tbuckley/cabot-search huggingface dataset:
Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis
Authors: Rafal P. Witek, Carl W. Stone, Gamze F. Karaca, Wing-Kin Syn, Thiago A. Pereira, Kolade M. Agboola, Alessia Omenetti, Youngmi Jung, Vanessa Teaberry, Steve S. Choi, Cynthia D. Guy, John Pollard, Peter Charlton, Anna Mae Diehl
Journal: Hepatology (2009)

Abstract Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease that culminates in cirrhosis. Cirrhosis occurs more often in individuals with nonalcoholic steatohepatitis (NASH) than in those with steatosis (nonalcoholic fatty liver [NAFL]). The difference between NAFL and NASH is the extent of hepatocyte apoptosis, which is more extensive in NASH. Because phagocytosis of apoptotic cells activates hepatic stellate cells (HSCs), we examined the hypothesis that a pan-caspase inhibitor, VX-166, would reduce progression of fibrosis in a mouse model of NASH. Male db/db mice were fed methionine/choline-deficient (MCD) diets to induce NASH and liver fibrosis. Mice were gavaged once daily with either the pan-caspase inhibitor VX-166 (6 mg/kg/d; Vertex, Abingdon, UK) or vehicle only and sacrificed at 4 or 8 weeks. Treatment with an MCD diet increased alanine aminotransferase (ALT), caspase-3 activity, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL)-positive cells, NASH, and fibrosis. Treatment of MCD-fed mice with VX-166 decreased active caspase-3, TUNEL-positive cells, and triglyceride content ( P &lt; 0.05). However, ALT levels were similar in VX-166–treated mice and vehicle-treated controls. Histological findings also confirmed that both groups had comparable liver injury (NAFLD activity score ≥6). Nevertheless, VX-166–treated MCD-fed mice demonstrated decreased α-smooth muscle actin expression (4 weeks, P &lt; 0.05; 8 weeks, P &lt; 0.005) and had reduced hepatic levels of collagen 1α1 messenger RNA (8 weeks, P &lt; 0.05). Hydroxyproline content and Sirius red staining of VX-166–treated livers confirmed decreases in fibrosis. Conclusion: Inhibiting hepatic apoptosis suppresses the development of fibrosis in mice with NASH. Beneficial effects on liver fibrosis were associated with reductions in hepatic steatosis, but occurred without obvious improvement in liver injury. These findings are consistent with evidence that apoptosis triggers HSC activation and liver fibrosis and suggest that caspase inhibitors may be useful as an antifibrotic NASH therapy. (Hepatology 2009.)
Incapable patients and the law
Authors: David W Hewitt
Journal: BMJ (2006)

Editor—Stewart writes that patients with dementia can be judged to be lacking capacity by a single medical opinion and transferred to an institutional facility “in their best interests,” with little chance of being able to leave and little or no access to appeal. 1 The law says that shouldn't happen, and in time, there will be legislation to prevent it.

In the Bournewood case, the European Court …
Role of dietary energy supplementation in growth of children with chronic renal insufficiency.
Authors: P R Betts, G Magrath, R H White
Journal: BMJ (1977)

The effect of dietary energy supplements in children with varying degrees of chronic renal insufficiency was investigated. Despite an increased energy intake of 8-4% there was no increase growth velocity, although some patients reported improved wellbeing and activity. The proportion of dietary energy supplied by protein fell significantly during supplementation. The evidence suggests that the reduced energy intake of children with chronic renal insufficiency is a related but not causal factor in their growth retardation.
Therapy for Bleeding Peptic Ulcers
Authors: John R. Saltzman, John K. Zawacki
Journal: New England Journal of Medicine (1997)

