tbuckley/cabot-search huggingface dataset:
STUDIES ON INFLAMMATION
Authors: Valy Menkin
Journal: The Journal of Experimental Medicine (1936)

Various types of inflammatory exudates have been obtained either by the introduction into normal tissues of a chemical irritant, or by a burn, or by bacteria in either dogs or rabbits. A study has also been made on an exudate of human origin. These exudates have all been found to contain a factor which induces prompt increase in the permeability of normal skin capillaries, demonstrable by the almost immediate accumulation from the circulation of trypan blue into areas of skin injected with the cell-free exudate. The active factor may be carried down with the precipitate resulting from the interaction of the exudate with either saturated ammonium sulfate or 20 per cent sodium sulfate. The active factor passes through a dialyzing membrane. It can be recovered from the dialysate as a protein-free crystalline material. The active factor manifests no property in common with histamine or presumably with the hypothetical H substance assumed to be closed related to histamine. This is indicated by the following considerations: (a) difference between the tissue staining pattern of the exudate or of its active fraction and that of histamine; (b) opposite effects by histamine and the active factor found in exudates on the tonicity of the isolated strip of guinea pig intestine. The observations presented in this report do not substantiate Lewis' hypothesis of histamine or of its closely related H substance as the primary cause of increased capillary permeability in inflammation. The present studies are being continued in an endeavor to free of its impurities and to identify the active crystalline-like material isolated from an inflammatory exudate. The details of this investigation will form the subject of a separate future communication.
Effects of temperature on chronotropic and inotropic responses of isolated canine atria to five sympathomimetic amines
Authors: Y. FURUKAWA, M. KOBAYASHI, S. CHIBA
Journal: Cardiovascular Research (1979)

The effects of temperature on both atrial pacemaker and contractile activities were investigated, using the isolated, blood-perfused canine atrial preparation with heparinised arterial blood conducted from the support dog. Lowering the temperature from 37° to 27°C consistently caused a linear decrease in sinus rate (107 to 51 beats·min−1) and progressive increase in the developed tension (100 to 175%). However the maximum rate of developed tension was hardly altered, since the duration of shortening and relaxation was longer than that in normothermia. The positive chronotropic and inotropic effects of dopamine, l-noradrenaline, l-adrenaline, l-isoprenaline and tyramine were compared at 37°, 32°, and 29°C. The order of potencies of chronotropic and inotropic effects of each amine was l-isoprenaline > l-noradrenaline ≳ l-adrenaline > dopamine > tyramine at each examined temperature. Percentage changes in positive inotropic effects at sub-maximal doses were slightly but not significantly depressed at a low temperature, but the positive chronotropic effects were markedly suppressed both in absolute and percentage values at a low temperature. The threshold doses for inducing positive inotropic effects of these amines were not very different when the temperature was lowered. However the threshold doses for inducing positive chronotropic effects were increased when the temperature was lowered. From these results, differential chronotropic and inotropic actions observed by sympathomimetic amines at different temperatures lead to the speculation that β1-type cardiac adrenergic receptors may not be homogenous.
Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential
Authors: Haiming Xu, Satyam Eleswarapu, Hartmut Geiger, Kathleen Szczur, Deidre Daria, Yi Zheng, Jeffrey Settleman, Edward F. Srour, David A. Williams, Marie-Dominique Filippi
Journal: Blood (2009)
GPs are rejecting commissioning roles because of lack of interest
Authors: C. White
Journal: BMJ (2012)

Concerns have been raised that GPs are shunning the opportunity to take on leadership roles in clinical commissioning groups in England, with some parts of the country struggling to appoint the required numbers of family doctors.

Speaking at a panel discussion on leadership in the public sector at the NHS Confederation annual conference in Manchester last week, Clare Gerada, chair of the Royal College of General Practitioners, said that many GPs were underwhelmed by the prospect of leading the emerging clinical commissioning groups (CCGs).

