tbuckley/cabot-search huggingface dataset:
Immune complexes and rheumatoid factors in canine arthritides.
Authors: S D Carter, S C Bell, A S Bari, D Bennett
Journal: Annals of the Rheumatic Diseases (1989)

Thirty two domestic dogs with naturally occurring polyarthritis were investigated to determine the contribution of autoimmunity in the pathological mechanisms. Comparisons were made with canine infective arthritis (12 dogs), osteoarthritis (32), and osteoarthritis secondary to rupture of the cranial cruciate ligament (19). Rheumatoid factors, immune complexes, and complement fixation (C1q binding) were measured in sera and synovial fluids. Compared with normal dogs (32), dogs with rheumatoid arthritis (RA) had increased serum and synovial fluid immune complexes and rheumatoid factors. Increases were generally also seen in dogs with other arthropathies, however. Rheumatoid factors were higher in sera than in synovial fluids. Rheumatoid factors correlated with immune complex levels and complexed rheumatoid factor only in the group of dogs with RA. Both rheumatoid factors and immune complexes may contribute to the pathogenesis of canine RA but are considered to arise as a result of non-specific inflammatory mechanisms in the non-rheumatoid groups.
Abortion in the first trimester
Authors: M. Brudenell
Journal: BMJ (1992)

tection should be available in time for the dipping season next year.General practitioners in rural areas can help by impressing on patients the importance of following the safety advice on the labels of all farm chemicals, including sheep dips, whether they contain organophosphates or not.Occasional reports are received of patients sus- pected to be suffering long term, recurrent effects from use of organophosphate sheep dips.Such effects do not equate with the known symptoms due to organophosphates used in sheep dips in Britain.The vague, flu-like symptoms of organophosphate poisoning resemble those of several zoonotic diseases (leptospirosis, brucellosis) en- countered in farm livestock.Awareness of the possibility of zoonotic disease is essential for a doctor faced with such symptoms in a patient who is associated with a farm.
Cardiac Involvement in Mitochondrial Diseases
Authors: Ryuichiro Anan, Masanori Nakagawa, Masaaki Miyata, Itsuro Higuchi, Shoichiro Nakao, Masahito Suehara, Mitsuhiro Osame, Hiromitsu Tanaka
Journal: Circulation (1995)

Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied.We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion.The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities.
Marriage Counseling in Medical Practice: A Symposium
Authors: Samuel Friedman
Journal: JAMA (1964)

The steadily increasing rate of divorce in our society indicates the desirability and need of more information and education in the field of marriage relationship. This book, recording symposia held in 1961 and 1962 under the sponsorship of the three North Carolina medical schools and two other organizations, admirably fulfills some of that need. There are four parts: marriage counseling by the physician, premarital medical counseling, concepts of marital diagnosis and therapy, and marriage counseling instruction in the medical school curriculum. In the lineup of contributors, Rex Speers proves an admirable lead-off man, with an excellent chapter on marriage counseling and the general practitioner. The language of Lansing's following chapter on sexual symptoms as presenting complaints is a welcome relief from the frequently encountered psychiatric jargon. It is lucid, down-to-earth, and entertaining. Eleanor Easley, a gynecologist and practical psychiatrist, deserves equal praise for her contribution on marriage problems and gynecologic
Genetic linkage studies in antithrombin‐deficient kindreds using a highly polymorphic trinucleotide short tandem repeat (str) within the human antithrombin gene
Authors: H. Ni, J. S. Waye, W. P. Sheffield, B. Eng, M. A. Blajchman
Journal: American Journal of Hematology (1994)

