tbuckley/cabot-search huggingface dataset:
Proof Arrives: Antilipids Save Lives
Authors: Marsha F. Goldsmith
Journal: JAMA (1994)

SCANDINAVIAN SKEPTICS carried the day over American enthusiasm. Results of a newly reported study may radically change the way cardiologists care for patients with coronary heart disease. In the United States, only one in four such patients is treated with lipidlowering drugs, despite an ardor for them based on what many European physicians considered flimsy evidence. The prevailing attitude across the ocean nurtured a rigorous scientific study that has produced proof of undeniable efficacy for anticholesterol agents. At the American Heart Association (AHA) annual meeting, in Dallas, Tex, Terje Pedersen, MD, head physician of the Coronary Care Unit at Aker University Hospital, Oslo, Norway, reported the long-awaited results of a study of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (Zocor, Merck &amp; Co Inc, Whitehouse Station, NJ). In heart attack survivors and persons with angina, this drug reduced not only the risk of heart attack but also the risk of
Corrigenda
Authors: T Hoashi, H Okochi, T Kadono, K Tamaki, M Nishida, S Futami, K Maekawa
Journal: British Journal of Dermatology (2008)

Accidental whole-body overexposure of radiation occurs very rarely. Radiation exposure causes DNA breaks in the cells and shows various clinical features, which are time dependent, dose dependent and tissue dependent. Neutron rays are more destructive than gamma rays but their actual effect on humans have been under-reported. We observed the time-dependent and the dose-dependent dermatological changes in a patient who was severely irradiated by neutron and gamma rays, with the aim of clarifying the clinicopathological features of severely irradiated skin. The detection of DNA breaks in keratinocytes was performed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique. The degenerative changes of the skin and the re-epithelialization varied in a time dependent and dose dependent manner. DNA breaks were significantly higher in irradiated keratinocytes. Neutron rays caused depth-dependent degeneration of the skin. Evaluation of DNA breaks in the skin cells might be a clue to estimate local dosimetry.
A Six-Year Follow-up of HIV-Infected Homosexual Men With Lymphadenopathy
Authors: Jonathan E. Kaplan
Journal: JAMA (1988)

Seventy-five homosexual men with generalized lymphadenopathy for at least three months (lymphadenopathy syndrome [LAS]), subsequently shown to be seropositive for antibody against human immunodeficiency virus, were enrolled in a prospective study in Atlanta in 1982 and 1983. As of Nov 30,1987, twenty-two (29%) of the 75 were known to have developed acquired immunodeficiency syndrome (AIDS) three to 60 months after enrollment and five to 69 months after onset of LAS. The six-year cumulative incidence of AIDS, by Kaplan-Meier survival analysis, was 38%. The cumulative incidence in years 4,5, and 6 (30%) was significantly higher than in years 1, 2, and 3 (11%), suggesting that the risk for AIDS increases after the third year of LAS and that many more study participants will eventually develop AIDS. A precipitous decline in the T-helper cell count frequently heralds the diagnosis of AIDS; this decrease appears to occur at different times after the onset of LAS in different persons. The four-year cumulative incidence of AIDS following observations of T-helper cell counts less than 200/mm<sup>3</sup>, 200 to 299/mm<sup>3</sup>, 300 to 399/mm<sup>3</sup>, and 400/mm<sup>3</sup>or greater was 84%, 41%, 25%, and 18%, respectively; these data are important for determining prognosis in the individual patient as well as for determining the suitability of candidates and baseline data for drug trials. (<i>JAMA</i>1988;260:2694-2697)
An Adenosine Triphosphatase Preparation from a Membrane-Sarcotubular Fraction of Guinea Pig Heart Muscle
Authors: VIVIAN KRESPI, HARRY A. FOZZARD, WILLIAM SLEATOR
Journal: Circulation Research (1964)

An adenosine triphosphatase ( ATP ase) was prepared from guinea pig heart muscle membranes. It was found to require magnesium for activity, and to be stimulated by the presence of sodium and potassium ions. The ATP ase was partially inhibited by strophanthin at concentrations of the order of 10 -6 M. The results confirm the observations of Auditore and Murray. 5
Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux.
Authors: D B Buxton, M Schwaiger, A Nguyen, M E Phelps, H R Schelbert
Journal: Circulation Research (1988)

