tbuckley/cabot-search huggingface dataset:
The biological fate of reserpine.
Authors: R E Stitzel
Journal: Pharmacological Reviews (1976)

Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted...
Spirometry changes due to prolonged exposure to high level of fluoride in drinking water
Authors: Nausheen Saifullah, Iftekhar Ahmed, Shahina Qayyum, Nazeer Khan, Masood Hameed Khan
Journal: European Respiratory Journal (2013)

Introduction:  fluorosis is dental and skeletal tissue changes due to increase fluoride exposure this can also result in systemic and biochemical changes. Pulmonary involvement is established as a result of toxic exposure to inhaled fluoride however animal studies have shown that chronic fluorosis causes by ingested fluoride can cause marked destruction in lung tissues. This can result in impairment of spirometry results.   Objective:  the study was done to observe the spirometry changes in effected population and compare it with control and correlate it with skeletal changes.   Method : People from Sammo Rind village Sindh with underground water fluoride concentration of 6-8 ppm were taken as cases, and from Gadap where level of flouride in drinking water is not high (less than 1ppm) were included as controls. Clinical examination, hematology and biochemical tests were performed Spirometry was done in all. Results were analyzed using SPSS 16.   Results:  121 cases and 121 controls were included in the study. Mean age was 30 and 33.47 in cases and control respectively. Males were 90 (74.4%) and 84(69.4%) and females were31 (25.6%) and 37(30.6%) in cases and controls respectively. Spirometery results were normal in only 22.31% cases verses 54.54% controls. Restrictive pattern was in 47.1% and 23%, obstructive defect was in 23% and 6.6% and combined defect was in 8.6% and 15.7% in cases and controls respectively. This was related to dental changes and serum ,plasma and urinary fluoride levels but not related chest wall deformity.   Conclusion:  study shows that lung function impairment occur in effected population and these are independent of skeletal deformities.
Death from ductal carcinoma in situ is very low except in young and black women, US data show
Authors: Susan Mayor
Journal: BMJ (2015)

The risk of death from breast cancer is very low in women with ductal carcinoma in situ (DCIS) except in those whose condition is diagnosed before age 35 and in black women, a long term follow-up study of US cancer data has shown.1 The findings have prompted calls for a change to more focused treatment of women with highest risk DCIS.2

The study, published in JAMA Oncology , followed up 108 196 women who had DCIS diagnosed from 1988 to 2011 using data from the Surveillance, Epidemiology, and End Results (SEER) registry. Researchers compared the participants’ risk of dying from breast cancer with women in the general population.

DCIS, or stage 0 breast cancer, accounts for around 20% of breast cancers detected …
Breathing-coordinated exercise improves the quality of life in hemodialysis patients.
Authors: T J Tsai, J S Lai, S H Lee, Y M Chen, C Lan, B J Yang, H S Chiang
Journal: Journal of the American Society of Nephrology (1995)

Breathing-coordinated exercise is a traditional Chinese exercise. These exercise maneuvers consist of slow diaphragmatic breathing, end-inspiratory pause, and Kegel's exercise. A total of 30 patients were enrolled in this study, with 12 patients as controls, to evaluate its effect on hemodialysis patients. Exercise was performed for 25 to 30 min twice a day for at least 3 months. Results from the exercise group showed a subjective improvement in appetite and physical strength, and an increase in the frequency of bowel movements, in addition to enhanced sexual activity and a significant increase in Karnofsky scores. Six patients in the exercise group underwent bicycle ergometry and demonstrated a stable maximal oxygen consumption, whereas the control group revealed a decline in maximal oxygen consumption. Photoelectric plethysmography and laser-Doppler flowmetry demonstrated a pulsatile enhancement of the peripheral microcirculation. Abdominal sonography revealed an oscillatory change in the diameter of the inferior vena cava. It was concluded that these gentle exercise maneuvers may improve the quality of life in hemodialysis patients, especially weak dialysis patients. The mechanism may be partly related to an improvement in microcirculation.
Airway smooth muscle behaviour is altered following coculture with fibrocytes
Authors: Ruth Saunders, Davinder Kaur, Camille Doe, Fay Hollins, Christopher Brightling
Journal: European Respiratory Journal (2012)

Asthma is a major cause of morbidity and mortality worldwide and its prevalence is increasing. The airway smooth muscle (ASM) in asthma is dysfunctional with increased mass and contractility. Fibrocytes (FC) are elevated in the peripheral blood and ASM in asthma and ASM has the potential to mediate FC recruitment (Saunders et al , J Allergy Clin Immunol, 2009;123:376-84). We hypothesised that FCs modify ASM behaviour to contribute to ASM dysfunction in asthma.

