and AMP kinase activation was increased by 64%. In early cardiac hypertrophy induced by angiotensin II, all specific PDE activities in left cardiac ventricles were increased, favoring an increase in cGMP hydrolysis by PDE1, PDE2 and PDE5. Increased cAMP hydrolysis was related to PDE4. We observed the establishment of two cardioprotective mechanisms and we suggest that these mechanisms could lead to increase intracellular cGMP: i) increased expression of BNP could increase "particulate" cGMP pool; ii) increased activation of AMPK, subsequent to increase in PDE4 activity and 5'AMP generation, could elevate "soluble" cGMP pool by enhancing NO bioavailability through NOX2 down-regulation. More studies are needed to support these assumptions. Nevertheless, our results suggest a potential link between PDE4 and AMPK/NOX2 and they point out that cGMP-PDEs, especially PDE1 and PDE2, may be interesting therapeutic targets in preventing cardiac hypertrophy. | en | apollo | train |
( _seepages 39–62_.)##### **_Symptoms_**
•yellowing of the skin and the whites of the eyes
•darkened urine
•pale-colored stools
##### TREATMENT
**Chinese Herbalism**
Treatment would be aimed at Dampness in the Gall Bladder and Liver, and useful herbs may include gardenia fruit, oriental wormwood, and the bark of the cork tree. **Herbalism**
Any of the following herbs can be used to tonify the liver: golden seal, verbena, barberry, blue flag, dandelion, and wild yam. ( _seepages 125 and _.) **Aromatherapy**
Oils that strengthen the liver include chamomile, cypress, lemon, peppermint, rosemary, and thyme. Use one or a blend of these oils in massage, or in a vaporizer in your room. ( _seepages 133–157_.) **Homeopathy**
Constitutional treatment would accord with the cause of the jaundice. Crotalus is appropriate for jaundice caused by hemolytic anemia. **Vitamins and Minerals**
•Drink fresh carrot and lemon juice daily. •Avoid alcohol and caffeine. •Eat plenty of fresh fruit and vegetables, as well as whole grains and cereals. #### **HIATUS HERNIA**
A hiatus hernia occurs when part of the stomach slides up through the esophageal opening in the diaphragm into the chest. As a result of this the stomach's contents regurgitate into the esophagus, which may cause damage and inflammation (esophagitis). The underlying cause of hiatus hernia is unknown, but this common condition tends to occur more often in obese people (and especially in women in later middle age), and in those who smoke. In some cases it is present at birth. ##### **_Symptoms_**
•severe heartburn (a burning pain behind the breastbone) that worsens on bending, straining, and lying down
•if esophagitis occurs there may be associated symptoms of acid in the mouth, difficulty in swallowing, and ulceration
##### TREATMENT
**Chinese Herbalism**
Treatment would be individual, but there are a number of herbs which will restore the balance. ( _seepages 39–62_.)( _seepage 340_.)Calc.fluor., a tissue salt, will help elasticity.#### **APPENDICITIS**
The appendix is 1–8in.(2–20cm.)long, about as thick as a pencil, and hollow.It consists mostly of lymphoid tissue, like the tonsils and adenoids, and is easily invaded by micro-organisms.One out of every 15 people develops appendicitis, the inflammation of an infected appendix. | en | apollo | train |
In addition, it may develop extraintestinal complications in systemic organs such as the joints, the skin, and the eyes.
The incidence of colorectal cancer (CRC) is significantly increased in UC patients who have extensive lesions for a long period of time, and it is also known that the incidence of cancers in the small and large intestines, especially in the rectum and anal canal region, is high in CD patients. Therefore, an efficient surveillance strategy for cancer development is expected to be established. IBD is not considered to be a disease that significantly affects the patients' life prognosis, although IBD patients have slightly shorter life prognosis compared to normal individuals.
