tbuckley/cabot-search huggingface dataset:
In vivo mechanisms precipitating torsades de pointes in a canine model of drug-induced long-QT1 syndrome
Authors: D GALLACHER, A VANDEWATER, H VANDERLINDE, A HERMANS, H LU, R TOWART, P VOLDERS
Journal: Cardiovascular Research (2007)

Congenital loss of function and drug-induced inhibition of the slowly-activating delayed-rectifier K(+) current (I(Ks)) cause impaired cardiac repolarization. beta-Adrenergic-receptor stimulation contributes to sympathetically-induced torsades de pointes (TdP). An in vivo model of long-QT1 (LQT1) syndrome and TdP in a species with I(Ks) characteristics relevant to man is lacking. We investigated the in vivo mechanisms of TdP in a novel canine model of drug-induced LQT1 syndrome.Adult beagle dogs (n=30; F/M) were anesthetized with lofentanil (0.075 mg/kg i.v.) and etomidate (1.5 mg/kg/hour). ECGs, left- (LV) and right-ventricular (RV) monophasic action potentials (MAPs), and intracavitary pressures were recorded simultaneously. Infusion of the I(Ks) blocker HMR1556 (0.025-0.050 mg/kg/min) mimicked LQT1, and bolus injections of isoproterenol (1.25-5 microg/kg) reproducibly triggered TdP in 94% of dogs (defibrillated if necessary).Isoproterenol evoked paradoxical repolarization prolongation during heart rate accelerations. Beat-to-beat variability [QT, LV MAP duration (MAPD(90))] and spatial dispersion of repolarization (T(peak)-T(end) interval, endo-minus epicardial MAPD(90), LV-RVMAPD(90)) were significantly increased. Early afterdepolarizations occurred predominantly in the endocardium and not the epicardium. During isoproterenol, secondary systolic contractions (aftercontractions; peak 25+/-6 mm Hg) arose in the LV (not RV) when TdP ensued. Prevention of TdP by esmolol (1.25 mg/kg), verapamil (0.4 mg/kg) or mexiletine (5 mg/kg) was only successful when repolarization prolongation was contained and aftercontractions remained absent.beta-Adrenergic challenges trigger TdP in a reproducible manner in this model of drug-induced LQT1. Paradoxical prolongation and increased temporal and spatial dispersion of repolarization precipitate TdP. Incremental LV systolic aftercontractions precede TdP, suggesting abnormal cellular Ca(2+) handling contributes to the arrhythmogenic mechanism.
Changes in the Patient’s Perception of His Therapist in the Process of Group and Individual Psychotherapy
Authors: Celina Brykczyńska
Journal: Psychotherapy and Psychosomatics (1990)

The patient's perception of his therapist seems to be one of the major components of the therapeutic relationship. The different psychotherapeutic setting seem to influence the dynamics of the therapeutic relationship along with some other therapist and patient variables. Two groups of patients treated in the Department of Neurotic Disorders of the Institute of Psychiatry and Neurology (Warsaw) were investigated 2 times during their course of psychotherapies (individual, group). The perception of the therapist was measured by the Adjective Raging Scales constructed for the purpose of this research. These data were correlated with the results of the ACL (Gough) as a measure of personality traits and with the intensity of the clinical symptoms.
Pneumocystis carinii: The Spectrum of Diffuse Interstitial Pneumonia in Patients with Neoplastic Diseases
Authors: BRIAN GOODELL
Journal: Annals of Internal Medicine (1970)

The prospective experience with 18 cases of diffuse interstitial pneumonia in patients receiving immunosuppressive chemotherapy indicates that Pneumocystis carinii is the commonest cause of this form of pneumonia, comprising a minimum of 44% of the cases. A retrospective review of autopsy material of 22 patients dying from diffuse interstitial pneumonia showed a similar frequency. Cases diagnosed as probable or proved viral pneumonia comprised 15% of the total patients. Isolated cases of cryptococcal and toxoplasma pneumonia were noted. Tissue should be obtained to clarify the diagnosis in patients with diffuse interstitial pneumonia. In the proper clinical setting, empirical therapy with pentamidine isethionate should be given to all patients presenting with this form of pneumonia since the prevalence of pneumocystis pneumonia is quite high, and the disease is potentially curable.
Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart.
Authors: S M Pogwizd, R H Hoyt, J E Saffitz, P B Corr, J L Cox, M E Cain
Journal: Circulation (1992)

BACKGROUND To determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT. METHODS AND RESULTS Mapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation. CONCLUSIONS Both intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction.
Serial production of controlled periods of temporary heart block used to unmask and assess latent ventricular automaticity during experimental acute myocardial ischemia
Authors: Leonid V. Rosenshtraukh, Ferdinand Urthaler, Evgeny P. Anjukhovsky, Gala G. Beloshapko, Gilbert R. Hageman, Thomas N. James
Journal: Journal of the American College of Cardiology (1986)
Medroxyprogesterone Acetate and Diabetes Mellitus
Authors: JOSEPH C. BOTTINO
Journal: Annals of Internal Medicine (1976)

