tbuckley/cabot-search huggingface dataset:
The Austin Flint Murmur and the <i>a</i> Wave of the Apexcardiogram in Aortic Regurgitation
Authors: ELIZABETH PARKER, ERNEST CRAIGE, W. P. HOOD
Journal: Circulation (1971)

Hemodynamic data from 45 patients with either aortic regurgitation (with and without the Austin Flint murmur) or aortic regurgitation and mitral stenosis were correlated with the a -wave percentage amplitude of the apexcardiogram. Changes in the a wave correlated well with corresponding changes in left heart pressures but not with variations in volume. Of 15 patients in whom the ratio of the a wave to the total excursion during systole ( a /H ratio) was [See Equation in PDF file]13%, 11 had left ventricular end-diastolic pressures (LVEDP) &gt;20 mm Hg. All patients with a /H ratios &gt;15% had abnormal LVEDP. The converse was not true; 13 patients had elevated LVEDP with normal a /H ratios. Patients with aortic regurgitation and mitral stenosis had a /H ratios similar to those of normal subjects. The Flint murmur showed a significant correlation with left ventricular volume changes. Its presence was valuable in prediction of a large regurgitant volume and a high left ventricular stroke volume. It was also present in association with elevated left atrial mean pressure and elevated LVEDP. Thus, two ancillary findings in aortic regurgitation, a high a wave in the apexcardiogram and the Austin Flint murmur, are of value in anticipating alterations in left ventricular hemodynamics as determined by left-sided catheterization and volume studies.
Liability for Transfusion-Acquired Disease
Authors: Andrew Gettinger
Journal: JAMA (1987)

To the Editor.—  The recent update by Rabkin and Rabkin 1 on individual and institutional liability for transfusion-acquired diseases is a welcome communication to clinicians who routinely administer blood products. I am concerned that the review may not completely reflect the current legal status of transfusion in New Hampshire, however. In 1971, the New Hampshire legislature passed a law (Strict Liability and Implied Warranties Limited, NH RSA 507:8-b) eliminating the concept of strict liability in tort and implied warranty in relation to the procurement, furnishing, donation, processing, distributing, or use of blood products. The statute specifically states that individuals or corporations are not liable for damages except those caused by negligence. This statute was still in effect as recently as the 1985 cumulative supplement. It is important for physicians practicing in New Hampshire to be aware that interpretation of §402A of the Restatement of Torts, Second, and the application of
Estrogen Receptor Regulation of Carbonic Anhydrase XII through a Distal Enhancer in Breast Cancer
Authors: Daniel H. Barnett, Shubin Sheng, Tze Howe Charn, Abdul Waheed, William S. Sly, Chin-Yo Lin, Edison T. Liu, Benita S. Katzenellenbogen
Journal: Cancer Research (2008)

Abstract The expression of carbonic anhydrase XII (CA12), a gene that encodes a zinc metalloenzyme responsible for acidification of the microenvironment of cancer cells, is highly correlated with estrogen receptor α (ERα) in human breast tumors. Here, we show that CA12 is robustly regulated by estrogen via ERα in breast cancer cells, and that this regulation involves a distal estrogen-responsive enhancer region. Upon the addition of estradiol, ERα binds directly to this distal enhancer in vivo, resulting in the recruitment of RNA polymerase II and steroid receptor coactivators SRC-2 and SRC-3, and changes in histone acetylation. Mutagenesis of an imperfect estrogen-responsive element within this enhancer region abolishes estrogen-dependent activity, and chromosome conformation capture and chromatin immunoprecipitation assays show that this distal enhancer communicates with the transcriptional start site of the CA12 gene via intrachromosomal looping upon hormone treatment. This distal enhancer element is observed in the homologous mouse genomic sequence, and the expression of the mouse homologue, Car12, is rapidly and robustly stimulated by estradiol in the mouse uterus in vivo, suggesting that the ER regulation of CA12 is mechanistically and evolutionarily conserved. Our findings highlight the crucial role of ER in the regulation of the CA12 gene, and provide insight into the transcriptional regulatory mechanism that accounts for the strong association of CA12 and ER in human breast cancers. [Cancer Res 2008;68(9):3505–15]
Flt3-ITD mutations in a mouse model of radiation-induced acute myeloid leukaemia
Authors: R Finnon, N Brown, J Moody, C Badie, C-H Olme, R Huiskamp, E Meijne, M Sutmuller, M Rosemann, S D Bouffler
Journal: Leukemia (2012)