Abstract PCR amplification and analysis of short tandem repeats (STR) have provided a useful tool for genetic linkage studies and for the diagnosis of genetic disorders. We have recently identified a novel trinucleotide STR, (ATT) (TAA), in the fifth intron of the human antithrombin gene (AT3) located on chromosome 1q23. PCR amplification, cloning, and sequence analysis revealed this AT3‐STR to be highly polymorphic with repeat units ranging in size from (ATT) 5 to (ATT) 18 Ten distinct alleles were found in 81 unrelated Caucasian individuals (162 alleles) with an observed heterozygosity of 81%. Genetic linkage studies using the AT3‐STR in two previously described antithrombin (AT)‐deficient kindreds, AT‐Hamilton (Ala 382 Thr) and AT‐Amiens (Arg 47 Cys), demonstrate, in a given kindred, that a specific AT3‐STR polymorphism is strongly associated with a particular AT mutation. Thus, this highly polymorphic AT3‐STR should be very useful in performing linkage studies in AT‐deficient kindreds as well as in investigating other chromosome 1‐related genetic disorders. © 1994 Wiley‐Liss, Inc.
Use of Glycosylated Hemoglobin Levels for Diagnosing Diabetes Mellitus-Reply
Authors: Anne L. Peters
Journal: JAMA (1997)

<h3>In Reply.</h3> —We agree that calculation of an ROC curve can be a useful method for evaluating the trade-off between sensitivity and specificity of a test. We initially determined the ROC curve for our data, but chose not to present it because we were only interested in evaluating the characteristics of the glycosylated hemoglobin level at a very high specificity (≥95%) to minimize the number of false-positive diagnoses for diabetes. We did not believe that the data were sufficient to warrant publishing the "fine structure" of the curve between 95% and 100%. The important point is that, regardless of the cutpoint used, glycosylated hemoglobin levels and 2-hour tests are not identical. However, since glycosylated hemoglobin levels are used to evaluate and guide therapy for diabetes, we believe that it may be one of the most useful diagnostic tests for identifying patients who have diabetes requiring treatment.
Mucosal protection against sulphide: importance of the enzyme rhodanese
Authors: R Picton
Journal: Gut (2002)

Background: Hydrogen sulphide (H<sub>2</sub>S) is a potent toxin normally present in the colonic lumen which may play a role in ulcerative colitis (UC). Two enzymes, thiol methyltransferase (TMT) and rhodanese (RHOD), are thought to be responsible for sulphide removal but supportive evidence is lacking. Aims: To determine the distribution of TMT and RHOD in different sites throughout the gastrointestinal tract and their efficacy as detoxifiers of H<sub>2</sub>S. Methods: Enzyme activities were measured in normal tissue resected from patients with cancer. TMT and RHOD activities were determined using their conventional substrates, 2-mercaptoethanol and sodium thiosulphate, respectively. For measurement of H<sub>2</sub>S metabolism, sodium sulphide was used in the absence of dithiothreitol. Thiopurine methyltransferase (TPMT), which in common with TMT methylates sulphydryl groups but is not thought to act on H<sub>2</sub>S, was also examined. Results: TMT, RHOD, and TPMT activities using their conventional substrates were found throughout the gastrointestinal tract with highest activity in the colonic mucosa. When H<sub>2</sub>S was given as substrate, no reaction product was found with TMT or TPMT but RHOD was extremely active (Km 8.8 mM, Vmax 14.6 nmol/mg/min). Incubation of colonic homogenates with a specific RHOD antibody prevented the metabolism of H<sub>2</sub>S, indicating that RHOD is responsible for detoxifying H<sub>2</sub>S. A purified preparation of RHOD also detoxified H<sub>2</sub>S. Conclusions: RHOD, located in the submucosa and crypts of the colon, is the principal enzyme involved in H<sub>2</sub>S detoxication. TMT does not participate in the detoxication of H<sub>2</sub>S.
Aplastic Anemia: Biology and Treatment
Authors: Robert Peter Gale, Richard E. Champlin, Stephen A. Feig, John H. Fitchen
Journal: Annals of Internal Medicine (1981)