Comments1 March 1976Medroxyprogesterone Acetate and Diabetes MellitusJOSEPH C. BOTTINO, M.D., CHARLES K. TASHIMA, M.D.JOSEPH C. BOTTINO, M.D.Search for more papers by this author, CHARLES K. TASHIMA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-3-341 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Sutton and associates (1) observed one patient with a family history of diabetes mellitus who developed irreversible insulin-dependent diabetes after 1 year of, therapy with medroxyprogesterone acetate. They attributed this isolated event to a chance occurrence, noting the absence of evidence that progestational agents adversely affect carbohydrate metabolism. The case described below suggests that the appearance of overt diabetes in their patient may not have been simply coincidental with progestational therapy.Our patient is a 51-year-old white woman who underwent a left radical mastectomy and prophylactic oophorectomy for carcinoma of the breast in 1963. She was referred...References1. SUTTONZWILLICHCREAGH FCC: Progesterone for outpatient treatment of Pickwickian syndrome. Ann Intern Med 83:476-479, 1975 LinkGoogle Scholar2. KALKHOFF R: Effects of oral contraceptive agents and sex steroids on carbohydrate metabolism. Annu Rev Med 23:429-438, 1972 CrossrefMedlineGoogle Scholar3. GERSHBERGZORRILLAHERNANDEZ HEA: Effects of medroxyprogesterone acetate on serum insulin and growth hormone levels in diabetics and potential diabetics. Obstet Gynecol 33:383-389, 1968 Google Scholar4. MUGGIACASSILETHOCHOA FPM: Treatment of breast cancer with medroxyprogesterone acetate. Ann Intern Med 68:328-337, 1968 LinkGoogle Scholar5. ANSFIELDDAVISELLERBY FHR: A clinical trial of megestrol acetate in advanced breast cancer. Cancer 33:907-910, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine The University of Texas System Cancer Center Houston, Texas 77025 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHyperglycemia Secondary to Nondiabetic Conditions and TherapiesHyperglycemia Secondary to Nondiabetic Conditions and TherapiesMegestrol Acetate: Promises and PitfallsPhysical, metabolic, and hormonal effects on men of long-term therapy with medroxyprogesterone acetate**Supported by the Department of Pediatrics, University of Texas Medical Branch; The Hogg Foundation; The Upjohn Company; and grant RR73 from the Clinical Research Center Program of the Division of Research Resource, National Institutes of Health, Public Health Service.Megestrol acetate 1 March 1976Volume 84, Issue 3Page: 341-342KeywordsCarbohydrate metabolismDiabetes mellitusInsulinOophorectomy Issue Published: 1 March 1976 PDF downloadLoading ...
Traumatic Hemolysis with Iron Deficiency Anemia in Patients with Aortic Valve Lesions
Authors: ELAINE EYSTER
Journal: Annals of Internal Medicine (1968)

Twelve patients with symptomatic aortic valve disease and 12 patients with aortic ball-valve prostheses were studied for evidence of traumatic hemolysis. Low or absent haptoglobins suggesting an accelerated rate of red cell destruction were found in 3 of the 12 patients with diseased valves and 11 of the 12 patients with ball-valve prostheses. Two patients with diseased valves and three patients with ball-valve prostheses had hemosiderinuria. All but one of these had increased 24-hr urine iron excretions. Of the five patients with hemosiderinuria, two had severe hemolysis with iron deficiency anemia secondary to urinary iron loss. One of these patients had a prosthetic aortic valve. The other had severe aortic stenosis. In the remaining three patients, hemolysis was minimal. In all patients studied there was a marked diurnal variation in urinary iron levels with significantly greater amounts of iron being excreted during periods of activity than during periods of rest. Ferrokinetic and chromium survival studies indicated hemolysis by random destruction of red cells of all ages in three patients. Fourteen and one half percent of the injected dose of radioactive iron was recovered in the form of hemoglobin and hemosiderin from the urine of one patient. It is concluded that mechanical hemolysis can result in iron deficiency anemia in patients with aortic valve disease as well as in those with prosthetic aortic ball valves. Hemolysis occurs by random destruction of cells of all ages rather than as a consequence of cell aging in such patients. Because urinary iron loss may occur with minimal hemolysis, urines should be examined for hemosiderin in all such patients with anemia, fragmented red cells, and decreased serum haptoglobins.
Commons committee warns of risks in restructuring primary care
Authors: Andrew Cole
Journal: BMJ (2006)

The government's plans to restructure primary care trusts in England and contract out most of the services provided to patients have been attacked by the parliamentary select committee on health as “ill judged” and “mismanaged.”