Acute myeloid leukaemia (AML) is one of the most common malignancies seen to occur in human populations exposed to ionising radiation.1 Mouse models have been widely used for quantitative and mechanistic studies of radiation leukaemogenesis; further, there is a similarity in the histopathological changes found in human AML and mouse AML. The majority of mouse radiation-induced AMLs (rAMLs) carry deletions of chromosome 2, and the Sfpi1/PU.1 haematopoietic transcription factor is located within the commonly deleted chromosome 2 region.2 In most rAMLs and rAML cell lines (70%), Sfpi1/PU.1 suffers hemizygous loss accompanied by point mutations in the region encoding the ETS DNA-binding domain, leading to base substitutions at the R235 residue of the protein.2, 3, 4 Sfpi1/PU.1 mutations have been identified in human AML, but these are rare; in contrast, the most common mutations in human AML involve the Flt3 receptor tyrosine kinase. Most of these mutations are internal tandem duplication (Flt3-ITD) of 3–400 bp5 that result in ligand-dependent dimerisation and receptor phosphorylation. The presence of a Flt3-ITD appears to confer a more severe phenotype and a poor prognosis for AML sufferers. The majority of the remaining non-ITD mutations in Flt3 occur in the second tyrosine kinase domain, being mostly point mutations within codon 835 or the deletion of 836.6
Changes in Career Satisfaction Among Primary Care and Specialist Physicians, 1997-2001
Authors: Bruce E. Landon, James Reschovsky, David Blumenthal
Journal: JAMA (2003)

<h3>Context</h3> A number of forces have changed the practice of medicine in the past decade. Evidence suggests that physicians are becoming less satisfied in this environment. <h3>Objectives</h3> To describe changes in career satisfaction in a large, nationally representative sample of physicians and to examine market and practice factors associated with changes in physician satisfaction. <h3>Design and Setting</h3> Data were collected from the first 3 rounds of the Community Tracking Study (CTS) Physician Survey, a series of nationally representative telephone surveys of physicians in 60 US sites conducted in 1996-1997 (round 1: 12 385 respondents; 65% response rate), 1998-1999 (round 2: 12 280 respondents; 61% response rate), and 2000-2001 (round 3: 12 389 respondents; 59% response rate) for the Center for Studying Health System Change. The second and third rounds of the survey included physicians sampled in the previous round, as well as new physicians. <h3>Participants</h3> Primary care and specialist physicians who spent at least 20 hours per week in direct patient care activities. <h3>Main Outcome Measures</h3> Changes in physicians' overall satisfaction with their career and the proportion of dissatisfied physicians in particular sites. <h3>Results</h3> Physician satisfaction levels declined marginally between 1997 and 2001, with most of the decline occurring between 1997 and 1999. Among primary care physicians, 42.4% were very satisfied in 1997, as were 43.3% of specialists, compared with 38.5% and 41.4%, respectively, in 2001. There were nearly equal increases in those who reported that they were somewhat satisfied. Overall means mask significant differences across the 60 sites. Among 12 sites randomly selected for more intensive study, the proportion of respondents who were somewhat or very dissatisfied ranged from 8.8% of physicians in Lansing, Mich (1999), to 34.2% in Miami, Fla (1997). Between 1997 and 1999, 25.6% of primary care physicians reported decreased satisfaction and 18.1% reported improved satisfaction, while approximately equal percentages reported increased (19.8%) and decreased (20.4%) satisfaction between 1999-2001. Findings were similar for specialist physicians. In multivariable models, the strongest and most consistent predictors of change in satisfaction were changes in measures of clinical autonomy, including increases in hours worked and physicians' ability to obtain services for their patients. Changes in exposure to managed care were weakly related to changes in satisfaction. <h3>Conclusions</h3> Our findings demonstrate that overall physician satisfaction levels over this time period did not change dramatically. In addition, satisfaction and changes in satisfaction vary greatly among sites. Rather than declining income, threats to physicians' autonomy, to their ability to manage their day-to-day patient interactions and their time, and to their ability to provide high-quality care are most strongly associated with changes in satisfaction.
German doctors accused of health insurance fraud
Authors: A. Tuffs
Journal: BMJ (2002)

A German practice association of 19 specialist doctors and a physiotherapist may have defrauded health insurance companies of a possible €10m (£6.4m; $10.1m) over the past five years.

