tbuckley/cabot-search huggingface dataset:
Spontaneous Disappearance of Viral Replication and Liver Cell Inflammation in Hbsag–Positive Chronic Active Hepatitis: Results of A Placebo Vs. Interferon Trial
Authors: Solko W. Schalm, Rudolf A. Heijtink
Journal: Hepatology (1982)

In 20 patients with HBsAg–and HBeAg–positive chronic active hepatitis, we determined the long–term effect of human leukocyte interferon as well as placebo treatment. During the 2–year follow–up period, HBsAg remained present in all patients, but the Dane particle markers HBeAg and DNA polymerase disappeared in two of 10 patients who had received interferon, and in 4 of 10 patients from the placebo group. Patients with loss of HBeAg initially had HBs antigenemia for a longer period as well as a lower serum concentration of both HBsAg and DNA polymerase, fewer HBcAg–containing hepatocyte nuclei, and higher serum transaminase levels than did the patients in whom HBeAg persisted. Disappearance of Dane particle markers was associated with a decrease in HBsAg titer, appearance of anti–HBe, normalization of the serum transaminases, and morphological transition to inactive chronic hepatitis. We conclude that, in HBsAg– and HBeAg–positive chronic active hepatitis, disappearance of Dane particle markers occurs in approximately 30% of the patients within a 2–year period and that arrest of active viral replication is associated with loss of activity of chronic hepatitis. Treatment with human leukocyte interferon in the doses used in this study did not change the natural course of the disease.
The future of singlehanded general practices
Authors: Azeem Majeed
Journal: BMJ (2005)

Recent developments put their future in doubt 

D o singlehanded general practices have a future in the United Kingdom's NHS? Singlehanded practices—those that have only one principal doctor with a contract with their primary care trust—have been dwindling in number for many years, and this decline has now become much more rapid. Between 1994 and 2003, the number of singlehanded general practitioners fell from 2959 to 2578 (from 10.8% to 8.5% of all general practitioners) in England.1 Between 2003 and 2004, the number fell by a further 660 to 1918 (now comprising 6.1%), a larger fall over one year than in the preceding nine years. Yet singlehanded doctors make up a much larger proportion of the primary care workforce in many other developed countries. For example, in the United States in 1998, 46% of family practitioners and 34% of general internists were practising alone.2

Ever since the foundation of the NHS, singlehanded general practitioners have made an important contribution in the UK, particularly in inner city and rural areas where recruiting general practitioners has proved difficult. These areas often have deprived populations and, in inner city …
Retortamonad Flagellates are Closely Related to Diplomonads—Implications for the History of Mitochondrial Function in Eukaryote Evolution
Authors: Jeffrey D. Silberman, Alastair G. B. Simpson, Jaroslav Kulda, Ivan Cepicka, Vladimir Hampl, Patricia J. Johnson, Andrew J. Roger
Journal: Molecular Biology and Evolution (2002)

We present the first molecular phylogenetic examination of the evolutionary position of retortamonads, a group of mitochondrion-lacking flagellates usually found as commensals of the intestinal tracts of vertebrates. Our phylogenies include small subunit ribosomal gene sequences from six retortamonad isolates—four from mammals and two from amphibians. All six sequences were highly similar (95%–99%), with those from mammals being almost identical to each other. All phylogenetic methods utilized unequivocally placed retortamonads with another amitochondriate group, the diplomonads. Surprisingly, all methods weakly supported a position for retortamonads cladistically within diplomonads, as the sister group to Giardia. This position would conflict with a single origin and uniform retention of the doubled-cell organization displayed by most diplomonads, but not by retortamonads. Diplomonad monophyly was not rejected by Shimodaira-Hasegawa, Kishino-Hasegawa, and expected likelihood weights methods but was marginally rejected by parametric bootstrapping. Analyses with additional phylogenetic markers are needed to test this controversial branching order within the retortamonad + diplomonad clade. Nevertheless, the robust phylogenetic association between diplomonads and retortamonads suggests that they share an amitochondriate ancestor. Because strong evidence indicates that diplomonads have secondarily lost their mitochondria (rather than being ancestrally amitochondriate), our results imply that retortamonads are also secondarily amitochondriate. Of the various groups of eukaryotes originally suggested to be primitively amitochondriate under the archezoa hypothesis, all have now been found to have physical or genetic mitochondrial relics (or both) or form a robust clade with an organism with such a relic.
More about Mass Disasters
Authors: William J. Curran
Journal: New England Journal of Medicine (1986)