“Very …
Health Planning, Blue Cross, and the Federal Antitrust Laws
Authors: William J. Curran
Journal: New England Journal of Medicine (1981)

THE Supreme Court is not known for hasty decision making. Rapid review is generally reserved for matters of national crisis in which determination cannot be delayed. The medicolegal field, or health-care law, has rarely presented issues demanding such pressing attention. In fact, in earlier years, much of this field was left to the states and regarded as particularly within the sensitivities of local law and custom.It was therefore a new experience for the nation's highest court to deal with an important medicolegal case in very rapid order. It is obvious that the reason for the expeditious treatment was the . . .
Recombinant interferon α‐2b in the treatment of polycythemia vera
Authors: Renato Cimino, Vincenzo Rametta, Carmela Matera, Giuseppina Mele, Vincenzo Mettivier, Felicetto Ferrara
Journal: American Journal of Hematology (1993)

We studied the effects of recombinant alpha 2-b interferon (alpha 2-b IFN) in a dose of 3 x 10(6)U intramuscularly three times a week for 1 year in 13 patients affected by polycythemia vera (PV) previously treated with phlebotomy only. Response to treatment was evaluated by reduction of the number of phlebotomies required to retain normal hematocrit value. Ten out of 13 patients (77%) responded to treatment; in 4 of them the exigency of phlebotomy was completely eliminated. In all responders a concomitant decrease of platelet count and splenomegaly was obtained. Treatment was well tolerated and side effects were easily controlled. We conclude that alpha-IFN may represent an attractive therapeutic option in the management of the proliferative stages of PV.
Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation
Authors: Guoxiang Liu, Jia Yu, Jinhui Ding, Chengsong Xie, Lixin Sun, Iakov Rudenko, Wang Zheng, Namratha Sastry, Jing Luo, Gay Rudow, Juan C. Troncoso, Huaibin Cai
Journal: Journal of Clinical Investigation (2014)

Subpopulations of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc) display a differential vulnerability to loss in Parkinson’s disease (PD); however, it is not clear why these subsets are preferentially selected in PD-associated neurodegeneration. In rodent SNpc, DA neurons can be divided into two subpopulations based on the expression of aldehyde dehydrogenase 1 (ALDH1A1). Here, we have shown that, in α-synuclein transgenic mice, a murine model of PD-related disease, DA neurodegeneration occurs mainly in a dorsomedial ALDH1A1-negative subpopulation that is also prone to cytotoxic aggregation of α-synuclein. Notably, the topographic ALDH1A1 pattern observed in α-synuclein transgenic mice was conserved in human SNpc. Postmortem evaluation of brains of patients with PD revealed a severe reduction of ALDH1A1 expression and neurodegeneration in the ventral ALDH1A1-positive DA subpopulations. ALDH1A1 expression was also suppressed in α-synuclein transgenic mice. Deletion of Aldh1a1 exacerbated α-synuclein–mediated DA neurodegeneration and α-synuclein aggregation, whereas Aldh1a1-null and control DA neurons were comparably susceptible to 1-methyl-4-phenylpyridinium–, glutamate-, or camptothecin-induced cell death. ALDH1A1 overexpression appeared to preferentially protect against α-synuclein–mediated DA neurodegeneration but did not rescue α-synuclein–induced loss of cortical neurons. Together, our findings suggest that ALDH1A1 protects subpopulations of SNpc DA neurons by preventing the accumulation of dopamine aldehyde intermediates and formation of cytotoxic α-synuclein oligomers.
Sexually transmitted diseases may reverse the 'revolution'
Authors: M. F. Goldsmith
Journal: JAMA (1986)

