tbuckley/cabot-search huggingface dataset:
Synaptic plasticity is complex; neurobiologists are not
Authors: Richard M. Vickery
Journal: Behavioral and Brain Sciences (1999)

The complexity of modern neurobiology in even a comparatively restricted area such as use-dependent synaptic plasticity is underestimated by the authors. This leads them to reject a neurobiological model of learning as conceptually parasitic on the psychology of conditioning, on the basis of objections that are shown to be unsustainable. An argument is also advanced that neurobiologists hold an intermediate version of the neuron doctrine rather than a conflated one. In this version, neurobiologists believe that psychology will eventually be underpinned by neurobiology but are agnostic about the extent of upheaval that this will produce in psychology.
Hypokalemic nephropathy in the rat. Role of ammonia in chronic tubular injury.
Authors: J P Tolins, M K Hostetter, T H Hostetter
Journal: Journal of Clinical Investigation (1987)

Chronic potassium deficiency results in progressive tubulointerstitial injury, associated with augmented renal ammoniagenesis. We investigated the role of elevated renal ammonia levels and the interaction of ammonia with the complement system in this injury. Potassium deficiency was induced in rats by feeding a low potassium diet. Experimental animals received 150 mM NaHCO3 or equimolar NaCl, as drinking water. After 3 wk, NaHCO3 supplemented rats demonstrated decreased ammonia production, less renal hypertrophy, less histologic evidence of injury, and less proteinuria. In in vitro studies on normal cortical tubular fragments, the addition of ammonia to serum in concentrations comparable to renal cortical levels in potassium-deficient animals significantly increased tubular deposition of C3 as quantitated by a radiolabeled antibody binding technique. Thus, alkali supplementation reduced chronic tubulointerstitial disease in a rat model of hypokalemic nephropathy. We propose that increased cortical ammonia levels contribute to hypokalemic nephropathy through ammonia-mediated activation of the alternative complement pathway.
Detoxification From Methadone Maintenance
Authors: Paul Cushman
Journal: JAMA (1976)

To the Editor.—  The recent article entitled Successful Detoxification From Methadone Maintenance by Riordan et al (235:2604, 1976) may leave the reader with some erroneous impressions. That some patients can be successfully detoxified after a period of time in methadone treatment has been well established (226:747, 1973). 1,2 That some of these detoxified patients can function well (ie, in a stable, narcotic-free state) has also been documented. Lest the reader get the impression that this is a common result of methadone maintenance treatment, it is important to examine the frequency with which this outcome is achieved in relation to the total number of patients entering treatment.  The Yale group classified 26 patients as drug-free and doing well out of a total population that clearly exceeded 242 (the subgroup listed as having been in treatment for at least 90 days) or 10.7% of the subtotal. This figure is in close agreement
Health bill will oblige staff to take account of NHS constitution
Authors: C. Dyer
Journal: BMJ (2008)

Bills to reinforce a new NHS constitution setting out the rights of patients and staff, to crack down on the irresponsible use of alcohol, and to reform the system of death certification form part of a thin legislative programme unveiled in the Queen’s speech.

A health bill will be published in the new year along with the final form of the NHS constitution, which is still in draft. The bill will create a duty to take account of the constitution, which will “set out the core principles of the service and the rights and responsibilities of patients and staff.”

Providers will be required to publish …
Why industry should register and disclose results of clinical studies—perspective of a recovering academic
Authors: Jesse A Berlin
Journal: BMJ (2005)

Although it's not typical, in a scholarly publication such as the BMJ , to add a personal perspective to a commentary, I believe that in this situation my background is relevant to the discussion. My doctoral dissertation, written in 1988, dealt with the topic of publication bias, which was well described in the Ottawa statement appearing in this issue.1 Since then, I've contributed to several studies of factors affecting publication, including an early empirical demonstration of publication bias.2

About six months ago, I moved from a university, where I had spent 15 years, to a position in a large pharmaceutical research and development group. Registration and disclosure of the results of clinical studies have, not surprisingly, been topics of numerous conversations where I work.

