tbuckley/cabot-search huggingface dataset:
Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function.
Authors: R S Ahima, D Prabakaran, J S Flier
Journal: Journal of Clinical Investigation (1998)

Leptin is thought to regulate energy balance through effects on food intake and thermogenesis. In addition, leptin may serve as a mediator of the neuroendocrine response to starvation, and may modulate the stress response and the timing of puberty. A role for leptin in development is suggested by the presence of neuroendocrine and structural neuronal abnormalities in ob/ob mice with genetic leptin deficiency. Here, we sought to determine the ontogeny of leptin expression and its relationship to the developing neuroendocrine axis. Leptin increased 5-10-fold in female mice during the second postnatal week independent of fat mass, and declined after weaning. The rise in leptin preceded the establishment of adult levels of corticosterone, thyroxine, and estradiol. In contrast to adult mice, leptin was not acutely regulated by food deprivation during the early postnatal period. Circadian rhythms of leptin, corticosterone, and thyroxine were regulated by food intake in adult mice. When ad libitum feeding was restricted to the light cycle, peak corticosterone levels were shifted to the beginning of the light cycle and coincided with the nadir of leptin. The inverse relationship between leptin and corticosterone was maintained such that a rise in leptin after feeding was associated with a decline in corticosterone. To determine whether changes in corticosterone during food restriction are mediated by leptin, we compared the patterns of corticosterone levels among ob/ob, db/db, and lean mice. Despite their higher basal levels of corticosterone, leptin deficiency in ob/ ob mice did not prevent the nocturnal rise in corticosterone. In contrast, the nocturnal surge of corticosterone was blunted in db/db mice. Therefore, it is likely that factors in addition to leptin are involved in the regulation of the circadian rhythm of corticosterone. The temporal relationship between leptin and other hormones in neonatal and adult mice suggests that leptin is involved in the maturation and function of the neuroendocrine axis.
Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines
Authors: Zhong Xie, Deepak P. Srivastava, Huzefa Photowala, Li Kai, Michael E. Cahill, Kevin M. Woolfrey, Cassandra Y. Shum, D. James Surmeier, Peter Penzes
Journal: Neuron (2007)
Putting More Prevention Into Medical Training
Authors: Bonnie I. Chi-Lum
Journal: JAMA (1995)

MEDICAL STUDENTS and primary care residents may not be receiving enough training in preventing disease. Two sessions at the 12th annual preventive medicine meeting, Prevention 95, held in New Orleans, La, focused on the teaching of preventive medicine in medical school and primary care residencies. Although no one discounts the importance of prevention, instructors of medical students and primary care residents report experiencing difficulty in finding adequate time to teach the fundamentals of preventive medicine along with the rest of the required curriculum. According to conference speaker S. Edwards Dismuke, MD, chair of the Department of Preventive Medicine at University of Kansas School of Medicine, Kansas City, "Just because community health is mentioned, it does not necessarily mean that the teaching of preventive medicine occurs in medical schools." <h3>Course Content Analyzed</h3> In preparation for a curriculum renewal at his school, Dismuke and colleagues analyzed all required medical school courses taught
Timing May Not Be Everything
Authors: Leigh Neumayer
Journal: JAMA Surgery (2013)

Ideally, any metric (especially a publicly reported one) should be reliable and valid. If it is a process measure, there should be a long track record of reports confirming that adherence to the measure is associated with significantly better results than nonadherence to the measure. Using large, validated, reliable data sets and sophisticated statistical analyses, Hawn et al1 have furthered their work showing little relationship between adherence to the publicly reported “quality” measure of the right antibiotic within 60 minutes of incision and improved outcomes. In this analysis, multiple statistical methods were used to tease out any potential associations. While there was a small association between antibiotic timing and surgical site infection in unadjusted analyses, the difference disappeared when the models were adjusted for patient, procedure, and antibiotic variables. This article is not a call to abandon prophylactic antibiotics when indicated, as most studies have shown a significant reduction in postoperative surgical site infections with their use (when compared with no antibiotics). However, it does once again strongly suggest that the current publicly reported measures are not associated with improved outcomes. As surgeons, we should work with federal and local agencies to define metrics that are more robustly associated with better outcomes for our patients.
Role of SPECT/CT Compared With MRI in the Diagnosis and Management of Patients With Wrist Trauma Occult Fractures
Authors: Solène Querellou, Laetitia Arnaud, Thomas Williams, Sylvain Breton, Danielle Colin, Pierre-Yves Le Roux, Emmanuel Nowak, Alexandra Le Duc-Pennec, Ronan Bouttier, Ronan Abgral, Philippe Guillo, Dominique Le Nen, Pierre-Yves Salaun
Journal: Clinical Nuclear Medicine (2013)