The public prosecutor for Hanover, close to where the practice is based in Burgdorf, was alerted to the association's alleged fraud by the Kassenarztliche Vereinigung (KV) (association of statutory health insurance doctors) of Lower Saxony after the KV discovered several improbable bills from the Burgdorf association.

German doctors do not have contracts with health …
Salmonellosis Associated With Homemade Ice Cream
Authors: Robert A. Gunn
Journal: JAMA (1978)

During the period 1966 to 1976, 22 outbreaks with 292 individual cases of salmonellosis associated with the consumption of homemade ice cream were reported to the Center for Disease Control. Salmonella typhimurium accounted for 45% of the outbreaks. The source of eggs used was known in 13 outbreaks, and all were ungraded farm- or home-produced eggs, a potential source of salmonellae. In 11 outbreaks, the method of preparation was known, and in all, the ice-cream custard had not been cooked before freezing.
In vivo regulation of glycolytic and gluconeogenic enzyme gene expression in newborn rat liver.
Authors: S Lyonnet, C Coupé, J Girard, A Kahn, A Munnich
Journal: Journal of Clinical Investigation (1988)

Glucagon and its second messenger, cAMP, are known to rapidly block expression of the L-type pyruvate kinase gene and to stimulate expression of phosphoenolpyruvate (PEP) carboxykinase gene in the liver in vivo. The respective roles, however, of hyperglucagonemia, insulinopenia, and carbohydrate deprivation in the inhibition of L-type pyruvate kinase gene expression during fasting are poorly understood. In addition, the long-term effects of physiological hyperglucagonemia on expression of the two genes are not known. In this study, we investigate the effects of long-term physiological hyperglucagonemia and insulinopenia induced by suckling (which provides a high-fat, low-carbohydrate diet) on expression of the two genes in the liver of normal newborn rats. We show that transcription of the L-type pyruvate kinase gene is inhibited at birth and remains low during the whole suckling period, whereas transcription of the PEP carboxykinase gene is maximal in the neonate, and then decreases despite very high levels of plasma glucagon during suckling. In contrast to the adult, however, in which L-type pyruvate kinase gene expression in the liver is blocked by cAMP and stimulated by carbohydrates, the regulation of L-type pyruvate kinase gene expression in the newborn undergoes a developmental maturation: the inhibitory effect of glucagon is never complete in developing rat liver and the stimulatory effect of glucose could not be detected during suckling, due to either hyperglucagonemia, immaturity of the gene regulatory system, or both.
Rapid Assessment of Corticotropin Reserve After Pituitary Surgery
Authors: Nelson B. Watts
Journal: JAMA (1988)

Corticotropin deficiency may occur after pituitary surgery, and, if unrecognized and untreated, it can be fatal. In this study the insulin tolerance test was used to assess hypothalamic-pituitary-adrenal reserve five to seven days after pituitary surgery, and postoperative morning serum cortisol concentration was compared with the insulin tolerance test for predicting corticotropin deficiency. In 35 patients with pituitary tumors studied prospectively, 27 had normal insulin tolerance test results five to seven days after pituitary surgery; in these patients, the morning serum cortisol concentration two to three days after surgery was 250 nmol/L (9 micrograms/dL) or greater. Eight patients had subnormal insulin tolerance test results or clinical evidence of adrenal insufficiency; the morning serum cortisol concentration in these patients was 80 nmol/L (3 micrograms/dL) or less. Postoperative adrenal insufficiency was transient (one to three months) in five of these eight patients. We retrospectively identified 45 patients whose postoperative morning serum cortisol values were 200 nmol/L (7 micrograms/dL) or greater; none of these patients had clinical evidence of adrenal insufficiency. We conclude that a morning serum cortisol level obtained two to three days after surgery and 24 hours after the discontinuation of hydrocortisone accurately predicts postoperative corticotropin reserve.
Diabetic Peripheral Neuropathy: Amelioration of Pain With Transcutaneous Electrostimulation
Authors: Dinesh Kumar, Howard J Marshall
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Thirty-one patients with symptoms and signs of peripheral neuropathy were randomized to the electrotherapy or sham treatment (control) group. The electrostimulation was given by a portable unit (H-Wave machine) than generated a biphasic, exponentially decaying waveform (pulse width 4 ms, 25–35 V, ≥ 2 Hz). Patients treated each of their lower extremities for 30 min daily for 4 weeks at home. Nine patients from the sham-treatment group participated for a second period, during which all of them received the active electrotherapy. Patient's degree of pain and discomfort was graded on a scale of 0 to 5. RESULTS In the sham-treated group (n = 13), the neuropathic symptoms improved in five (38%) patients, and the pain score declined from 2.92 ± 0.13 to 2.38 ± 0.26 (P &amp;lt; 0.04), suggesting a procedure-related placebo effect. In the electrotherapy group (n = 18), symptomatic improvement was seen in 15 (83%) cases, 3 of which were completely asymptomatic; the pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 (P &amp;lt; 0.01) and the posttreatment pain scores were considerably lower (P &amp;lt; 0.03), indicating a substantial treatment effect over and above any placebo influence. Patients in the electrotherapy group reported greater reduction in symptoms (52 ± 7% vs. 27 ± 10% in control subjects, P &amp;lt; 0.05) on an analog scale. Moreover, the electrotherapy decreased pain scores (from 3.0 ± 0.62 to 1.56 ± 0.32, P &amp;lt; 0.02) in nine patients who had received sham treatment earlier. CONCLUSIONS A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy. This novel modality offers a potential non-pharmacological treatment option.
Improving the Supply of Physicians in Rural Areas
Authors: John E. Verby
Journal: JAMA (1992)

