tbuckley/cabot-search huggingface dataset:
Supraventricular pacemaker underdrive in the absence of sinus nodal influences in the conscious dog.
Authors: J M Loeb, D K Murdock, W C Randall, D E Euler
Journal: Circulation Research (1979)

The ability to reduce and maintain heart rate by electrical stimulation (underdrive) was tested in three groups of chronically instrumented dogs: sinoatrial node intact, ectopic atrial pacemaker produced by injection of rapidly hardening latex into the sinoatrial nodal artery, and idioventricular pacemaker produced by injection of formalin into the atrioventricular node. In the conscious unsedated state, underdrive of sinoatrial or idioventricular pacemakers resulted in competition between driven and intrinsic foci. However, the cycle length of ectopic atrial pacemakers could be increased by 148.4 +/- 30.7 msec (P less than 0.001) and maintained at that value. Cessation of underdrive resulted in a period of pacemaker suppression similar to that produced following overdrive. Single premature stimuli produced marked cycle length prolongations in dogs with ectopic atrial foci. Total autonomic blockade had no significant effect on the production of underdrive. Thus, the results of the present experiments provide evidence for maintained capture of cardiac pacemakers at rates significantly below intrinsic control and indicate that underdrive varies as a function of pacemaker site. Underdrive may explain the failure of junctional escape in the presence of slower atrial rhythms.
Effect of Bronchoconstriction on Airway Remodeling in Asthma
Authors: Christopher L. Grainge, Laurie C.K. Lau, Jonathon A. Ward, Valdeep Dulay, Gemma Lahiff, Susan Wilson, Stephen Holgate, Donna E. Davies, Peter H. Howarth
Journal: New England Journal of Medicine (2011)

Asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to eosinophilic inflammation. In vitro studies indicate, however, that the compressive mechanical forces that arise during bronchoconstriction may induce remodeling independently of inflammation. We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in patients with asthma.We randomly assigned 48 subjects with asthma to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and eosinophilic inflammation) or methacholine (which causes bronchoconstriction without eosinophilic inflammation); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or albuterol followed by methacholine (to control for nonbronchoconstrictor effects of methacholine). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges.Allergen and methacholine immediately induced similar levels of bronchoconstriction. Eosinophilic inflammation of the airways increased only in the allergen group, whereas both the allergen and the methacholine groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17 μm in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94 μm in the methacholine group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid-Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the methacholine group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and methacholine groups.Bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management.
Pregnancy and breast cancer
Authors: Ludger Barthelmes, Louise A Davidson, Christopher Gaffney, Christopher A Gateley
Journal: BMJ (2005)

Breast cancer is rare in young women, with an increase in incidence in the fourth and fifth decades. A trend is to defer childbearing to later in life. The issues of pregnancy and breast cancer are of importance as some women discover their breast cancer while pregnant and some may not have completed their family at the time of treatment. We discuss the case of a woman whose breast cancer was diagnosed during pregnancy. We review the choices she was faced with at the time of diagnosis and after treatment.

To review the effects of pregnancy on outcome in patients with breast cancer we included all studies after 1990 by searching Medline, CINAHL, and Embase combining the headings “pregnancy” and “breast neoplasm”. To investigate the outcome of breast cancer in pregnant women who underwent a termination after being diagnosed during pregnancy, we included all studies published after 1980 personally known to us. For the effects of chemotherapy and radiotherapy given during pregnancy, we searched Medline combining the headings “breast neoplasm”, “radiotherapy”, and the relevant chemotherapy agents. To assess whether delayed administration of chemotherapy impairs outcome, we searched Medline with the term “delay adj chemotherapy” combined with the heading “breast neoplasm”.

A 33 year old woman with a four year old child presented to her doctor with a painless lump in her right breast. On examination a discrete lump was felt in the upper half of the breast. The doctor referred the woman to a rapid access breast clinic, where a 1.5 cm lump and an area of increased nodularity was confirmed. The features on palpation were indeterminate for type of lesion. Ultrasound guided core biopsies were carried out as ultrasonography and mammography suggested a carcinoma (figs 1 and 2). While awaiting an appointment for the result of the biopsies, the …
Differential acute effects of aldosterone, dexamethasone, and hyperkalemia on distal tubular potassium secretion in the rat kidney.
Authors: M J Field, B A Stanton, G H Giebisch
Journal: Journal of Clinical Investigation (1984)

