tbuckley/cabot-search huggingface dataset:
Has 'obstruction' hindered our understanding of hypertrophic cardiomyopathy?
Authors: J M Criley, R J Siegel
Journal: Circulation (1985)

HCM is a disorder associated with significant morbidity and mortality and a propensity to cause sudden, often unexpected death. The similarity to the symptom complex of aortic stenosis and the presence of a pressure gradient justified the initial assumption that obstruction was of prime importance in HCM and that relief of obstruction was the focal point of rational therapy. However, it is our belief that the dogma of obstruction has impeded progress in and obscured the understanding of HCM and interpretation of its manifestations. The purpose of this article is to call attention to significant discrepancies in the obstructive concept that have been reinforced as new techniques emerged that have allowed further study of the disease. Since neither the presence of a gradient nor SAM can be justifiably equated with the presence of an obstruction, it is proposed that the appellation "obstruction" be reserved for those cases in which the rate of outflow or the rate or degree of ventricular emptying are demonstrably impeded, as in aortic stenosis. Therapy with beta-adrenergic-receptor and calcium channel-blocking agents have shown promise for alleviating symptoms and possibly prolonging life without systematically or predictably affecting the pressure gradient, probably because of their beneficial effects on ventricular relaxation and diastolic filling. Antiarrhythmic therapy has been effective in reducing mortality. Ideally, prevention or regression of the pathologic hypertrophy should be the major focus of future therapeutic interventions in hypertrophic cardiomyopathy.
The Acute Effect of Clamped Hyperglycemia on the Urinary Excretion of Inflammatory Cytokines/Chemokines in Uncomplicated Type 1 Diabetes
Authors: David Z.I. Cherney, James W. Scholey, Etienne Sochett, Timothy J. Bradley, Heather N. Reich
Journal: Diabetes Care (2010)

OBJECTIVE Acute glycemic variability contributes to diabetic complications potentially through induction of inflammation. Our objective was to determine whether acute hyperglycemia affects urinary secretion of inflammatory cytokines/chemokines in humans with uncomplicated type 1 diabetes. RESEARCH DESIGN AND METHODS Blood pressure, renal hemodynamics (inulin and paraaminohippurate clearances), and urine samples were obtained after 6 h of clamped euglycemia (4–6 mmol/l) and hyperglycemia (9–11 mmol/l) on two consecutive days in subjects with type 1 diabetes (n = 25). Forty-two urinary cytokines/chemokines were measured using a Luminex platform. RESULTS Clamped hyperglycemia produced an expected increase in glomerular filtration rate (131 ± 4 to 148 ± 8 ml/min/1.73 m2). Clamped hyperglycemia was associated with significant increases in urinary eotaxin, fibroblast growth factor-2, granulocyte-macrophage colony-stimulating factor, interferon-α 2, interleukin-2 and -12, monocyte chemoattractant protein-3, macrophage-derived chemokine, macrophage inflammatory protein-1α, platelet-derived growth factor, tumor necrosis factor-α, and CD40 ligand (P &amp;lt; 0.05). CONCLUSIONS Acute hyperglycemia results in increased urinary excretion of inflammatory cytokines/chemokines in humans with uncomplicated type 1 diabetes, and this may contribute to kidney injury.
EMG mapping of the quadriceps in patellofemoral pain syndrome during functional activities: a pilot study
Authors: V Balachandar, R Twycross-Lewis, D Morrissey, C J Barton, R C Woledge
Journal: British Journal of Sports Medicine (2011)

