tbuckley/cabot-search huggingface dataset:
Low-level exposure to methylmercury modifies muscarinic cholinergic receptor binding characteristics in rat brain and lymphocytes: physiologic implications and new opportunities in biologic monitoring.
Authors: T Coccini, G Randine, S M Candura, R E Nappi, L D Prockop, L Manzo
Journal: Environmental Health Perspectives (2000)

Methylmercury (MeHg) affects several parameters of cholinergic function. These alterations are thought to play a role in MeHg neurotoxicity. In vitro experiments have indicated that MeHg acts as a strong competitive inhibitor of radioligand binding to muscarinic cholinergic receptors (mAChRs) in rat brain. Furthermore, rat brain mAChRs share several pharmacologic characteristics of similar receptors present on lymphocytes. Using the muscarinic antagonist [(3)H]quinuclidinyl benzilate (QNB) to label receptors, we investigated the in vivo interactions of MeHg with rat brain mAChRs. We also investigated whether MeHg-induced central mAChR changes are reflected by similar alterations in splenic lymphocytes. Exposure to low doses of MeHg--0.5 or 2 mg/kg/day in drinking water--for 16 days significantly increased (20-44% of control) mAChRs density (B(max)) in the hippocampus and cerebellum without affecting receptor affinity (K(d)). The effect of MeHg did not occur immediately; it was not apparent until 2 weeks after the termination of treatment. No significant changes in [(3)H]QNB binding were observed in the cerebral cortex. In splenic lymphocytes, mAChR density was remarkably increased (95-198% of control) by day 14 of MeHg exposure and remained enhanced 14 days after the cessation of treatment. These results suggest up-regulation of mAChRs in selected brain regions (hippocampus and cerebellum) after prolonged low-level ingestion of MeHg in rats. These cerebral effects are delayed in onset and are preceded by a marked increase in density of mAChRs on lymphocytes. In chronic MeHg exposure, peripheral lymphocytes may represent a sensitive target for the interaction of MeHg with mAChRs and, therefore, may be predictive indicators of later adaptive response involving cerebral mAChRs. Additionally, the effect of MeHg on lymphocyte mAChRs in vivo indicates that this receptor system should be investigated further as a possible target for MeHg immunotoxicity.
Disturbances in Body Fluid Osmolality
Authors: George Dunea
Journal: JAMA (1977)

This book is the latest consequence of our amphibious ancestors' decision to crawl onto dry land and evolve from fish to physiologist. It is a good book, complete, erudite, and up to date. It encompasses a sizable segment of the new body of knowledge that within living memory has revolutionized the biomedical sciences, but it suffers, perhaps, from attempting to be all things to all people, by serving as a source of information for the physiologist as well as a reference book for the clinician. The first five chapters are heavy going and should be read in the same way as the later Henry James novels— slowly, and preferably aloud. These chapters deal with the molecular structure of vasopressin and related octapeptides, with their circulatory and natriuretic actions, and with the mechanisms of water and solute transport across epithelial membranes. There are detailed discussions of the adenylate cyclase—cyclic adenosine monophosphate
TEMPORARY COMMISSIONS, I.M.S
Authors: R. H. Elliot
Journal: BMJ (1920)

CORLRESPONDENQE.( Tnip-B-Rrmnw ,.Ar-ZDSAL JOUa"AL in Treasury notes and an album containing an iUuminated address and the names of 700 subscribers.The address expressed the esteem felt for Dr. Larking's great and devoted services to
Substance P potentiates the algogenic effects of intraarterial infusion of adenosine
Authors: Achille Gaspardone, Filippo Crea, Fabrizio Tomai, Maria Iamele, David C. Crossman, Marco Pappagallo, Francesco Versaci, Luigi Chiariello, Pier A. Gioffrè
Journal: Journal of the American College of Cardiology (1994)