To determine the specific effects on renal potassium transport of acute elevations in plasma aldosterone, dexamethasone, and potassium concentrations, we studied adrenalectomized rats prepared such that each factor could be varied independently. Clearance data alone could not be used to deduce the underlying tubular transport effects, however, since infusion of each of these agents was associated with a marked change in urinary flow rate, which may itself have influenced potassium excretion. We therefore used a technique of continuous microperfusion, in vivo, of single superficial distal tubules to evaluate potassium secretion at constant luminal flow rate during each experimental maneuver. Acute aldosterone infusion was associated with a 90% stimulation of potassium secretion by microperfused tubules. However, total kidney sodium excretion and urinary flow rate were markedly reduced, and these factors opposed the direct tubular action of aldosterone, resulting in no net change in the amount of potassium excreted into the final urine. Conversely, dexamethasone had no direct effect on potassium secretion by single microperfused tubules, but it caused a sharp increase in urinary flow and sodium excretion, and secondarily enhanced urinary potassium excretion by 50%. Hyperkalemia per se stimulated renal potassium excretion both via a direct tubular effect and by increasing urinary flow rate. We conclude that urinary potassium excretion after infusion of each of these agents represents the net result of direct tubular effects and secondary flow-mediated changes.
Conserved Motifs Reveal Details of Ancestry and Structure in the Small TIM Chaperones of the Mitochondrial Intermembrane Space
Authors: Ian E Gentle, Andrew J Perry, Felicity Hazel Alcock, Vladimir A Likic, Pavel Dolezal, Ee Ting Ng, Anthony Wayne Purcell, Malcolm McConnville, Thomas Naderer, Anne-Laure Chanez, Fabien Charriere, Caroline Aschinger, Andre Schneider, Kostas Tokatlidis, Trevor James Lithgow
Journal: Molecular Biology and Evolution (2007)

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of ∼10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans. Using hidden Markov models, we find that many eukaryotes have proteins equivalent to the Tim8 and Tim13 and the Tim9 and Tim10 subunits. Some eukaryotes provide "snapshots" of evolution, with a single protein showing the features of both Tim8 and Tim13, suggesting that a single progenitor gene has given rise to each of the small TIMs through duplication and modification. We show that no "Tim12" family of proteins exist, but rather that variant forms of the cognate small TIMs have been recently duplicated and modified to provide new functions: the yeast Tim12 is a modified form of Tim10, whereas in humans and some protists variant forms of Tim9, Tim8, and Tim13 are found instead. Sequence motif analysis reveals acidic residues conserved in the Tim10 substrate-binding tentacles, whereas more hydrophobic residues are found in the equivalent substrate-binding region of Tim13. The substrate-binding region of Tim10 and Tim13 represent structurally independent domains: when the acidic domain from Tim10 is attached to Tim13, the Tim8–Tim1310 complex becomes essential and the Tim9–Tim10 complex becomes dispensable. The conserved features in the Tim10 and Tim13 subunits provide distinct binding surfaces to accommodate the broad range of substrate proteins delivered to the mitochondrial inner and outer membranes.
Antiarrhythmic Therapy for Prevention of Implantable Cardioverter Defibrillator Shocks
Authors: Abdul Wase
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward
Authors: Yijun Cui, Sean B Ostlund, Alex S James, Chang Sin Park, Weihong Ge, Kristofer W Roberts, Nitish Mittal, Niall P Murphy, Carlos Cepeda, Brigitte L Kieffer, Michael S Levine, James David Jentsch, Wendy M Walwyn, Yi E Sun, Christopher J Evans, Nigel T Maidment, X William Yang
Journal: Nature Neuroscience (2014)
Oral Glucose Tolerance and Hormonal Response in Heroin-dependent Males
Authors: J. L. Reed, A. H. Ghodse
Journal: BMJ (1973)

Tests on 12 heroin addicts showed that their response to a glucose load differed from that in normal controls. Though the fasting blood sugar was normal, the rise in blood glucose after a standard 50-g oral glucose tolerance test was delayed and the rise smaller than in the controls. The heroin addicts had high resting insulin levels and a delayed peak response to an oral glucose load, and their growth hormone response was also abnormal.
The Presentation and Diagnosis of 100 Patients with Primary Biliary Cirrhosis
Authors: Sheila Sherlock, P. J. Scheuer
Journal: New England Journal of Medicine (1973)

PRIMARY biliary cirrhosis1 , 2 (chronic nonsuppurative destructive cholangitis)3 was formerly diagnosed only in its late, icteric stage. One or more laparotomies had usually been performed to exclude surgical jaundice. Now the disease can usually be recognized earlier and without surgery. Diagnosis is based on knowledge of the clinical presentation, the cholestatic liver-function tests, the positive serum mitochondrial antibody (M) test4 5 6 and the liver biopsy appearances.3 , 7 This report describes 100 patients seen at the Royal Free Hospital between 1965 and 1972 who were diagnosed as having primary biliary cirrhosis.MethodsSerum total bilirubin, alkaline phosphatase (expressed as King-Armstrong units, normal, 4 to . . .
Thyroid Diseases Among Atomic Bomb Survivors in Nagasaki
Authors: Shigenobu Nagataki
Journal: JAMA (1994)

