tbuckley/cabot-search huggingface dataset:
Estrogen Replacement Therapy in Breast Cancer Survivors
Authors: Jeffrey A. Perlman
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The Special Communication on ERT in breast cancer survivors<sup>1</sup>noted potential National Cancer Institute support of new clinical investigations. A National Cancer Institute Working Group considered certain hormone combinations for short-term menopausal symptom relief studies but did not support the contention by Cobleigh et al that ERT or ERT with tamoxifen can yet be safely tested in large phase III trials.<sup>2</sup> The article provided limited evidence on ERT safety for breast cancer survivors. First, data on recurrence and survival effects were presented but were limited to studies of "past" or "ever recorded" ERT use. These studies were confounded by the reversible nature of hormonal promotion; meaningful contingencies of current or long-term use were not presented.<sup>2</sup>The recurrence/survival studies were also too small to address the central question of the relative risk (RR) of tumor reactivation or second primary tumor. Survival studies may also have
Captopril and Hypertension
Authors: Daniel T. O'Connor
Journal: JAMA (1981)

This volume, the proceedings of a conference on captopril and hypertension, aims to cover three areas: (1) the physiology of blood pressure control and its alterations in hypertension, (2) the development of angiotensinconverting enzyme inhibitors, and (3) the clinical use of converting enzyme inhibitors. The chapters are well organized and lucidly written by noted authorities in each field. The chapters in section 1 are not especially germane to converting enzyme inhibition, but do provide up-to-date and informative glimpses of several areas of blood pressure research. Sections 2 and 3, on converting enzyme inhibitor development and clinical use, are in large part reprinted from the journal<i>Progress in Cardiovascular Diseases</i>, late 1978, which published a symposium on captopril at that time. Chapters on the clinical use of captopril are somewhat slanted, and perhaps slightly out of date, in that they focus only on blockade of the renin system as the antihypertensive
P50 Sensory Gating in Multiplex Schizophrenia Families From a Pacific Island Isolate
Authors: Marina Myles-Worsley
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Multiplex schizophrenia families from Palau, Micronesia, were assessed with P50 sensory gating to 1) test for replication of the association between this inhibitory neurobiological trait and familial schizophrenia in non-Caucasian subjects and 2) evaluate the ability of the P50 trait to serve as an endophenotype in a genetic linkage study of these families. METHOD: A paired-stimulus auditory event- related potential paradigm was used to examine P50 sensory gating in 85 schizophrenia patients (56 medicated with typical antipsychotics and 29 unmedicated), 83 of their first-degree relatives (46 parents and 37 siblings), and 29 normal comparison subjects. RESULTS: Auditory sensory gating as measured by the P50 ratio was similarly impaired in medicated and unmedicated schizophrenia patients compared to the normal subjects, and medication dose had no significant effect on any P50 variable. This impairment extended to first-degree relatives, who also showed significantly higher P50 ratios than the normal subjects. Abnormal P50 ratios were found in 64.7% of the schizophrenia patients and 51.8% of their first-degree relatives but only 10.3% of the normal subjects. CONCLUSIONS: P50 sensory gating deficits were confirmed in Palauan schizophrenia families. Rates of abnormal P50 sensory gating in relatives versus normal subjects resulted in a risk ratio of 5.0. Impairment was independent of medication effects, indicating that the P50 paradigm measures a stable neurobiological trait unaffected by treatment with typical antipsychotics. These results suggest that this trait can fulfill the major criteria for an endophenotype for genetic liability to schizophrenia in these multiply affected Palauan families.
Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.
Authors: R Bertoni, J Sidney, P Fowler, R W Chesnut, F V Chisari, A Sette
Journal: Journal of Clinical Investigation (1997)

The present study was designed to determine if highly conserved hepatitis B virus (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected patients. Peripheral blood mononuclear cells from 67 patients with acute hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated with three panels of peptides, each of which bind with high affinity to several class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these patients, 8 of the 19 peptides tested were found to represent CTL epitopes recognized by two or more alleles in each supertype. Two sets of nested peptides were recognized in the context of alleles with completely unrelated peptide binding specificities. Finally, promiscuous recognition by the same CTL of a given peptide presented by target cells expressing different A2 subtypes was also commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized by acutely infected or convalescent patients in the context of a wide range of HLA alleles have been identified. These results demonstrate the functional relevance of the supertype grouping of HLA class I molecules in a human viral disease setting. Furthermore, they represent a significant advance in the development of a totally synthetic vaccine to terminate chronic HBV infection and support the feasibility of a systematic approach to development of similar vaccines for prevention and treatment of other chronic viral infections.
LETTER FROM CAIRO, EGYPT.
Authors: J. A. S. Grant
Journal: JAMA (1889)