Objectives. This study investigated whether substance P potentiates the muscular and cardiac pain caused by the intraarterial infusion of adenosine, an autocoid known to induce muscular and cardiac ischemic-like pain in humans. Background. Substance P is involved in the generation of neurogenic inflammation and causes cutaneous hyperalgesia. Because substance P is present in perivascular nerves it might also cause muscular and cardiac hyperalgesia. To test this hypothesis its effects on adenosine-induced muscular and cardiac pain were investigated in humans. Methods. A randomized, crossover study of the algogenic effects of the intrailiac infusion of increasing scalar doses (from 125 to 2,000 μg/min) of adenosine or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion of substance P plus the same doses of adenosine, was carried out in nine patients with no evidence of peripheral vascular disease. A similar protocol was carried out by infusing increasing scalar doses of adenosine (from 50 to 800 μg/min) or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion of substance P plus the same doses of adenosine, into the left coronary artery of eight patients with angina. Pain severity, assessed by a visual analog scale, is presented as median. The remaining data are presented as mean value ± 1 SD. Results. All patients experienced pain during both adenosine and substance P plus adenosine infusion; no patient experienced pain during the infusion of substance P alone. During intrailiac infusion, all patients experienced pain in the right leg that occurred earlier (207 ± 152 vs. 321 ± 154 s, p < 0.05) and was greater (47 vs. 30 mm, p < 0.05) during the simultaneous infusion of substance P plus adenosine than during the infusion of adenosine. Similarly, during intracoronary infusion, all patients experienced chest pain that occurred earlier (409 ± 242 vs. 596 ± 210 s, p < 0.05) and was greater (51 vs. 33 mm, p < 0.05) during the simultaneous infusion of substance P plus adenosine than during infusion of adenosine. No patient exhibited electrocardiographic signs of ischemia. Conclusions. Substance P does not cause muscular or cardiac pain, but it provokes muscular and cardiac hyperalgesia.
Cause, Effect, and Correction
Authors: W. Clarke Wescoe
Journal: JAMA (1963)

YOU HAVE JUST HEARD from Dr. Willard an analysis of the financial status of American medical schools that clearly delineated the title of this portion of the morning's program. That there are "have" and "have-not" medical schools is not a matter of debate—rather, it is one of the facts of life in today's medical education. Someone obviously spent a great deal of time in phrasing the titles of the morning's presentations. They are eye-catching titles, designed to stimulate interest. That they have accomplished their purpose is indicated by the size of the audience. But titles attractive to audiences may impose crushing burdens on the speaker. It is difficult for some of us to live up to the advance billing. The title of my presentation, for instance, presages perspicacity and promises prescience that cannot possibly be produced by the speaker. What you are about to hear is neither perfect in its
Daily Treatment with Sildenafil Reverses Endothelial Dysfunction and Oxidative Stress in an Animal Model of Insulin Resistance
Authors: Delphine Behr-Roussel, Alexandra Oudot, Stéphanie Caisey, Olivier L.E. Coz, Diane Gorny, Jacques Bernabé, Chris Wayman, Laurent Alexandre, François A. Giuliano
Journal: European Urology (2007)
"Reciprocal" depression of the ST segment in acute myocardial infarction.
Authors: K Jennings, D S Reid, D G Julian
Journal: BMJ (1983)

In acute myocardial infarction depression of the ST segment in leads distant from those showing ST elevation has been considered to be "reciprocal" but might reflect local ischaemia. To examine this possibility 103 consecutive patients who underwent exercise testing early after myocardial infarction were reviewed. Treadmill exercise testing was performed a mean of 12 (range 5-30) days after infarction using a limited Naughton protocol. Thirty five (34%) of the patients had had reciprocal change, defined as greater than or equal to 1 mm ST depression in leads remote from the site of the infarct, within 48 hours of infarction. Twenty two (63%) of the 35 patients developed exercise induced ST depression in the leads previously showing reciprocal change. Coronary artery disease was assessed in 10 of these patients by arteriography and in four at necropsy: all but one had stenosis of greater than or equal to 50% in a coronary artery supplying the reciprocal territory in addition to the disease in the vessel to the infarct site. Of patients with reciprocal ST depression, 23.5% experienced nonfatal reinfarction, pulmonary oedema after discharge, or death compared with only 9.5% of patients without reciprocal ST depression. Eight (23.5%) patients with reciprocal depression had ventricular fibrillation while in hospital compared with only two (3%) patients without. Reciprocal ST depression in acute myocardial infarction may reflect ischaemia in territory distant from the site of infarction and is associated with a high risk of fatal arrhythmias and late morbidity.
Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans.
Authors: S Ranger, M Talajic, R Lemery, D Roy, C Villemaire, S Nattel
Journal: Circulation (1991)