<h3>Objective.</h3> —To elucidate the current thyroid disease status for the Nagasaki Adult Health Study cohort of the Radiation Effects Research Foundation. <h3>Design.</h3> —Survey study. <h3>Setting.</h3> —Nagasaki, Japan. <h3>Participants.</h3> —Cohort members of the Nagasaki Adult Health Study who received biennial health examinations from October 1984 to April 1987 (n=2856). A total of 2587 subjects remained after exclusion of persons exposed in Hiroshima or in utero and those who were not in Nagasaki at the time of the bombing. Thyroid radiation dose by the dosimetry system established in 1986 was available for 1978 of the 2587 subjects. <h3>Main Outcome Measures.</h3> —Thyroid diseases were diagnosed using uniform procedures including ultrasonic scanning. The relationship of the prevalence of each thyroid disease with thyroid radiation dose, sex, and age was analyzed using logistic models. <h3>Results.</h3> —A significant dose-response relationship was observed for solid nodules, which include cancer, adenoma, adenomatous goiter, and nodules without histological diagnosis, and for antibody-positive spontaneous hypothyroidism (autoimmune hypothyroidism) but not for other diseases. The prevalence of solid nodules showed a monotonic dose-response relationship, yet that of autoimmune hypothyroidism displayed a concave dose-response relationship reaching a maximum (±SE) level of 0.7±0.2 Sv. <h3>Conclusions.</h3> —The present study confirmed the results of previous studies by showing a significant increase in solid nodules with dose to the thyroid and demonstrated for the first time a significant increase in autoimmune disease among atomic bomb survivors. A concave dose-response relationship indicates the necessity for further studies on the effects of relatively low doses of radiation on thyroid disease. (<i>JAMA</i>. 1994;272:364-370)
Eradication of tuberculosis by 2050 impossible without new vaccine
Authors: R. Smith
Journal: BMJ (2009)

The search for new drugs and vaccines to target tuberculosis has seen a “phenomenal sea change,” with more than 20 products in the pipeline, delegates heard at the Simply, Stopping Tuberculosis conference in Rio de Janeiro.

However, Jerald Sadoff, president of Aeras Global TB Vaccine Foundation, warned that the aim of the Stop TB Partnership to eradicate the disease by 2050 will be unreachable without a new vaccine. The existing vaccine, BCG, works in only 15-40% of children and possibly not at all in adults, he said.

The conference heard that the main …
Association of serum fetuin-A levels with mortality in dialysis patients
Authors: M.M.H. Hermans, V. Brandenburg, M. Ketteler, J.P. Kooman, F.M. van der Sande, E.W. Boeschoten, K.M.L. Leunissen, R.T. Krediet, F.W. Dekker
Journal: Kidney International (2007)
Advances in Breast Cancer: Pathways to Personalized Medicine
Authors: Olufunmilayo I. Olopade, Tatyana A. Grushko, Rita Nanda, Dezheng Huo
Journal: Clinical Cancer Research (2008)

Abstract Breast cancer is a complex disease caused by the progressive accumulation of multiple gene mutations combined with epigenetic dysregulation of critical genes and protein pathways. There is substantial interindividual variability in both the age at diagnosis and phenotypic expression of the disease. With an estimated 1,152,161 new breast cancer cases diagnosed worldwide per year, cancer control efforts in the postgenome era should be focused at both population and individual levels to develop novel risk assessment and treatment strategies that will further reduce the morbidity and mortality associated with the disease. The discovery that mutations in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancers has radically transformed our understanding of the genetic basis of breast cancer, leading to improved management of high-risk women. A better understanding of tumor host biology has led to improvements in the multidisciplinary management of breast cancer, and traditional pathologic evaluation is being complemented by more sophisticated genomic approaches. A number of genomic biomarkers have been developed for clinical use, and increasingly, pharmacogenetic end points are being incorporated into clinical trial design. For women diagnosed with breast cancer, prognostic or predictive information is most useful when coupled with targeted therapeutic approaches, very few of which exist for women with triple-negative breast cancer or those with tumors resistant to chemotherapy. The immediate challenge is to learn how to use the molecular characteristics of an individual and their tumor to improve detection and treatment, and ultimately to prevent the development of breast cancer. The five articles in this edition of CCR Focus highlight recent advances and future directions on the pathway to individualized approaches for the early detection, treatment, and prevention of breast cancer.
Abnormal lung lymphatics and respiratory failure.
Authors: S F Moss, D C Currie, E A Sheffield, M Baxter, B Corrin, T W Evans
Journal: Thorax (1989)

