tbuckley/cabot-search huggingface dataset:
Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.
Authors: W E Yarger, D D Schocken, R H Harris
Journal: Journal of Clinical Investigation (1980)

Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the vasodilator kinins, because the effect was not diminished by administration of either carboxypeptidase B (which destroys the kinins) or Trasylol (which blocks kinin synthesis). Thus, these results suggest that both angiotensin II, as well as metabolites of the PG-TX system, may be important determinants of postobstructive renal hemodynamics in the rat.
'Collateral casualties' climb in drug war
Authors: A. A. Skolnick
Journal: JAMA (1994)

SINCE PRESIDENT Nixon declared war on drugs in 1972, the nation's primary remedy for illicit drug use has been an escalation of federal, state, and local law enforcement activities aimed at discouraging use by punishing both dealers and users. However, an increasing number of health, law, and other experts say the current policy is clearly failing and shows no sign of ever doing more good than harm. Advocates for reform are calling for an objective cost-benefit analysis of current prohibition laws and of alternative approaches that place more emphasis on harm reduction than on the complete elimination of "recreational" illicit drug use. Yet despite the nation's long, bitter, and expensive war on drugs, much vital data remain uncollected—such as the total number of illegal-drug addicts killed by overdoses. "There appears to be an unwillingness among many national leaders to collect all the data needed for an objective analysis of the
FATAL LEPTO-MENINGITIS DUE TO ENDOMETRITIS ORIGINATING FROM THE DIPLOCOCCUS PNEUMONIÆ.
Authors: ERNEST B. SANGREE
Journal: JAMA (1897)

A few days since I had an opportunity to perform an autopsy especially interesting through its unexpected outcome. Autopsies are difficult to obtain in this region, und this one was obtained because of the well-known suspiciousness and ignorance of the negroes. Several weeks since I was permitted to hold one on the body of a woman simply because she was supposed to have been "hoodooed" to death. In this case I was informed by the decedent's roommate that "the lady next door had sold them five cents worth of dumplin's an' I aint sayin' she was poisoned but she said 'Oh Sallie, I'm poisoned, I knows I is,' an' I ate the dumplin's too but they didn't hurt me an' I wants you to fin' out all about it, I does." Though, under the circumstances, it was impossible to get any consecutive and clear history of the case, this is
Food and Drug Administration surveillance of dermatology-related and nondermatology-related prescription drug advertising in the U.S.A., 2000-2003
Authors: A.L. Cowden, K.A. Katz
Journal: British Journal of Dermatology (2006)

Background Spending on advertising of prescription medicines in the U.S.A. is increasing by nearly a billion dollars yearly. The Food and Drug Administration (FDA) is legally mandated to regulate pharmaceutical advertising in the U.S.A. Prior studies have documented inaccuracies in pharmaceutical advertisements, in the U.S.A. and the rest of the world. Objectives To assess trends in FDA surveillance of dermatology‐related prescription drug advertising, and to investigate pharmaceutical companies’ responses to FDA regulatory actions. Methods We analysed all FDA citations of prescription drug advertisements issued during 2000–2003, and responses from cited companies to our mailed requests for follow‐up information. Results Twenty‐four dermatology‐related drugs from 21 companies accounted for 30 (15·2%) of the 198 letters sent by the FDA; of these, 18 letters cited advertisements or promotions of these medications for dermatology‐related uses. The most common violation cited overall was insufficient communication of risk (32·4% overall, 33·9% dermatology‐related). Most FDA letters cited physician‐targeted advertising (71·6% overall, 62·1% dermatology‐related). The number of dermatology‐related letters sent declined by 69·2% from 2000 (n = 13) to 2003 (n = 4), paralleling the 69·6% decline in the total number of letters sent (n = 79 in 2000, n = 24 in 2003). Compared with 2000, the FDA took longer to issue citation letters in 2003 for advertisements overall [hazard ratio (HR) 0·47, 95% confidence interval (CI) 0·27–0·72, P = 0·001], although this trend was not present for dermatology‐related advertisements (HR 1·12, 95% CI 0·39–3·29, P = 0·83). Eight of the 16 companies (50%) that received requests from the authors for information replied. Seven of the eight (87·5%) reported complying with FDA requests to discontinue the cited advertisements, while one (12·5%) reported disagreeing with the citation and successfully clarifying the issue with the FDA. Conclusions Dermatology‐related advertisements accounted for 15·2% of FDA citations of pharmaceutical advertisements between 2000 and 2003. Recent controversy over pharmaceutical advertising may lead to changes in pharmaceutical advertising practices and surveillance of pharmaceutical advertising in the U.S.A.
Intracardiac Phonocardiography in Man
Authors: DAVID H. LEWIS, GEORGE W. DEITZ, JOHN D. WALLACE, JAMES R. BROWN
Journal: Circulation (1957)