“The risks of the proposals contained in Commissioning a Patient-led NHS [the Department of Health document outlining the reforms] are high and there is little evidence that the costs will be outweighed by the benefits,” it said. “Major restructuring should only be undertaken if there is an overwhelming argument in its favour; in this case there is not.”

The committee warns that the reforms—which aim to cut drastically the …
Geographic Pattern of Hodgkin's Disease in the United States
Authors: Kathreen Gimbrere
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Cole et al<sup>1</sup>have previously reported unusually low mortality rates of Hodgkin's disease among young whites in 11 Southern states of the United States, 1949 to 1954 and 1959 to 1961. We examined mortality data for 1960 to 1975 and found that the rates have remained low among young adults in this region. Neither study detected an unusual geographic distribution of Hodgkin's disease among whites older than 45 years of age. In our study, mortality rates for Hodgkin's disease among whites aged 15 to 34 years were 9% to 35% lower in the 11 Southern states than in the entire United States (Figure). The rates were reduced among both young men and women. This age-limited finding antedated the development of effective therapy for Hodgkin's disease and is unlikely to be due to results of treatment. In addition, incidence rates of this neoplasm were also low among
Amended funding has forced college to this position
Authors: I D Gainsford
Journal: BMJ (1995)

EDITOR,—Linda Beecham's item concerning increases in course fees for medical students who are pursuing their medical course as a second degree refers to a doubling of fees for the clinical course at King's College London.1 I would like to clarify the situation. For a limited period in the early 1990s higher education institutions were provided with additional funds to allow them to compensate home students who were responsible for funding …
Diagnostic value of measurement of serum type I procollagen carboxy terminal peptides in patients with scirrhous carcinoma of the stomach.
Authors: K Kohda, N Ito, M Ohwada, K Morita, N Watanabe, Y Kohgo, Y Mogi, Y Niitsu
Journal: Gut (1991)

We have evaluated the radioimmunoassay for type I procollagen carboxy terminal peptide (type I C-peptide), which is liberated from type I procollagen during its conversion to collagen, in the serodiagnosis of scirrhous carcinoma of the stomach. The mean (SD) serum concentration of type I C-peptide in 39 normal subjects was 41.7 (19.7) ng/ml. The mean serum values and the positive ratio of type I C-peptide in 11 patients with stages II and III scirrhous carcinoma of the stomach were 91.2 (41.9) ng/ml and 54.5%, respectively. In 10 patients with other types of gastric carcinoma, the mean type I C-peptide values were not significantly different from the normal value. Serum type I C-peptide values reflected the clinical course of scirrhous gastric carcinoma in five patients who underwent either operation or chemotherapy. The measurement of serum type I C-peptide concentrations could provide a useful way of diagnosing and monitoring scirrhous carcinoma of the stomach.
Comparative Study of "Virugon" and Penicillin in Measles
Authors: A. G. Brown, G. H. Renton, P. Griffiths
Journal: BMJ (1962)

VENO-OCCLUSIVE DISEASE OF ILIVER BEDIBsHNAL that this is the case.It remains possible that the toxic agent in our cases is contained in contaminated food.Further investigations of this source will be undertaken.Summary Veno-occlusive disease of the liver is discussed, particularly with reference to its aetiology and incidence.Twelve cases seen in African children are analysed.The age incidence of these cases was lower than in those reported from Jamaica, and it appeared in general that the younger the child the more likely he was to succumb to the illness.Another poor prognostic criterion appeared to be a raised serum bilirubin level; almost all patients with an abnormally high level died.A toxic aetiology in our cases has not been proved.
Aggressive Fluid and Sodium Restriction in Acute Decompensated Heart Failure
Authors: Graziella Badin Aliti, Eneida R. Rabelo, Nadine Clausell, Luís E. Rohde, Andreia Biolo, Luis Beck-da-Silva
Journal: JAMA Internal Medicine (2013)

