tbuckley/cabot-search huggingface dataset:
Mechanism of Natriuresis after Closure of Chronic Arteriovenous Shunts
Authors: Henry Mandin
Journal: Journal of Clinical Investigation (1973)

Animals subjected to certain cardiovascular manipulations, such as arteriovenous fistulas, diminish their urinary sodium excretion. It has been shown that closure of such fistulas results in a prompt increase in the rate of sodium excretion. However, the nature of the renal mechanisms increasing the excretion of sodium when the initial cardiovascular abnormality is corrected has remained unclear. Since the elucidation of such mechanisms might provide information pertinent to other sodium-retaining states, the effect of closure of chronic Teflon-Silastic arteriovenous shunts was studied in desoxycorticosterone acetate (DOCA)-treated dogs by utilizing micropuncture techniques.Nephron filtration rates were measured first during a control period with open arteriovenous shunts and then again after closure of the shunts in 12 dogs. Nephron filtration rate rose 32% while total glomerular filtration rate (GFR) decreased 8%. After closure of the arteriovenous shunt, fractional reabsorption increased 6%, while total kidney filtration fraction increased from 0.31 to 0.35. Renal plasma flow decreased from a mean of 111 ml/min to 90 ml/min. Closure of the arteriovenous shunts increased sodium excretion from a mean of 21 mueq/min to 45 mueq/min. Concomitantly, a redistribution of filtrate to superficial nephrons occurred. Since pharmacological doses of DOCA were being administered while total GFR was not increased and fractional reabsorption of sodium in the proximal tubule was not inhibited, it was concluded that filtrate distribution to superficial nephrons may have contributed to the observed natriuresis, although alternate explanations were also deemed possible.
Israeli minister orders hepatitis B vaccine for survivors of suicide bomb attacks
Authors: J. Siegel-Itzkovich
Journal: BMJ (2001)

All survivors of Palestinian suicide bomb attacks in Israel will from now be vaccinated against hepatitis B, the health ministry decided last week.

The policy was set after the ministry's infectious disease laboratory found that two of the recent suicide bombers were carriers of hepatitis B and that a passer by who was wounded in the blast had a fragment of a bomber's bone in his body.

Dr Paul Slater, the ministry's chief epidemiologist, said no case of …
Histopathology of the Endometrium
Authors: Robert E. Scully
Journal: JAMA (1972)

This volume translates into English a scholarly 1969 German text that deals in an encyclopedic manner with disorders of the endometrium. Almost half the 1,100 references cited come from the foreign literature, affording the English-speaking reader a unique contact with the most important European work in the field. The author's approach is one of clinical, physiological, and pathological correlation, with strong emphasis on the principle that optimal evaluation of the endometrium demands the close cooperation of the clinician and the pathologist. Abundant factual data are excerpted from the literature and interpreted in the light of the author's experience. One flaw in the method of presentation is the frequent interweaving of fact and interpretation in such a way that the inexperienced reader may not be able to distinguish the two. As an example, a description of the postmenopausal endometrium is followed by the statement that it is the "petrified" remains of
Consultative Geriatric Assessment
Authors: Alan K. Schultz
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The study by Epstein et al<sup>1</sup>emphasizes the importance of targeting patients for geriatric assessment. Epstein et al found no differences in benefits for ambulatory patients randomly assigned to treatment via a geriatric assessment, a second-opinion internist, or a traditional health maintenance organization. It is well documented that patients who benefit from geriatric assessment are those whose health is significantly compromised relative to the average health status of persons older than 65 years.<sup>2,3</sup>Dementia, falls, incontinence, malnutrition, and isolation are a few of the disorders for select targeting of patients for geriatric assessment. The baseline health status of the patients in the study by Epstein et al was good. In general, they were not debilitated, did not have a social situation that posed significant risk, and did not represent the most rapidly increasing segment of the elderly population: those aged 85 years and older. With
EDUCATIONAL NUMBER, SESSION 1930-31: A REVIEW OF THE MEDICAL CURRICULUM
Authors: H. R. Dean
Journal: BMJ (1930)

THE most difficult problem in tle medical curricuiluml' is the result of the growth in the medical sciences which lhas taken place duringg the thirty.years of this century, -for the imiedical studclenit of 1930 is requiired to kntowr rnuch -more tliain liis p)re(lecessor of 1900.Phiysics and chemiiistry have
620. SMC-Specific Transcription Elements for Improved Adenoviral-Mediated Transgene Expression in Saphenous Veins
Authors: Angelika B. Kritz, Song Wan, Anthony P. C. Yim, Paul A. Kingston, Andrew H. Baker
Journal: Molecular Therapy (2005)