Aplastic anemia is characterized by decreased bone marrow function with inadequate production of erythrocytes, granulocytes, and platelets. Marrow failure may be caused by absence of or defects in hematopoietic stem cells, abnormalities of the bone marrow microenvironment, ineffective cell-to-cell interactions, or immune disorders. Although most patients with aplastic anemia have normal immunity, some have abnormalities of T- and B-lymphocytes. Rare patients have an immune cause of marrow failure. Treatment of aplastic anemia involves blood transfusions and withdrawal of potential causal factors. Efforts to stimulate hematopoiesis with androgens, corticosteroids, and other drugs have been largely unsuccessful. Some patients may recover after treatment with antithymocyte globulin or other immunosuppressive agents. Bone marrow transplantation is the preferred treatment for patients with severe aplastic anemia who have a human-leukocyte-antigen-identical related donor. Transplants of hematopoietic stem cells obtained from alternative sources, such as fetal liver cells or stem cells from long-term, in-vitro cultures, also may be useful.
Approach to risk assessment for genotoxic carcinogens based on data from the mouse skin initiation-promotion model.
Authors: F Burns, R Albert, B Altshuler, E Morris
Journal: Environmental Health Perspectives (1983)

Tumor induction data in the mouse skin initiation-promotion system were found to be consistent with a quadratic function where the coefficient of the linear term depended on the dose of the promoter. The model implies that the existence of promoters may be more important at low doses of the carcinogen than at high doses where most testing is performed. Experiments are described showing that the initiating effect of carcinogenic chemicals, such as benzo(a)pyrene, 7,12-dimethyl-benz(a)anthracene, nitroquinoline oxide and beta-propiolactone, accumulates in a linear, irreversible manner at low doses. Even when 7,12-dimethylbenz(a)anthracene was applied intragastrically to pregnant females, initiating activity was found in the skins of exposed offspring about in proportion to dose applied and number of cells at risk. The initiated cells essentially represent a potential for cancer that has a high probability for expression in the presence of a promoter. Risk then can be interpreted in terms of the accumulated dose of initiator which alone presents a small risk of cancer. However, a promoter may substantially expand the overall risk, possibly by clonally expanding the initiated cells. Promotion needs to be sustained since there is a reduction of cancer risk if promotion is ended early. Some tissues, such as mouse bladder, may be intrinsically promoted more than others so that comparisons between tissues and between species are best made when the combination of intrinsic promotion and response to extrinsic promotion are comparable.
What did audit achieve? Lessons from preliminary evaluation of a year's medical audit.
Authors: J Gabbay, M C McNicol, J Spiby, S C Davies, A J Layton
Journal: BMJ (1990)

OBJECTIVE--To evaluate the experience of a year9s audit of care of medical inpatients. DESIGN--Audit of physicians by monthly review of two randomly selected sets of patients9 notes by 12 reviewers using a detailed questionnaire dedicated to standards of medical records and to clinical management. Data were entered into a database and summary statistics presented quarterly at audit meetings. Assessment by improvement in questionnaire scores and by interviewing physicians. SETTING--1 District general hospital. PARTICIPANTS--About 40 consultant physicians, senior registrars, and junior staff dealing with 140 inpatient records. MAIN OUTCOME MEASURES--Median scores (range 1 to 9) for each item in the questionnaire; two sets of notes were discussed monthly at "general" audit meetings and clinical management of selected common conditions at separate monthly meetings. RESULTS--A significant overall increase in median scores for questions on record keeping occurred after the start of the audit (p less than 0.01), but interobserver variation was high. The parallel audit meetings on clinical management proved to be more successful than the general audits in auditing medical care and were also considered to be more useful by junior staff. CONCLUSIONS AND ACTION--Medical audit apparently resulted in appreciable improvements in aspects of care such as clerking and record keeping. Analysis of the scores of the general audits has led to the introduction of agreed standards that can be objectively measured and are being used in a further audit, and from the results of the audits of clinical management have been developed explicit guidelines, which are being further developed for criterion based audit.
Patterns of Ventriculo-Atrial Conduction in the Wolff-Parkinson-White Syndrome
Authors: HEIN J. WELLENS, DIRK DURRER
Journal: Circulation (1974)