UC and CD are collectively referred to as IBD because the two diseases share common or similar features; however, disease location, morphology, and pathophysiology are clearly different between them, and they are considered to be independent diseases. Moreover, it is necessary to classify them because diagnostic procedures, therapeutic interventions, and follow-up observation are somewhat different. Notably, it is called ''IBD unclassified'' when colonic lesions have the features of IBD which cannot be classified as UC or CD. patients are more likely to develop the disease between their late 10s and early 30s. - In Western countries, there tend to be more women among IBD patients, especially CD patients, but there is a male predominance in Japan. | en | apollo | train |
Hyaluronic acid, also known as hyaluronan, is a clear, gooey substance that is naturally produced by your body. The largest amounts of it are found in your skin, connective tissue and eyes. Its main function is to retain water to keep your tissues well lubricated and moist. It helps in reducing the appearance of fine lines and wrinkles, it Improves contours & reduces the appearance of scars.
As we age, the production rate of this acid declines which is why dermatologists encourage people to take it as a supplement in the methods such as serums, creams, lotions and injections. Topical treatments can soothe redness and dermatitis, while injections can make skin appear firmer.
Anti-Aging – By applying hyaluronic acid, the moisture content acts as a filler and smoothens out the wrinkles.
Provides & maintains moisture– Hyaluronic acid helps in retaining moisture in the skin.
Protective Barrier– It acts as a barrier for your skin against external factors such as the environment, pollution, weather, etc., which can dry up your skin.
Reduces Eye Discomfort– Hyaluronic acid liquid drops are beneficial for various eye disorders, injuries, pre and post-eye surgery, cataract, repairing of a detached retina, corneal transplant, etc.
Relief from Joint Pains– Hyaluronic acid in the form of supplements are beneficial in providing relief for aching joints. It is often used as a treatment for osteoarthritis.
You know your body actually produces hyaluronic acid, it is found naturally in almost every cell in the body although occurs in high concentrations in specific body locations.
How Do I Use Hyaluronic Acid in My Skincare?
Serums are thinner in consistency with more potent concentration of ingredients to deliver great results. When using a serum, wait at least 15 minutes after applying for the serum to completely absorb into skin before you move to the next step in your routine.
Another great way is to use a moisturizer that includes HA packing a hydration punch. Get better result use both a serum and lotion that features HA!
Microneedling is done with derma roller, which is essentially a handheld roller with several tiny needles, or a pen like device, which usually offers greater control for the operator to treat smaller areas, where the needles gently penetrate below the surface of the skin. When used together, hyaluronic Acid and microneedling results in increasing the production of collagen to improve the strength & structure of the skin, & also diminishing visible signs of aging by revealing smoother and tighter skin.
Injectable hyaluronic acid (HA) is a type of temporary dermal filler. As we age, the fat, muscles, bone, and skin in our face begins to thin. This loss of volume leads to sagging appearance of the face, folds, wrinkles, fine lines, and thin lips. Injectable HA is used to reduce the appearance of fine lines, wrinkles, facial folds, and to create structure and volume to the face and lips. The effects of injectable hyaluronic acid are seen immediately.
Where to get Hyaluronic Acid?