At …
RANTES in human allergen-induced rhinitis: cellular source and relation to tissue eosinophilia.
Authors: K Rajakulasingam, Q Hamid, F O'Brien, E Shotman, P J Jose, T J Williams, M Jacobson, J Barkans, S R Durham
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Human allergen-induced rhinitis is associated with recruitment and activation of CD4+ T lymphocytes and eosinophils. RANTES is a novel CC chemokine that is a potent chemoattractant for both memory T cells and eosinophils. We therefore investigated RANTES in the nasal mucosa after local allergen provocation. Nasal lavage was performed, and biopsies from the inferior nasal turbinate were taken from 14 atopic, seasonal rhinitic patients and seven normal subjects for as long as 6 h after challenge with a grass pollen extract and after a control (allergen diluent) challenge. In five of seven rhinitics tested, radioimmunoassay of nasal fluid demonstrated increases in RANTES at 2 to 4 h (p < 0.05). Nasal allergen challenge provoked significant increases in RANTES mRNA (p = 0.0015) and protein (p = 0.01) containing cells in the nasal submucosa at 6 h. No changes were observed in normal subjects. Increases in RANTES mRNA+ cells correlated with the associated increases in eosinophils (r = 0.78, p = 0.001). Colocalization studies revealed that the majority of RANTES mRNA+ cells were macrophages (51%) followed by eosinophils (15%), T lymphocytes (11%), and mast cells (3%). Our results demonstrate that allergen-induced rhinitis is associated with release of RANTES and upregulation of RANTES mRNA and protein+ cells, predominantly macrophages, in the nasal mucosa. RANTES synthesis, release, or receptor antagonism may represent a potential target for antiallergy treatment.
Government Studies of Physician-Owned Laboratories-Reply
Authors: Brian Biles
Journal: JAMA (1990)

<h3>In Reply.—</h3> The testimony cited in our article summarized the findings of research studies undertaken by the Inspector General and General Accounting Office in 1988 and 1989 and was presented before the Subcommittee on Health of the Committee on Ways and Means of the US House of Representatives on June 1, 1989.<sup>1</sup>Both studies involved primary data collection and analysis of Medicare claims data. In the Inspector General's study, two surveys of health care providers were conducted to determine the prevalence of physician financial arrangements with other health entities and the nature of such arrangements. One survey was of physicians and the other of independent clinical laboratories, physiological laboratories, and suppliers of durable medical equipment. Medicare claims information from the Health Care Financing Administration was used to assess utilization patterns for physicianowners identified in the survey of health care businesses.<sup>2</sup> The General Accounting Office study involved a survey
Cubilin- and megalin-mediated uptake of albumin in cultured proximal tubule cells of opossum kidney
Authors: Xiao Yue Zhai, Rikke Nielsen, Henrik Birn, Karina Drumm, Sigrid Mildenberger, Ruth Freudinger, Søren K. Moestrup, Pierre J. Verroust, Erik I. Christensen, Michael Gekle
Journal: Kidney International (2000)
Alleviation of systemic manifestations of multicentric Castleman's disease by thalidomide
Authors: Fa‐Chyi Lee, Shakil H. Merchant
Journal: American Journal of Hematology (2003)

Abstract Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology. Although HHV‐8 (human herpesvirus type 8) has been suggested as a possible etiologic agent in a subpopulation of cases, appropriate treatment of the HHV‐8 infection has not produced regression of the disease. Additionally, other treatment modalities, including steroids and various regimens of chemotherapy, do not consistently provide good control of the disease. Clinical signs and symptoms of the disease are primarily mediated by cytokines, especially interleukin‐6 (IL‐6). We report a case of multicentric Castleman's disease that responded dramatically to single agent thalidomide. A powerful cytokine disruptor, thalidomide may have good therapeutic efficacy in treating MCD and related cytokine‐mediated disorders. Am. J. Hematol. 73:48–53, 2003. © 2003 Wiley‐Liss, Inc.
Exposure of Rats to Environmental Tobacco Smoke during Cerebellar Development Alters Behavior and Perturbs Mitochondrial Energetics
Authors: Brian F. Fuller, Diego F. Cortes, Miranda K. Landis, Hiyab Yohannes, Hailey E. Griffin, Jillian E. Stafflinger, M. Scott Bowers, Mark H. Lewis, Michael A. Fox, Andrew K. Ottens
Journal: Environmental Health Perspectives (2012)