Patellofemoral pain syndrome (PFPS) arises from patellofemoral articulation, caused in part by inefficient quadriceps muscle activity. Many studies have used surface electromyography (sEMG) to investigate quadriceps activity, with conflicting results. This study is novel in the use of 64-channel surface EMG combined with motion capture. The aim was to create three-dimensional (3-D) EMG maps based on quadriceps muscle amplitude, muscle onset, and lower-limb kinematics in participants with and without patellofemoral pain (PFP) during functional activity using a 2×2 factorial design. Two participants with PFP and three asymptomatic controls were recruited. 64-channel EMG onset and amplitude from the vastus lateralis (VL), rectus femoris (RF), and vastus medialis oblique (VMO) muscles, and motion-analysis data were collected simultaneously during functional activity. Correlation coefficients (CCs) were calculated for within subject and between subject groups. CCs identified significant patterns of activity within subject groups (P&lt;0.01), and more varied patterns in the PFP group. Visual analysis identified that vastii muscle activity was higher in PFP participants than controls for a given movement. Evidence suggests that patterns of activity are more variable in PFP participants. Variability in quadriceps muscle activity may result in erratic patella-kinematics, lateral directed tension, and an increased load on the lateral patella facet resulting in PFP. There is currently a paucity of research investigating patterns of quadriceps muscle activity in PFPS, which needs to be addressed considering its role in the theoretic rational for PFPS. There is substantial scope for further research, and findings may lead to an application towards screening, rehabilitation, and diagnosis. EMG patterns of activity within subject groups are consistent during functional movement. Patterns of activity are more variable, and VMO contraction appears less efficient in PFP participants than in asymptomatic controls
The Role of Immunoglobulin E in Allergy and Asthma
Authors: THOMAS A. E. PLATTS-MILLS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<PATHOPHYSIOLOGIC ROLE OF ...IgE PHARMACOKINETICSIS IgG IMPLICATED IN ASTH...RELATIVE ROLES OF IgE AND...CONCLUSIONSReferencesCITING ARTICLES
Sulphasalazine and lung toxicity
Authors: S.D. Parry, C. Barbatzas, E.T. Peel, J.R. Barton
Journal: European Respiratory Journal (2002)

Sulphasalazine prescribing is on the increase. Pulmonary toxicity and blood dyscrasias are rare side-effects. Numerous case reports have been published implicating sulphasalazine in pulmonary toxicity. The authors searched the literature for cases of sulphasalazine induced lung toxicity and the 50 cases identified are discussed here. All published case reports/letters referring to sulphasalazine and lung toxicity were studied. The search terms “sulphasalazine” and “sulfasalazine” were combined with the terms “lung”, “pulmonary disease”, “pneumonitis” and “pleuritis” using Medline and PubMed databases. Typical presentation of sulphasalazine-induced lung disease was with new onset dyspnoea and infiltrates on chest radiography. Common symptoms were cough and fever. Crepitations on auscultation and peripheral eosinophilia were noted in half of the cases. Sputum production, allergy history, rash, chest pain and weight loss were inconsistent findings. Pulmonary pathology was variable, the commonest being eosinophilic pneumonia with peripheral eosinophilia and interstitial inflammation with or without fibrosis. Fatal reports were infrequent. Most patients were managed by drug withdrawal with 40% prescribed corticosteroids. In conclusion, sulphasalazine lung disease should be distinguished from interstitial lung disease due to underlying primary disease. Despite the increase in sulphasalazine prescribing, pulmonary toxicity remains rare. The majority of patients with suspected sulphasalazine-induced lung disease improved within weeks of drug withdrawal and the need for corticosteroids is debatable.
Tendon and ligament injuries: the genetic component
Authors: Alison V September, Martin P Schwellnus, Malcolm Collins
Journal: British Journal of Sports Medicine (2007)

Tendons and ligaments within the upper and lower limbs are some of the more common sites of musculoskeletal injuries during physical activity. Several extrinsic and intrinsic factors have been shown to be associated with these injuries. More recently, studies have suggested that there is also, at least in part, a genetic component to the Achilles tendon, rotator cuff and anterior cruciate ligament injuries. However, specific genes have not been suggested to be associated with rotator cuff or anterior cruciate ligament injuries. Sequence variants of the tenascin C ( TNC ) gene, on the other hand, have been shown to be associated with Achilles tendinopathies and Achilles tendon ruptures, whereas a variant of the collagen V α 1 ( COL5A1 ) gene has also been shown to be associated with Achilles tendinopathies. Both genes encode for important structural components of tendons and ligaments. The COL5A1 gene encodes for a component of type V collagen, which has an important role in regulating collagen fibre assembly and fibre diameters. The TNC gene, on the other hand, encodes for TNC, which regulates the tissue’s response to mechanical load. To date, only variants in two genes have been shown to be associated with Achilles tendon injuries. In addition, although specific genes have not been identified, investigators have suggested that there is also a genetic component to both rotator cuff and anterior cruciate ligament injuries. In future, specific genotypes associated with increased risk of injury to specific tendons and ligaments can prevent these injuries by identifying individuals at higher risk.
A Sharp Right Turn
Authors: Anupam K. Mohanty, Michael T. Flannery, Brad L. Johnson, Patrick G. Brady
Journal: New England Journal of Medicine (2006)