FCs were isolated from peripheral blood, ASM from bronchial biopsies and lung resection material. ASM contraction was assessed by collagen gel contraction, and potential mechanisms for increased mass by migration, proliferation and survival assays.

Contraction of collagen gels impregnated with ASM cultured with FCs for 3-4d vs ASM alone increased significantly (i.e. reduction in area under curve of gel size as a percentage of the original size plotted over 30 min (AUC30), Table 1). ASM wound healing (WH) increased significantly in the presence of supernatants (SNs) from FC±ASM 7d cultures vs control media, but no additional WH was seen in the presence of FC or FC+ASM SNs vs ASM SNs alone (Table 1). ASM proliferation and survival was unaffected by culture with FCs/FC SNs for 7d.

View this table:

Table 1





Localisation of FCs to the ASM-bundle could contribute to the hypercontractility of ASM in asthma, which is integral to the pathophysiology of asthma. The mechanism by which this occurs requires further investigation, but has the potential to provide future therapeutic targets.
Epidemiology of Cancer of the Cervix II, Buffalo, New York&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Graham, W Schotz
Journal: JNCI Journal of the National Cancer Institute (1979)

An investigation was done to determine whether patients with cancer of the cervix from Buffalo and Kenmore, New York, differed from a random sample of women from the same communities on a variety of parameters associated with marital and reproductive history. A comparison of the 285 patients and 1,620 controls showed that patients were more likely than controls to have been black and non-Jewish, to have married young, to have had more than one husband, and to have been young at the time of their first pregnancy. In addition, they were more likely to have frequently used the vaginal douche and to have used it over many years. As frequency of douche increased, so did risk of cervix cancer.
Inflammatory biomarkers as outcome predictors of acute respiratory failure on top of chronic obstructive pulmonary diseases (COPD)
Authors: Hanaa Shafiek, Nashwa Abd-Elwahab, Mohamed El-hoffy, Yehia Khalil, Manal Baddour, Akram Degady
Journal: European Respiratory Journal (2013)

The aim of the work is to assess the value of interleukin-6 (IL-6), interleukin-8 (IL-8) and C-reactive protein (CRP) in predicting the outcome of acute respiratory failure (ARF) on top of COPD. Methods: Serum samples were collected from 33 patients with COPD presented with ARF for IL-6, IL-8, and CRP analysis on admission and after 72 hours. Sputum samples were taken for microbiological evaluation. Results: Twenty-five patients (75.8%) survived and 8 patients (24.2%) died during the study. Causative microorganism was detected in 66%. Gram-negative and atypical bacteria were the most common pathogen (31% and 28% resp; single or co-pathogen.) without statistically significant association with the outcome (p= 0.262). The IL-6 on admission was significantly higher (p= 0.03) among the non-survivors (257.1 ± 269.1 pg/ml) vs. the survivors (17.9 ± 25.8 pg/ml). The IL-6 level after 72 hours showed statistical significance (p= 0.03) in predicting the outcome as the highest value was among the non-survivors (24.2%) (IL-6= 98.3±153.6 pg/ml), followed by those discharged on oxygen therapy/continuous positive airway pressure (43%) (IL-6= 39.6±88.1 pg/ml) then those discharged on room air (33%) (IL-6=2.2±8.2 pg/ml). Both the CRP and IL-8 were higher among the non-survivors than survivors without significant difference (p >0.05). The CRP level >2.3 mg/L on admission had the best sensitivity of predicting in-hospital mortality (85.7%) and the IL-6 level > 46.1 pg/ml had the best specificity (83%).Conclusions: High IL-6 is associated with in-hospital mortality. Both CRP and IL-6 levels when are used together, they become good in-hospital mortality predictors.
Risk factors and outcomes of airway complications after lung transplant in the Portuguese Center
Authors: Ana Sofia Santos, Ricardo Coelho, Raquel Rosa, Dionísio Maia, Tiago Sá, Vânia Caldeira, Alexandra Borba, Ivan Bravio, Fernando Martelo, Luísa Semedo, José Fragata, João Cardoso
Journal: European Respiratory Journal (2014)

