tbuckley/cabot-search huggingface dataset:
Hormone Replacement Therapy, Prothrombotic Mutations, and the Risk of Incident Nonfatal Myocardial Infarction in Postmenopausal Women
Authors: Bruce M. Psaty
Journal: JAMA (2001)

ContextEstrogens are known to be prothrombotic, and findings from the Heart and Estrogen/progestin Replacement Study suggest that in women with clinically recognized heart disease, hormone replacement therapy (HRT) may be associated with early harm and late benefit in terms of coronary events.Objective To assess whether, as hypothesized, prothrombotic mutations modify the association between HRT use and incidence of first myocardial infarction (MI). Design and SettingPopulation-based, case-control study conducted in a Seattlebased health maintenance organization.Participants Cases were 232 postmenopausal women aged 30 to 79 years who had their first nonfatal MI between 1995 and 1998.Controls were a stratified random sample of 723 postmenopausal women without MI who were frequency-matched to cases by age, calendar year, and hypertension status.Main Outcome Measure Risk of first nonfatal MI based on current use of HRT and the presence or absence of coagulation factor V Leiden and prothrombin 20210 G→A variants among cases and controls, stratified by hypertension. ResultsOne hundred eight MI cases and 387 controls had hypertension and 124 MI cases and 336 controls did not.Among hypertensive women, the prothrombin variant was a risk factor for MI (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.52-12.1)and, in this stratum, there was also a significant interaction between use of HRT and presence of the prothrombin variant on risk of MI.Compared with nonusers of HRT with wild-type genotype, women who were current users and who had the prothrombin variant (n=8) had a nearly 11-fold increase in risk of a nonfatal MI (OR, 10.9; 95% CI, 2.15-55.2).The interaction with the prothrombin variant was more pronounced in analyses assuming 100% compliance than in those assuming 80% compliance with HRT.The interaction was absent among nonhypertensive women and was less pronounced if hypertensive and nonhypertensive women were combined into 1 group.No interaction was found for factor V Leiden in either hypertensive or nonhypertensive women.Among hypertensive women, the estimates were affected only in trivial ways by adjustment, and the interaction with the prothrombin variant was specific to HRT.Conclusions Our results suggest that among postmenopausal hypertensive women, the association between HRT use and MI risk differed between those with and without the prothrombin 20210 G→A variant.If these findings are confirmed in other studies, screening for the prothrombin variant may permit a better assessment of the risks and benefits associated with HRT in postmenopausal women.
A CASE OF ACONITINE POISONING CAUSING CARDIAC COLLAPSE
Authors: Edward F. Hartung
Journal: JAMA (1930)

This case of aconitine poisoning is reported primarily to acquaint physicians with the possibility of its unsuspected occurrence. There are probably other cases of mild and severe aconitine poisoning throughout the United States which are being overlooked. Aconitine is a drug that finds little usefulness nowadays and naturally does not enter the physician's mind. Records of aconitine poisoning in any form are unusual in modern medical literature. In my perusal of the literature back to 1883, I could find only three case reports of aconitine poisoning in man with specific mention of its effect on the heart. There were no recent cases. Also, this is apparently the only case in man in which electrocardiographic records were obtained. <h3>REPORT OF CASE</h3> E. O., a merchant, aged 31, weighing about 242 pounds (110 Kg.), drank at about 4 p. m. a small amount of whisky which he had purchased a few weeks
Acute Bacterial Endocarditis Caused by<i>Erysipelothrix rhusiopathiae</i>
Authors: William L. Schiffman, Asher Black
Journal: New England Journal of Medicine (1956)