The diagnosis of wrist fractures, especially scaphoid fractures, remains a challenge because of nonunion risk. Currently, new hybrid technologies are emerging such as SPECT/CT systems, which combine functional and anatomical data sets. So, we wanted to evaluate the utility of SPECT/CT in the management of occult carpal fractures.In this study, all patients addressed at the orthopedic department at Brest University Hospital for wrist pain after trauma with initial normal plain radiographs were prospectively included. Patients with normal radiographs but with signs strongly suggestive of clinical fracture underwent a bone SPECT/CT and an MRI of the wrist. Therapeutic management took into account the results of all modalities, and all patients were followed up for at least 6 months and reviewed by the same surgeon. SPECT/CT findings were compared with those of the other modalities and follow-up.From December 2009 to May 2011, 57 patients were enrolled. Fifty-seven SPECT/CT and 52 MRI scans were obtained. Twenty-eight patients had normal imaging results, whereas 29 patients presented bone bruise and/or fractures. Ten patients were concordant according to SPECT/CT and MRI; 2 patients presented fractures on SPECT/CT without MRI performed; 17 patients had partially discordant results. Only 1 patient presented a nonunion at the follow-up, whereas both investigations were positive.This study highlights the good performances of SPECT/CT, which allows the detection of most occult carpal fractures. When a carpal occult fracture is strongly suspected clinically, SPECT/CT might be proposed at first intention after normal radiographs.
<i>CTLA4</i>Variants, UV-Induced Tolerance, and Risk of Non-Melanoma Skin Cancer
Authors: Marleen M. Welsh, Katie M. Applebaum, Steven K. Spencer, Ann E. Perry, Margaret R. Karagas, Heather H. Nelson
Journal: Cancer Research (2009)

Although skin tumors are highly immunogenic, exposure to UV radiation is known to suppress immune responses via regulatory T cells. Specifically, the activity of cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is integral in regulating the development of UV-induced tolerance and, concomitantly, skin cancers. Due to the inverse relationship between tumor surveillance and autoimmunity, we hypothesize that the same genetic variant in the CTLA4 locus that increases risk for autoimmune diseases is associated with decreased risk of non-melanoma skin cancer (NMSC). We analyzed whether the polymorphism CT60 or haplotypes of CTLA4 influence odds of developing the major types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), in a population-based case-control study of Caucasians in New Hampshire (849 controls, 930 BCC, and 713 SCC). The CTLA4 CT60 GG genotype was associated with decreased odds for BCC and SCC, controlling for age, sex, lifetime number of severe sunburns, and skin type [BCC: odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.5-0.9; SCC: OR, 0.7; 95% CI, 0.5-1.0]. For BCC, this decrease was apparent largely among those with a higher lifetime number of severe sunburns (P(interaction) = 0.0074). There were significantly decreased odds of disease associated with two haplotypes, which possess the CT60 G allele. Additionally, lifetime number of severe sunburns modestly altered the effects of the CTLA4 haplotypes in BCC, and the association seemed driven by the CT60 single nucleotide polymorphism. In conclusion, genetic variation at the CTLA4 locus may be etiologically important in NMSC, the most prevalent malignancy in the United States.
Review: Hydroxyethyl starch increases mortality and acute kidney injury in critically ill patients
Authors: John Myburgh
Journal: Annals of Internal Medicine (2013)