During the past 50 years, mortality from acute bleeding in the upper gastrointestinal tract has remained at 6 to 10 percent, despite improved medical and surgical treatments, the development of diagnostic and therapeutic endoscopy, and the availability of intensive care units.1 One contributing factor is that patients tend to be older and to have more coexisting illnesses than ever before.2 The widespread use of aspirin and other nonsteroidal antiinflammatory agents, even at low doses taken to prevent cardiovascular disease, has also substantially increased the risk of bleeding.3 Fortunately, in 70 to 80 percent of patients with upper gastrointestinal bleeding, the . . .
617 Procreation medically assisted (PMA) and transmission of hepatitis C virus (HCV): Absence of HCV RNA in purified sperm fraction in HCV patients with presence of viral RNA in semen
Authors: P HALFON, C GEORGETTI, V CHABERTORSONI, J CHINCHOLLE, H KHIRI, J FERYN, P TERRIOU, L CRAVELLO, F FRANQUEBALME, R ROULIER
Journal: Hepatology (2003)
English teenager given heart transplant against her will
Authors: C. Dyer
Journal: BMJ (1999)

<b>Objective:</b> To investigate abnormal prion protein (PrP) deposition in the peripheral nervous system (PNS) in human prion diseases. <b>Methods:</b> Eight patients with prion diseases were examined: three with sporadic Creutzfeldt–Jakob disease (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann–Sträussler–Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain presented clinically with peripheral neuropathy, and showed demyelination in 12% of the teased fibres of the sural nerve. The PNS was investigated by immunohistochemical and western blotting analyses of PrP. <b>Results:</b> In immunohistochemical studies, granular PrP deposits were detected in some neurones of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients. The atypical case of sCJD with peripheral neuropathy showed no obvious PrP deposition in the nerves. Western blotting analysis of the PNS from the dCJD patients revealed a small amount of protease K resistant PrP in the dorsal root ganglia and peripheral nerves. <b>Conclusions:</b> Abnormal PrP deposition occurs in the dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in the PNS are not correlated with clinical manifestation of peripheral neuropathy in CJD.
Can hospital mortality comparisons ever be fit for purpose?
Authors: W. Holland, M. McKee
Journal: BMJ (2013)

Farihah Tariq talks to <b>Tim Lavy</b> about relocating continents for an entire year with his family to work at Comprehensive Community Based Rehabilitation in Tanzania (CCBRT), while his exchange partner, Richard Bowman, a fellow paediatric ophthalmologist from the overseas disability charity CBM, cared for his patients in Scotland
Age and urine concentration after desmopressin.
Authors: J P Monson, P Richards
Journal: BMJ (1978)

7) Contrary to much practice streptomycin has been relegated to deal with "difficult" patients, ethionamide has been placed in "reserve," and thiacetazone, much used in the developing coun- tries, has not been mentioned.(8) Perhaps most significant is the failure to discuss the importance of monitoring the patient's progress through sputum cultures and drug sensitivity testing.Dr Seaton rightly notes some of the pitfalls met with in the treatment ofindividual patients.However, even the most affluent countries might have difficulty in justifying the use of expensive chest physician time to check on the accuracy of the pharmacist or the drug handling of the patient.It is the com- munity nurse or auxiliary health worker who should play the primary role in the treatment of all ambulatory patients, not just the vagrants and alcoholics.
[155] HEPATIC VENOUS OUTFLOW OBSTRUCTION AFTER ORTHOTOPIC LIVER TRANSPLANTATION -A SINGLE CENTRE 10 YEAR EXPERIENCE
Authors: S.G. Farid, J. Rehman, S. Ganti, A. Al-Mukhtar, D. Kessel, J. Patel, R.K. Prasad
Journal: Journal of Hepatology (2007)
Binding of Biosynthetic Human Insulin to Human Antibodies and Receptors
Authors: KG Petersen, K Schlüter, S Steinhilber, L Kerp
Journal: Diabetes Care (1981)