BACKGROUND Rate-dependent conduction slowing by class I antiarrhythmic agents has clinically important consequences. Class I drugs are known to produce use-dependent sodium channel blockade. If rate-dependent conduction slowing by class I agents is due to sodium channel blocking actions, the kinetics of conduction slowing should be similar to those of depression of sodium current indexes in vitro. The purpose of the present investigation was to study the onset time course of ventricular conduction slowing caused by a variety of class I agents in humans. METHODS AND RESULTS Twenty-seven patients undergoing electrophysiological evaluation for antiarrhythmic therapy were studied. Changes in QRS duration at initiation of ventricular pacing at cycle lengths of 400 and 500 msec were used to evaluate the kinetics of drug action. Mean time constants for each drug were similar to values for Vmax depression reported in vitro studies: flecainide, 24.9 +/- 11.6 beats in eight patients (versus 34.5 beats reported for Vmax block); propafenone, 17.8 +/- 6.9 beats in five patients (versus 8.4-20.8 beats); quinidine, 7.0 +/- 2.4 beats in six patients (versus 5.6-6.2 beats); and amiodarone, 3.6 +/- 2.0 beats for eight patients (versus 3.0 beats). Time constants were significantly different among the various drugs tested (p = 0.0002 at a cycle length of 400 msec; p = 0.002 at 500 msec), and there was a strong correlation (r = 0.89, p less than 0.0001) between values obtained at a cycle length of 400 msec and those at a cycle length of 500 msec. No rate-dependent changes in QRS duration were seen at onset of ventricular pacing among eight age- and disease-matched control patients not taking class I antiarrhythmic drugs, including three patients subsequently showing such changes during type I antiarrhythmic drug therapy. CONCLUSIONS We conclude that class I agents produce use-dependent QRS prolongation in humans with characteristic kinetics for each agent that are similar to the kinetics of Vmax depression in vitro. These results suggest that rate-dependent ventricular conduction slowing by antiarrhythmic drugs in humans is due to use-dependent sodium channel blockade.
Systemic Manifestations after a Skin Test with Penicilloyl-Polylysine
Authors: Edwin Ettinger, Donald Kaye
Journal: New England Journal of Medicine (1964)

PENICILLIN hypersensitivity is a major problem.1 Various skin tests have been used to determine if patients are hypersensitive to penicillin before the institution of therapy. These procedures involve patch tests, scratch tests or intradermal injection of penicillin.1 2 3 Anaphylaxis has been reported to occur despite negative results for hypersensitivity by each of these methods.3 Recently, an intradermal test has been evaluated that utilizes a penicillin degradation product, penicilloyl, which is conjugated with polylysine.4 5 6 The results of this test have been reported to correlate closely with penicillin allergy.5 , 6 To our knowledge no systemic reactions have been reported after the intradermal injection of . . .
Abstract P3-13-01: Delayed Chemotherapy-Induced Nausea and Vomiting in Asian Women with Breast Cancer
Authors: L Bourdeanu, J Mortimer, G Somlo, A Hurria, C Chung, P Frankel, TH. Luu
Journal: Cancer Research (2010)