Answer is Kutiz Skin Clinic- It has one of the best dermatologist of Gurgaon, Dr Jyoti Malik. Treatment for HA can be done on your skin, lips, etc which can give you quick results. The effect usually lasts for about nine months to two years. | en | apollo | train |
As adults, these medicated youth reach for alcohol, drugs, or even street drugs to cope.They learn to equate coping with drugs rather than with their inner resources.Medicating young people and modifying their emotions must have some impact on how they learn to deal with their feelings.Moreover, a whole generation of antidepressant users has been created from young people growing up on Ritalin®.Yet the public depends on this tremendously flawed system of voluntary reporting by doctors to know whether a drug or a medical intervention is harmful. Pharmacology texts also will tell doctors how hard it is to separate drug side effects from disease symptoms. Treatment failure is most often attributed to the disease and not the drug or doctor. Doctors are warned, "Probably nowhere else in professional life are mistakes so easily hidden, even from ourselves." It may be hard to accept, but it is not difficult to understand why only one in twenty side effects is reported to either hospital administrators or the FDA. If hospitals admitted to the actual number of errors for which they are responsible, which is about twenty times what is reported, they would come under intense scrutiny. Jerry Phillips, associate director of the FDA's Office of Post Marketing Drug Risk Assessment, confirms this number. "In the broader area of adverse drug reaction data, the 250,000 reports received annually probably represent only 5% of the actual reactions that occur." Dr. Jay Cohen, who has extensively researched adverse drug reactions, notes that because only 5% of adverse drug reactions are reported, there are in fact 5 million medication reactions each year. ### Medicating Our Feelings
Patients seeking a more joyful existence and relief from worry, stress, and anxiety are frequently swayed by the messages endlessly displayed on TV and billboards. Often, instead of gaining relief, they fall victim to the myriad iatrogenic side effects of antidepressant medication. Moreover, a whole generation of antidepressant users has been created from young people growing up on Ritalin®. Medicating young people and modifying their emotions must have some impact on how they learn to deal with their feelings. They learn to equate coping with drugs rather than with their inner resources. As adults, these medicated youth reach for alcohol, drugs, or even street drugs to cope.Today's marketing of mood-modifying drugs such as Prozac® and Zoloft® makes them not only socially acceptable, but almost a necessity in today's stressful world.You cannot turn on TV without hearing a pitch for drugs for social anxiety, depression, or lethargy. | en | apollo | train |
According to its theory, every divine characteristic is a therapy and every symptom is a healing tool.Theotherapy involves determining, more or less unconsciously, which Greek god or goddess best symbolizes one's disease, and treating the disease by trying to adopt those godly characteristics one considers positive and sustainable.The massage is said to provide stimulation to the MERIDIAN. **thakradhara** (Ind.) A technique in AYURVEDA in which medicated and diluted yogurt is poured on to the forehead continuously for 40–60 minutes. The treatment is said to cure depression, insomnia, psoriasis, stress and stress-related disorders and cool the eyes. **thalassotherapy** (New Age) SPA treatments in which sea and seawater products such as seaweed and seaweed wraps are used. The treatment normally includes daily bathing in a heated sea-water pool with jets, mud bath, seaweed bath (ALGOTHERAPY), hydro-massage and AROMATHERAPY. Thalassotherapy is found useful for relaxation, stress management, muscle and skin restoration and weight-control. Mineral-rich Dead Sea water and Dead Sea weeds are used for better results. **tharpanam** (Ind.) Also, netra tharpanam. A popular treatment in AYURVEDA in which medicated ghee is applied gently for twenty or thirty minutes. The treatment is said to have a cooling effect on the eyes, prevent eye diseases and relieve eye strain. **theocentric therapy** (New Age) Also, Christian psychological counselling; theocentric counselling, theocentric psychological Counselling, theocentric psychological and educational therapies, theocentric psychology. A Christian healing system as propagated by LaSalle University in Mandeville, Louisiana. **theotherapy** (Occ.) A form of self-healing as developed by Peter Lemesurier, based on the notion that every divine characteristic is positive and sustainable and works as a therapy. Theotherapy involves determining, more or less unconsciously, which Greek god or goddess best symbolizes one's disease, and treating the disease by trying to adopt those godly characteristics one considers positive and sustainable. According to its theory, every divine characteristic is a therapy and every symptom is a healing tool.**therapeutic massage** (New Age) A relaxing form of massage consisting usually of soothing strokes and rubbing.**therapeutic prayer** (Occ.)A powerful form of expression of one's gratitude to nature and god, and the energy obtained in the process is utilized for the welfare of others, through mind, words and actions.**therapeutic Shiatsu** (Occ.) | en | apollo | train |
Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate.