An unanticipated consequence of the sexual revolution and the advent of reliable contraception has been a dramatic increase in sexually transmitted diseases (STDs) among those with multiple sex partners.  It has been estimated that each year in the US there are 3 million cases of chlamydia 200000-500000 new cases of genital herpes and at least 1 million cases each of pelvic inflammtory disease (PID) trichomonal infection and genital warts.  Although syphilis cases decreased from 75579 in 1982 to 68000 in 1985 largely as a result of homosexual mens safer sex practices the number of cases of congenital syphilis increased from 239 in 1983 to 370 in 1985.  In addition the 6-year trend toward a decrease in the number of cases of gonorrhea was reversed in 1985.  Of concern is the reluctance of private physicians to report cases of gonorrhea to the Centers for Disease Control (CDC) or another public health agency so that contacts can be traced.  CDC officials argue that the PID and possible infertility that can develop in females infected with untreated gonorrhea is far more important than the right to privacy of male victims.  It is further believed that a large proportion of the 70000 ectopic pregnancies seen each year largely in older women are related to PID.  Reported rates of gonorrhea and chlamydia are highest among blacks of both sexes in lower socioeconomic groups although the former infection is on the rise on college campuses.  Efforts are continuing to develop more sensitive specific tests for the diagnosis of chlamydia.  Another focus of research efforts is herpes simplex virus type 2 (HSV-2) infection.  Recent data suggest this virus may be transmitted asymptomatically and affect as many as 20-60% of Americans.  Controlled trials of anti-HSV-2 vaccines are expected within 2 years.  There is growing concern that herpes may be associated with human papillomavirus a factor in a variety of cancers.
Hypercalcemia Associated with Cancer
Authors: Andrew F. Stewart
Journal: New England Journal of Medicine (2005)

A 47-year-old woman with a history of breast cancer presents with confusion and dehydration. The serum calcium level is 18.0 mg per deciliter. She has postural hypotension and low central venous pressure. The serum phosphorus level is 5.0 mg per deciliter, the blood urea nitrogen level 80 mg per deciliter, the serum creatinine level 2.0 mg per deciliter, and the albumin level 3.3 g per deciliter. Bone scintigraphy reveals no evidence of skeletal involvement by the tumor. How should she be treated?
Intrahepatic portal occlusion by microspheres: a new model of portal hypertension in the rat.
Authors: V Jaffe, B Alexander, R T Mathie
Journal: Gut (1994)

Available experimental models of portal hypertension are based either on cirrhosis or externally applied portal vein constricting devices. A new method is described of raising portal pressure, which uses intraportally injected microspheres to block intrahepatic portal radicles, which has the advantages of retaining normal liver architecture and providing a more clinically relevant intrahepatic obstruction to portal flow. Measured aliquots of microspheres (15, 25, 50, 90 microns) or equivalent volumes of saline were injected into a peripheral portal tributary (caecal vein) of 22 normal rats. The resultant changes in arterial, portal, and splenic pulp pressures were monitored. Sequential microsphere injections produced graduated rises in portal pressure up to a peak of 18.5-22.5 mm Hg (8.7-12.4 mm Hg increase from basal), which declined gradually to a steady state pressure of 13.3-15.1 mm Hg (4.0-5.0 mm Hg increase). There was no significant difference between pressure increases produced by microspheres of differing sizes. It is concluded that portal hypertension can be produced acutely by blocking portal radicles with microspheres. The maximum pressure achieved, however, is substantially less than that obtained by total portal vein occlusion (mean: 57.6 mm Hg). This suggests the existence of functional intrahepatic portal systemic shunts not previously described in the normal liver.
Smoke and Developing Brains
Authors: M. J. Friedrich
Journal: JAMA (2012)

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A Simple Method of Endoscopy-guided Insertion of Nasogastric Tubes
Authors: K.F. Siu, N.W. Lee, J. Wong
Journal: Endoscopy (1984)

We report here a simple method of fixing a nasogastric tube to an upper GI endoscope which allows the tube to be inserted under vision when the normal upper gastrointestinal passage have been distorted by previous surgery or disease.
Reaccrediting general practice.
Authors: J. Russell
Journal: BMJ (1992)

secondary to primary care.Psychiatrists must realise this and start taking the criticisms of their clients and clients to be, the general practitioners in their area, more seriously than they do at present.This question needs to be addressed: if fundholding general practitioners are given the choice between a hospital oriented psychiatry service and other, equally effective, services that may be cheaper and are more flexible, how long before they start putting psychiatrists out of work?
Hypertrophic gastritis associated with increased gastric mucosal prostaglandin E2 concentrations in a patient with the carcinoid syndrome.
Authors: E J Boyd, G Hulks, J S Thomas, K E McColl
Journal: Gut (1988)