The interest in my recent column1 on the ethical and public policy issues surrounding the industrial mass disaster in Bhopal, India, prompts me to offer the Journal readership some comments on another form of mass disaster — the airliner crash that results in hundreds of deaths.Nine years ago, I wrote a column2 on the worst air-travel disaster in history — the collision of two jumbo jets on the ground at Tenerife in the Canary Islands. I focused on the medicolegal investigation of the cause of the crash and the forensic difficulties involved in identification of the victims.In this . . .
The Efficacy of Tolrestat in the Treatment of Diabetic Peripheral Neuropathy: A meta-analysis of individual patient data
Authors: Antonio Nicolucci, Fabrizio Carinci, Jay G Graepel, Thomas C Hohman, Frederick Ferris, John M Lachin
Journal: Diabetes Care (1996)

OBJECTIVE The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal. RESULTS The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by &amp;gt; 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30–2.52) and 1.70 (1.15–2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels. CONCLUSIONS After a treatment duration ranging between 24–52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease
Authors: Wahid Boukouaci, Marc Busson, Régis Peffault de Latour, Vanderson Rocha, Caroline Suberbielle, Djaouida Bengoufa, Nicolas Dulphy, Philippe Haas, Catherine Scieux, Habiba Amroun, Eliane Gluckman, Rajagopal Krishnamoorthy, Antoine Toubert, Dominique Charron, Gérard Socié, Ryad Tamouza
Journal: Blood (2009)
Prevalence of Diabetes and Impaired Glucose Tolerance in Aragón, Spain
Authors: Benito Tamayo-Marco, Eduardo Faure-Nogueras, María José Roche-Asensio, Emilio Rubio-Calvo, Enrique Sánchez-Oriz, José Antonio Salvador-Oliván
Journal: Diabetes Care (1997)

OBJECTIVE To determine the prevalence of diabetes and impaired glucose tolerance (IGT) and to investigate their associated cardiovascular risk factors in Aragón, Spain. RESEARCH DESIGN AND METHODS We performed a population-based cross-sectional study with stratified and purposive sampling of residents aged 10–74 years. A sample of 935 subjects (427 men and 508 women) was selected. All except those with a previous history of diabetes underwent an oral glucose tolerance test (OGTT), and World Health Organization (WHO) criteria were used for diagnosis of undiagnosed diabetes and IGT. Plasma lipid levels, blood pressure, BMI, and waist-to-hip ratio were also measured. RESULTS The prevalence of diagnosed and undiagnosed diabetes and IGT was 3.1, 3.0, and 7.2%, respectively. In the age range of 30–64 years, the age-adjusted prevalence of diabetes (using the world population of Segi) was 7.1% in men and 5.6% in women. Both diabetes and IGT were associated with high blood pressure, high triglyceride levels, low HDL cholesterol levels, and overweight and upper-body fat distribution. Only upper-body fat distribution in women was significantly higher in subjects with diabetes than in subjects with IGT. CONCLUSIONS The prevalence of diabetes in Aragón was moderately high (6.1%) and comparable with that reported in other white populations around the world. The proportion of unknown cases of diabetes was nearly 50%. Cardiovascular risk factors associated with diabetes and IGT supported the existence of an insulin resistance or metabolic syndrome, but there were not sufficient differences between diabetes and IGT to suggest a possible pathogenetic relation of hyperinsulinemia and associated risk factors.
Aging, Amyloid, and Cardiomyopathy
Authors: Merrill D. Benson
Journal: New England Journal of Medicine (1997)