The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm(2)/h to 49.96μg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm(2)/h. Passive flux for the drug was 1.57μg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm(2)/h in comparison with passive diffusion flux of 0.19μg/cm(2)/h. The difference in flux values was also statistically significant. Stainless steel solid microneedles and microneedle rollers increased percutaneous penetration of verapamil hydrochloride and amlodipine besylate. It may be feasible to develop transdermal microneedle patches for these drugs. | en | apollo | train |
For example, some children have fewer ASD-related symptoms when they have a fever or are treated with corticosteroid medications for another problem, suggesting that inflammation may play a role in ASD symptoms.,
Research is ongoing into the best ways to treat and improve ASD symptoms by untangling and addressing all these different factors in a truly holistic approach. With careful attention to a healthy lifestyle, good health care, and ongoing behavioral management, some children outgrow or learn to overcome some of their behavioral and social challenges, just as older adults who have had a stroke can learn to use a paralyzed limb with intensive physical therapy. Since we do not know how to predict which children will overcome their symptoms or to what extent they will adapt or normalize, it is our obligation as caregivers to provide every child the best chance of flourishing while additional research points the way to ever-more-helpful therapies and preventive strategies. DIAGNOSING AUTISM
The diagnosis of autism or ASD depends on careful observation, not on a single test of blood, urine, or other fluids, or on X-rays or other laboratory tests. Your physician may order tests to make sure symptoms aren't due to other medical problems. Diagnosis is based on structured, consistent observations using a scale or instrument such as
• Autism Diagnostic Interview Scale–Revised (ADI-R)
• Autism Diagnostic Observation Scale (ADOS)
• Childhood Autism Rating Scale (CARS)
If your pediatrician or family physician suspects autism, you may be referred to a hearing specialist to check hearing and make sure that deafness isn't responsible for communication difficulties.You may also ask for a referral to a geneticist for testing to make sure your child doesn't have a genetic problem such as Fragile X that can cause developmental disabilities. | en | apollo | train |
* Periodic ALT concentrations in at-risk breeds helps identify affected dogs for early intervention.* Determining hepatic Cu concentrations at greater than 1 year of age aids in diagnosing affected animals.A liver registry is available for Bedlington terriers that are proven unaffected on the basis of hepatic Cu concentration < 400 μg/g DW at 1 year of age or gene testing.Zinc may lack efficacy dogs with high Cu concentrations (> 1,000 μg/g DW) and hepatitis where chelation therapy is preferred. Vomiting is a frequent side effect of zinc. Low doses of zinc given with a low-Cu diet in previously chelated Labrador retrievers was no more effective than low-Cu diet alone. Antioxidants
* d-αtocopherol (vitamin E 10 U/kg q24h PO); use adjunctively. * SAMe; use adjunctively. Hepatoprotectants
* Silibinin (milk thistle extract)—undetermined utility in Cu storage hepatopathy. * Ursodeoxycholic acid—recommended if chronic hepatitis (see Hepatitis, Chronic Active) and high TSBA. CONTRAINDICATIONS
Ascorbic acid (vitamin C)—not recommended; may augment Cu hepatotoxicity. POSSIBLE INTERACTIONS
Penicillamine or trientine may not be effective with concurrent zinc therapy. FOLLOW-UP
PATIENT MONITORING
* Liver enzymes q3–6 months; evaluate body weight and condition. * Measure hepatic Cu concentration within 1 year of initiated treatment. * If using zinc—assess serum zinc concentrations in the first 2–3 weeks and until stable and in non-toxic range (200–500 μg/dL), then every 4–6 months thereafter. PREVENTION/AVOIDANCE
* Breed only Bedlington terrier dogs that do not carry the genetic defect. A liver registry is available for Bedlington terriers that are proven unaffected on the basis of hepatic Cu concentration < 400 μg/g DW at 1 year of age or gene testing. * Determining hepatic Cu concentrations at greater than 1 year of age aids in diagnosing affected animals. * Periodic ALT concentrations in at-risk breeds helps identify affected dogs for early intervention.* Excess zinc (oral dose of > 200 mg/day or blood concentration of > 800 μg/dL) can cause hemolytic anemia.EXPECTED COURSE AND PROGNOSIS
* Poor prognosis in acutely affected young dogs with fulminant hepatic failure or older dogs with cirrhosis.* Fair prognosis in young dogs with mild to moderate acute hepatic injury usually respond to chelation therapy. | en | apollo | train |
B-CLL in PLL transformation associated with hypercalcemia.