A 65 year old man presented with respiratory failure, pleural effusions, fine reticulonodular shadowing on a chest radiograph, and severe impairment of carbon monoxide diffusing capacity (transfer factor). Open lung biopsy showed only dilated pleural and subpleural lymphatic channels. Hypoplastic deep pulmonary lymphatics may have led to respiratory failure.
EVALUATION OF THERAPEUTIC FACTORS IN PHARMACOLOGIC SHOCK
Authors: L. S. LIPSCHUTZ, R. W. CAVELL, R. LEISER, E. N. HINKO, S. H. RUSKIN
Journal: American Journal of Psychiatry (1939)

1. Seven of 20, or 35 per cent, of a group of chronic schizophrenic patients were benefited by insulin to the point of social recovery or marked improvement, as compared with a 20 per cent spontaneous remission rate in a control group of 30 patients. 2. Coma was found to be essential for the production of improvement, its effectiveness being increased when combined with intensive resocialization activities. 3. Metrazol was only one-half as effective as insulin in chronic schizophrenia, but justified its use because of its greater ease of administration and lesser cost. In chronically disturbed patients its use frequently resulted in moderate degrees of improvement resulting in better ward adjustment. 4. Paranoid schizophrenia responded best to insulin; agitated catatonia to metrazol. 5. Neither the age of the patient nor the degree of hereditary taint could be correlated with the therapeutic responses. 6. In involutional melancholia and manic-depressive psychosis, depressed phase, metrazol treatment appeared to constitute a direct attack upon the specific psychopathology of the disease. A theoretic formulation to explain this action was offered. 7. The relatively long duration of schizophrenia in first admissions to the Eloise Hospital was noted and the need for earlier recognition and more prompt admission stressed, so as to enhance our therapeutic effectiveness.
Effect of a Clinical Practice Improvement Intervention on Chlamydial Screening Among Adolescent Girls
Authors: Mary-Ann B. Shafer
Journal: JAMA (2002)

THE most commonly reported bacterial sexually transmitted disease (STD) in the United States, with 3 million to 4 million cases occurring annually. 1The infection rate among female adolescents (2406/100 000) is 6 times higher than the national average for all women. 2More than 75% of C trachomatis infections are asymptomatic. 1,32][3] Chlamydia trachomatis infections cost the US health care system $3 billion to $4 billion annually. 1Early detection coupled with treatment can significantly reduce the infection burden and reproductive sequelae. 4,5Broadbased screening programs have successfully decreased the C trachomatis rate and pelvic inflammatory disease in young women by 60%, 4 lowered hospitalization rates, 6 and have been found to be cost-effective. 7,8In response, most
England gets more medical students
Authors: S. Knight
Journal: BMJ (1999)

Background: To evaluate longitudinal variations of serum HER-2/neu extracellular domain (sHER-2) in metastatic breast cancer patients receiving combined trastuzumab treatment. Patients and Methods: Thirty-three patients were monitored by serial sHER-2 ELISA (Oncogene Science). Results were compared to time to progression (TTP) and survival from treatment initiation. Non parametric statistical tests were used. Results: Median sHER-2 before first injection was 41.37 ng/ml (range 7.54-1597.00 ng/ml, n=32). Mean sHER-2 levels differed significantly between responders (n=20) and non responders (n=13) (p&lt;0.0001). Median TTP (266 days, range 35-1000 days) was unrelated to clinico-biological variables at diagnosis or number and site of metastases before treatment. Patients with pre-treatment sHER-2 levels ≤30 ng/ml (n=14) had a significantly longer TTP than the group with sHER-2 &gt; 30 ng/ml (n=18) (p=0.0346) and sHER-2 levels were of prognostic value for overall survival from first injection (p=0.0150). Conclusion: Our results show that monitoring serum HER-2/neu levels during metastatic breast cancer can provide a real time assessment of a woman9s HER-2/neu status and can provide important information for therapeutic decisions.
Screening for Cervical Carcinoma
Authors: H. C. McLaren
Journal: BMJ (1973)

this problem we have collected the following information.In November 1972, 5,165 patients were sent for a radiological examination at the Radclffe Infirmary; 2,158 were females, and 181 of these who were between the ages of 15 and 45 years had examinations of the abdomen and pelvic regions.At the Nuffield Orthopaedic Centre for the same month the total was 1,321 patients; 702 were females and 87 of these between the ages of 15 and 45 had eamntions of the abdomen and