Pathman et al<sup>1</sup>are to be congratulated on their research of the comparative rural retention of National Health Service Corps (NHSC) physicians compared to non-NHSC physicians. There is a curious absence of significant documentation by the NHSC concerning retention of NHSC physicians compared to other rural physician programs and their success in retaining rural physicians.<sup>2-4</sup> See also pp 1552 and 1559. While I was director of the Rural Physician Associate Program (RPAP) for 20 years in Minnesota, I studied and experienced the reasons why medical students and physicians remain in or leave a rural community. The RPAP is a clinical clerkship during which third- and fourth-year medical students spend 9 to 12 months with a seasoned preceptor in a rural community.<sup>3</sup>They return to the medical school for their senior year with a host of attitudes, behaviors, and skills unobtainable by their non-RPAP classmates in the urban
Case 44-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Edwin W. Salzman, Stanley J. Robboy
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 66-year-old woman was admitted to the hospital because of mental deterioration.She was described as "emotionally unstable" but was physically well until seven months previously, when she began to have episodic belching with bouts of severe pain in the right upper abdominal quadrant that followed the ingestion of rich foods and were relieved by vomiting. Three months before admission pain and swelling in the right calf developed, and she entered another hospital. A diagnosis of thrombophlebitis was made, and heparin and warfarin were administered. A single stool specimen gave a + test for occult blood; sigmoidoscopic . . .
Quantitation of countercurrent exchange during passive absorption from the dog small intestine: evidence for marked species differences in the efficiency of exchange.
Authors: J H Bond, D G Levitt, M D Levitt
Journal: Journal of Clinical Investigation (1977)

The present investigation was designed to quantitatively assess the possible influence of countercurrent exchange on passive absorption from the small intestine of the dog. Villus blood flow was measured with a modification of the microsphere method. Simultaneously, the absorption from the gut lumen of five diffusible gases (H2, He, CH4, 133Xe, and CO) was determined. Villus blood flow averaged 0.247 +/- 0.03 (SEM) ml/min per g. The observed absorption of H2, He, CH4, and 133Xe was only 16.2 +/- 1.8, 12.8 +/- 2.3, 12.0 +/- 1.8, and 15.8 +/- 1.4 %, respectively, of what this villus blood flow could carry away if it reached perfect equilibrium with the luminal gases. This low absorption rate could result from diffusion limitation to absorption or countercurrent exchange. The diffusive permeability of the barrier seperating the luminal gases and villus blood flow was assessed by measuring the absorption rate of CO. Because absorbed CO binds tightly to hemoglobin, it cannot exchange, and when present in low concentrations its uptake is entirely diffusion limited. Knowledge of the diffusion rate through tissue of the unbound gases relative to that of CO made it possible to calculate the degree to which each of the unbound gases should equilibrate with villus tip blood. The percentage equilibration between lumen and blood at the villus tip for H2, He, CH4, and 133Xe was 99.7, 99.9, 75.6, and 36.0% , respectively. Each of these values greatly exceeded the percentage equilibration of blood leaving the villus (calculated from the observed absorption rate and villus blood flow) and indicated an exchange of 83.8, 87.2, 84.1, and 56.1% of initially absorbed H2, He, CH4, and 133Xe. This result is in accord with theoretical calculations which suggest that countercurrent exchange should be exceedingly efficient in the dog. The striking effect of countercurrent exchange on passive absorption in the dog differs from our previous studies in the rabbit where no exchange was demonstrated. This marked species difference may result from anatomical differences in villus architecture. The dog has long, densely packed villi while the rabbit has broad, widely spaced villi. In the dog, only the villus tips may equilibrate with the lumen, hence a countercurrent gradient may be established in the villus. The entire villus of the rabbit may equilibrate with the lumen and no gradient for countercurrent exchange can therefore be established.
Uptake of Calcium by Glycerinated Cardiac Slices
Authors: ALAN S. FAIRHURST, DONALD A. PALUS, DONALD J. JENDEN
Journal: Circulation Research (1967)