Top of pageAbstract
Coronary artery bypass grafting (CABG) using autologous saphenous veins (SV) is an essential procedure to restore blood supply to the heart. However, long-term patency rates remain poor (93%, 74% and 41% at 1, 5 and 10 years post-grafting1) as vascular damage and remodeling often leads to neointima formation and accelerated atherosclerosis. Pharmacological interventions are largely ineffective and since the saphenous vein is accessible for ex vivo modification prior to arterial grafting, this presents an ideal window of opportunity for gene therapy. Several candidate therapeutic genes predicted to counteract vein graft failure have shown success pre-clinically but clinical translation is yet to take place. One of the most important issues is optimisation of transgene expression locally in the vein graft following gene delivery. We therefore assessed the ability of first-generation adenoviral vectors harbouring different promoter and post-transcriptional regulatory elements (Figure 1, ref. 2) for their expression levels in saphenous vein cells in vitro, ex vivo and in vivo.

Our results demonstrate that Ad-PREP [in which lacZ expression is driven by the murine CMV promoter (mCMV), the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) and a fragment of the smooth muscle myosin heavy chain promoter (RE)] produces significantly higher lacZ expression levels in primary saphenous vein smooth muscle cells (20-fold vs. RAd35 at m.o.i. 250) and endothelial cells (8-fold), but not in hepatocytes (1.23-fold), compared to RAd35, a standard Ad5-hCMV-bgal vector. This was particularly evident after short virus:cell incubation times (of 30 minutes), clearly relevant to the clinical setting. High levels of lacZ expression were also achieved with this vector following infection of human saphenous vein segments ex vivo, and 7 days after grafting autologous saphenous veins into pig carotid arteries in vivo.

These results demonstrate that high transgene expression levels in saphenous vein can be achieved by the mCMV promoter, in combination with smooth muscle cell-specific and post-transcriptional regulatory elements.
Cardiac mast cell regulation of matrix metalloproteinase-related ventricular remodeling in chronic pressure or volume overload
Authors: J JANICKI, G BROWER, J GARDNER, M FORMAN, J STEWARTJR, D MURRAY, A CHANCEY
Journal: Cardiovascular Research (2005)

The chronic elevation in ventricular wall stress secondary to ventricular volume or pressure overload leads to structural remodeling of the muscular, vascular and extracellular matrix components of the myocardium. While initially a compensatory response, the progressive hypertrophy and ventricular dilatation induced by this condition ultimately have a detrimental effect on ventricular function, resulting in heart failure. Fibrillar collagen provides the skeletal framework which interconnects the cardiomyocytes, thereby maintaining ventricular shape and size and contributing to tissue stiffness. Accordingly, these myocardial collagen fibers must be disrupted for ventricular dilatation, sphericalization and wall thinning to occur. The presence of an abundant, latent matrix metalloproteinase (MMP) population which coexists with myocardial fibrillar collagen has been documented. Thus, the potential for collagen degradation to exceed synthesis exists should there be significant activation of this latent MMP system. Mast cells are known to store and release a variety of biologically active mediators including TNF-α and proteases such as tryptase and chymase, which can induce MMP activation. Increased cardiac mast cell density has been implicated in the pathophysiology of human end-stage cardiomyopathy and experimental myocardial infarction, hypertension and chronic volume overload secondary to mitral regurgitation and aorto-caval fistula. The potential role of cardiac mast cells in activating MMPs, which then results in fibrillar collagen degradation and adverse myocardial remodeling secondary to chronic volume and pressure overload will be the subject of this review.
136 Antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, non-genotype 1
Authors: M REISER, H HINRICHSEN, Y BENHAMOU, R SENTJENS, H WEDEMEYER, L CALLEJA, X FORNS, J CROENLEIN, C YONG, G NEHMIZ
Journal: Hepatology (2003)
Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis
Authors: Rosa M. Pascale, Maria M. Simile, Maria R. De Miglio, Maria R. Muroni, Diego F. Calvisi, Giuseppina Asara, Daniela Casabona, Maddalena Frau, Maria A. Seddaiu, Francesco Feo
Journal: Hepatology (2002)