<i>The Sanitary Condition of India and its Teachings</i>.<sup>1</sup> In our last article we gave an account by an eye witness of the normal sanitary condition of a native hamlet in the suburbs of Calcutta, while no epidemic was raging. We now propose to lay before our readers an account of a visit, in December, 1887, to an Indian cholera stricken village also in the suburbs of Calcutta, in order that we may profit by the lessons taught us by the sad narrative. The epidemic here described is only part of that cholera epidemic, which has been spreading over the length and breadth of India since last year, and which is now raging in all its intensity in the Punjab. As all our readers know, India is the hot-bed of cholera, where it is always present in its endemic form, and where every three or four years it assumes an
284 Diagnostic value of fibrosis biochemical markers (fibrotest) for the screening of oesophageal varices in patients with chronic liver disease
Authors: D THABUT, J TRABUT, S LECALVEZ, V THIBAUT, J MASSARD, C DARONDEL, J MOUSSALLI, M MUNTEANU, F IMBERTBISMUT, D MESSOUS
Journal: Hepatology (2003)
PRE-HOSPITAL REPERFUSION STRATEGIES IN EARLY PRESENTERS OF ST-ELEVATION ACUTE MYOCARDIAL INFARCTION
Authors: Yves Lambert, Sophie Bataille, Xavier Mouranche, Jean-Michel Juliard, Christian Spaulding, Nicole Karam, Hugues Lefort, Fran-ois Duoas, Severine Cahuin-Graud, Patricia Jabre, Xavier Jouven, Frederic Lapostolle
Journal: Journal of the American College of Cardiology (2014)
Degraded collagen induces calpain-mediated apoptosis and destruction of the X-chromosome-linked inhibitor of apoptosis (xIAP) in human vascular smooth muscle cells
Authors: K VONWNUCKLIPINSKI, P KEUL, S LUCKE, G HEUSCH, J WOHLSCHLAEGER, H BABA, B LEVKAU
Journal: Cardiovascular Research (2005)

Objective: The extracellular matrix (ECM) of the atherosclerotic lesion is a crucial determinant of its stability, while its degradation by matrix metalloproteinases (MMPs) has been implied in plaque rupture. As accumulation of both MMP-derived collagen fragments and apoptotic smooth muscle cells (SMC) is observed at sites of plaque rupture, we tested the effect of polymerized and degraded type I collagen on the susceptibility of SMC to apoptosis. Methods: Human SMC were cultured on monomeric or polymerized collagen, and collagen gels were degraded by collagenase. Apoptosis was evaluated using antibodies to active caspases and their substrates. Calpain and caspase activity were measured using fluorogenic substrates. Results: Culture of SMC on polymerized collagen led to increased apoptosis compared to culture on monomeric collagen. In addition, we observed a distinct proteolytic degradation of the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis (xIAP). As MMP-1 was strongly activated in SMC on polymerized collagen, we examined the effect of degraded collagen fragments on xIAP cleavage and apoptosis. Degraded collagen induced rapid proteolytic processing of xIAP identical to that on polymerized collagen. We identified calpains as the proteolytic enzymes responsible for xIAP processing as: i) they were rapidly activated by degraded collagen; ii) recombinant calpain II processed xIAP in an identical manner, and iii) inhibition of calpains by BAPTA or calpeptin abrogated xIAP degradation in intact cells. The functional consequence of xIAP processing by calpains was a loss of its caspase-inhibitory potential. Calpain activation distinctly preceded caspase activation, and inhibition of calpains suppressed apoptosis. Conclusions: Collagen fragments proteolytically released from the ECM by MMPs may propagate apoptosis of SMC by calpain-mediated inactivation of anti-apoptotic proteins such as xIAP. This may be a novel mechanism of SMC apoptosis in biological settings of enhanced collagen degradation such as vascular remodeling, neointima formation, and atherosclerotic plaque rupture.
The Spatial Orientation of the Plane Including the Mean QRS and T Vector of the Normal Electrocardiogram
Authors: NOBORU KIMURA
Journal: Circulation (1953)