A case of a 69 year old man in whom hypertrophic gastritis was associated with the carcinoid syndrome is reported. Concentrations of prostaglandin E2 were increased in plasma, gastric juice, gastric mucosa and urine. He had marked hypochlorhydria in response to pentagastrin stimulation (Peak acid output (PAO) pg:0.2 mmol/h). After successful hepatic arterial embolisation of the metastases (as indicated by an 85% decrease in 24 h urinary 5-HIAA) the concentrations of prostaglandin E2 decreased in the plasma, gastric juice and gastric mucosa. The gastric mucosal hypertrophy regressed and secretion of acid in response to pentagastrin returned (PAO pg:9.0 mmol/h). These findings suggest that the carcinoid tumour was producing a substance which stimulated increased local synthesis of prostaglandin E2 in the gastric mucosa, with concomitant gastric mucosal hypertrophy and inhibition of gastric acid secretion.
Rational Use of Analgesic and Antiinflammatory Drugs
Authors: Leslie J. Crofford
Journal: New England Journal of Medicine (2001)

“Take two aspirin and call me in the morning”? Clinical decision making is no longer so straightforward. Millions of patients take analgesic and antiinflammatory medications regularly. The reasons are simple: these drugs are effective in relieving pain and inflammation,1 and aspirin provides protection from cardiovascular thrombosis.2,3 Osteoarthritis and other painful chronic conditions occur in a population of patients who often have coexisting medical conditions, including conditions associated with an increased risk of cardiovascular disease. Thus, aspirin is frequently prescribed for patients taking other analgesic and antiinflammatory agents. Since the mechanism of action of all these drugs is the inhibition . . .
Characterization of ionotrophic purinergic receptors in hepatocytes
Authors: Daniel S. Emmett, Andrew Feranchak, Gordan Kilic, Livia Puljak, Bonnie Miller, Svjetlana Dolovcak, Ryan McWilliams, Brian R. Doctor, Gregory J. Fitz
Journal: Hepatology (2007)

Ionotrophic purinergic (P2X) receptors function as receptor-gated cation channels, where agonist binding leads to opening of a nonselective cation pore permeable to both Na+ and Ca2+. Based on evidence that extracellular adenosine 5′-triphosphate (ATP) stimulates glucose release from liver, these studies evaluate whether P2X receptors are expressed by hepatocytes and contribute to ATP-dependent calcium signaling and glucose release. Studies were performed in isolated hepatocytes from rats and mice and hepatoma cells from humans and rats. Transcripts and protein for both P2X4 and P2X7 were detectable, and immunohistochemistry of intact liver revealed P2X4 in the basolateral and canalicular domains. In whole cell patch clamp studies, exposure to the P2X4/P2X7 receptor agonist 2′3′ - O -(4-benzoyl-benzoyl)-adenosine 5′-triphosphate (BzATP; 10 μM) caused a rapid increase in membrane Na+ conductance. Similarly, with Fluo-3 fluorescence, BzATP induced an increase in intracellular [Ca2+]. P2X4 receptors are likely involved because the calcium response to BzATP was inhibited by Cu2+, and the P2X4 modulators Zn2+ and ivermectin (0.3-3 μM) each increased intracellular [Ca2+]. Exposure to BzATP decreased cellular glycogen content; and P2X4 receptor messenger RNA increased in glycogen-rich liver samples. Conclusion: These studies provide evidence that P2X4 receptors are functionally important in hepatocyte Na+ and Ca2+ transport, are regulated by extracellular ATP and divalent cation concentrations, and may constitute a mechanism for autocrine regulation of hepatic glycogen metabolism. (Hepatology 2007.)
Mental health in Europe
Authors: Graham Thornicroft, Diana Rose
Journal: BMJ (2005)

New action plan will help improve care, especially in eastern Europe 

I n January 2005 the Mental Health Declaration for Europe and the Mental Health Action Plan for Europe were endorsed by the ministers of health of the 52 member states in the European region of the World Health Organization at a meeting in Helsinki.1 2 An unprecedented array of organisations of service users, non-governmental organisations, and professionals had been consulted in preparing these statements, which now set a clear policy direction for the development of mental health services in the wider Europe for at least the next decade. In which direction is the new policy going and how far is it wise?