The kinetics of [1-14C]acetate oxidation in isolated perfused rat hearts have been determined over a range of perfusion conditions. Effluent measurements demonstrated that 14CO2 cleared biexponentially over 50 minutes after bolus injection of [1-14C]acetate into normoxic hearts perfused with 5 mM glucose and 10 mU/ml insulin. The clearance half-time (t1/2) for the predominant initial clearance phase was 3.1 +/- 0.5 minutes (n = 4). MVO2 was varied over a fourfold range by hypoxia and phenylephrine stimulation (t1/2, 7.2 +/- 1.2 and 2.2 +/- 0.2 minutes, respectively) and in the presence of alternate substrates (lactate, 2 mM; DL-3-hydroxybutyrate, 20 mM; and palmitate, 0.1 mM), which did not modify either tricarboxylic acid (TCA) cycle flux or acetate kinetics. A good correlation (r = 0.93) was observed between k, the rate constant for the initial phase of 14CO2 clearance, and TCA cycle flux, estimated from oxygen consumption. In contrast to results with [1-14C]acetate, lactate (2 mM) increased t1/2 for 14CO2 clearance from a bolus injection of [1-14C]palmitate from 3.0 +/- 0.4 minutes (n = 3) at control to 4.3 +/- 0.2 minutes (n = 3, p less than 0.01). Addition of acetate in nontracer amounts (0.5 or 5 mM) caused significant underestimation of TCA cycle flux when estimated with [1-14C]acetate. 14CO2 clearance accounted for 88-98% of total effluent 14C between 10 and 20 minutes after [1-14C]acetate bolus injection; rate constants for clearance of 14CO2 and total 14C clearance were very similar during this period, and these two rate constants did not differ significantly from each other under any conditions tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of Adrenal Ornithine Decarboxylase by Adrenocorticotropic Hormone and Cyclic AMP
Authors: R. Richman, C. Dobbins, S. Voina, L. Underwood, D. Mahaffee, H. J. Gitelman, J. Van Wyk, R. L. Ney
Journal: Journal of Clinical Investigation (1973)

Adrenal ornithine decarboxylase activity was stimulated in a dose-related manner after administration of ACTH or dibutyryl ((6)N-2'-O-dibutyryl) cyclic AMP to hypophysectomized rats. Little effect was observed for 2 h, but striking increases in enzyme activity were observed 4 h after administration of these substances. Effects of ACTH and dibutyryl cyclic AMP were not secondary to stimulation of steroidogenesis, since hydrocortisone had no effect on adrenal ornithine decarboxylase although it did stimulate activity of the enzyme in the liver and kidney.ACTH, given subcutaneously to hypophysectomized rats, induced striking increases in adrenal cyclic AMP levels within 15-30 min with a fall towards the base line in 1 h. Increases in ornithine decarboxylase activity lag several hours after this endogenous cyclic AMP peak, in contrast to the stimulatin of steroidogenesis by the nucleotide that requires only 2-3 min. After graded doses of ACTH, increases in adrenal cyclic AMP levels at 30 min were paralleled by proportional increases in adrenal ornithine decarboxylase activity 4 h after hormone treatment. Whereas maximal levels of adrenal steroidogenesis have been observed at tissue cyclic AMP levels of 6 nmol/g. ACTH is capable of inducing increases in nucleotide levels up to 200 nmol/g or more. These high tissue levels of cyclic AMP, although unneccessary for maximal steroidogenesis, appear to stimulate adrenal ornithine decarboxylase activity. Several results in addition to the time lag in the stimulation of ornithine decarboxylase activity suggest a mechanism involving accumulation of the enzyme or some factor needed for its activity rather than direct activation of the enzyme by cyclic AMP. Thus, the addition of cyclic AMP directly to the ornithine decarboxylase assay mixture in vitro was without stimulatory effect. In addition, actinomycin D or cycloheximide in doses sufficient to block adrenal RNA and protein synthesis, respectively inhibited the stimulation of ornithine decarboxylase activity by ACTH in vivo. An adrenocortical cancer was found to maintain ornithine decarboxylase activity at very high levels, but did so at much lower cyclic AMP levels than those of ACTH-stimulated adrenals. It is concluded that ACTH stimulates adrenal ornithine decarboxylase activity and that this effect may be mediated by cyclic AMP. However, cyclic AMP be mediated by appear to be a determinant of the high level of enzyme activity found in adrenocortical cancer.
General practitioners' views of their FHSA
Authors: C M Vaughan-Griffiths
Journal: BMJ (1993)