For measurement of the spatial orientation of planes in the analysis of the spatial vectorcardiogram, a simple device is developed to be used with Simonson's vector analyzer for the conventional electrocardiogram. The prospective value of this method is shown for the measurement of the plane including the mean QRS and T vector.
The design of probiotic studies to substantiate health claims.
Authors: Glenn R. Gibson, Robert J. Brummer, Erika Isolauri, Herbert Lochs, Lorenzo Morelli, Theo Ockhuizen, Ian R. Rowland, Jürgen Schrezenmeir, Catherine Stanton, Kristin Verbeke
Journal: Gut Microbes (2011)

The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials.
Haemorrhagic episodes in haemophilia: a 5-year prospective study.
Authors: J. Stuart, S. H. Davies, R. A. Cumming, R. H. Girdwood, A. Darg
Journal: BMJ (1966)

The use of fresh frozen plasma and of human and animal anti haemophilic fractions in the management of patients with classical haemophilia A allows effective treatment of their bleeding episodes, so that the risk to life is reduced and life expectancy itself is prolonged. Ramgren (1962) has estimated that there has been a doubling of the age at death of haemo philiacs in Sweden since 1942 compared with the period 1900-42. There have, however, been no parallel advances in the prevention of the disease, apart from genetic counselling and sterilization, since there is no method of correcting the genetic anomaly at the chromosome level. Thus there is a steadily increasing haemophilic population whose medical and social care results in an increasing burden to the community. The increasing importance of the medicosocial aspects of haemophilia has merited several excellent retrospective studies (Favre-Giliy, 1957 ; Ikkala, 1960 ; Ramgren, 1962 ; Wilkinson, Nour-Eldin, Israels, and Barrett, 1961) of the course of the disease and its social and economic consequences. The inherent disadvantages of any retrospective study are no less evident when applied to haemophilia. While accurate records can be made of school attendance, periods of unemployment, hospital admissions, etc., it is much more difficult to acquire clinical details of the less severe episodes which have necessitated tem porary los? of work or schooling but which have not required referral to hospital.
Hazards from Asbestos — More Problems for Hospital Staffs
Authors: John Lister
Journal: New England Journal of Medicine (1976)

IN this country the field of occupational medicine has possibly been somewhat neglected, but the findings of a recent report by the Parliamentary Commissioner, or Ombudsman, clearly emphasize the need both for an efficient occupational health service and for a competent factory inspector. The inquiry was undertaken at the request of a member of Parliament who was concerned about the high rate of asbestosis occurring in relation to an asbestos plant in the village of Hebden Bridge in his Yorkshire constituency. The plant known as Acre Mill, which is now closed, had been manufacturing a number of products from raw . . .
Cell survival in canine aortic heart valves stored in nutrient medium
Authors: B. MOCHTAR, A. W M VAN DER KAMP, E. J M ROZA-DE JONGH, J. NAUTA
Journal: Cardiovascular Research (1984)

For transplantation of viable aortic valves a period of preservation will generally be needed. To maintain cell viability during this preservation period valves can be stored in nutrient medium after sterilisation in an antibiotic solution. To obtain quantitative data about the survival of aortic valve fibroblasts after preservation, we determined the number of viable fibroblasts in canine aortic valves after several weeks of preservation. The results shows that after storage of 1 week in nutrient medium cell survival is about 80%, after 2 weeks cell survival has declined substantially, while after 3 weeks survival is already unacceptably low. Storage for periods over 4 weeks results in almost completely non-viable aortic valves. These results show that only valves preserved for 1 to 2 weeks in nutrient medium can be considered as viable aortic valves.
Europe’s drug companies are better than those in US in making drugs accessible to poor countries
Authors: Andrew Jack
Journal: BMJ (2008)

Drug companies in Europe do more to make drugs available and affordable to the world’s poor countries than their counterparts in the United States or Japan, concludes a new type of assessment of company policies.

The Access to Medicines Index (www.atmindex.org), a Dutch foundation established by Wim Leereveld, a former marketing consultant to the drug industry, tries to strip away the public relations rhetoric to quantify and compare meaningful corporate contributions.