A 60-year-old man presented to the emergency department for evaluation of rectal bleeding, syncope, and pain in the right leg. Five days earlier, diffuse abdominal pain that worsened with movement had developed in association with nausea, anorexia, and malaise. Shortly before admission, the patient had a single episode of gross hematochezia and hematuria followed by syncope, as well as intense pain in the right leg.
Metabolism of 1,3-Bis(tetrahydro-2-furanyl)-5-fluorouracil in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Fujimoto, H Ishigami, T Minami, M Miyazaki, K Itoh, K Kimura
Journal: JNCI Journal of the National Cancer Institute (1979)

1,3-Bis(tetrahydro-2-furanyl)-5-fluorouracil (FD-1) is a new masked compound of fluorinated pyrimidine and a derivative of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207). The pharmacokinetics of FD-1 and FT-207 were compared in the livers and kidneys of control mice and in mice (DD males) pretreated with phenobarbital. The half-time in the liver of FD-1 orally administered was about 40 minutes, whereas that of FT-207 in the liver was about 3 hours. Hepatic concentrations of 5-fluorouracil (FUra) originating from FD-1 were three to five times as much as those originating from FT-207. FD-1 formed 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-T-F-FU) and FT-207 by a ratio of about 3 to 10, respectively. Although FD-1 had a short period of half reduction, FT-207 and 3-T-F-FU had a half-time lasting for 3--4 hours. In contrast, the renal concentration of FD-1 was one-third that of FT-207. Oral administration of FD-1 to the mice pretreated with phenobarbital elevated the FT-207 and 3-T-F-FU levels in the livers to twice the levels in the control mice and further elevated the FUra levels in the livers to twice the levels in the controls. These results indicate that FD-1 is catabolized in the liver by microsomal enzymes (including cytochrome P450) faster than is FT-207, which consequently enlarges the hepatic pool of the intermediates on the way to FUra formation.
Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma
Authors: V. Sorbello, G. Ciprandi, A. Di Stefano, G. M. Massaglia, G. Favatà, S. Conticello, M. Malerba, G. Folkerts, M. Profita, G. Rolla, F. L. M. Ricciardolo
Journal: Allergy (2014)

Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH)17 chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe asthmatics and controls in relation to neutrophilia and asthma exacerbations. Cryostat sections of nasal/bronchial biopsies obtained from 14 SA and 14 mild asthma (MA) stable atopic patients with rhinitis, and seven healthy controls were analyzed by immunohistochemistry for neutrophils, IL-17A and IL-17F expression. Atopic SA showed an increase in asthma exacerbations number, IL-17F and IL-17A expression in nasal/bronchial lamina propria compared to MA and controls, and a higher expression of bronchial neutrophils in SA compared to MA and controls. In all asthmatics, significant relationships were found between bronchial IL-17F and neutrophils/FEV1, nasal IL-17F and bronchial neutrophil/IL-17 markers and between the latter and exacerbations, suggesting that nasal IL-17F might be informative on bronchial IL17-driven neutrophilia in atopic SA.
Couple has the right to refuse test on newborn child
Authors: D. Payne
Journal: BMJ (2001)

The US attorney general, John Ashcroft, has authorised the Drug Enforcement Administration to take action against any doctor who prescribes lethal drugs for terminally ill patients, even though doctor assisted suicide is legal in one of the country's states.