Introduction:  Lung transplant (LT) is a therapeutic option for patients with end-stage lung disease. However it is still associated with complications, namely airway complications (AC), which are an important source of morbido-mortality.   Objectives:  Evaluate the incidence of AC in a consecutive series of patients (pt) submitted to LT at our center between 01/2008 and 02/2013 and identify risk factors. Pts who died in the first month were excluded (6pts). Recipient variables (age, gender, diagnosis, airway colonization), graft variables (isquemic time; microbial isolation) and post-surgical variables (mechanical ventilation time, need of extra-corporeal circulation, need of vasopressor drugs and airway infection) were analyzed using Mann-Whitney and Pearson9s chi-square tests.   Results:  Sixty pt underwent LT – 24 double LT, 36 single LT, with a total of 84 airway anasthomosis. Main indications for LT were pulmonary fibrosis (48.3%-29pt), cystic fibrosis/other bronchiectasis (31.7%-19pt), COPD/alpha 1 antitrypsin deficiency (15%-9pt) and sarcoidosis (5%-3pt). Of the 84 anasthomosis, AC developed in 24 (28.6%), but only 4 needed endobronchial therapy (4.7%). One pt died directly related to AC. Only the graft isquemic time was a significant predictor of AC ( p =0.03), with a mean time of 361min (max. 650, min. 126). The 12 month survival for pt with AC was 75% and 86% for those without complication ( p >0.05).   Conclusions:  At our center AC after LT are frequent. However, the rate of severe complications is low but can have a clinical impact on pts survival. Also, we found a significant relation between graft isquemic time and development of AC, which ultimately affects LT outcome.
Dependence of Tumor Spectrum on Route of Administration in Sprague-Dawley Rats as a Result of Single or Multiple Injections of Methyl(acetoxymethyl)nitrosamine&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J J Berman, J M Rice, M L Wenk, P P Roller
Journal: JNCI Journal of the National Cancer Institute (1979)

Methyl(acetoxymethyl)nitrosamine (DMN-OAc). which selectively induces intestinal tumors in rats when injected ip, was administered by different routes (iv, orally, sc, and ip) in single and multiple treatments and in both aqueous and nonaqueous vehicles to groups of 30 noninbred Sprague-Dawley (Charles River CD) rats. Five-week-old rats were administered 0.10 mmole DMN-OAc/kg body weight, which is one-half the acute ip median lethal dose, as a single dose via the various routes indicated. Rats given multiple ip or sc administrations received either 0.02 or 0.04 mmole DMN-OAc/kg per injection. Males only were used in each study; however, in the studies in which single ip injections were given, both sexes were used. Single ip injections of 0.1 mmole DMN-OAc/kg resulted in a high incidence of epithelial tumors of the intestinal tract in rats of both sexes. Males developed more tumors; 70 tumors were observed in 29 males versus 41 tumors in 29 females. Doubling the dose and dividing it into multiple ip injections increased the incidence of epithelial tumors of the intestines. Five injections of 0.04 mmole/kg resulted in 168 intestinal tumors in 29 male rats. In rats treated ip a significant incidence of nervous system tumors was found, principally schwannomas arising from small nerves in the serosae of abdominal organs. Treatment by routes other than ip virtually eliminated the selectivity of DMN-OAc for the intestines. Single oral administrations of 0.1 mmole DMNOAc/kg dissolved in buffer or vegetable on resulted in high yields of stomach tumors, many of which were adenocarcinomas. Few tumors were induced elsewhere, and the vehicle of administration had little effect on tumor yield or type. Single or multiple sc injections of DMN-OAc produced a high yield of mammary and soft tissue tumors at the site of injection, as well as a significant incidence of tumors at distant sites, especially the lungs and Zymbal's glands. Single iv injections of 0.1 mmole DMN-OAc/kg resulted in a high yield of lung, Zymbal gland, and nervous system tumors, particularly endocardial neurinomas.
Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis
Authors: Steven J. Barrer
Journal: Annals of Internal Medicine (2015)