Environmental tobacco smoke (ETS) exposure is linked to developmental deficits and disorders with known cerebellar involvement. However, direct biological effects and underlying neurochemical mechanisms remain unclear.We sought to identify and evaluate underlying neurochemical change in the rat cerebellum with ETS exposure during critical period development.We exposed rats to daily ETS (300, 100, and 0 µg/m3 total suspended particulate) from postnatal day 8 (PD8) to PD23 and then assayed the response at the behavioral, neuroproteomic, and cellular levels.Postnatal ETS exposure induced heightened locomotor response in a novel environment on par initially with amphetamine stimulation. The cerebellar mitochondrial subproteome was significantly perturbed in the ETS-exposed rats. Findings revealed a dose-dependent up-regulation of aerobic processes through the modification and increased translocation of Hk1 to the mitochondrion with corresponding heightened ATP synthase expression. ETS exposure also induced a dose-dependent increase in total Dnm1l mitochondrial fission factor; although more active membrane-bound Dnm1l was found at the lower dose. Dnm1l activation was associated with greater mitochondrial staining, particularly in the molecular layer, which was independent of stress-induced Bcl-2 family dynamics. Further, electron microscopy associated Dnm1l-mediated mitochondrial fission with increased biogenesis, rather than fragmentation.The critical postnatal period of cerebellar development is vulnerable to the effects of ETS exposure, resulting in altered behavior. The biological effect of ETS is underlain in part by a Dnm1l-mediated mitochondrial energetic response at a time of normally tight control. These findings represent a novel mechanism by which environmental exposure can impact neurodevelopment and function.
Variability of colonic function in healthy subjects.
Authors: J B Wyman, K W Heaton, A P Manning, A C Wicks
Journal: Gut (1978)

Twenty healthy subjects eating normal diets made repeated five-day stool collections, the 10 females making their collections in four to six successive weeks. In most subjects there were striking variations in transit time, measured by Hinton's method. The variability of average faecal wet and dry weight, faecal volume, and the frequency of defaecation was equally great, suggesting that the transit time variations were genuine. The size of individual stools varied even more, often tenfold or more. Faecal water content was relatively constant. There were no significant differences between males and females, and in the females there were no obvious changes related to the phases of the menstrual cycle. The normal variability of colonic function should be taken into account in planning experiments and in interpreting existing data.
Care of the Arthritic Hand
Authors: Kingsbury G. Heiple
Journal: JAMA (1983)

This fourth edition of Flatt's Care of the Arthritic Hand remains the most concise and useful guide to the management of arthritic problems in the wrist and hand available for the last 20 years. It still is a rather astonishing tour de force of exposition and technique for such a small and readable volume. The first three chapters covering general principles of care, kinesiology, and nonoperative treatment are well worth perusal by any physician, family practitioner, internist, or rheumatologist managing rheumatoid arthritis, and there are probably few of them who are not involved in rheumatoid care, considering the ubiquity of this disease in America today.  The rest of the volume deals with general consideration of soft-tissue management in arthritis and operative management of soft-tissue problems, conservative and operative management of joint disease in the fingers and the thumb, and the pathomechanics of ulnar drift. This last chapter contains a great
Points: Fatal overdose of phenylpropanoline
Authors: J. Kinsella
Journal: BMJ (1984)

September, p 591) confirmed brain death in the usual way before resuscitation was finally abandoned after four hours.The usual tests of brain death are tests of brain stem function.These tests should be preceded by essential preconditions and necessary exclusions.An essential precondition is irremediable structural brain damage.A necessary exclusion is acute intoxication.'In their patient neither of these criteria was satisfied.Their patient had not responded to intensive resuscitation and had remained hypotensive and anuric.As there had been no recovery and no prospect of recovery it may have been reasonable to discontinue resuscita- tion.It is not possible to use tests of brain death to support this decision as it was impossible to meet the currently accepted preconditions and exclusions which are required to give the tests validity.
Pacemaker current, membrane resistance, and K+ in sheep cardiac Purkinje fibres
Authors: M. Vassalle, H. Kotake, C.-I Lin
Journal: Cardiovascular Research (1992)