In 36 patients with the Wolff-Parkinson-White syndrome, ventriculo-atrial (VA) conduction was studied using the single test stimulus method. In 22 patients no significant change in VA conduction time occurred following test stimuli with increasing prematurity suggesting exclusive VA conduction by way of the accessory pathway, an accessory pathway with a shorter refractory period than the His-AV node pathway, or identical refractory periods in both pathways. In 14 patients showing this VA conduction pattern tachycardias could be initiated by a single early ventricular premature beat. This finding lends credence to the hypothesis that the accessory pathway is an essential link in the tachycardia circuit. In two of the five patients showing exclusive VA conduction over the His-AV node pathway single re-entrant beats with antegrade conduction over the accessory pathway could be elicited by appropriately timed ventricular premature beats. In one patient showing this pattern a sustained tachycardia with AV conduction over the accessory pathway could be initiated. A total of eight patients did not show VA conduction over the accessory pathway.
Site-Specific Amino Acid Replacement Matrices from Structurally Constrained Protein Evolution Simulations
Authors: María Silvina Fornasari, Gustavo Parisi, Julian Echave
Journal: Molecular Biology and Evolution (2002)

Evolutionary amino acid replacement rates depend on local structural environment (Overington et al. 1992; Koshi and Goldstein 1995). Recent models of protein evolution aim to take such site heterogeneity into account by using site-specific amino acid replacement matrices (Lio and Goldman 1998; Thorne 2000). This is a difficult task, mainly because of a lack-of-data problem: too many sequences would be needed to fit the large number of parameters required to specify the replacement matrix for each site. Two strategies have been used to tackle this problem. A first type of model assumes that protein sites can be classified into a limited number of structural classes. Then, class-specific replacement matrices are obtained by analyzing large databases of sequences (Thorne, Goldman, and Jones 1996; Lio et al. 1998). These models are promising, provided the assumption of universality of structural classes is a reasonable one. However, such replacement matrices cannot be fitted to the actual sequence family under analysis. A second strategy is to develop models that depend on a reduced number of parameters (Halpern and Bruno 1998; Koshi and Goldstein 1998). These models have the advantage that they can, in principle, be fitted to the analyzed family. On the other hand, it is possible that the high reduction in the number of parameters oversimplifies such models to be generally applicable. Here we report a third strategy, which allows the determination of site-specific replacement matrices adapted to the sequence family under study, using just one member of the known structure. The lack-of-data problem is overcome by using large amounts of simulated sequence data generated using a structurally constrained protein evolution (SCPE) model developed recently (Parisi and Echave 2001). We apply the method to a case taken as an example and compare it with other models of protein evolution. We will deal with Markov models that assume that sequence sites evolve independently of each other. Even though this assumption is unrealistic, it is most often indispensable if the model is to be used for phylogenetic inference purposes. For a given site, an independentsites Markov model is completely characterized by a 20 3 20 matrix Q composed by the instantaneous timeindependent replacement rates Qij between amino acids
US drug trials expand outside academic centres
Authors: F. Charatan
Journal: BMJ (1999)

Since the emergence of managed care in the United States in 1990, clinical trials of new drugs have shifted from researchers working in university hospitals and medical schools to individual doctors with little experience in clinical research.

The growth of drug testing can be seen in the numbers of doctors who participate. In 1990, 4307 doctors conducted research studies, but in 1997, 11662 doctors conducted studies. While the number of academic and medical school researchers doubled, from 2225 to 4431, their “market share” dropped from one third to a quarter of the total. This has led to real competition between academia, medical schools, and private doctors for the lucrative research dollar.

The New York Times, which carried out a 10 month study of the drug testing industry, recently reported a story about Dr Robert Fiddes, who is currently serving …
Non-steroidal anti-inflammatory drugs (NSAID) sensitivity in chronic idiopathic urticaria (CIU): Selective involvement of cyclooxygenase 1 (COX-1) and overproduction of cysteinyl-leukotrienes (cys-LTs)
Authors: M. Setkowicz, A. Zembowicz, L. Mastalerz, W. Radziszwski, A. Szczeklik
Journal: Journal of Allergy and Clinical Immunology (2003)
Renal Failure in Phenazopyridine Overdose
Authors: Donald A. Feinfeld
Journal: JAMA (1978)