The binding of biosynthetic human insulin (BHI) and pork insulin to anti-pork insulin antibodies was tested at an insulin concentration of 4 microunits/ml. Identical binding data were obtained. The binding of the two insulins to mononuclear lymphocytes was also identical. The data are compared to previous results obtained with synthetic human insulin. Previously, we investigated the in vitro properties of fully synthetic human insulin from Dr. Rittel, Ciba-Geigy, Basel. Receptor binding of this human insulin was identical to pork insulin. The binding properties of the new BHI from Lilly (Indianapolis) were studied with human antibodies and freshly isolated human monocytes.
Role of integrins in the periodontal ligament: organizers and facilitators
Authors: Malgorzata Barczyk, Anne Isine Bolstad, Donald Gullberg
Journal: Periodontology 2000 (2013)

Abstract The periodontal ligament is the tissue that connects teeth to bone. The periodontal ligament is a fascinating tissue from a cell biologist's point of view, and because of its special properties and stem‐cell content it has also come into the limelight in emerging fields of regenerative medicine. An increased range of genetically modified mouse models offer new tools for studying molecular mechanisms of tooth development. However, owing to species‐specific organization of the tooth apparatus, the use of genetic animal models to study the role of the periodontal ligament in normal human tooth physiology and tooth pathology is challenging.
Rheumatoid Arthritis and Amyloid Disease
Authors: W. Yeoman, J. V. Wilson
Journal: BMJ (1947)

The occurrence of amyloid disease as a complication of chronic sepsis is well known.It can also occur as a primary systemic disease process.As a complication of rheumatoid arthritis it is still rare enough to warrant the publication of the following case, especially as the majority of cases published in' England where amyloidosis has been associated with rheumatism have been in children with Still's disease.As Trasoff et al. (1944) have reviewed the literature no attempt will be made to do so here.Suffice it to say that the first mention of the association of these two conditions was in 1903, when almost simultaneously Whitman and Spitzy each reported a case where arthritis was complicated by amyloidosis.The next case to be reported was by Carroll and Nelson (1927).Since then just over thirty cases have appeared in the literature. Clinical HistoryThe patient was a female, unmarried, aged 28, and weighed 7 st.12 lb.(50 kg.).She was admnitted to the Royal Bath Hospital for the first time on June 27, 1946.She had no unusual illness as a child, and there was no history of " growing pains."There was no family history of rheumatism.She left school at the age of 16 and worked in an office until she was 22, when in March, 1940, her knees began to swell, and she was treated with rest in bed, first at home for two months and then in hospital for six months.In January, 1941, she had an attack of acute appendicitis and her appendix was removed.In November, 1941, her left hip became painful and she was given injections of gold, about fifteen in all, and her knees and legs were put in plaster.
499 FULL GENOME ULTRA-DEEP PYROSEQUENCING IDENTIFIES GG-TO-GA HYPERMUTATION AS NOVEL PREDICTOR FOR TREATMENT RESPONSE TO PEGYLATED INTERFERON ALFA-2A IN HBEAG-NEGATIVE CHRONIC HEPATITIS B
Authors: B. Beggel, C. Münk, M. Däumer, K. Hauck, G. Lawyer, D. Häussinger, T. Lengauer, A. Erhardt
Journal: Journal of Hepatology (2012)
NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance
Authors: P Ballerini, M Busson, S Fasola, J van den Akker, H Lapillonne, S P Romana, P Marynen, O A Bernard, J Landman-Parker, R Berger
Journal: Leukemia (2005)
Defective Intestinal Phosphate Absorption in Familial and Non-familial Hypophosphataemia
Authors: J. R. Condon, J. R. Nassim, A. Rutter
Journal: BMJ (1970)

With an oral phosphate tolerance test a primary defect in intestinal phosphate absorption was found in patients with untreated familial and non-familial hypophosphataemia. It is suggested that this plays a major part in the aetiology of rickets and osteomalacia in these disorders. Vitamin D was shown to have a beneficial effect on intestinal transport of phosphate, though defective absorption was not completely corrected. If intestinal phosphate absorption is normal, oral phosphate supplements will maintain normal plasma phosphate levels even in the presence of a pronounced renal phosphate leak.In familial and non-familial hypophosphataemia the phosphate tolerance test may be a more sensitive index of genetic abnormality than a low plasma phosphate. It may be helpful in distinguishing several syndromes at present classified under non-familial hypophosphataemia, as well as assessing the response to treatment with vitamin D and in investigating intestinal transport of phosphate.
Eating behaviour and obesity
Authors: E. Denney-Wilson, K. J Campbell
Journal: BMJ (2008)