A 64-year-old woman is reported with Stage I (Rai) chronic lymphocytic leukaemia (CLL), in whom hypercalcemia developed when an increased proportion of prolymphocytic cells characterized a transformation of CLL in prolymphocytoid leukaemia (CLL/PL). Although hypercalcemia is more frequently found in T-cell leukaemia associated with human T lymphotropic lymphocyte type I, scattered reports indicate that patients with B-CLL can also be affected with this metabolic disturbance. The case described here, progressed with an indolent course of CLL for 26 months, when she was admitted with a very aggressive disease characterized by a high WBC count, splenomegaly and hypercalcemia. Despite an effort to achieve a clinical remission, she failed treatment and death was attributed to unresponsive hypercalcemia. The mechanism of hypercalcemia in such cases is unclear as no parathyroid adenoma or second malignant tumor was found ante mortem. This electrolytic disturbance would appear to be a direct consequence of the transforming leukaemia and a possible mechanism involving a secreted humoral factor that could lead to altered calcium metabolism. | en | apollo | train |
78yo female pedestrian versus car.
She was hit to the legs at >60kph and then thrown several meters. She was intubated at the scene due to decreasing GCS and transported to ED via HEMS.
She had no evidence of chest injuries. She had an epigastric bruise extending across the abdome, L elbow and thumb bruising and R open distal tib fib fractures. EFAST was negative. No other injuries were noted. She had normal LL pulses.
She was stable during transport except for a drop in SBP to 60 just prior to landing. A unit of pack cells was started by HEMS.
In the ED, she initially stabilised after the unit of pack cells, but then continued to have episodes of hypotension. ED cardiac ultrasound revealed a hyperdynamic LV, small collapsing IVC. Further pack cells were given but the source of bleeding was still indeterminate. Frustratingly, repeat EFAST was still negative!!
I didn't think to look at the aorta!
CTs revealed no injuries in the chest, no organ injury in the abdomen. However, the spleen was variegated with a prominent splenic artery ?splenic artery dissection with associated infarction. The abdominal aorta was not dilated but it was surrounded 180 degrees with ?haematoma: suggesting ? traumatic aortic dissection.
The patient was brought back to ED. She had ongoing episodes of hypotension which responded to fluid resuscitation.
These are her US images done upon return to ED.
Trans aorta (mid) showing a normal sized aorta anterior to the vertebra with surrounding haematoma (see below).
colour doppler images showing blood flowing into haematoma (see below).
Isolated abdominal aortic dissection is rare (1). There are only a handful of case reports of abdominal aortic dissection as a sequelae of blunt abdominal trauma (2,3). It has been described post MVA (3) and even Heimlich manoeuver (4) in elderly and young patients. It is most often picked up by CT. US diagnosis in the ED in the setting of trauma has not been described.
Some EFAST courses recommend starting the EFAST with a view of the aorta. Maybe in the patient with unexplained hypotension post abdominal trauma ultrasound images of the abdominal aorta should be considered.
1. Trimarchi S, Tsai T, Eagle KA, et al. International Registry of Acute Aortic Dissection (IRAD) investigators. Acute abdominal aortic dissection: insight from the International Registry of Acute Aortic Dissection (IRAD). J Vasc Surg 2007;46:913–19.
3. Martí M, Pinilla I, Baudraxler F, Simón MJ, Garzón G. A case of acute abdominal aortic dissection caused by blunt trauma. Emerg Radiol (2006) 12: 182–185. | en | apollo | train |