ERYSIPELOTHRIX rhusiopathiae, first described by Koch in 1880, was identified by Löffler1 in 1882 as the causative organism of swine erysipelas. Swine erysipelas affects mainly pigs, but infections with Ery. rhusiopathiae occur in other common barnyard animals, such as sheep, horses and fowl. Fish, as well as oysters and lobsters, also can be infected with this organism.In man the organism can cause erysipeloid, septicemia with arthritis and endocarditis. The erysipeloid form, first described by Rosenbach2 (1884) is usually a mild, localized cutaneous infection. His description of the skin lesions has not been improved upon. In 1887 he3 described them . . .
Interleukin 1 alpha causes rapid activation of cytosolic phospholipase A2 by phosphorylation in rat mesangial cells.
Authors: J Gronich, M Konieczkowski, M H Gelb, R A Nemenoff, J R Sedor
Journal: Journal of Clinical Investigation (1994)

We have shown previously that interleukin 1 (IL-1) stimulates eicosanoid production in glomerular mesangial cells (MC) by de novo synthesis of a 14-kD, group II phospholipase A2 (PLA2). IL-1-stimulated prostaglandin E2 synthesis precedes expression of this enzyme, suggesting that another PLA2 isoform must be more rapidly activated. In the presence but not absence of calcium inophore, [3H]arachidonate release is increased significantly as early as 5 min after addition of IL-1, and IL-1 concurrently stimulates a Ca(2+)-dependent phospholipase activity, which was characterized as the cytosolic form of PLA2 (cPLA2). IL-1 does not alter either cPLA2 mRNA expression or mass in serum-stimulated MC, suggesting that cPLA2 activity is increased by a posttranslational modification. IL-1 treatment for 30 min doubles 32P incorporation into immunoprecipitable cPLA2 protein, concordant with the increase in enzyme activity. Immunoblot analysis of extracts derived from IL-1-treated (30 min) cells demonstrates a decreased mobility of cPLA2, and treatment of MC lysates with acid phosphatase significantly reduces cytokine-activated cPLA2 activity, further indicating that IL-1 stimulates phosphorylation of the enzyme. IL-1 treatment (24 h) of serum-deprived MC doubled cPLA2 mRNA, protein, and activity. In summary, IL-1 increases cPLA2 activity in a biphasic, time-dependent manner both by posttranslational modification and de novo synthesis. We consider cPLA2 activation a key step in IL-1-stimulated synthesis of pro-inflammatory, lipid mediators, and an integral event in the phenotypic responses induced in target cells by this cytokine.
Home BP Measurement and Borderline Hypertension
Authors: Richard F. Gillum
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The conclusions of "Usefulness of Home BP Determination in Treating Borderline Hypertension" (1982;248:555) about detecting change are similar to those of our study,<sup>1,2</sup>which evaluated the effects of the nonpharmacologic intervention, sodium restriction, and potassium augmentation.<sup>3</sup>In addition to verifying the feasibility of using home BP determinations to detect small changes in BP, we performed cost-effectiveness analyses that demonstrated a substantial advantage for home BP determinations over clinic measurements.
Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events
Authors: Vanesa Caruso, Augusto Di Castelnuovo, Susana Meschengieser, Maria A. Lazzari, Giovanni de Gaetano, Sergio Storti, Licia Iacoviello, Maria Benedetta Donati
Journal: Blood (2010)
Progression From Compensated Hypertrophy to Failure in the Pressure-Overloaded Human Heart
Authors: Stefan Hein, Eyal Arnon, Sawa Kostin, Markus Schönburg, Albrecht Elsässer, Victoria Polyakova, Erwin P. Bauer, Wolf-Peter Klövekorn, Jutta Schaper
Journal: Circulation (2003)

The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF.Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed.These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.
Clinicopathologic and Pedigree Differences in Amsterdam I–Positive Hereditary Nonpolyposis Colorectal Cancer Families According to Tumor Microsatellite Instability Status
Authors: Laura Valle, Jose Perea, Pablo Carbonell, Victoria Fernandez, Ana M. Dotor, Javier Benitez, Miguel Urioste
Journal: Journal of Clinical Oncology (2007)