between patient and doctor, facilitating diagnosis and management, but in hospital it is neglected.In Bath we are setting up video facilities in outpatient clinics to assess, analyse, and, hopefully, improve our techniques.Two weeks' introduction covering all aspects of practice work is not considered unusual for a trainee in general practice.Neither was the protected three hours a week of tutorials, lunchtime lectures, and a day release course and the encouragement to attend outside courses.There was a half day off a week.Learning was centred on the trainee and not arbitrary, responding to the needs of the student.This sort of arrangement, which is structured but in which the student is not spoon fed, puts many hospital specialties to shame; The Royal College of General Practitioners is beginning to put pressure on those hospital posts incorporated into vocational training schemes to offer similar educa- tional programmes.Hopefully, this will filter through to the less privileged members of other institutions.All too often in hospital the reality is of a world that struggles to find adequate time for study, where there is little structured training and no half days to relieve the pressure.Morale is low among juniors; I wonder why.Just as general practitioners spend a proportion of their time training in hospitals so hospital practice can learn from primary care.I join with Cubitt in recommending that all hospital practitioners, trained or in training, should try to spend some time in general practice.
Stretch marks during pregnancy: a review of topical prevention
Authors: K. Korgavkar, F. Wang
Journal: British Journal of Dermatology (2014)

Striae gravidarum (SG), or stretch marks developing during pregnancy, affect up to 90% of women. While not medically dangerous, SG can be disfiguring, causing emotional and psychological distress. However, studies specifically addressing the prevention of SG, especially during pregnancy, are sparse. Furthermore, the molecular pathogenesis of SG is unclear and may differ from that of striae from other causes. Considering these factors, we review topical modalities that have been used specifically for preventing SG during pregnancy. We identify two major strategies (end points) addressed by these modalities, namely (i) preventing the de novo development of SG and (ii) reducing the severity of SG that have recently developed. We also identify risk factors for the development of SG and suggest that pregnant women with these risk factors are an appropriate target population for prevention. In reviewing the literature, we find that there is limited evidence that centella, and possibly massage with bitter almond oil, may prevent SG and/or reduce their severity. There is weak evidence that hyaluronic acid prevents SG. Tretinoin holds promise for reducing the severity of new-onset SG, but its use is limited by its pregnancy category. Finally, cocoa butter and olive oil are not effective for preventing SG or reducing the severity of lesions. We conclude that reliable methods for preventing SG are scarce. Furthermore, available topical modalities generally lack strong evidence from rigorous, well-designed, randomized controlled trials with ample numbers of subjects. Thus, further research is necessary to elucidate SG pathogenesis, which may lead to effective prevention modalities.
Qualities of a good surgeon
Authors: R K Choudhary
Journal: BMJ (2004)

He is a good surgeon who possesses courage and presence of mind, a hand free from perspiration, tremorless grip of sharp and good instruments, and who carries his operation to success and to the advantage of his patient, who has entrusted his life to the surgeon. The surgeon should respect the absolute surrender and treat his patient as his own son.