This paper describes a new method for the detection of sound from within the heart in man. It employs the technic and equipment of underwater listening developed and used by the Navy in antisubmarine warfare. Records are shown to illustrate the localization of heart sound production to an extent not possible by phonocardiograms from the chest wall. The technic has proved helpful in the evaluation of patients with valvular and congenital heart disease.
Referral pattern to the allergist for hay fever in a health‐care system with open access to specialists
Authors: C. Francillon, B. Burnand, Ph. Frei, J. Duc, J. P. Lantin, A. Leimgruber, A. Pécoud
Journal: Allergy (1995)

Little is known about referral patterns to the allergist for hay fever. In a system with open access to the specialist, we investigated the reasons for consulting an allergist in 126 patients who completed a questionnaire on their first visit. Both sexes were equally represented, the median age was 29 years, the duration of the disease and the duration of seasonal symptoms were 9 years and 10 weeks (median), respectively, and 54% of patients reported a history suggestive of asthma. The symptoms were highly variable; on average, 5.6 on a 10‐cm visual analog scale. Most of the patients (94%) had been treated for hay fever before. Only 30% were referred by another physician, the rest being self‐referred. The reasons for referral were investigated. The overall motivation to consult was related to symptom severity in 63% of the patients; 37% consulted for other reasons, including an expectation of greater “know‐how” on the part of the allergist concerning specific diagnosis, treatment, and advice or counseling. The stimulus triggering the consultation was clearly not related to symptoms or disease in 25% of the cases. We conclude from these data that many patients are clearly interested in benefiting from the professional skill of a fully trained allergist.
SPECIFICS FOR THE CURE OF INEBRIETY.
Authors: T. D CROTHERS
Journal: JAMA (1893)

When any great truth begins to receive public recognition it is always first welcomed by the credulous and visionary enthusiast, who surrounds it with the most extravagant expectations. This brings out the charlatan and empiric who studies to turn all such facts and conditions to his own personal profit. In this way the credulity of the one and the charlatanism of the other envelop the truth with a confusion and mystery that often conceal it for a long time. Only the student and the scientist realize that behind this glamor and illusion there is a uniform evolutionary movement along different lines from that suggested to the popular mind. The growth of the truth is through separate periods and stages. The first stage is that of indifference, neglect, and denial. Then follows the credulous period, in which the truth is partially recognized and accepted, with extravagant conceptions, associated with wild empirical
First-Trimester Circulating 25-Hydroxyvitamin D Levels and Development of Gestational Diabetes Mellitus
Authors: Mahlatse Makgoba, Scott M. Nelson, Makrina Savvidou, Claudia-Martina Messow, Kypros Nicolaides, Naveed Sattar
Journal: Diabetes Care (2011)

OBJECTIVE To investigate the association between first-trimester maternal serum levels of 25-hydroxyvitamin D (25-OH-D) as measured by liquid chromatography-tandem mass spectrometry and development of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We conducted a case-control study involving 248 women in the first-trimester of pregnancy, 90 of whom developed GDM and 158 remained normoglycemic. RESULTS Although booking 25-OH-D levels correlated negatively with 2-h glucose post-oral glucose tolerance test and positively with HDL cholesterol, as well as with ethnicity, obesity, and smoking (all P &amp;lt; 0.05), there were no statistically significant differences in baseline maternal mean 25-OH-D levels between those who subsequently developed GDM, 18.9 ng/mL (SD 10.7) and those who remained normoglycemic, 19.0 ng/mL (10.7) (P = 0.874), even after adjustment for possible confounders including sampling month (P = 0.784). CONCLUSIONS Our large and well-phenotyped prospective study did not find evidence of an association between first-trimester maternal levels of 25-OH-D and subsequent development of GDM.
Low levels of brain chemical drives mice to drink
Authors: M. Cockerill
Journal: BMJ (1998)

New animal research, published last week, may help to explain why some individuals crave alcohol more than others. Researchers at the University of Washington in Seattle have found a causative link between the level of a particular molecule in a mouse's brain and the drinking habits of the mouse.