PHENAZOPYRIDINE hydrochloride (Pyridium) is widely used for analgesia of the lower urinary tract. The drug is thought to be safe; information for the prescriber cautions only against its use in renal failure, and a standard textbook of Pharmacology does not mention nephrotoxicity (other than stone formation) or complications of overdose in its section on the drug.<sup>1</sup>We report here a case of acute tubular necrosis in a previously healthy adolescent following acute overdosage with phenazopyridine. <h3>Report of a Case</h3> A 13-year-old girl, in prior good health and with a normal developmental history, was admitted to the gastroenterology service with a 24-hour history of yellow skin color and dark urine. On the day of admission, she had had several episodes of vomiting and abdominal cramps. Initial physical findings included normal temperature, pulse rate of 80 beats per minute and regular, and blood pressure of 120/70 mm Hg with no postural
Progressive Loss of Syk and Abnormal Proliferation in Breast Cancer Cells
Authors: Maria Moroni, Viatcheslav Soldatenkov, Li Zhang, Ying Zhang, Gerald Stoica, Edmund Gehan, Banafsheh Rashidi, Baljit Singh, Metin Ozdemirli, Susette C. Mueller
Journal: Cancer Research (2004)

Abstract The tumor suppressor gene Syk tyrosine kinase is absent or reduced in invasive breast cancer tissues and cell lines; its loss in breast tissues is linked to poor prognosis and metastasis. Also, evidence shows that in vitro Syk is involved in regulating proliferation. Here, we show by in situ hybridization on breast tissue sections that the loss of Syk expression is progressive during tumor development. Strikingly, Syk is already partially lost in normal epithelial tissue adjacent to the cancer lesion. In vivo, cell proliferation (as measured by the proliferative index Ki67) increased from normal to ductal carcinoma in situ to invasive, whereas Syk in situ staining in the same tissues decreased. In vitro, the presence of Syk was associated with reduced cell proliferation in an epidermal growth factor receptor-overexpressing breast cancer cell line, BT549, whereas changes in apoptosis were undetected. Concomitantly, the kinase activity of the proto-oncogene Src was reduced by ∼30%. A 5-fold increase in abnormal mitoses was observed in the Syk-transfected cells compared with vector control. We propose that Syk is involved in the regulation of cell proliferation, possibly by controlling mechanisms of mitosis and cytokinesis via Src signal transduction pathway(s). Because of its progressive and early loss during tumor onset and development, monitoring of Syk loss in breast epithelial cells by noninvasive techniques such as ductal lavage may be a powerful tool for screening purposes.
secondary Failure to Treatment with Oral Antidiabetic Agents in Non-insulin-dependent Diabetes
Authors: Leif C Groop, Risto Pelkonen, Saija Koskimies, Gian F Bottazzo, Deborah Doniach
Journal: Diabetes Care (1986)

To study the etiopathogenesis of secondary drug failure to treatment with oral antidiabetic agents in patients with non-insulin-dependent diabetes (NIDD) we compared 60 “nonresponders” with 60 “responders” to treatment with oral drugs. Secondary drug failure was defined as mean diurnal blood glucose &amp;gt;12 mmol/L after an initial good response of ≥2 yr. The nonresponders were characterized by 50% lower C-peptide concentrations than the responders (P &amp;lt; 0.001). We could not, however, define a critical C-peptide level to discriminate between patients requiring and not requiring insulin therapy. There was a wide overlap of individual C-peptide values between responders and nonresponders that attenuates the clinical value of single C-peptide measurements in predicting therapy. Only by serial measurements over a period of time was it possible to achieve information about changes in beta cell function. The nonresponders showed increased frequency of islet cell (P &amp;lt; 0.01), thyroid antimicrosomal (P &amp;lt; 0.01), and gastric parietal cell antibodies (P &amp;lt; 0.02). In nonresponders, HLA-antigen B8 was increased (P &amp;lt; 0.05) and HLA-B7 decreased (P &amp;lt; 0.01) compared with frequencies of responders. In conclusion, impaired beta cell function is a characteristic feature of many, but not all, NIDD patients who fail on treatment with oral antidiabetic drugs. The presence of islet cell and thyrogastric antibodies can unmask a distinct group of NIDD patients with a high risk of secondary drug failure and subsequent insulin dependency. HLA typing may further help to predict secondary failure in NIDD.