Preneoplastic and neoplastic hepatocytes undergo c-Myc up-regulation and overgrowth in rats genetically susceptible to hepatocarcinogenesis, but not in resistant rats. Because c-Myc regulates the pRb-E2F pathway, we evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrain differences in gene expression occurred in normal liver. Overexpression of c-myc, Cyclins D1, E, and A, and E2F1 genes, at messenger RNA (mRNA) and protein levels, rise in Cyclin D1-CDK4, Cyclin E-CDK2, and E2F1-DP1 complexes, and pRb hyperphosphorylation occurred in nodules and HCCs of F344 rats. Expression of Cdk4, Cdk2, p16(INK4A), and p27(KIP1) did not change. In nodules and/or HCCs of Wistar and BN rats, low or no increases in c-myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16(INK4A) overexpression and pRb hypophosphorylation. In conclusion, these results suggest deregulation of G1 and S phases in liver lesions of susceptible rats and block of G1-S transition in lesions of resistant strains, which explains their low progression capacity.
Resolution of Muscle Calcification in Rhabdomyolysis and Acute Renal Failure
Authors: MOHAMMAD AKMAL
Journal: Annals of Internal Medicine (1978)

We studied four patients with acute renal failure associated with nontraumatic rhabdomyolysis to evaluate the presence and progression of calcium deposits in damaged muscle tissue. Conventional and electron radiography and technetium-99m diphosphonate (TcDP) scans were done during the oliguric phase of acute renal failure and repeated after renal function returned to normal. Three patients showed deposits of calcium by conventional radiography and all by electron radiography and TcDP during the oliguric period. When the patients recovered renal function and muscle injuries healed, calcium deposits disappeared. The results show that calcium deposits in damaged muscle occur during the oliguric phase of acute renal failure due to rhabdomyolysis and the calcification disappears with recovery of renal failure; and TcDP scans are the most sensitive method of detecting calcium deposits in these patients.
Vitamin B12 deficiency in chronic gastritis
Authors: I. J. Wood, M. Ralston, B. Ungar, D. C. Cowling
Journal: Gut (1964)

EDITORIAL SYNOPSIS This study covers a group of elderly persons who suffer from chronic atrophic gastritis and resulting vitamin B12 deficiency.Increasing weakness, loss of memory, and mental depression were common symptoms and flatulent dyspepsia was sometimes a troublesome recurring complaint.These symptoms were improved by treatment with vitamin B12.Even if untreated, persons in this group rarely develop severe pernicious anaemia.vitamin B,2 levels the maximum response test meal of Kay (1953) was used.
Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice
Authors: Makoto Ochi, Hideki Ohdan, Hiroshi Mitsuta, Takashi Onoe, Daisuke Tokita, Hidetaka Hara, Kohei Ishiyama, Wendy Zhou, Yuka Tanaka, Toshimasa Asahara
Journal: Hepatology (2004)

Although it is known that activation of natural killer (NK) cells causes liver injury, the mechanisms underlying NK cell-induced killing of self-hepatocytes are not clear. We demonstrated that liver NK cells have cytotoxicity against normal syngeneic hepatocytes in mice. Polyinosinic-polycytidylic acid (poly I:C) treatment enhanced hepatocyte toxicity of liver NK cells but not that of spleen NK cells. Unlike NK cells in other tissues, approximately 30%-40% of liver NK cells constitutively express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). An in vitro NK cell cytotoxic assay revealed that hepatocyte toxicity of liver NK cells from both naïve and poly I:C-treated mice was inhibited partially by an anti-TRAIL monoclonal antibody (mAb) alone and completely by the combination with anti-Fas ligand (FasL) mAb and a perforin inhibitor, concanamycin A, indicating contribution of TRAIL to NK cell-mediated hepatocyte toxicity. The majority of TRAIL + NK cells lacked expression of Ly-49 inhibitory receptors recognizing self-major histocompatibility complex class I, indicating a propensity to targeting self-hepatocytes. Poly I:C treatment significantly upregulated the expression of Ly-49 receptors on TRAIL − NK cells. This might be a compensatory mechanism to protect self-class I-expressing cells from activated NK cell-mediated killing. However, such compensatory alteration was not seen at all in the TRAIL + NK cell fraction. Thus, liver TRAIL + NK cells have less capacity for self-recognition, and this might be involved in NK cell-dependent self-hepatocyte toxicity. In conclusion, our findings are consistent with a model in which TRAIL-expressing NK cells play a critical role in self-hepatocyte killing through poor recognition of MHC. (Hepatology 2004;39:1321-1331.)
Eosinophil-dependent bromination in the pathogenesis of asthma
Authors: Jay W. Heinecke
Journal: Journal of Clinical Investigation (2000)