The molecule involved--neuropeptide Y--has already attracted the attention of drug companies because of its suspected effects on appetite and anxiety. But these new findings will draw extra …
Antitumor effects of interleukin-7 and adoptive immunotherapy on human colon carcinoma xenografts.
Authors: W J Murphy, T C Back, K C Conlon, K L Komschlies, J R Ortaldo, T J Sayers, R H Wiltrout, D L Longo
Journal: Journal of Clinical Investigation (1993)

The antitumor properties of recombinant human IL-7 (rhIL-7) on a human tumor was evaluated by engrafting a human colon carcinoma into immunodeficient mice and then treating the mice with rhIL-7 and adoptively transferred human peripheral blood T cells. It was found that rhIL-7 alone had no effect on the survival of the tumor-bearing recipients. However, the combination of rhIL-7 and human T cells significantly promoted the survival of the recipients compared with mice receiving either treatment by itself. When the surviving mice were analyzed 6 mo later for the degree of human cell engraftment, the recipients receiving both rhIL-7 and human T cells had greater numbers of human CD8+ T cells in the spleens. However, the human T cells recovered from the surviving mice showed low lytic activity against the tumor in vitro. Supernatants from human T cells cultured with the tumor and rhIL-7 in vitro were found to inhibit tumor growth and were demonstrated to contain high levels of IFN-gamma. Antibodies to IFN-gamma neutralized the growth inhibition of the tumor both in vitro and in vivo demonstrating that the in vivo mechanism underlying the antitumor effects of this regimen was partly dependent on the production of IFN-gamma by the T cells and not their cytolytic capability. Interestingly, systemic administration of rhIFN-gamma to tumor-bearing mice yielded little antitumor effect suggesting that adoptive immunotherapy with rhIL-7 was superior possibly because of the continuous local release of the cytokines. Therefore, rhIL-7 may be of clinical use as an antineoplastic agent and the human/mouse model is a potentially important preclinical model for in vivo evaluation of the efficacy of this and other immunotherapies.
Staphylococcal α-Toxin Provokes Coronary Vasoconstriction and Loss in Myocardial Contractility in Perfused Rat Hearts
Authors: Ulf Sibelius, Ulrich Grandel, Michael Buerke, Doris Mueller, Ladislau Kiss, Hans-Joachim Kraemer, Ruediger Braun-Dullaeus, Werner Haberbosch, Werner Seeger, Friedrich Grimminger
Journal: Circulation (2000)

Background —Cardiac performance is severely depressed in septic shock. Endotoxin has been implicated as the causative agent in Gram-negative sepsis, but similar abnormalities are encountered in Gram-positive sepsis. We investigated the influence of the major exotoxin of Staphylococcus aureus, staphylococcal α-toxin, in isolated perfused rat hearts. Methods and Results —α-Toxin 0.25 to 1 μg/mL caused a dose-dependent increase in coronary perfusion pressure that more than doubled. In parallel, we noted a decrease in left ventricular developed pressure and the maximum rate of left ventricular pressure rise (dP/dt max ), dropping to a minimum of &lt;60% of control. These changes were accompanied by a liberation of thromboxane A 2 and prostacyclin into the coronary effluent. The release of creatine kinase, lactate dehydrogenase, potassium, and lactate did not surpass control heart values, and leukotrienes were also not detected. Indomethacin, acetylsalicylic acid, and the thromboxane receptor antagonist daltroban fully blocked the α-toxin–induced coronary vasoconstrictor response and the decrease in left ventricular developed pressure and dP/dt max , whereas the lipoxygenase inhibitor nordihydroguaiaretic acid, the platelet activating factor antagonist WEB 2086, and the α-adrenergic antagonist phentolamine were entirely ineffective. Inhibition of nitric oxide synthase even enhanced the α-toxin–induced increase in coronary perfusion pressure and the loss in myocardial performance. Conclusions —Purified staphylococcal α-toxin provokes coronary vasoconstriction and loss in myocardial contractility. The responses appear to be largely attributable to the generation of thromboxane and are even enhanced when the endogenous nitric oxide synthesis is blocked. Bacterial exotoxins, such as staphylococcal α-toxin, may thus be implicated in the loss of cardiac performance encountered in Gram-positive septic shock.
When Does the Incongruence Length Difference Test Fail?
Authors: Pierre Darlu, Guillaume Lecointre
Journal: Molecular Biology and Evolution (2002)

This paper examines the efficiency of the incongruence length difference test (ILD) proposed by Farris et al. (1994) for assessing the incongruence between sets of characters. DNA sequences were simulated under various evolutionary conditions: (1) following symmetric or asymmetric trees, (2) with various mutation rates, (3) with constant or variable evolutionary rates along the branches, and (4) with different among-site substitution rates. We first compared two sets of sequences generated along the same tree and under the same evolutionary conditions. The probability of a Type-I error (wrongly rejecting the true hypothesis of congruence) was substantially below the standard 5% level of significance given by the ILD test; this finding indicates that the choice of the 5% level is rather conservative in this case. We then compared two data sets, still generated along the same tree, but under different evolutionary conditions (constant vs. variable evolutionary rate, homogeneity vs. heterogeneity rate of substitution). Under these conditions, the probability of rejecting the true hypothesis of congruence was greater than the 5% given by the ILD test and increased with the number of sites and the degree to which the tree was asymmetric. Finally, the comparison of the two data sets, simulated under contrasting tree structures (symmetric vs. asymmetric) but under the same evolutionary conditions, led us to reject the hypothesis of congruence, albeit weakly, particularly when the number of informative sites was low and among-site substitution rate heterogeneous. We conclude that the ILD test has only limited power to detect incongruence caused by differences in the evolutionary conditions or in the tree topology, except when numerous characters are present and the substitution rate is homogeneous from site to site.
Pruning an Old Root: Premedical Science and Medical School
Authors: Edmund D. Pellegrino
Journal: JAMA (1980)