In past decades, rheumatic heart disease, syphilitic heart disease, hypertensive heart disease, and even nutritional deficiencies were common enough for physicians to consider these diagnoses in patients presenting with congestive heart failure. In recent years, however, our attention has been directed to coronary atherosclerosis, and the idea that older patients with heart failure could have cardiac diseases other than coronary atherosclerosis is rarely considered. The article by Jacobson et al. in this issue of the Journal on the incidence of cardiac amyloid deposition in blacks is therefore important.1 Jacobson et al. point out that we should be alert to a . . .
Infusions of Allogeneic Natural Killer Cells as Cancer Therapy
Authors: Wing Leung
Journal: Clinical Cancer Research (2014)

Abstract Natural killer (NK) cells are normal white blood cells capable of killing malignant cells without prior sensitization. Allogeneic NK cell infusions are attractive for cancer therapy because of non–cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, failure of homing to tumor sites, effector dysfunction, exhaustion, and tumor cell evasion. Capitalizing on the wealth of knowledge generated by recent NK cell biology studies and the advancements in biotechnology, substantial progress has been made recently in improving therapeutic efficiency and reducing side effects. A multipronged strategy is essential, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of adult and pediatric cancers are under way. The unique properties of human NK cells open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies. Clin Cancer Res; 20(13); 3390–400. ©2014 AACR.
Queen should remove her crest from cigarette packets
Authors: D. Goldberg
Journal: BMJ (1996)

Telling patients there is nothing wrong Randomised controlled trials are needed EDrroR,-It is still unclear from the literature whether investigative tests reassure patients with anxieties about the presence of serious disease.' 2 Ray Fitzpatrick discusses some of the possible reasons for this, including psychiatric morbidity, poor communication, and the "wild card effects" mentioned in the study by I G McDonald and colleagues.3Other psychological processes in patients are
The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: Results of a prospective, multicenter, open-label study
Authors: Alice B. Gottlieb, Robert E. Kalb, Andrew Blauvelt, Michael P. Heffernan, Howard L. Sofen, Laura Korb Ferris, Francisco A. Kerdel, Stephen Calabro, Jim Wang, Urs Kerkmann, Marc Chevrier
Journal: Journal of the American Academy of Dermatology (2011)
Heat serum inactivation as a mandatory procedure for antiactin antibody detection in cell culture
Authors: E L Cancado, L S Vilas-Boas, C P Abrantes-Lemos, N F Novo, G Porta, L C Da Silva, A A Laudanna
Journal: Hepatology (1996)

In autoimmune hepatitis (AIH), the smooth-muscle antibody is specific for polymerized actin. Detection of antiactin antibody (AAA) has been hampered by technical problems. We have investigated AAA in 30 sera from patients with liver diseases and smooth-muscle antibody. AAA was detected by indirect immunofluorescence in 1:40, 1:80, and 1:160 dilutions. Five techniques were performed using fibroblasts: with vinblastine (A); without drugs (B); with sodium citrate (C); without drugs but with heat serum inactivation (D); and with sodium citrate and heat serum inactivation (E). For comparative analysis, we considered: the total number of AAA-positive sera regardless of the dilution in which reactivity was observed, as well as in each dilution separately; and the comparison of AAA intensity between 1:40 x 1:80, 1:40 x 1:160, and 1:80 x 1:160 dilutions. AAA was more positive in techniques B, C, D, and E than in A ( P &lt; .001) in general, and in each dilution separately. AAA was more positive in technique D than in B in 1:40 ( P = .0005) and 1:80 dilutions ( P = .03), as well as in E than in C ( P = .0001) in 1:40 dilution. Techniques B and D yielded results similar to C and E, respectively. AAA staining was significantly more intense in 1:80 and 1:160 than in 1:40 dilution in A, B, and C; it was both significantly less intense in 1:80 and 1:160 than in 1:40 dilution and in 1:80 than in 1:160 in techniques D and E. We concluded that heat inactivation increased AAA seropositivity/intensity in 1:40 and 1:80 dilutions, preventing false-negative results; actin polymerization with sodium citrate did not enhanced AAA seropositivity/intensity. The technique with vinblastine was the least effective.
Prions and Neurodegenerative Diseases
Authors: Franklin H. Epstein, Stanley B. Prusiner
Journal: New England Journal of Medicine (1987)