Objective: The pacemaker current in cardiac Purkinje fibres has been attributed to either a decrease in potassium conductance or an increase in a non-specific (Na-K) conductance. The former mechanism would be associated with an increase in membrane resistance (Rm) and the latter with a decrease in Rm. The aim of this study was to obtain evidence in support of one or other mechanism by measuring Rm during the pacemaker current (Idd) under conditions where there is a small or no extracellular potassium depletion. Methods: Hearts were obtained from anaesthetised sheep and thin strands of ventricular Purkinje fibres were shortened to ≤ 1.6 mm. Purkinje fibres were voltage clamped to potentials positive and negative to the potassium equilibrium potential (Ek) using a two microelectrode technique. Small current pulses were superimposed on Idd to measure Rm changes. Procedures were used that decrease either the background potassium current Iki or Idd in order to dissect changes in Rm due to K depletion from those due to Idd. Results: Rm increased during Idd, whether the pacemaker current increased or decreased as a function of time. Increasing [K]u from 2.7 to 5.4 mmol·litre−1 decreased Rm and during hyperpolarising steps increased the instantaneous current but did not change Idd amplitude. In 2.7 mmol·litre−1 K, caesium (Cs, 2 mmol·litre−1) increased the holding current (Ih), had little effect on the instantaneous current, and eliminated Idd and associated Rm changes. In 5.4 and 10.8 mmol·litre−1 K, Cs increased Ih and decreased Idd amplitude and in 10.8 mmol·litre−1 K Cs decreased the instantaneous current on hyperpolarisation. If the current was reversed, Cs decreased but did not abolish it. In normal [K]0, barium (Ba, 0.05-0.5 mmol·litre−1) increased Ih and Rm, reduced the instantaneous current but did not increase Idd amplitude. In high [K]o, Ba instead increased the amplitude and rate of development of Idd. When Cs was applied in the presence of Ba, Idd was reduced or eliminated depending on [K]0. Conclusions: The changes in membrane resistance during the pacemaker current cannot be accounted for by K depletion and suggest that in the range of diastolic depolarisation the pacemaker current results predominantly from a time dependent decrease in K conductance.
ON BRIGHT'S DISEASE
Authors: Robt. C. R. Jordan
Journal: BMJ (1855)

IqoY. 2 iMb._nw, when th di"&e again showed itelf, and he w Msd, Oot.9th.H. wa put at once on the treat- t.-ut mnid, d up to the presnt date he is > Uyv r diseass of the skin, this appeared at the sung of the year, and agin at the fall.Is the dis- ae one of the secondary or tertiary sequel.s of syphilis, or is it an example of hereditary syphilis, or is it " scro- fulSs"?Many instances of secondary syphilitic ulcera- tim about the ala of the nose and lips have fallen under my notice, which have immediately yielded to the proto- iib of mecury combined with quinine and opium.I partularly bear in mind one case of a female patient at the Western Dispensary, Westminster, who, I see, by reference to my ae-book, came under my care for the first time in the year 148.She suffered from ulceration on the side of * The only ase thbat 1 am aware of is that mentioned by Dr. Bird, in which a man was poisoned by the vapours arising from the burning of a mixtwre of coal ashes with chalk. (Guy's Hospital Reports, No. viii
TCT-743 Stratification of survival after transcatheter aortic valve replacement based on vascular complication by VARC-1 or VARC-2 criteria
Authors: Kazuaki Okuyama, Hasan Jilaihawi, Mohammad Kashif, Omar R. Sadruddin, Jigar Patel, Vikas Soni, Heera Pokhrel, Tarun Chakravarty, Mamoo Nakamura, Raj Makkar
Journal: Journal of the American College of Cardiology (2013)
Effect of physiotherapy attendance on outcome after anterior cruciate ligament reconstruction: a pilot study
Authors: J A Feller, K E Webster, N F Taylor, R Payne, T Pizzari
Journal: British Journal of Sports Medicine (2004)