Source Citation Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA. 2013;309:678-88. 23423413
DETECTION OF RECURRENT AND METASTATIC COLORECTAL CANCER WITH IMMUNE SCINTIGRAPHY-COMPARISON WITH CT
Authors: C. M. Schmidt, J. W. Ryan, M. D. Cooper, M. R. Weiser, G. E. Block
Journal: Clinical Nuclear Medicine (1992)

Schmidt, C. M. A.B.; Ryan, J. W. M.D.; Cooper, M. D. M.B. B.Ch.; Weiser, M. R. M.D.; Block, G. E. M.D. Author Information
Portable Anaesthetic Apparatus for Use in the Antarctic
Authors: J. F. Nunn
Journal: BMJ (1961)

The addition of small doses of spironolactone permitted sodium diuresis with limited potassium loss, presumably by blocking electrolyte exchange in the distal tubules.Corresponding doses of spironolactone, given alone, produced minimal sodium loss.Large doses of spironolactone were ineffective in three patients with cardiac failure, but produced marked sodium loss in one patient with cardiac failure and in two patients with cirrhosis and ascites.Aldosterone alone may account primarily for the sodium retention in patients with cirrhosis and estab- lished ascites, and may be the dominant factor also in some cases of congestive heart failure.In most patients with congestive failure, changes of renal haemodynamics may be responsible for sodium retention.Our results suggest that these haemodynamic changes were not induced by an excess of circulating catechol amines.Patients who responded to prednisolone showed a decrease of urinary aldosterone followed by a sodium diuresis.
Inhibition of prolyl 4‐hydroxylase prevents left ventricular remodelling in rats with thoracic aortic banding
Authors: Jens Fielitz, Sebastian Philipp, Lars Roman Herda, Evelyn Schuch, Bernhard Pilz, Carola Schubert, Volkmar Günzler, Roland Willenbrock, Vera Regitz‐Zagrosek
Journal: European Journal of Heart Failure (2006)
The tragedy of errors
Authors: H. Karcher
Journal: BMJ (1996)

In a documentary forming part of its series Gesundheitsmagazin Praxis (Health Magazine Medical Practice) German ZDF TV traced the history of bovine spongiform encephalopathy from 1985, when the first three cases were detected in Kent, to the present, when BSE has definitely become an affliction of the grey matter of European Union politicians.

To establish its thesis that the BSE story was a tragedy of errors from its very beginning and that its outcome is all but certain, the programme interviewed several British, Swiss, and German scientists engaged in studies of spongiform encephalopathies. It also included shots of patients with Creutzfeldt-Jakob disease (CJD)—pictures familiar to British television viewers, …
SURVEY OF THE DISTRIBUTION OF STEROID DEHYDROGENASES IN SEBACEOUS GLANDS OF HUMAN SKIN
Authors: K. C. CALMAN, A. V. MUIR, J. A. MILNE, H. YOUNG
Journal: British Journal of Dermatology (1970)

SUMMARY.— This paper reports the results of a survey carried out using human skin to investigate the distribution of 3β-hydroxysteroid dehydrogenase, 16β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase over the skin surface. In common with other work, sebaceous glands were found in greater numbers in the face, scalp and thoracic region. The enzymes occur at all ages, although there was an apparent increase in activity in the 20–30 age group. The enzymes occur in both sexes, although there is a difference with the 17β-HSD, the enzyme occurring more frequently in male skin biopsies. The enzymes occur in all surface areas of the human body and differences from a previous survey are noted. In particular the enzymes are found in the scalp, the perineal region, the arms, legs and abdomen, as well as the face and chest. The difference between the localization of the 3β-HSD and 17β-HSD within sebaceous glands is described.
EPILEPSY—ITS PSYCHOPATHOLOGY, AND MEDICOLEGAL RELATIONS.
Authors: H. A. TOMLINSON
Journal: JAMA (1903)