CREUTZFELDT–JAKOB disease (CJD), kuru, and the Gerstmann–Sträussler syndrome are human neurodegenerative diseases that can be transmitted experimentally to animals. In 1920, Creutzfeldt described a progressive dementing illness in a 22-year-old woman. The following year, Jakob described four older patients with a clinically similar presentation and course.1 During the ensuing four decades, numerous cases of CJD were described clinically and pathologically. Although most cases of CJD present with a progressive dementia characterized initially by loss of memory, diminished intellect, and poor judgment, a few cases present as progressive cerebellar syndromes, with diminished coordination, tremor, and ataxia. Patients with the ataxic form . . .
Absence of Focal Compensatory Enlargement or Constriction in Diseased Human Coronary Saphenous Vein Bypass Grafts
Authors: Toshihiko Nishioka, Huai Luo, Hans Berglund, Neal L. Eigler, Chong-Jin Kim, Steven W. Tabak, Robert J. Siegel
Journal: Circulation (1996)

Background No in vivo data are available on the occurrence of compensatory enlargement or vessel constriction in diseased human coronary saphenous vein bypass grafts (SVBGs). The aim of this intravascular ultrasound (IVUS) study was to examine to what extent lumen reduction is accompanied by (1) vessel wall thickening and (2) arterial wall constriction in SVBGs. Methods and Results We used IVUS to examine 43 SVBGs from 42 patients (32 men, 10 women; mean age, 72±5 years) 8 to 23 (11±4) years after SVBG. IVUS images were obtained with a 3.5F monorail ultrasound catheter with a 30-MHz frequency and were analyzed at the lesion site, the reference site, and an intermediate site. The lumen area was significantly ( P &lt;.01) decreased; the vessel wall area (SVBG cross-sectional area minus lumen area) and the plaque area (area within the external elastic lamina minus lumen area) were significantly ( P &lt;.01) increased from the reference site through the lesion site. However, SVBG cross-sectional area was the same at these three sites (24.0±8.1 versus 24.4±8.6 versus 24.5±8.6 mm 2 , P =NS), and the external elastic lamina area was also quite constant in each vessel (17.8±6.0 versus 17.7±6.4 versus 17.6±6.2 mm 2 , P =NS). Conclusions These in vivo IVUS data from human coronary SVBGs demonstrate that (1) no focal compensatory enlargement or vessel constriction occurred in stenotic segments compared with the reference segments and that (2) the absence of focal compensatory enlargement appears to be a potentially important factor in the progression of stenoses in coronary SVBGs.
Indications for Lumbar Puncture
Authors: Charles M. Poser
Journal: JAMA (1967)

<h3>To the Editor:—</h3> I should like to voice my exception to the statement in Dr. Alexander's excellent paper on "Lumbar Puncture" (<i>JAMA</i><b>201</b>:316, 1967) that increased intracranial pressure is the absolute contraindication to the performance of a routine lumbar puncture, except in the hands of a surgeon who is prepared to handle the entire problem. This has been repeated over and over again for many years. Lumbar puncture should never be considered as a routine procedure. The need for specifying indications and contraindications can be eliminated by this simple statement: lumbar puncture and examination of the spinal fluid are indicated<i>only</i>when the information that can be obtained in this way, and in no other way, is absolutely necessary for the diagnosis. Lumbar puncture is occasionally necessary in the presence of signs of increased intracranial pressure in order to obtain diagnostic information from the examination of the spinal fluid
Further privatisation is inevitable under the proposed NHS reforms
Authors: C. Peedell
Journal: BMJ (2011)

The government’s health reforms fulfil commonly accepted criteria for privatisation

Repeated government denials about NHS privatisation don’t stand up to scrutiny. In response to widespread criticism of the proposed reforms of the NHS in England, the health secretary, Andrew Lansley, the prime minister, David Cameron, the deputy prime minister, Nick Clegg, and the chancellor of the exchequer, George Osborne, have repeatedly claimed that there will be no privatisation of the NHS in England. The Department of Health website even states that “Health Minsters have said they will never privatise the NHS” (http://bit.ly/mtd8iF). However, these claims and promises fail to acknowledge the evidence that privatisation is an inevitable consequence of many of the policies contained in the Health and Social Care Bill.