In Oregon, people are allowed to kill themselves with a doctor's prescription. Under the state's Death with Dignity Act (1997), twice approved by its voters, a terminally ill patient may take lethal drugs if two doctors agree that the person has less than six months to live …
Abnormal Norepinephrine Clearance and Adrenergic Receptor Sensitivity in Idiopathic Orthostatic Intolerance
Authors: Giris Jacob, John R. Shannon, Fernando Costa, Raffaello Furlan, Italo Biaggioni, Rogelio Mosqueda-Garcia, Rose Marie Robertson, David Robertson
Journal: Circulation (1999)

Background —Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of ≥30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. Methods and Results —Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55±5% versus 30±7%, P &lt;0.02). After tyramine, NE spillover did not change significantly in patients but increased 50±10% in control subjects ( P &lt;0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5±0.05 versus 1.0±0.1 μg, P &lt;0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105±11 versus 210±12 μg, P &lt;0.001). Baroreflex sensitivity was lower in patients (12±1 versus 18±2 ms/mm Hg, P &lt;0.02), but the intrinsic heart rate was similar in both groups. Conclusions —The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.
The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid
Authors: W.C. Zamboni, D.I. Lüftner, M.J. Egorin, M. Schweigert, O. Sezer, T. Richter, J.J. Natale, K. Possinger
Journal: Annals of Oncology (2001)
Randomized Controlled Trial of the Use of Compensatory Strategies to Enhance Adaptive Functioning in Outpatients With Schizophrenia
Authors: D I Velligan, C C Bow-Thomas, C Huntzinger, J Ritch, N Ledbetter, T J Prihoda, A L Miller
Journal: American Journal of Psychiatry (2000)

Cognitive adaptation training is a novel psychosocial treatment approach designed to improve adaptive functioning by using compensatory strategies in the home or work environment to bypass the cognitive deficits associated with schizophrenia. The authors tested the effect of cognitive adaptation training on level of adaptive functioning in outpatients with schizophrenia.Forty-five patients with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned for 9 months to one of three treatment conditions: 1) standard medication follow-up, 2) standard medication follow-up plus cognitive adaptation training, and 3) standard medication follow-up plus a condition designed to control for therapist time and provide environmental changes unrelated to cognitive deficits. Comprehensive assessments were conducted every 3 months by raters who were blind to treatment condition.Significant differences were found between the three treatment groups in levels of psychotic symptoms, motivation, and global functioning at the end of the 9-month study period. Patients in the cognitive adaptation training group overall had higher levels of improvement, compared with those in the remaining treatment conditions. In addition, the three groups had significantly different relapse rates over the 9-month study: 13% for the cognitive adaptation training group, 69% for the group in which therapist time and environmental changes were controlled, and 33% for the group who received standard follow-up only.Compensatory strategies may improve outcomes for patients with schizophrenia.
Susceptibility Factors to Ozone-related Mortality
Authors: Massimo Stafoggia, Francesco Forastiere, Annunziata Faustini, Annibale Biggeri, Luigi Bisanti, Ennio Cadum, Achille Cernigliaro, Sandra Mallone, Paolo Pandolfi, Maria Serinelli, Roberta Tessari, Maria Angela Vigotti, Carlo A Perucci
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Acute effects of ozone on mortality have been extensively documented in clinical and epidemiological research. However, only a few studies have focused on subgroups of the population especially vulnerable to these effects.To estimate the association between exposure to ozone and cause-specific mortality, and to evaluate whether individual sociodemographic characteristics or chronic conditions confer greater susceptibility to the adverse effects of ozone.A case-crossover analysis was conducted in 10 Italian cities. Data on mortality were collected for the period 2001 to 2005 (April-September) for 127,860 deceased subjects. Information was retrieved on cause of death, sociodemographic characteristics, chronic conditions from previous hospital admissions, and location of death. Daily ozone concentrations were collected from background fixed monitors.We estimated a 1.5% (95% confidence interval [CI], 0.9-2.1) increase in total mortality for a 10 microg/m(3) increase in ozone (8-h, lag 0-5). The effect lasted several days for total, cardiac and respiratory mortality (lag 0-5), and it was delayed for cerebrovascular deaths (lag 3-5). In the subgroup analysis, the effect was more pronounced in people older than 85 years of age (3.5%; 95% CI, 2.4-4.6) than in 35- to 64-year-old subjects (0.8%; 95% CI, -0.8 to 2.5), in women (2.2%; 95% CI, 1.4-3.1) than in men (0.8%; 95% CI, -0.1 to 1.8), and for out-of-hospital deaths (2.1%; 95% CI, 1.0-3.2), especially among patients with diabetes (5.5%; 95% CI, 1.4-9.8).A greater vulnerability of elderly people and women was indicated; subjects who died at home and had diabetes emerged as especially affected.
Shifting concepts in rectal cancer management
Authors: Lauren Kosinski, Angelita Habr‐Gama, Kirk Ludwig, Rodrigo Perez
Journal: CA A Cancer Journal for Clinicians (2012)