If there is anything harder than planting a new idea, it is uprooting an old one. Everyone shrinks from the periodic pruning that old ideas demand if they are to remain healthy. To evict an old idea is to precipitate a panic of identity. What, then, must be our response to the study by Dickman and associates elsewhere in this issue (p 2506)? They challenge one of the most cherished notions of medical educators—the indispensability of college preparation in science for perform. ance in medical school and, implicitly, for practice as well. Indeed, they show that nonscience majors do as well as, and in some instances better than, science majors during both the basic and clinical years and that they choose the same specialties later on. These conclusions will be heretical to many educators. The idea that medicine is synonymous with science is so inextricably insinuated into their minds that
Dietary supplement with vitamin C prevents nitrate tolerance.
Authors: E Bassenge, N Fink, M Skatchkov, B Fink
Journal: Journal of Clinical Investigation (1998)

Enhanced formation of superoxide radicals has been proposed to play a major role in the development of nitrate tolerance in humans. We tested the effects of vitamin C (Vit-C) supplementation on glyceroltrinitrate (GTN)-induced hemodynamic effects during 3-d nonintermittent transdermal administration of GTN (0.4 mg/h) in nine healthy subjects. Tolerance development was monitored by changes in arterial pressure, dicrotic digital pulse pressure, and heart rate. Studies with GTN, Vit-C, or GTN/Vit-C were successively carried out at random in three different series in the same subjects. GTN treatment caused an immediate rise in arterial conductivity (a/b ratio of dicrotic pulse), but within 2 d of initiating GTN, the a/b ratio progressively decreased and reached basal levels. In addition, there was a progressive loss of the orthostatic decrease in blood pressure. However, coadministration of Vit-C and GTN fully maintained the GTN-induced changes in the orthostatic blood pressure, and the rise of a/b ratio was augmented by 310% for the duration of the test period. Changes in vascular tolerance in GTN-treated subjects were paralleled by upregulation of the activity of isolated platelets, which was also reversed by Vit-C administration. These findings demonstrate that dietary supplementation with Vit-C eliminates vascular tolerance and concomitant upregulation of ex vivo-washed platelet activity during long-term nonintermittent administration of GTN in humans.
Studies of the secretion of corticotropin-releasing factor and arginine vasopressin into the hypophysial-portal circulation of the conscious sheep. II. The central noradrenergic and neuropeptide Y pathways cause immediate and prolonged hypothalamic-pituitary-adrenal activation. Potential involvement in the pseudo-Cushing's syndrome of endogenous depression and anorexia nervosa.
Authors: J P Liu, I J Clarke, J W Funder, D Engler
Journal: Journal of Clinical Investigation (1994)

Studies were performed to determine the effects of intracerebroventricular norepinephrine (NE) or neuropeptide Y (NPY) on the ovine hypothalamic-pituitary-adrenal (HPA) axis. NE (50 micrograms) increased mean hypophysial-portal corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) levels (1 h, 1.3- and 2.9-fold; 4 h, 2.2- and 5.7-fold) and caused acute and sustained increases in mean plasma ACTH and cortisol. NPY (50 microgram) also increased mean CRF and AVP levels (1 h, 1.4- and 4.2-fold; 4 h, 1.1- and 1.9-fold), increased pituitary-adrenal activity at 1 h, and caused ACTH hypersecretion at 4 h. When added to cultured ovine anterior pituitary cells, NPY neither increased basal ACTH release nor augmented CRF- or AVP-induced ACTH release. We conclude that: (a) activation of either the central noradrenergic or NPY pathways causes an acute and sustained stimulation of the ovine HPA axis; (b) such activation increases the AVP/CRF ratio, suggesting a dominant role for AVP in the ovine stress response; and (c) the central noradrenergic or NPY systems may cause sustained HPA activation by attenuating or disrupting the glucocorticoid negative feedback on those brain areas concerned with regulation of the HPA axis. The possible roles of the central noradrenergic and NPY systems in the etiology of the hypercortisolemia of endogenous depression and anorexia nervosa are discussed.