The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (ADHF) are unclear.To compare the effects of a fluid-restricted (maximum fluid intake, 800 mL/d) and sodium-restricted (maximum dietary intake, 800 mg/d) diet (intervention group [IG]) vs a diet with no such restrictions (control group [CG]) on weight loss and clinical stability during a 3-day period in patients hospitalized with ADHF.Randomized, parallel-group clinical trial with blinded outcome assessments.Emergency room, wards, and intensive care unit.Adult inpatients with ADHF, systolic dysfunction, and a length of stay of 36 hours or less.Fluid restriction (maximum fluid intake, 800 mL/d) and additional sodium restriction (maximum dietary intake, 800 mg/d) were carried out until the seventh hospital day or, in patients whose length of stay was less than 7 days, until discharge. The CG received a standard hospital diet, with liberal fluid and sodium intake.Weight loss and clinical stability at 3-day assessment, daily perception of thirst, and readmissions within 30 days.Seventy-five patients were enrolled (IG, 38; CG, 37). Most were male; ischemic heart disease was the predominant cause of heart failure (17 patients [23%]), and the mean (SD) left ventricular ejection fraction was 26% (8.7%). The groups were homogeneous in terms of baseline characteristics. Weight loss was similar in both groups (between-group difference in variation of 0.25 kg [95% CI, -1.95 to 2.45]; P = .82) as well as change in clinical congestion score (between-group difference in variation of 0.59 points [95% CI, -2.21 to 1.03]; P = .47) at 3 days. Thirst was significantly worse in the IG (5.1 [2.9]) than the CG (3.44 [2.0]) at the end of the study period (between-group difference, 1.66 points; time × group interaction; P = .01). There were no significant between-group differences in the readmission rate at 30 days (IG, 11 patients [29%]; CG, 7 patients [19%]; P = .41).Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at 3 days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary.clinicaltrials.gov Identifier: NCT01133236.
Clinical, ultrasound and hormonal markers of androgenicity in acne vulgaris
Authors: S. WALTON, W.J. CUNLIFFE, K. KECZKES, A.S. EARLY, H.H.G. MCGARRIGLE, M. KATZ, R.A. REESE
Journal: British Journal of Dermatology (1995)

Androgenic stimulation of sebaceous glands is an important factor in the development of acne. We examined 36 females (aged 14-34 years), selected because none had received oral contraceptives, anti-androgen therapy, or systemic antibiotics during the previous year, or isotretinoin therapy, prior to their participation in the study. Subjects were divided into groups on the basis of acne severity, as follows: physiological, mild and moderate. Only two patients had polycystic ovaries on ultrasound examination. Seven patients had irregular menses; none had evidence of hirsutism. We found that the severity of acne, based on the acne grade, was highly correlated with the inflammatory lesion count, and less correlated with the sebum excretion rate. Either acne grade or inflammatory lesion count could be related to some of the five androgenic hormone determinants; free testosterone (TESTOS), delta 4 androstenedione (DELTA 4), sex hormone binding globulin (SHBG), dehydroepiandrostenedione sulphate (DHEAS) and dihydrotestosterone (DHT). Multiple linear regression analysis determined the best model for predicting ACNE scores as involving DELTA 4 and DHEAS (positive effects), and SHBG (negative effect), P < 0.005, R2 = 0.36). In none of the patients were the levels of DHEAS or SHBG outside the normal range. The findings in the two patients with polycystic ovaries did not differ significantly from those in the remainder of the patients.
Nuclear Medicine and Diagnosis of Renal Abnormalities
Authors: Wade E. Plauche
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Regarding the recent article "Urinary Tract Obstruction" by Older et al (1981;245:1854), no mention is made of the role of radionuclide (RN) studies in the identification and quantification of urinary tract obstruction. Nuclear medicine techniques play a dynamic role in many institutions in the radiological diagnosis of renal abnormalities, as do the abdominal roentgenogram, excretory urography, sonography, computed tomography, retrograde pyelography, and antegrade pyelography. The specific RN imaging and functional studies that are available include the renal flow study, renal and urinary tract imaging, and the renogram.
Translocation of endothelial nitric oxide synthase: Another feat of amlodipine, a cardiovascular jack-of-all-trades
Authors: B MAYER
Journal: Cardiovascular Research (2006)

See article by Batova et al.  [12]  (pages 478–485) in this issue. 

The antihypertensive drug amlodipine (Norvasc®) is a long-acting, third-generation Ca2+ channel blocker that has been shown to limit the progression of atherosclerosis and to decrease the incidence of cardiovascular events in humans [1]. It is generally well tolerated and often used in combination with diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and statins [2–4]. Amlodipine exhibits nanomolar affinity to dihydropyridine as well as benzothiazepine and phenylalkylamine binding sites of voltage-dependent L-type Ca2+ channels [5]. It is several-fold more lipophilic than the first- and second-generation Ca2+ channel blockers and adopts a well-defined position in the bilayer membrane [6]. It has been suggested that partitioning of amlodipine to membranes results in beneficial modification of the structure of cholesterol-rich membranes of vascular smooth muscle cells, an effect that might contribute to atheroprotection [7].

Besides the well-documented inhibition of L-type Ca2+ channels, amlodipine exerts additional effects that contribute to the improvement of vascular function in hypertension and ischemic heart disease [8]. There is both in vitro and in vivo evidence indicating that dihydropyridines including amlodipine act as antioxidants preventing the progression of atherosclerosis by interfering with lipid peroxidation. However, amlodipine has pharmacological properties distinct from other Ca2+ channel blockers. Probably most relevant to the antihypertensive and antiplatelet effects of the drug is the release of endothelium-derived nitric oxide (NO). …