The meaning of privatisation is complex, covering a range of ideas in law, politics, economics, and philosophy. However, the World Health Organization has defined privatisation in healthcare as “a process in which non-governmental actors become increasingly involved in the financing and/or provision of healthcare services” (J Muschell, Technical Briefing Note on Privatization in Health , 1995, WHO/TFHE/TBN/95.1).

So the government’s attempt to deny privatisation of the NHS by claiming that NHS services will remain publicly funded and free at the point of delivery does not escape the WHO definition if services are delivered by non-governmental actors, such as private and …
Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation
Authors: Ruth R. French, Vadim Y. Taraban, Graham R. Crowther, Tania F. Rowley, Juliet C. Gray, Peter W. Johnson, Alison L. Tutt, Aymen Al-Shamkhani, Martin J. Glennie
Journal: Blood (2007)
Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated components in vitro.
Authors: J K Roche, C Fiocchi, K Youngman
Journal: Journal of Clinical Investigation (1985)

To explore the auto-reactive potential of cells infiltrating the gut mucosa in idiopathic chronic inflammatory bowel disease, intestinal lamina propria mononuclear cells (LPMC) were isolated, characterized morphologically and phenotypically, and evaluated for antigen-specific reactivity. The last was assessed by quantitating LPMC cytotoxic capabilities against purified, aqueous-soluble, organ-specific epithelial cell-associated components (ECAC) characterized previously. Enzyme-isolated inflammatory bowel disease LPMC were constituted primarily by T lymphocytes (57 +/- 12% OKT 3-positive), B lymphocytes (18 +/- 9% surface immunoglobulin-positive), and macrophages (11 +/- 6% esterase-positive), and were responsive to phytohemagglutinin (mean uptake 86,933 cpm/5 X 10(5) cells). LPMC present in abnormal segments from 71% of patients with chronic inflammatory bowel disease were cytotoxic for ECAC isolated from colon (12.5 +/- 8.9% specific lysis) and small bowel (7.1 +/- 6.5%), but not for kidney control antigen (0.8 +/- 1.1%) isolated in a manner analogous to that used for ECAC (P less than 0.02). In contrast, despite comparable responses to phytohemagglutinin (mean uptake 59,200 cpm/5 X 10(5) cells), LPMC from histologically normal mucosa of patients with benign (adult megacolon, Hirshsprung's disease, diverticulosis) or malignant disease failed to lyse indicator cells labeled with colon-derived ECAC (0.3 +/- 0.08%), small bowel-derived ECAC (0.4 +/- 1.11%), or kidney antigen (0.29 +/- 0.79%). LPMC reactivity for individual gel-purified macromolecules of small bowel-derived ECAC (designated as the "P" series of components) was greatest against component P1 (by 2-3-fold), but was detectable against three other purified components as well. The addition of patient's serum did not enhance cytotoxicity to ECAC. Characterization of the cytotoxic cell showed that it was nonadherent to plastic surfaces, bore T lymphocyte-specific markers detectable by OKT 11 and OKT 3 monoclonal antibodies, and could be depleted by removal of cells with receptors for sheep erythrocytes. ECAC-specific reactivity was markedly reduced (greater than 93%) in most experiments when LPMC were preincubated for 1 h with ECAC. These data support the concept that autosensitization to several epithelial cell-associated components has occurred in patients with chronic inflammatory bowel disease, and provide initial evidence that antigen-specific, cell-mediated mechanisms may play a role in the pathogenesis of these disorders.
TGF-β1 signaling and Krüppel-like factor 10 regulate bone marrow–derived proangiogenic cell differentiation, function, and neovascularization
Authors: Akm Khyrul Wara, ShiYin Foo, Kevin Croce, Xinghui Sun, Basak Icli, Yevgenia Tesmenitsky, Fehim Esen, Jung-Soo Lee, Malayannan Subramaniam, Thomas C. Spelsberg, Eli I. Lev, Dorit Leshem-Lev, Reena L. Pande, Mark A. Creager, Anthony Rosenzweig, Mark W. Feinberg
Journal: Blood (2011)