In this issue of the JCI, Wu et al. (1) provide the first direct evidence that brominating species may contribute to the tissue damage that accompanies asthma.The peroxidase of eosinophils generates these reactive species, and the selective recruitment and activation of eosinophils in lung tissue is a hallmark of this inflammatory disease.Asthma, which is reaching epidemic proportions in the developed world, is characterized by narrowed airways that are hyperresponsive to stimulation (reviewed in refs. 2 and 3).Its clinical hallmarks are paroxysms of dyspnea, cough, and wheezing.The chronic airway narrowing reflects inflammation, extracellular matrix deposition, and hypersecretion of mucus.Allergen exposure and other nonspecific stimuli trigger the constriction of smooth muscle cells in the bronchiolar wall, resulting in acute airway constriction and onset of symptoms.Allergens appear to lack intrinsic toxicity, but they become deleterious when they induce an IgE response (Figure 1) after contacting mucosal surfaces.Antigen-presenting cells then stimulate Th2 cells, a subtype of CD4 + T-helper cells, to form proinflammatory cytokines.In turn, the cytokines prompt B cells to generate allergen-specific IgE.Cytokines also trigger the release of eosinophils from bone marrow and recruit them into lung tissue.In asthmatic individuals, allergen exposure promotes the cross-linking of the IgE to its receptor on mast cells, resulting in mast-cell degranulation and the early phase of bronchoconstriction.The late-phase inflammatory response of asthma involves recruitment and activation of additional cells, including eosinophils, basophils, neutrophils, and macrophages.Eosinophils and the eosinophil peroxidase.Under normal conditions, eosinophils are a minor component of the circulating phagocytic white blood cell population (4).However, in asthmatic individ-
Human rights in Kurdistan
Authors: K Yildiz
Journal: BMJ (1994)

EDITOR, - C M Milroy's personal view about his recent mission to south east Turkey will help to raise awareness among the British medical profession of the terrible situation of the Kurdish people in Turkey.1 The Kurdistan Human Rights Project is an independent, non-political project that was founded and is based in Britain. It is committed to the protection of the human rights of all people in Kurdistan, …
Thrombin Potently Stimulates Cytokine Production in Human Vascular Smooth Muscle Cells but Not in Mononuclear Phagocytes
Authors: Roger Kranzhöfer, Steven K. Clinton, Kenji Ishii, Shaun R. Coughlin, John W. Fenton, Peter Libby
Journal: Circulation Research (1996)

Thrombosis frequently occurs during atherogenesis and in response to vascular injury. Accumulating evidence supports a role for inflammation in the same situation. The present study therefore sought links between thrombosis and inflammation by determining whether thrombin, which is present in active form at sites of thrombosis, can elicit inflammatory functions of human monocytes and vascular smooth muscle cells (SMCs), two major constituents of advanced atheroma. Human α-thrombin (EC 50 , ≈500 pmol/L) potently induced interleukin (IL)-6 release from SMCs. The tethered-ligand thrombin receptor appeared to mediate this effect. Furthermore, α-thrombin also rapidly increased levels of mRNA encoding IL-6 and monocyte chemotactic protein-1 (MCP-1) in SMCs. In contrast, only α-thrombin concentrations of ≥100 nmol/L could stimulate release of IL-6 or tumor necrosis factor-α (TNFα) in peripheral blood monocytes or monocyte-derived macrophages. Lipid loading of macrophages did not augment thrombin responsiveness. Likewise, only α-thrombin concentrations of ≥100 nmol/L increased levels of IL-6, IL-1β, MCP-1, or TNFα mRNA in monocytes. Differential responses of SMCs and monocytes to thrombin extended to early agonist-mediated increases in [Ca 2+ ] i . SMCs and endothelial cells, but not monocytes, contained abundant mRNA encoding the thrombin receptor and displayed cell surface thrombin receptor expression detected with a novel monoclonal antibody. Thus, the level of thrombin receptors appeared to account for the differential thrombin susceptibility of SMCs and monocytes. These data suggest that SMCs may be more sensitive than monocytes/macrophages to thrombin activation in human atheroma. Cytokines produced by thrombin-activated SMCs may contribute to ongoing inflammation in atheroma complicated by thrombosis or subjected to angioplasty.
US conference looks at improving patient safety
Authors: N. MacReady
Journal: BMJ (1999)