Abstract Background: Chemotherapy-induced nausea and vomiting (CINV) remain among the most frequently reported distressing side effects associated with a doxorubicin-based chemotherapy regimen, and it can significantly affect patients’ quality of life and compliance with therapy. Despite the significant advances in antiemetic management in preventing and controlling CINV, as many as 50% of patients still experience some degree of nausea and vomiting. The main risk factor for the degree of CINV is the emetogenic potential of the chemotherapeutic agents. However, several patient-related risk factors have been identified, including individuals’ genetic makeup. Although several studies have noted that ethnicity influences nausea and vomiting related to motion sickness, fluorescein dye, and pregnancy, no studies have evaluated the relationship between ethnicity and CINV; specifically, if there is a higher incidence of severe CINV in patients of Asian descent. Methods: A retrospective, comparative, correlational chart review was performed to abstract all relevant variables. The association between CINV and ethnicity was examined through chi square analysis. Results: Data from a convenience sample of 300 women with breast cancer who received chemotherapy that includes doxorubicin between 2004 and 2008 at City of Hope in Duarte, CA, were evaluated. The sample consisted of Caucasians (46.3%), African Americans (3.7%), Asians (24.0%), and Hispanics (26.0%). The results of this study indicate that Asian women with breast cancer undergoing treatment with chemotherapy that includes doxorubicin experienced statistically significantly more severe CINV (grade ≥ 2) than their non-Asian counterparts (X2 = 10.601, p = .001). Conclusion: This study provides strong but preliminary evidence that Asian ethnicity plays a role in the development of severe CINV. When managing chemotherapy toxicities in women with breast cancer, healthcare providers are advised to optimize their patients’ outcomes by ensuring that therapy is tailored according to each patient's individual risk profile. Consideration of the antiemetic therapy should accommodate patient characteristics, specifically being of Asian descent. In this way, effective prevention of CINV can be maximized during a patient's initial treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-01.
A Simple Prediction Rule for All-Cause Mortality in a Cohort Eligible for Bariatric Surgery
Authors: Raj S. Padwal, Scott W. Klarenbach, Xiaoming Wang, Arya M. Sharma, Shahzeer Karmali, Daniel W. Birch, Sumit R. Majumdar
Journal: JAMA Surgery (2013)

Current eligibility criteria for bariatric surgery use arbitrarily chosen body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) thresholds, an approach that has been criticized as arbitrary and lacking evidence.To verify the importance of BMI as a mortality predictor, to identify other important mortality predictors, and to construct a mortality prediction rule in a population eligible for bariatric surgery.We studied individuals from a population-representative register who met contemporary eligibility criteria for bariatric surgery (BMI, ≥35.0 alone or 30.0-34.9 with an obesity-related comorbidity) from January 1, 1988, through December 31, 1998. We used binary logistic regression to construct a parsimonious model and a clinical prediction rule for 10-year all-cause mortality.The United Kingdom General Practice Research Database, a population-representative primary care registry.Fifteen thousand three hundred ninety-four patients aged 18 to 65 years.Bariatric surgery.Ten-year all-cause mortality.Mean (SD) age was 46.9 (11.9) years, BMI was 36.2 (5.5), and 63.2% of the patients were women. All-cause mortality was 2.1%, and mean follow-up duration was 9.9 years. The final model, which included age (odds ratio, 1.09 per year [95% CI, 1.07-1.10]), type 2 diabetes mellitus (2.25 [1.76-2.87]), current smoking (1.62 [1.28-2.06]), and male sex (1.50 [1.20-1.87]), had a C statistic of 0.768. Although BMI significantly predicted mortality (odds ratio, 1.03 per unit [95% CI, 1.01-1.05]), it did not improve model discrimination or calibration. We divided clinical prediction rule scoring into 4 tiers. All-cause mortality was 0.2% in tier 1, 0.9% in tier 2, 2.0% in tier 3, and 5.2% in tier 4.All-cause 10-year mortality in obese individuals eligible for bariatric surgery can be estimated using a simple 4-variable prediction rule based on age, sex, smoking, and diabetes mellitus. Body mass index was not an important mortality predictor. Further work is needed to define low, moderate, and high absolute risk thresholds and to provide external validation.
THE USE OF IODIN IN THE PREPARATION OF THE PATIENT FOR DELIVERY
Authors: Herbert Thoms
Journal: JAMA (1918)

<h3>To the Editor:</h3> —The use of tincture of iodin in the preparation for abdominal section has become so general that its value as an antiseptic is well established. That its use in obstetrics has not become more general is surprising, especially when its many advantages are considered. The maintenance of asepsis even in the normal delivery offers many problems that are not encountered in surgical work. The main objection to the use of iodin in this connection seems to be that first, many skins in the region of the vulva cannot tolerate its use, and secondly, many patients complain bitterly of burning and smarting subsequent to its application. During the past few months at the Grace Hospital we have used several preparations or strengths of the tincture and have concluded that tincture of iodin, one-third strength, or tincture of Iodine, U. S. P., one part, Alcohol, two parts, offers a
Pathologic Findings in Twelve Fatal Cases of Toxic Shock Syndrome
Authors: ALLEN LEE PARIS
Journal: Annals of Internal Medicine (1982)