The background to these new policies is a clear divide between the countries of western Europe, which have largely completed the process of deinstitutionalisation, and the position in most central and east European states, in which the transition from institutional care to a more balanced mix of services is starting only now (figures …
Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats.
Authors: D Schwartz, M Mendonca, I Schwartz, Y Xia, J Satriano, C B Wilson, R C Blantz
Journal: Journal of Clinical Investigation (1997)

Excess NO generation plays a major role in the hypotension and systemic vasodilatation characteristic of sepsis. Yet the kidney response to sepsis is characterized by vasoconstriction resulting in renal dysfunction. We have examined the roles of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the renal effects of lipopolysaccharide administration by comparing the effects of specific iNOS inhibition, -N6-(1-iminoethyl)lysine (L-NIL), and 2,4-diamino6-hydroxy-pyrimidine vs. nonspecific NOS inhibitors (nitro- -arginine-methylester). cGMP responses to carbamylcholine (CCh) (stimulated, basal) and sodium nitroprusside in isolated glomeruli were used as indices of eNOS and guanylate cyclase (GC) activity, respectively. LPS significantly decreased blood pressure and GFR (112+/-4 vs. 83+/-4 mmHg; 2.66+/-0.29 vs. 0. 96+/-0.22 ml/min, P < 0.05) and inhibited the cGMP response to CCh. GC activity was reciprocally increased. L-NIL and 2, 4-diamino-6-hydroxy-pyrimidine administration prevented the decrease in GFR (2.71+/-0.28 and 3.16+/-0.18 ml/min, respectively), restored the normal response to CCh, and GC activity was normalized. In vitro application of L-NIL also restored CCh responses in LPS glomeruli. Neuronal NOS inhibitors verified that CCh responses reflected eNOS activity. L-NAME, a nonspecific inhibitor, worsened GFR (0.41+/-0.15 ml/min), a reduction that was functional and not related to glomerular thrombosis, and eliminated the CCh response. No differences were observed in eNOS mRNA expression among the experimental groups. Selective iNOS inhibition prevents reductions in GFR, whereas nonselective inhibition of NOS further decreases GFR. These findings suggest that the decrease in GFR after LPS is due to local inhibition of eNOS by iNOS, possibly via NO autoinhibition.
Club doctors and physiotherapists
Authors: Claire Hay
Journal: British Journal of Sports Medicine (2001)

Club doctors and physiotherapistsEDITOR,-Waddington et al 1 are to be congratulated on highlighting the need to provide the best available care to professional footballers.Their paper is, however, inherently biased by factors that detract from the validity of their conclusions.For example, they have provided no evidence for their postulation that non-chartered physiotherapists are more vulnerable to threats to their clinical autonomy than other qualified professionals.Published quotations from the semistructured interviews are of an emotive nature, and the quoted questions posed by the interviewer are clearly leading.It is well recognised that responses in such interviews can be greatly influenced by the manner in which they are posed.The authors make no comparison of methods used by chartered and non-chartered physiotherapists, and their outcomes.Similarly there has been no comparison between the performance of club doctors with or without postgraduate qualifications in sports medicine, and, moreover, no evidence produced of actual harm resulting.Indeed, in recent months in Scottish League football, the Dundee club doctor restored circulation to the foot of a player following a serious ankle injury, and the Dumbarton club doctor restarted the breathing of an apnoeic player.In a recent survey of 15 players in a Scottish football club (unpublished work), 13 stated that they had been discouraged by the (non-chartered) physiotherapist and nine by the (non-specialist) club doctor from training or competing while injured, and none had been encouraged by either to return to playing before complete recovery.Indeed, 10 confessed to concealment of the true severity of injuries, perhaps reflecting the ethos at that particular club.Care oVered to professional footballers merits careful evaluation.However, this should be detailed, methodical, and independent of bias, such as that which can arise when studies are commissioned and funded by interested parties.