Abstract The management of rectal cancer has transformed over the last 3 decades and continues to evolve. Some of these changes parallel progress made with other cancers: refinement of surgical technique to improve organ preservation, selective use of neoadjuvant (and adjuvant) therapy, and emergence of criteria suggesting a role for individually tailored therapy. Other changes are driven by fairly unique issues including functional considerations, rectal anatomic features, and surgical technical issues. Further complexity is due to the variety of staging modalities (each with its own limitations), neoadjuvant treatment alternatives, and competing strategies for sequencing multimodal treatment even for nonmetastatic disease. Importantly, observations of tumor response made in the era of neoadjuvant therapy are reshaping some traditionally held concepts about tumor behavior. Frameworks for prioritizing and integrating complex data can help to formulate treatment plans for patients. CA Cancer J Clin 2012;. © 2012 American Cancer Society.
Improvement in Brain Oxygenation and Clinical Improvement in Patients With Strokes Treated With Papaverine Hydrochloride
Authors: John S. Meyer
Journal: JAMA (1965)

Intravenous injection of papaverine hydrochloride in doses of 64 mg was found to increase the oxygen available to the brain in subjects suffering from acute stroke (cerebral thromboembolism) proven by arteriography. This was established by continuous measurement of cerebral arteriovenous differences for oxygen pressure and saturation. Both the latter showed significant increases. Cerebral venous carbon dioxide pressure (Pco<sub>2</sub>) decreased and cerebral venous pH increased significantly. Analysis of cerebral arteriovenous differences indicated that the increase in oxygen available to the brain was due to increased cerebral blood flow despite some decrease in arterial Pco<sub>2</sub>due to hyperventilation. The increase in cerebral blood flow occurred even in the presence of high Pco<sub>2</sub>values and was greater in older subjects than in younger subjects. Clinical evaluation of two groups of subjects with acute stroke (proven by arteriography) who were selected for treatment in a random manner indicated that the group of subjects who underwent treatment with papaverine improved more than those that did not receive this drug (0.01 &lt;P&lt;0.05).
Epidermolysis bullosa simplex with mottled pigmentation with noncicatricial alopecia: identification of a recurrent p.P25L mutation in<i>KRT5</i>in four affected family members
Authors: H. Nagai, N. Oiso, S. Tomida, K. Sakai, S. Fujiwara, Y. Nakamachi, S. Kawano, A. Kawada, K. Nishio, C. Nishigori
Journal: British Journal of Dermatology (2015)

Abstract Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare subtype of EBS that is characterized by blistering, mottled pigmentation of the trunk and limbs, punctate hyperkeratosis of the palms and soles, and dystrophic nails.(1) EBS-MP is caused by a mutation in the KRT5 or KRT14 gene encoding keratin 5 (K5) and keratin 14 (K14), respectively.(1, 2) Dermatopathia pigmentosa reticularis (DPR), caused by a KRT14 mutation, is characterized by reticulate pigmentation, noncicatricial alopecia, onychodystrophia and loss of dermatoglyphics.(3) Here, we report cases of EBS-MP with noncicatricial alopecia, a clinical feature of DPR, with a recurrent p.P25L mutation in KRT5 in four Japanese family members. This article is protected by copyright. All rights reserved.