Pathologic changes in 12 fatal cases of toxic shock syndrome occurred in the vagina, cervix, lung, liver, and kidney. Desquamation and ulceration of the cervical and vaginal mucosa were seen in all six cases where adequate specimens were submitted. Hyaline membrane formation characteristic of "shock lung" was found in all lung tissues. Periportal inflammation was found in all liver specimens and acute tubular necrosis was seen in eight of the 12 kidney specimens. Although not specific for toxic shock syndrome, the findings are consistent with the hypothesis that the illness is caused by a staphylococcal toxin.
Comparison of Two Methods of Diagnostic Lung Lavage in Ventilated Infants with Lung Disease
Authors: PETER A. DARGAVILLE, MICHAEL SOUTH, PETER N. McDOUGALL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The methods of nonbronchoscopic lung lavage used for collection of samples of epithelial lining fluid (ELF) in intubated patients are poorly standardized and incompletely validated. In infants with lung disease requiring ventilatory support, we evaluated two techniques of small volume saline lavage for the collection of a specimen suitable for pulmonary surfactant analysis. We aimed to compare apparent origin of the return fluid obtained by each method, equivalence and agreement of the estimates of measured pulmonary surfactant concentration, and the relative strength of association between surfactant indices and lung dysfunction. Fifty-three contemporaneous paired samples of lung lavage fluid suitable for surfactant analysis were collected from 31 infants using tracheal aspirate (TA, 4 x 0.5 ml saline), and then nonbronchoscopic bronchoalveolar lavage (NB-BAL, 3 x 1 ml/kg). Return fluid from TA had higher mean ELF concentration of total protein and IgA secretory component (SC), and a lower surfactant protein A (SP-A) concentration than NB-BAL, indicating that the TA lavage was sampling ELF more proximally in the tracheobronchial tree (protein: TA 7.7 versus NB-BAL 4.7 mg/ml; SC: 21 versus 1.8 microgram/ml; SP-A: 9.8 versus 19 microgram/ml; all p < 0.01). Mean concentration of surfactant indices in ELF differed only for SP-A, but for all indices, paired values showed poor agreement on Bland-Altman analysis, highlighting the potential imprecision associated with small volume lung lavage. TA return fluid yielded estimates of surfactant indices which were at least equivalent to NB-BAL in prediction of the severity of lung dysfunction. We conclude that NB-BAL return fluid has more distal origin, but analysis of TA fluid may have equal validity in the estimation of indices of pulmonary surfactant. The results of individual estimates of ELF constituents in a single sample of lavage fluid should be interpreted with caution, even when standardized sampling techniques are employed.
The Electrocardiogram during Exercise
Authors: SAMUEL BELLET, OTTO F. MULLER
Journal: Circulation (1965)

The electrocardiogram after exercise has proved to be an extremely valuable tool in the diagnosis of coronary artery disease. However, it fails to record the events during the actual period of exercise at the time of the greatest stress on the circulation. Recent technics have enabled us to take the electrocardiogram during the period of exercise. Data presented indicate that the electrocardiogram taken during this period of exercise adds much to the information obtained in the postexercise electrocardiogram; at times, this information may be crucial in determining evidence of abnormalities in the exercise study. The tracings may be solely positive or more markedly positive during the period of exercise. Evidence of such changes would be helpful in diagnosis and in the early termination of the exercise test. It is our belief that the complete electrocardiographic exercise study should include tracings taken both during and after exercise, and the data obtained during both of these periods should be available for evaluation. Although the complete exercise test adds much to the diagnosis of coronary artery disease, the presence of a normal test does not necessarily exclude this state. Evaluation of the tracing taken during exercise is in its infancy. Much still needs to be done relative to (a) more adequate standardization of the type of exercise to suit the individual subject, (b) improvement of standardization of apparatus, (c) standardization of leads and their placement, and (d) more rigid standardization of criteria for normality and abnormality.