Dr Richard Cook, an anaesthetist at the University of Chicago, works daily with the most advanced equipment available. Yet he keeps several syringes nearby, filled either with succinylcholine (suxamethonium chloride) or thiopental (thiopentone). “The world isn't always a perfect place,” he explained. When disaster looms, “you need a path of retreat, a way to back away.” The importance of finding simple alternatives to complex equipment was one of the recommendations Cook made last week at the Southern California Patient Safety forum held in Los Angeles.

Traditional …
Understanding the toll of premature death among men in eastern Europe
Authors: M. McKee, V. Shkolnikov
Journal: BMJ (2001)

The effects of apomorphine, bulbocapnine and haloperidol on <i>dl</i>-<i>p</i>-methoxyamphetamine (PMA)- and <i>d</i>-amphetamine-induced locomotor activities were studied in mice and rats. Small doses of PMA or of apomorphine given alone did not increase the locomotor activity. When both PMA and apomorphine were injected into mice or rats, a marked increase in locomotor activity was induced. The increased locomotor activity caused by a high dose of PMA or by small doses of <i>d</i>-amphetamine was blocked effectively by bulbocapnine or haloperidol. PMA, even in high doses, did not induce stereotyped behavior. <i>d</i>-Amphetamine, but not PMA, antagonized bulbocapnine-induced catalepsy in mice. The results are consistent with the biochemical findings that PMA is as effective as <i>d</i>-amphetamine in causing the release of norepinephrine from central norepinephrine-containing neurons, but is much less effective than <i>d</i>-amphetamine in causing the release of dopamine from central dopamine-containing neurons. The results indicate that activation of both central norepinephrine and dopamine receptors is important for the increased locomotor activity after the administration of <i>d</i>-amphetamine.
Intracranial pressure waves and intracranial hypertension in rats with ischemic fulminant hepatic failure
Authors: Stephen Webster, Jeanne Gottstein, Andres T. Blei, Robert Levy
Journal: Hepatology (1991)

Brain edema and intracranial hypertension are a major cause of death in fulminant hepatic failure. We have shown that brain water measured in rats after hepatic devascularization (portacaval anastomosis followed in 24 to 48 hr by ligation of the hepatic artery) increases with the progression of encephalopathy. In this study, we examined whether intracranial hypertension develops in this model of fulminant hepatic failure. Using a fiberoptic pressure transducer, intracranial pressure rose from 3.3 ± 1.1 mm Hg to 23.7 ± 2.7 mm Hg (mean ± S.E.M.) by the time the corneal reflex was lost; intracranial pressure was unchanged in control rats. Immediately after ligation of the hepatic artery, intracranial pressure was normal and remained stable until the last hours of the experiment, when it progressively rose, suggesting a loss of intracranial compliance. In addition, sudden and short episodes of marked increases in intracranial pressure (&gt;50 mm Hg) not related to seizure activity markedly decreased cerebral perfusion pressure. Internal carotid artery blood flow, an indirect measure of cerebral perfusion, decreased 29% ± 12% by the end of the experiment. The time elapsed from ligation of the hepatic artery until loss of the corneal reflex (range 340 to 940 min) was related to the change in cerebral perfusion pressure, suggesting that an increase in systemic arterial pressure at the time of the initial rise in intracranial pressure may result in an increased length of survival. In this animal model, widely used to study the pathogenesis of hepatic encephalopathy, intracranial hypertension invariably appears in the terminal phase of the course. The development of intracranial pressure waves may be an indication that brain herniation is imminent. (Hepatology 1991;14:715-720.)
Obesity related illness consumes a sixth of US healthcare budget
Authors: J. Lenzer
Journal: BMJ (2010)

The medical costs of obesity in the United States may be double previous estimates, a new study concludes.

As much as 17% of medical expenditure in the US goes towards the treatment of illnesses caused by obesity, says the study (www.nber.org/papers/w16467), from the National Bureau of Economics Research, an independent, non-profit organisation that is based in Cambridge, Massachusetts.

The authors, John Cawley, associate professor of policy analysis and management at Cornell University, Ithaca, New York, and Chad Meyerhoefer, assistant professor of economics at Lehigh University, Bethlehem, Pennsylvania, analysed data …