To establish the clinicopathologic and familial differences within Amsterdam I-positive families, showing either tumor microsatellite instability (MSI) or microsatellite stability (MSS) in order to confirm or deny the existence of hereditary nonpolyposis colorectal cancer (HNPCC) without defects in the mismatch repair system.Sixty-four Amsterdam I-positive families were included in the study for which full, three-generation, family medical histories and colorectal paraffin-embedded tumors were obtained. Both personal and clinicopathologic information of patients were collected. In all cases, both the MSI status and the mismatch repair (MMR) protein expression were analyzed. MMR genetic testing was performed on the MSI families.Of the Amsterdam I-positive families, 59.4% were tumor MSI, and 40.6% were tumor MSS. When comparing both groups, the statistical differences were observed in the age of onset (MSI, 41 years; MSS, 53 years); in the colorectal tumor location, more frequently proximal in MSI cases; in fewer mucinous tumors in MSS; and loss of MMR protein expression in the MSI tumors. Regarding the individual and familial cancer history, we observed a predominance of individuals with multiple primary tumors in MSI pedigrees, as well as differences in the type of tumors developed within the family.Our findings support the suspicion of another hereditary colorectal syndrome different from HNPCC and characterized by MSS, the normal MMR immunohistochemical expression, the presence of only colorectal tumors, and the absence of individuals with multiple primary tumors. All these circumstances suggest the existence of a non-MMR gene being responsible for this new syndrome.
Accuracy of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) for Measuring Children’s Competence to Consent to Clinical Research
Authors: Irma M. Hein, Pieter W. Troost, Robert Lindeboom, Marc A. Benninga, C. Michel Zwaan, Johannes B. van Goudoever, Ramón J. L. Lindauer
Journal: JAMA Pediatrics (2014)

An objective assessment of children's competence to consent to research participation is currently not possible. Age limits for asking children's consent vary considerably between countries, and, to our knowledge, the correlation between competence and children's age has never been systematically investigated.To test a standardized competence assessment instrument for children by modifying the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to investigate its reliability and validity, and to examine the correlation of its assessment with age and estimate cutoff ages.This prospective study included children and adolescents aged 6 to 18 years in the inpatient and outpatient departments of allergology, gastroenterology, oncology, ophthalmology, and pulmonology from January 1, 2012, through January 1, 2014. Participants were eligible for clinical research studies, including observational studies and randomized clinical trials.Competence judgments by experts aware of the 4 relevant criteria-understanding, appreciation, reasoning, and choice-were used to establish the reference standard. The index test was the MacCAT-CR, which used a semistructured interview format.Interrater reliability, validity, and dimensionality of the MacCAT-CR and estimated cutoff ages for competence.Of 209 eligible patients, we included 161 (mean age, 10.6 years; 47.2% male). Good reproducibility of MacCAT-CR total and subscale scores was observed (intraclass correlation coefficient range, 0.68-0.92). We confirmed unidimensionality of the MacCAT-CR. By the reference standard, we judged 54 children (33.5%) to be incompetent; by the MacCAT-CR, 61 children (37.9%). Criterion-related validity of MacCAT-CR scores was supported by high overall accuracy in correctly classifying children as competent against the reference standard (area under the receiver operating characteristics curve, 0.78). Age was a good predictor of competence on the MacCAT-CR (area under the receiver operating characteristics curve, 0.90). In children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%). The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%).The MacCAT-CR demonstrated strong psychometric properties. In children aged 9.6 to 11.2 years, consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR. The results contribute to a scientific underpinning of regulations for clinical research directed toward children.
Thromboxane A2 receptor blocking abrogates donor-specific unresponsiveness to renal allografts induced by thymic recognition of major histocompatibility allopeptides.
Authors: G Remuzzi, M Noris, A Benigni, O Imberti, M H Sayegh, N Perico
Journal: The Journal of Experimental Medicine (1994)