Epilepsy, independent of any gross disease or lesion of the brain, to which it is a sequence, has no distinctive morbid histology, so far as known. Gowers<sup>1</sup>says : "In considering, then, the pathology of epilepsy, we must seek other evidence as to its nature than that which is afforded by the negative anatomy of the idiopathic disease, and must draw our inferences from the morbid changes in organic disease attended by convulsion, from the results of experiment, and from the facts ascertained by the clinical study of the disease." It is seldom that an opportunity is offered for the study of the histology of the brain in idiopathic epilepsy before the development of those changes which are common to all forms of degeneration, and which obscure everything else. The occasional epileptic who dies of some intercurrent disease, during the earlier stages of his epilepsy, does not present any brain
Effects of interleukin‐4 and interferon‐γ on the secretion of IgG4 from human peripheral blood mononuclear cells
Authors: M. Sutherland, K Blaser, J. Pène
Journal: Allergy (1993)

Whereas IgE antibodies are linked with allergy, IgG4 antibodies may reflect the state of immunity and protection against a particular antigen. It has been shown that interleukin (IL)‐4 is required for induction of IgE synthesis. In order to elucidate the role of IL‐4 in the production of IgG4 and to compare IgG4 and IgE regulatory processes, we quantified these immunoglobulin isotypes after in vitro culture of peripheral blood mononuclear cells (PBMC) in the presence of IL‐4. The production of IgG4 was increased by IL‐4 under the same conditions which are optimal for IgE production but not among PBMC from all donors, depending on the magnitude of spontaneous IgG4 secretion: IL‐4 was effective only when the spontaneous secretion of IgG4 was &lt; 7% of the total IgG secretion; it had no effect when spontaneous IgG4 production was &gt;7% of total IgG. The IL‐4‐induced IgE response was consistently obtained when IgG4 was &lt; 7% of total IgG but was markedly diminished or absent when IgG4 was &gt; 7% of total IgG. If Staphylococcus aureus strain Cowan 1 (SAC) was present during the 48‐h preincubation step, spontaneous IgG4 production was increased, but the stimulatory effect of this mitogen on immunoglobulin production, including IgG4, was markedly blocked by the addition of IL‐4. In contrast, IL‐4‐induced IgE synthesis was strongly blocked by the presence of SAC. Finally, secretion of IgG4 (spontaneous and IL‐4‐induced) was suppressed among cells from most donors by interferon‐γ (IFN‐γ). These results suggest that IL‐4 has opposite effects on in vitro IgG4 production and that the in vitro synthesis of both IgG4 and IgE appears to be regulated similarly by IL‐4 and IFN‐γ, whereas additional signals promote the production of one isotype in preference to the other. It is possible that activated B cells respond to IL‐4 less well than do nonactivated cells.
Universal HIV screening of pregnant women in England: cost effectiveness analysis
Authors: M J Postma, E J Beck, S Mandalia, L Sherr, M D S Walters, H Houweling, J C Jager
Journal: BMJ (1999)

To estimate the cost effectiveness of universal, voluntary HIV screening of pregnant women in England.Cost effectiveness analysis. Cost estimates of caring for HIV positive children were based on the stage of HIV infection and calculated using data obtained from a London hospital between 1986 and 1996. These were combined with estimates of the health benefits and costs of antenatal screening so that the cost effectiveness of universal, voluntary antenatal screening for HIV infection in England could be estimated.Lifetime, direct costs of medical care of childhood HIV infection; life years gained as a result of the screening programme; net cost per life year gained for different pretest counselling costs; and different prevalence rates of pregnant women who were unaware that they were HIV positive.Estimated direct lifetime medical and social care costs of childhood HIV infection were pound178 300 using a 5% discount rate for time preference (1995-6 prices). In high prevalence areas screening pregnant women for HIV is estimated to be a cost effective intervention with a net cost of less than pound4000 for each life year gained. For areas with comparatively low prevalence rates, cost effectiveness could be less than pound20 000 per life year gained, depending on the number of pregnant women who are unaware that they are infected and local screening costs.Our results confirm recent recommendations that universal, voluntary antenatal HIV screening should be implemented in the London area. Serious consideration of the policy should be given for other areas in England depending on local prevalence and screening costs.
Pyridoxal–5′–Phosphate and Alkaline Phosphatase
Authors: Lawrence Lumeng
Journal: Hepatology (1986)