<h3>Background:</h3> Patients with Crohn’s disease have an increased risk for systemic thromboembolism. Their platelets are hyperactive and possess an elevated endogenous content of CD40 ligand (CD40L), a tumour necrosis factor α family protein member. Under basal conditions and after stimulation, these platelets express more CD40L on their surface and release higher amounts of soluble (s)CD40L than control platelets, through a mechanism that might be mediated by matrix metalloproteinases (MMPs). <h3>Objective:</h3> The aim of this work is to study whether enhanced sCD40L release secondary to changes in the platelet content of MMPs contributes to the higher state of activation of platelets from patients with Crohn’s disease. <h3>Methods:</h3> State of activation, CD40L and metalloproteinases content of platelets isolated from patients with Crohn’s disease and age- and sex-matched control individuals were analysed, respectively, by flow cytometry, western blot and gelatin zymography. <h3>Results:</h3> The hyperactive state of platelets from patients with Crohn’s disease might rely on their enhanced release of sCD40L, since its inhibition by a broad-range inhibitor of MMPs (GM6001) reduced fibrinogen binding induced by platelet stimulation. Analysis of the content of MMPs in platelets from patients with Crohn’s disease showed an exclusive increase in MMP-9 activity. Moreover, MMP-9 inhibition diminished sCD40L release and fibrinogen binding to activated platelets. <h3>Conclusions:</h3> The results suggest that platelets from patients with Crohn’s disease release more sCD40L than controls as a consequence of their higher endogenous content of CD40L and of MMP-9, which is involved in CD40L shedding. The increased levels of released sCD40L might be responsible, at least in part, for the high state of activation of platelets from patients with Crohn’s disease.
Influence of Race on the Management of Lower Extremity Ischemia
Authors: Tyler S. Durazzo, Stanley Frencher, Richard Gusberg
Journal: JAMA Surgery (2013)

Among patients presenting with critical lower extremity ischemia, it has been previously documented that white individuals are more likely to undergo revascularization than nonwhite individuals, with the disparity largely attributed to differences in resources and access to care.To investigate the amputation disparity between white and nonwhite patients with critical lower extremity ischemia in more detail using a larger data set than previous studies, with a focus on the role of confounding factors such as access and hospital resources.All hospital discharge records from the Nationwide Inpatient Sample of adult patients with the primary diagnosis of critical lower extremity ischemia from 2002-2008 were examined in detail using multiple logistic regression (n = 774,399).Rates of amputation and revascularization for peripheral vascular disease across race/ethnicity.Controlling for confounding factors, black patients were found to have 1.77 times the odds of receiving an amputation compared with white patients (95% CI, 1.72-1.84; P < .001). Further analysis revealed the black to white odds ratio paradoxically increased with increasing revascularization capacity of the presenting hospital, from a low of 1.43 (95% CI, 1.23-1.65) to a high of 1.98 (95% CI, 1.83-2.24). The amputation disparity also paradoxically increased for patients living in wealthier zip codes.Black patients have greater odds of undergoing amputation than white patients, even after correcting for an array of confounding parameters. Contrary to current beliefs that the disparity is mainly secondary to differences in access, this study found that the disparity was magnified in settings where resources were greatest. Whether the explanation lies primarily in patient-specific, physician-specific, or institutional-specific factors remains to be determined but is critical to better understanding our health care system and maintaining approaches that are consistently fair and equitable.
Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.
Authors: J J Rafter, V W Eng, R Furrer, A Medline, W R Bruce
Journal: Gut (1986)