In many centres patients are routinely referred for physiotherapy after anterior cruciate ligament (ACL) reconstruction. However, to date the role and amount of supervised physiotherapy required has not been clearly established.To establish whether there was any difference in outcome between a group of patients who attended physiotherapy regularly after ACL reconstruction and a group who attended only infrequently.Ten patients who had attended physiotherapy infrequently (mean 1.9 visits) during the first six months after ACL reconstructive surgery were matched for age, sex, graft type, and activity level and occupation before injury with 10 patients who had attended physiotherapy regularly (mean 26.5 visits). Outcome was assessed at 12 months using the Cincinnati knee rating system and the IKDC form.Compared with the regular physiotherapy group, patients in the minimal physiotherapy group had fewer symptoms (mean Cincinnati symptom score 46.2 v 43.4, p = 0.045). There was also a trend towards higher overall Cincinnati knee scores in the minimal physiotherapy group (mean 93.7 v 87.3, p = 0.06) but no difference in IKDC ratings.These preliminary results indicate that some patients who choose to attend physiotherapy on a very limited basis after ACL reconstruction can achieve satisfactory, if not better, outcomes than patients who attend physiotherapy regularly.
Gas-generating polymeric microspheres for long-term and continuous in vivo ultrasound imaging
Authors: Hyun Su Min, Eunah Kang, Heebeom Koo, Jaeyoung Lee, Kwangmeyung Kim, Rang-Woon Park, In-San Kim, Youngseok Choi, Ick Chan Kwon, Moonhee Han
Journal: Biomaterials (2011)
Does zygosity influence the metabolic profile of twins? A population based cross sectional study
Authors: P. Poulsen, A. Vaag, H. Beck-Nielsen
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To study the influence of zygosity on the metabolic variables involved in the pathophysiology of type 2 diabetes. <b>Design:</b> Population based cross sectional study. <b>Setting:</b> Odense University Hospital, Denmark <b>Participants:</b> 125 monozygotic twin pairs and 178 dizygotic twin pairs of the same sex born between 1921 and 1940. <b>Main outcome measures:</b> Clinical characteristics of monozygotic and dizygotic twins with or without a family history of type 2 diabetes <b>Results:</b> Absolute prevalences of type 2 diabetes and impaired glucose tolerance according to the World Health Organisation criteria were similar in both the monozygotic and the dizygotic twins as were measurements of height, weight, body mass index, waist to hip ratio, and fasting plasma glucose and insulin concentrations. During the oral glucose tolerance test, monozygotic twins had a higher incremental plasma insulin area under the curve than dizygotic twins (10.05 (SD 0.68) <i>v</i> 9.89 (0.72) pmol/l×minutes, P&lt;0.01) indicating insulin resistance. In twins with normal glucose tolerance and without first degree relatives or co-twins with type 2 diabetes or impaired glucose tolerance, both the glucose and insulin areas under the curve were higher among monozygotic twins (glucose 214.4 (88.3)<i>v</i> 189.8 (78.4) mmol/l×minutes, P&lt;0.05; insulin 20 040(14 865-32 554) <i>v</i> 17 625 (12 330-23 640) pmol/l×minutes, P=0.08). <b>Conclusion:</b> Zygosity influences both plasma glucose and plasma insulin concentrations during an oral glucose tolerance test. This supports an intrauterine influence on glucose homeostasis and perhaps on insulin resistance in humans. <h3>Key messages</h3> Zygosity affects glucose homeostasis and insulin resistance but has no influence on body weight and fat distribution Differences in glucose metabolism between monozygotic and dizygotic twins are independent of a family history of type 2 diabetes The validity of causal conclusions from classic twin studies may be questioned
The Role of Neutrophil Elastase in Chronic Inflammation
Authors: Gerd Döring
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.