Susrata, recognised as the father of Indian surgery, who wrote his treatise 2500 years ago
Urinary levels of trichloroacetic acid, a disinfection by-product in chlorinated drinking water, in a human reference population.
Authors: Antonia M Calafat, Zsuzsanna Kuklenyik, Samuel P Caudill, David L Ashley
Journal: Environmental Health Perspectives (2002)

Trichloroacetic acid (TCAA), a known mouse liver carcinogen and a possible human carcinogen, is found in chlorinated drinking water. We measured TCAA in archived urine samples from a reference population of 402 adults using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. TCAA was detected in 76% of the samples examined at concentrations ranging from < 0.5 micro g TCAA/L to more than 25 micro g/L; the 90th percentile concentration was 23 micro g/L (22 micro g TCAA/g creatinine); and the geometric mean and median concentrations were 2.9 micro g/L (2.6 micro g/g creatinine) and 3.3 micro g/L (3.2 micro g/g creatinine), respectively. The frequency of detection of TCAA in urban areas was higher than in rural areas (p = 0.00007), and sex and place of residence (i.e., urban vs. rural) were found to have a significant interaction in modulating the levels of TCAA (p = 0.012). Urban residents had higher mean levels of TCAA (men, 5.3 micro g/L, 3.8 micro g/g creatinine; women, 2.9 micro g/L, 2.8 micro g/g creatinine) than did rural residents (men, 2.2 micro g/L, 1.7 micro g/g creatinine; women, 2.6 micro g/L, 2.7 micro g/g creatinine). The higher frequency of detection of TCAA in urban than in rural areas and higher levels of TCAA among urban than among rural residents may reflect the fact that urban residents use primarily chlorinated water from public water supplies, whereas those in rural areas are more likely to obtain water from private wells, which typically are not chlorinated.
Pharmacotherapy of Depression: Applications for the Outpatient Practitioner
Authors: J. Raymond DePaulo
Journal: JAMA (1992)

The editor describes this book as a discussion of antidepressant treatment strategies intended for office-based physicians, apparently both psychiatrists and nonpsychiatrists. He cautions that the book is not a "how-to" manual for treating depression. Generally, multiauthored compendia on treatment of particular disorders are fraught with problems. They tend to be obsolete by publication time, chapters may overlap and present contradictory messages, and the quality of the writing may vary enormously. With rare exceptions, the editor of this volume has cleared the high hurdles and, in doing so, provides a book of substance and even some style. The best of the chapters give brief overviews of particular empirical treatment strategies and discuss their methodological and mechanistic implications. The chapters on neurotransmitter receptor sensitivity, anticonvulsants, and thyroid augmentation provide enlightening discussion of how medications with apparently opposite effects on thyroid function might have similar clinical effects on affective disorders. The issue is
Prophylactic heparin in palliative care: …to a challenging idea
Authors: John C Chambers
Journal: BMJ (2006)

Ramifications of screening for breast cancerSee Research p 689 in 4 cancers detected by mammography are pseudocancersEditor-In this issue Zackrisson et al report on follow-up data from the Malmö mammographic screening trial and conclude that the rate of overdiagnosis of breast cancer was 10%. 1 They do not, however, calculate the risk we believe is most relevant to women considering mammography: What is the chance that a screen detected cancer represents overdiagnosis?After 15 years of follow-up, there were 1320 diagnosed in the screened group and 1205 in the control group (table 1).The excess detection of 115 cancers associated with screening led to their conclusion of an overdiagnosis rate of 10% (115/1205).However, because the intervention had stopped 15 years earlier and yet breast cancer cases continue to accumulate in both groups, the approach understates the risk of overdiagnosis.A more relevant denominator is the number of cancers found in the screened group at the end of the trial-741 (table 2).This addresses the question: Were I found to have cancer after being randomised to screening, how likely is it to represent overdiagnosis?As shown in the figure, using this denominator the risk of overdiagnosis is 15% (115/741).However, many of the cancers detected in the screened group are not detected by screening.They are instead clinically detected (either during the interval between screening examinations or among nonattenders).The most relevant denominator is the number of screen detected cancers found at the end of the trial.This addresses the question: Were I found to have cancer by a mammogram, how likely is it to represent overdiagnosis?Although this denominator is not reported by Zackrisson et al, the original BMJ article describing Malmö reported that 64% of the cancers detected in the screened group were detected by screening mammography. 2Thus one can deduce that the number of screen detected cancers at the end of the trial was about 475.As shown in the figure, using this denominator the risk of overdiagnosis is 24% (115/475).
Intercaval Block in Normal Canine Hearts
Authors: Ruediger Becker, Alexander Bauer, Stephan Metz, Ralf Kinscherf, Julia C. Senges, Kirsten D. Schreiner, Frederik Voss, Wolfgang Kuebler, Wolfgang Schoels
Journal: Circulation (2001)