A single pass perfusion system was used in anaesthetised, restrained rats to examine the effect of changing the composition of the perfusion fluid on the damage caused to the colonic epithelium by deoxycholic acid. Damage to the colonic surface was monitored with light microscopy, transmission and scanning electron microscopy and with measurements of deoxyribonucleic acid and carbohydrate in the perfusate. New scoring techniques for monitoring alterations in surface epithelium of light microscopy sections were used. The damaging effect of 5 mM deoxycholic acid to the colonic epithelium is inhibited by lowering the pH of the perfusion fluid from 7.9 to 5.5, or by increasing the calcium concentration from 0 to 4 mM. This inhibition is shown to be because of a decreased amount of bile acid in solution. Thus it is not the total concentration of deoxycholic acid in the colon that is responsible for the colonic damage, but the concentration in solution. Although extrapolation to the human situation must be made with caution, the concentration of bile acid in solution in the faecal water may be more relevant to colonic mucosal damage than total bile acid concentration.
Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.
Authors: T Kayo, A Koizumi
Journal: Journal of Clinical Investigation (1998)

Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus musculus castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and 8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait locus analysis using blood glucose levels of 118 F2 mice at 2 wk of age and 5-8 wk of age located Mody within 3 cM of D7Mit258. Histopathological investigation revealed hypoplastic islets (approximately 33% of that of wild-type mice) and a lower density of beta cells (approximately 20% of wild-type) with a reciprocal dominance of alpha cells (four times that of wild-type) in Mody homozygotes. Electron microscopic observations revealed a specific decrease in the number of insulin secretory granules and a lower density of beta cells. Ratios of insulin to glucagon contents confirmed specific decreases in insulin content: 0.01 for homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These results suggest that Mody is involved in both islet growth and beta cell function.
The JAK3-selective inhibitor PF-956980 reverses the resistance to cytotoxic agents induced by interleukin-4 treatment of chronic lymphocytic leukemia cells: potential for reversal of cytoprotection by the microenvironment
Authors: Andrew J. Steele, Archibald G. Prentice, Kate Cwynarski, A. Victor Hoffbrand, Stephen M. Hart, Mark W. Lowdell, Edward R. Samuel, R. Gitendra Wickremasinghe
Journal: Blood (2010)
Special Problems in Treating Tuberculosis
Authors: Peter Barnes
Journal: Annals of Internal Medicine (1994)

Letters1 March 1994Special Problems in Treating TuberculosisPeter Barnes, MDPeter Barnes, MDUniversity of Southern California School of Medicine; Los Angeles, CA 90033Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-5-199403010-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Salomon, Perlman, and Goldstein present their experience with ofloxacin, ethambutol, and an aminoglycoside in HIV-infected patients with tuberculosis who developed hepatotoxicity while receiving standard antituberculous therapy. My limited experience with this combination therapy in patients with tuberculosis and without HIV infection also suggests that this regimen is adequate to keep the disease under control until the patient can tolerate more standard agents. We agree that additional evaluation of the microbiologic efficacy of this combination is needed.I disagree with Dr. Johnson that corticosteroids should be used liberally in patients with tuberculous pericarditis because of methodologic concerns in ...References1. Strang JI, Gibson DG, Mitchison DA, Girling DJ, Kakaza HH, Allen BW, et al. Controlled clinical trial of complete open surgical drainage and of prednisolone in treatment of tuberculous pericardial effusion in Transkei. Lancet. 1988; 2:759-64. Google Scholar2. Strang JI, Gibson DG, Nunn AJ, Kakaza HH, Girling DJ, Fox W. Controlled trial of prednisone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. Lancet. 1987; 2:1418-22. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Southern California School of Medicine; Los Angeles, CA 90033 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1994Volume 120, Issue 5Page: 440-441KeywordsConfidence intervalsDeath ratesHIV infectionsTuberculosis ePublished: 15 August 2000 Issue Published: 1 March 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...