Recent in vitro studies have documented that thromboxane (Tx)A2 induces thymocyte apoptosis by acting on specific receptors abundantly expressed on the surface of immature T lymphocytes. No information is available on the in vivo relevance of this observation in development of self- or acquired tolerance. We and others have previously documented that injection of donor cells into adult thymus of experimental animals induced specific systemic unresponsiveness to allografts in the rat and mouse models. More recently, we have shown that intrathymic injection of synthetic class II major histocompatibility complex (MHC) allopeptides resulted in donor-specific unresponsiveness to renal allografts. The induction of unresponsiveness was abrogated by recipient thymectomy within the first week. We now report the effect of TxA2 blockade on acquired thymic tolerance to renal allografts induced by intrathymic injection of synthetic class II MHC allopeptides in the Wistar-Furth (WF) to Lewis rat strain combination. Administration of the TxA2 receptor blocker prior to transplantation or 2 wk postengraftment completely abrogated the unresponsive state. In addition, inhibiting the TxA2-forming enzyme by aspirin or dexamethasone also abolished the induction of acquired thymic tolerance. Evidence is also provided for a critical "dose" of peptides to be injected into the thymus to induce systemic unresponsiveness to renal allografts. These data, coupled with observations that activated peripheral T cells can circulate through the thymus, provide evidence that TxA2/TxA2 receptor interaction in the thymic microenvironment, leading to anergy/programmed cell death of activated T cells, may play an important role in the development of acquired unresponsiveness in vivo.
Corticotropin-releasing hormone regulates IL-6 expression during inflammation
Authors: Maria Venihaki, Pieter Dikkes, Allison Carrigan, Katia P. Karalis
Journal: Journal of Clinical Investigation (2001)

Stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by proinflammatory cytokines results in increased release of glucocorticoid that restrains further development of the inflammatory process. IL-6 has been suggested to stimulate the HPA axis during immune activation independent of the input of hypothalamic corticotropin-releasing hormone (CRH). We used the corticotropin-releasing hormone–deficient (Crh+/+) mouse to elucidate the effect of CRH deficiency on IL-6 expression and IL-6–induced HPA axis activation during turpentine-induced inflammation. We demonstrate that during inflammation CRH is required for a normal adrenocorticotropin hormone (ACTH) increase but not for adrenal corticosterone rise. The paradoxical increase of plasma IL-6 associated with CRH deficiency suggests that IL-6 release during inflammation is CRH-dependent. We also demonstrate that adrenal IL-6 expression is CRH-dependent, as its basal and inflammation-induced expression is blocked by CRH deficiency. Our findings suggest that during inflammation, IL-6 most likely compensates for the effects of CRH deficiency on food intake. Finally, we confirm that the HPA axis response is defective in Crh+/+/IL-6+/+ mice. These findings, along with the regulation of IL-6 by CRH, support the importance of the interaction between the immune system and the HPA axis in the pathophysiology of inflammatory diseases.
THE SURGICAL TREATMENT OF NON-PEDUNCULATED ABDOMINAL TUMORS.Read in the Section of Obstetrics and Diseases of Women at the Forty-first Annual Meeting of the American Medical Association, held in Nashville, Tenn., May, 1890.
Authors: HENRY O. MARCY
Journal: JAMA (1890)

The ovarian cystoma which develop without a pedicle are rare, and yet are met with sufficiently often to make their study of interest and practical importance. They have been called intra-ligamentous, under the belief that they develop with in the folds of the broad ligament, but I have never been able to demonstrate such origin. The explanation offered is that, by some error of development, the embryonic ovary becomes displaced. It has also been assumed that adhesions of the ovary to the folds of the broad ligament might cause these to grow with the tumor, and thus form a capsule over it. The ovary, when not diseased, is often found with some degree of variation of attachment, as well as distribution of vessels. The pedicle may be so short that the deeper portion is almost, or quite within the reflexion of the peritoneal investment of the ligaments. When such a
John Andrew Carron Brown
Authors: R. Warren
Journal: BMJ (2008)

John Carron Brown was known affectionately by his Norwich colleagues as JCB. After qualification and completion of positions as house surgeon at the Middlesex Hospital, John served as ship’s surgeon with the Royal Mail Shipping Company before, in 1952, becoming house physician at the Royal Sussex County Hospital. His general surgical training continued through St John and Elizabeth’s Hospitals and Redhill and Reigate Hospital before returning to the Middlesex Hospital and obtaining his FRCS.