Partially glycerinated cardiac slices have been used to assess the effects of ryanodine and of mitochondrial and other inhibitors on calcium transport in systems that appear to retain a high degree of functional integrity. Strips of rabbit ventricle were extracted in 50% (w/v) glycerol for 24 hr at 4°C and slices 100 µ thick were cut on the freezing microtome. Such slices can bind 30 to 40 µmole of calcium/g of protein when incubated in medium containing 45 Ca in the form of a Ca-EGTA buffer, binding being decreased with increasing times of glycerination. The concentrations of ATP and of Ca 2+ required for halfmaximal activity are 5 x 10 -5 M and 10 -7 M respectively; both ATP and creatine phosphate must be present to elicit maximal uptake. Calcium accumulation appears to be attributable to the sarcoplasmic reticulum rather than to mitochondria, and is inhibited by caffeine, Salyrgan and ryanodine. Uptake is stimulated by oligomycin, but is not affected by azide, ouabain, carbachol, eserine, epinephrine or norepinephrine.
Seventeen years' experience of a voluntarily based drug rationalisation programme in hospital.
Authors: J. A. Baker, A. F. Lant, C. A. Sutters
Journal: BMJ (1988)

A study was carried out analysing the operation of a drug rationalisation programme in a central London teaching district that had evolved from experience over 17 years. Creation of a limited list of about 700 drugs had been achieved by local consensus. Drug selection was based on appraisal of efficacy, safety, and cost and was undertaken by means of collaborative participation of most consultant specialists in the district. Educative and other non-restrictive strategies for reinforcing the rationalisation policy had achieved a consistently high rate of compliance in prescribing recommended drugs. The concept of selectivity in drug use and its continuous local reappraisal had a beneficial impact on the prescribing habits of doctors at all levels of seniority as well as on the training of medical undergraduates and nurses in the therapeutic use of medicines. Peer review and self audit were encouraged by use of an extensive monitoring system which incorporated continuous "facilitative" dialogue between ward pharmacists and prescribers. Two models of drug rationalisation programme were studied, the second of which together with other local initiatives had been associated with substantial and sustained reductions in drug spending each year over nine years since 1978. It is concluded that the second drug rationalisation programme model substantially improves the cost effective use of drugs in hospital and furthermore has the potential of being extended to general practice, especially in types of prescribing that are common to both forms of patient care.
Cellular immunity in systemic lupus erythematosus as evidenced in vitro by leucocyte migration inhibition tests.
Authors: M Okubo, Y Nagura, D Pompa, G Treser, K Lange
Journal: Annals of the Rheumatic Diseases (1977)

A leucocyte migration inhibition test was performed on 26 patients with systemic lupus erythematosus (SLE) and on 35 control subjects using three different antigens, fetal calf thymus DNA, baker's yeast RNA, and calf thymus extractable nuclear antigen (ENA). Leucocyte migration was inhibited by DNA in 17 out of 26 SLE patients (65-3%), and in only 2 of the 35 controls (5-7%). When RNA or ENA was added none of the patients or controls showed inhibition. In SLE patients migration inhibition by DNA was significantly correlated with the presence of proteinuria and/or granular casts in urinary sediment. When the migration inhibition test was positive, immunofluorescence verified active histology of the glomeruli obtained by a percutaneous renal biopsy.