Markedly increased circulating concentrations of pyridoxal–5′–phosphate (PLP) were found in each of 14 patients representing all clinical forms of hypophosphatasia, an inborn error characterized by deficient activity of the tissue–nonspecific (bone/liver/kidney) isoenzyme of alkaline phosphatase (AP). The mean PLP concentration in plasma was 1,174 n M (range, 214 to 3,839 n M ) in the patients and 57 ± 26 n M (mean ± S.D.) in 38 control subjects. In four affected children, urinary excretion of the PLP degradation product, 4–pyridoxic acid, was unremarkable during consumption of normal quantities of dietary vitamin B 6 . Our findings identify increased circulating PLP concentration as a marker for hypophosphatasia and provide further evidence that tissue–nonspecific AP acts in vitamin B 6 metabolism. Tissue–nonspecific AP appears to function as an ectoenzyme to regulate extracellular but not intracellular levels of PLP substrate. Performing assays of circulating PLP concentrations alone to assess vitamin B 6 nutrition may be misleading in disorders associated with altered AP activity.
THIRD INTERNATIONAL CONGRESS ON THE HISTORY OF MEDICINE
Authors: E. B. Krumbhaar
Journal: JAMA (1922)

<h3>To the Editor:</h3> —The third international congress on the history of medicine was held at the Royal Society of Medicine in London, July 17 to 22, under the honorary presidency of Sir Norman Moore and the acting presidency of Dr. Charles Singer, two of the leading medical historians of the English-speaking world. Distinguished representatives from every country of Europe, except Germany, Austria, Russia and one or two of the Balkan states, attended the scientific meetings. At the Royal College of Physicians, its president, Sir Humphry Rolleston, gave a most entertaining discourse on the history of the institution, and its splendid historical library and portrait gallery of distinguished members was exhibited. The scientific program was chiefly devoted to medieval epidemics and to the history of anatomy. In the former topic, important papers were given by Tricot-Royer, a former president of the association, Professor Simpson, Wickersheimer, Mrs. Singer and others. The subjects
THE STANDARDIZATION OF PARATHYROID ACTIVITY
Authors: ADOLPH M. HANSON
Journal: JAMA (1928)

The method used in the extraction of the parathyroid hormone is a vigorous treatment involving boiling in a solution of a strong mineral acid in order to liberate the activity, possibly as a result of some hydrolytic action. 1 The methods that yield the active principles from other endocrine glands do not yield the activity of the parathyroid, whereas the method that has proved successful for the parathyroid is known to decompose most of the other known active endocrine principles.  Two methods are available for the standardization of active parathyroid extracts on dogs. The method proposed by Collip 2 is based on the production of hypercalcemia, an abnormal condition, in normal dogs. The method that I find most satisfactory is based on my early work on dogs in which operation had been performed. 3 Following the operation of parathyroidectomy there is a rapid fall in the blood serum calcium, which
The effects of arterial flow on platelet activation, thrombus growth, and stabilization
Authors: Judith M.E.M. Cosemans, Anne Angelillo-Scherrer, Nadine J.A. Mattheij, Johan W.M. Heemskerk
Journal: Cardiovascular Research (2013)

Injury of an arterial vessel wall acutely triggers a multifaceted process of thrombus formation, which is dictated by the high-shear flow conditions in the artery. In this overview, we describe how the classical concept of arterial thrombus formation and vascular occlusion, driven by platelet activation and fibrin formation, can be extended and fine-tuned. This has become possible because of recent insight into the mechanisms of: (i) platelet-vessel wall and platelet–platelet communication, (ii) autocrine platelet activation, and (iii) platelet–coagulation interactions, in relation to blood flow dynamics. We list over 40 studies with genetically modified mice showing a role of platelet and plasma proteins in the control of thrombus stability after vascular injury. These include multiple platelet adhesive receptors and other junctional molecules, components of the ADP receptor signalling cascade to integrin activation, proteins controlling platelet shape, and autocrine activation processes, as well as multiple plasma proteins binding to platelets and proteins of the intrinsic coagulation cascade. Regulatory roles herein of the endothelium and other blood cells are recapitulated as well. Patient studies support the contribution of platelet- and coagulation activation in the regulation of thrombus stability. Analysis of the factors determining flow-dependent thrombus stabilization and embolus formation in mice will help to understand the regulation of this process in human arterial disease.