Letters1 September 2015Surgery Versus Nonsurgical Treatment of Lumbar Spinal StenosisSteven J. Barrer, MDSteven J. Barrer, MDFrom Abington Memorial Hospital, Abington, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5129 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I found Delitto and colleagues' article (1) at odds with not only my experience but that of other published studies. The way that the data and results were reported leaves more questions than answers.The authors do not state whether the 169 patients who were deemed eligible for surgery had physical therapy (PT) first. If not, the 87 patients assigned to surgery had no PT, which, in an elective setting, is a breach of the standard of care. If so, then we can assume that PT was unsuccessful in all 169 patients.Of the 82 patients assigned ...Reference1. Delitto A, Piva SR, Moore CG, Fritz JM, Wisniewski SR, Josbeno DA, et al. Surgery versus nonsurgical treatment of lumbar spinal stenosis: a randomized trial. Ann Intern Med. 2015;162:465-73. [PMID: 25844995] doi:10.7326/M14-1420 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Steven J. Barrer, MDAffiliations: From Abington Memorial Hospital, Abington, Pennsylvania.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L15-0315. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSurgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Anthony Delitto , Sara R. Piva , Charity G. Moore , Julie M. Fritz , Stephen R. Wisniewski , Deborah A. Josbeno , Mark Fye , and William C. Welch Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Peter A. Robertson , William R. Sears , and John E. Cunningham Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Alfonse T. Masi and Sam Betts Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Anthony Delitto , Sara R. Piva , Charity G. Moore , and William C. Welch Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Alfonse T. Masi and Sam Betts Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Peter A. Robertson , William R. Sears , and John E. Cunningham Surgery Versus Nonsurgical Treatment of Lumbar Spinal Stenosis Anthony Delitto , Sara R. Piva , Charity G. Moore , and William C. Welch Metrics 1 September 2015Volume 163, Issue 5Page: 396KeywordsConflicts of interestDisclosurePhysiotherapyStenosisSurgery ePublished: 1 September 2015 Issue Published: 1 September 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Radiation risks
Authors: S. Darby
Journal: BMJ (1999)

At a conversation with friends about last month's accident at the JCO uranium processing plant at Tokaimura, Japan,1 one of them said, “but nuclear power has a very safe record.” He was right, but in 20 years of studying radiation risks this was the first time I had heard anyone not involved in the nuclear industry or with radiation in some other way say anything nice about nuclear power.

The origins of public mistrust of nuclear power are easy to understand Its beginnings are closely connected with nuclear weapons, undoubtedly terrible things. An atmosphere of secrecy and deception also existed in those early days: not even the cabinet was informed about the decision to build the British bomb.2 In addition there have been spectacular accidents such as Chernobyl, Three Mile Island, and the 1957 Windscale fire. All have caused alarm disproportionate to their measurable harm, perhaps in the way that crashes of crowded commuter trains inspire more dread than a steady (and in total much larger) trickle of road deaths. This history, plus the fact that any risk associated with nuclear power is usually perceived as imposed rather than a matter of individual choice, provides ample explanation for the twinge of mistrust that often greets official …
Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue.
Authors: R J Cersosimo, W K Hong
Journal: Journal of Clinical Oncology (1986)

Epirubicin (4'-epidoxorubicin) is an antineoplastic agent derived from doxorubicin. The compounds differ in the configuration of the hydroxyl group at the 4' position. Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Epirubicin is administered by intravenous (IV) injection. It is metabolized by the liver and primarily eliminated in the bile. About 10% of the drug is eliminated in the urine. Dosage adjustments are recommended for patients with liver metastases or elevated liver function tests. The elimination half-life of epirubicin is 30 to 40 hours. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, and pancreatic cancer. There is also evidence of activity against gastric cancer, small-cell lung cancer, and acute leukemia. Epirubicin has limited activity as a single agent against head and neck tumors or non-small-cell lung cancer, but may be beneficial in combination with other agents. The overall activity of epirubicin appears to be comparable with that of doxorubicin. However, more studies are needed to define its role in combination chemotherapeutic regimens. The acute dose-limiting toxicity of epirubicin is myelosuppression. Nausea, vomiting, and alopecia are also common. Epirubicin may cause transient cardiac arrhythmias and alterations of the electrocardiogram. Chronic therapy is limited, but available data indicate that epirubicin can be administered in higher cumulative doses than doxorubicin before cardiotoxicity limits further therapy.
KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections
Authors: C. Tascini, B.A. Lipsky, E. Iacopi, A. Ripoli, F. Sbrana, A. Coppelli, C. Goretti, A. Piaggesi, F. Menichetti
Journal: Clinical Microbiology and Infection (2015)