JCB trained as an obstetrician and gynaecologist at the Chelsea Hospital for Women, the Middlesex Hospital, and Addenbrooke’s Hospital, Cambridge. He was appointed as a consultant in Norwich in 1963.

John led a busy life in …
Evaluation of a New In-vitro Blood Test for Determining Thyroid Status: The Effective Thyroxine Ratio
Authors: S. C. Thorson, E. K. Mincey, H. W. McIntosh, R. T. Morrison
Journal: BMJ (1972)

Estimation of serum thyroxine concentration in test serum was performed in the presence of test serum itself and expressed as a fraction (Effective Thyroxine Ratio, E.T.R.) of serum thyroxine concentration similarly determined in normal serum. From studies of serum obtained from euthyroid, hyperthyroid, and hypothyroid patients and from euthyroid pregnant women and women taking contraceptive (oestrogen) medication, the E.T.R. estimation has been shown to have a diagnostic accuracy (99%) in defining thyroid status comparable to that shown by the free thyroxine index (98%). Because of the ease and rapidity with which the procedure can be completed, estimation of E.T.R. shows promise as a single, accurate measure of thyroid status.
The Coming Election of Direct Representatives on the General Medical Council
Authors: H. R. Ker
Journal: BMJ (1891)

The presence of the human immunodeficiency virus (HIV) genome was investigated by applying in situ hybridisation techniques to peripheral blood mononuclear cells (PBMCs). Twenty asymptomatic anti-HIV seronegative homosexual men were the subjects of our study. The cells were hybridised with: (1) an SP 64 plasmid containing the nine-kilobase SstI-SstI viral insert from the lambda BH 10 recombinant clone; this can recognise both viral RNA and proviral DNA, and (2) with a pA01 plasmid containing HBV DNA genome. The DNA probes were modified by inserting an antigenic sulfone group in the cytosine moieties and the visualisation was performed by a double antibody immunohistochemical reaction. In two subjects both the HIV genome and HBV DNA were detected whereas another two subjects were positive for HBV DNA and for the HIV genome respectively. Thus people who are seronegative for anti-HIV specific antibodies may be infected with HIV.
Dopamine D<sub>2</sub> Receptor Density and Personal Detachment in Healthy Subjects
Authors: Alan Breier, Lisa Kestler, Caleb Adler, Igor Elman, Neil Wiesenfeld, Anil Malhotra, David Pickar
Journal: American Journal of Psychiatry (1998)

The purpose of this study was to examine the relationship between the personality trait involving personal detachment and dopamine D2 receptor specific binding in healthy subjects.Eighteen adult subjects completed the Karolinska Scales of Personality and the Tridimensional Personality Questionnaire and participated in a study that used [11C]raclopride positron emission tomography (PET) to quantify striatal D2 receptor binding.A significant relationship was found between D2 receptor specific binding and detachment scores on the Karolinska Scales of Personality but not between D2 receptor specific binding and attachment scores on the Tridimensional Personality Questionnaire. In an exploratory analysis, the authors found a significant relationship between binding and the sentimentality cluster on the Tridimensional Personality Questionnaire but on no other personality clusters scores on the Tridimensional Personality Questionnaire or Karolinska Scales of Personality.These findings replicate those of a recent report that personal detachment scores on the Karolinska Scales of Personality are related to dopamine D2 receptor density and extends this finding by suggesting that the relationship is relatively specific to the trait defined by the Karolinska Scales of Personality and does not generalize to other forms of detachment.
One-side-coated insert as a unique ophthalmic drug delivery system
Authors: Hitoshi Sasaki, Toshiaki Nagano, Koji Sakanaka, Shigeru Kawakami, Koyo Nishida, Junzo Nakamura, Nobuhiro Ichikawa, Junji Iwashita, Tadahiro Nakamura, Mikiro Nakashima
Journal: Journal of Controlled Release (2003)