The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities.To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10x10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S(1)S(1)=200 ms) and introduction of up to 2 extrastimuli (S(2), S(3)). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1+/-0.4 versus 0.5+/-0.2 m/s, P<0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5+/-0.3 versus 0.6+/-0.2 m/s, P=NS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not >30 ms. During S(3) stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region.Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.
Streptozotocin Diabetes CORRELATION WITH EXTENT OF DEPRESSION OF PANCREATIC ISLET NICOTINAMIDE ADENINE DINUCLEOTIDE
Authors: Tom Anderson, Philip S. Schein, Mary G. McMenamin, David A. Cooney
Journal: Journal of Clinical Investigation (1974)

The diabetogenic activity of streptozotocin has been correlated with a reduction in pyridine nucleotide synthesis in the mouse pancreatic islet. To determine the specificity of this reduction for diabetogenicity, a comparative study of streptozotocin, its cytotoxic moiety, 1-methyl-1-nitrosourea, and alloxan was performed. Streptozotocin administered intraperitoneally (i.p.) producd a dose-related reduction in islet NAD which was proportional to the degree of diabetogenicity. A diabetogenic dose, 200 mg/kg, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.224 mumol/ml and reduced the mean islet NAD from a control of 0.78 to 0.15 pmol. At borderline, 150 mg/kg, and nondiabetogenic, 100 mg/kg, doses, plasma concentrations reached 0.161 and 0.136 mumol/ml, and NAD was 0.36 and 0.86 pmol/islet, respectively. 1-Methyl-1-nitrosourea, 100 mg/kg, attained a maximum N-nitroso intact 1-methyl-1-nitrosourea concentration of 0.162 mumol/ml and reduced the mean NAD to 0.58 pmol/islet, and was nondiabetogenic; 200 mg/kg attained a peak plasma concentration of 0.344 mumol/ml and depressed NAD to 0.38 pmol/islet, and was inconsistently diabetogenic. Islet NAD of 0.4 pmol/islet or greater is required for integrity of the beta cell. A diabetogenic dose of alloxan, 500 mg/kg, did not depress NAD, 0.85 pmol/islet, therefore confirming that its mechanism of diabetogenicity differs from that of streptozotocin. In vivo uptake of [methyl-(14)C]streptozotocin by islets was 3.8 times that of [methyl-(14)C]-1-methyl-1-nitrosourea, whereas uptake by the exocrine pancreas favored 1-methyl-1-nitrosourea over streptozotocin 2.4:1. The decreased islet uptake of 1-methyl-1-nitrosourea correlates with the 3.5 times increased molar dosage required to produce islet NAD depression comparable to that of streptozotocin, 150 mg/kg. These studies indicate that the glucose carrier of streptozotocin facilitates uptake of its cytotoxic group, 1-methyl-1-nitrosourea, into islets.
I. Apologia
Authors: HENRY BUCHWALD, RICHARD B. MOORE, RICHARD L. VARCO
Journal: Circulation (1974)

The authors have now had ten years of clinical experience with the partial ileal bypass operation for management of the hyperlipidemias. The human trial was preceded by and has been continuously complemented by research in the animal laboratory in an effort to provide a metabolic data base which will facilitate understanding of the rationale and effects of this means of lipid lowering therapy. In addition, the determination of cholesterol dynamics as influenced by partial ileal bypass has been studied in the clinical setting. Other independent investigators have published in this field confirming and extending our findings and, at times, differing in their results and conclusions. We have attempted both to review the extensive past literature in this area and to add previously unpublished original material in a three-part presentation: Part I, Apologia; Part II, Laboratory Experience; and Part III, The Clinical Status of the Partial Ileal Bypass Operation. At a time when the medical community must come to grips with the question of whether lipid lowering will influence the atherosclerotic risk rate, this task was undertaken in order to offer a comprehensive overview of what are the effective and safe means available to achieve lipid reduction.