Top ranked is GlaxoSmithKline, the UK based company that has been involved in researching a range of new treatments for diseases in the developing world. It also offers “tiered” pricing to sell drugs at large discounts to low income …
The Use of Lithium in Affective Disorders: I. Acute Endogenous Depression
Authors: RONALD R. FIEVE, STANLEY R. PLATMAN, ROBERT H. PLUTCHIK
Journal: American Journal of Psychiatry (1968)

A double-blind study involving 29 patients was designed to investigate the efficacy of lithium compared with imipramine in the treatment of acute endogenous depression. After two to three weeks, there was evidence of a moderate to strong antidepressant effect of imipramine, while lithium produced only a weak to mild antidepressant effect. The authors discuss these findings in the light of other reports on the use of lithium in the treatment of acute endogenous depression.
Let's add some psychology (and maybe even some evolution) to the mix
Authors: Daniel Brian Krupp, Pat Barclay, Martin Daly, Toko Kiyonari, Greg Dingle, Margo Wilson
Journal: Behavioral and Brain Sciences (2005)

Henrich et al.'s nice cross-cultural experiments would benefit from models that specify the decision rules that humans use and the specific developmental pathways that allow cooperative norms to be internalized. Such models could help researchers to design further experiments to examine human social adaptations. We must also test whether the “same” experiments measure similar constructs in each culture, using additional methods and measures.
Sepsis After Platelet Transfusions
Authors: David Ciavarella
Journal: JAMA (1992)

To the Editor.  —I read with interest the painstaking and well-executed study of Morrow et al 1 on transfusion-associated sepsis (TAS) after platelet transfusion. transfusion-associated sepsis occurred in seven of 29 738 transfusions, of which 10219 were platelet pools from multiple donors (MD) and 19519 were single donors (SD) obtained by apheresis. However, since the 10219 MD transfusions averaged 7.3 U of platelet concentrates per transfusion, a more pertinent denominator is the sum of all donor exposures, not transfusions. Thus, TAS occurred in seven of 94118 [(10219 × 7.3) + 19519] donor exposures, a rate of 0.0074%, or about one per 13460 exposures. This risk is some 30 to 40 times less than that of TA hepatitis and about five to 10 times greater than that of TA human immunodeficiency virus (HIV). 2   When the data in Morrow et al's Table 1 is recalculated (Table) using donor exposures as the
Effect of general practitioner education on adherence to antihypertensive drugs: cluster randomised controlled trial
Authors: Nudrat Noor Qureshi, Juanita Hatcher, Nish Chaturvedi, Tazeen H Jafar
Journal: BMJ (2007)

<b>Objective</b> To determine the impact of a simple educational package for general practitioners on adherence to antihypertensive drugs. <b>Design</b> Cluster randomised controlled trial. <b>Setting</b> Six randomly selected communities in Karachi, Pakistan. <b>Participants</b> 200 patients with hypertension taking antihypertensive drugs; 78 general practitioners. <b>Intervention</b> Care by general practitioners specially trained in management of hypertension compared with usual care. <b>Main outcome measure</b> Correct dosing, defined as percentage of prescribed doses taken, measured with electronic medication event monitoring system (MEMS) bottle. <b>Results</b> 200 patients were enrolled, and 178 (89%) successfully completed six weeks of follow-up. Adherence was significantly greater in the special care group than in the usual care group (unadjusted mean percentage days with correct dose 48.1%, 95% confidence interval 35.8% to 60.4%, versus 32.4%, 22.6% to 42.3%; P=0.048). Adherence was also higher among patients who had higher levels of education (P&lt;0.001), were encouraged by family members (P&lt;0.001), believed in the effect of drugs (P&lt;0.001), and had the purpose of the drugs explained to them (P&lt;0.001). <b>Conclusions</b> Special training of general practitioners in management of hypertension, emphasising good communication between doctors and patients, is more effective than usual care provided in the communities in Karachi. Such simple interventions should be adopted by other developing countries that are now facing an increasing burden of hypertension. <b>Trial registration</b> Clinical trials NCT00330408.
INTERRUPTIONS IN METABOLISM.
Authors: I. N. LOVE
Journal: JAMA (1897)

In the term metabolism we mean to express the group of phenomena whereby organic beings transform foodstuffs into complex tissue elements, and convert complex substances into simple ones, in the production of energy; in other words the entire process of tissue building, which includes the proper throwing off of unused débris and the elimination of excretory matter, the complete scheme of nutrition, tissue making, production of energy and the elimination of waste matter. After an individual has secured his growth, if no mistake has been made, we have an animal mechanism which, under proper conditions, should be good for seventy or eighty years of continued work. Any break in the continuity of this mechanism can safely be interpreted as due to an interruption in metabolism. This interruption may be and generally is at first a light one and if taken promptly may be easily corrected. If this be neglected and
MATERIA MEDICA AND THERAPEUTICS.
Authors: Martyn Paine
Journal: JAMA (1884)

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