tbuckley/cabot-search huggingface dataset:
A Controlled Trial of Oral Propranolol Compared With Injection Sclerotherapy for the Long–Term Magnagement of Variceal Bleeding
Authors: David Westaby, Rex J. Polson, Alexander E.S. Gimson, Peter C. Hayes, Karen Hayllar, Roger Williams
Journal: Hepatology (1990)

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina.
Authors: G A Mitchell, L C Brody, J Looney, G Steel, M Suchanek, C Dowling, V Der Kaloustian, M Kaiser-Kupfer, D Valle
Journal: Journal of Clinical Investigation (1988)

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G----A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.
HO-3867, a Safe STAT3 Inhibitor, Is Selectively Cytotoxic to Ovarian Cancer
Authors: Kellie S. Rath, Shan K. Naidu, Pushpa Lata, Hemant K. Bid, Brian K. Rivera, Georgia A. McCann, Brent J. Tierney, Adam C. ElNaggar, Veronica Bravo, Gustavo Leone, Peter Houghton, Kálmán Hideg, Periannan Kuppusamy, David E. Cohn, Karuppaiyah Selvendiran
Journal: Cancer Research (2014)

STAT3 is well corroborated preclinically as a cancer therapeutic target, but tractable translational strategies for its blockade by small molecule inhibitors have remained elusive. In this study, we report the development of a novel class of bifunctional STAT3 inhibitors, based on conjugation of a diarylidenyl-piperidone (DAP) backbone to an N-hydroxypyrroline (-NOH) group, which exhibits minimal toxicity against normal cells and good oral bioavailability. Molecular modeling studies of this class suggested direct interaction with the STAT3 DNA binding domain. In particular, the DAP compound HO-3867 selectively inhibited STAT3 phosphorylation, transcription, and DNA binding without affecting the expression of other active STATs. HO-3867 exhibited minimal toxicity toward noncancerous cells and tissues but induced apoptosis in ovarian cancer cells. Pharmacologic analysis revealed greater bioabsorption and bioavailability of the active (cytotoxic) metabolites in cancer cells compared with normal cells. The selective cytotoxicity of HO-3867 seemed to be multifaceted, eliciting differential activation of the Akt pathway in normal versus cancer cells. RNAi attenuation experiments confirmed the requirement of STAT3 for HO-3867-mediated apoptosis in ovarian cancer cells. In vivo testing showed that HO-3867 could block xenograft tumor growth without toxic side effects. Furthermore, in primary human ovarian cancer cells isolated from patient ascites, HO-3867 inhibited cell migration/invasion and survival. Our results offer preclinical proof-of-concept for HO-3867 as a selective STAT3 inhibitor to treat ovarian cancer and other solid tumors where STAT3 is widely upregulated.
The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study
Authors: M. El-Darouti, S. Marzouk, R. Abdel Hay, A. El Tawdy, M. Fawzy, T. Leheta, H. Gammaz, N. Al Gendy
Journal: British Journal of Dermatology (2009)

Pemphigus vulgaris (PV) represents a potentially life-threatening autoimmune blistering disease in which IgG autoantibodies are directed against cell-cell adhesion molecules. Tumour necrosis factor (TNF)-alpha has been suggested to have a possible role in the mechanism underlying acantholysis.This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV.The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regimen except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-alpha levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients.The serum level of TNF-alpha was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-alpha in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2.The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-alpha, and this decrease was associated with rapid clinical improvement.
Screening for impaired visual acuity in middle age in general practice.
Authors: D H Stone, D J Shannon
Journal: BMJ (1978)

Screening for impaired distant visual acuity was one component of a controlled trial of multiphasic screening in middle age carried out in two general practices. The prevalence of impaired visual acuity (6/18 or worse in the better eye) at the initial screening in 1967 was 9.6% overall, ranging from 5.9% in people aged 40-49 years to 16.3% in those aged over 60. The question "Do you have difficulty seeing distant objects?" had a low sensitivity and high specificity, rendering it unsatisfactory for use in mass population screening for visual impairment. The prevalences of impaired visual acuity in the screening and control groups at the survey in 1972 showed no significant differences in any age group. Mass screening for defects of visual acuity in the course of a multiphasic examination is thus unlikely to reduce the prevalence of impaired distant visual acuity in the community.
Sleep Deprivation and Performance of Residents
Authors: Steven Goodman
Journal: JAMA (1989)

To the Editor. —  I read the recent article of Deaconson et al 1 with great interest, followed by astonishment. The notion that performance on psychometric tests, spurred by financial incentives, is directly related to the quality of patient care is absurd. I wondered why this study, with conclusions so politically sensitive and contrary to the prevailing beliefs, appeared without editorial comment.  The words that define this study's problem are, We conclude that the repetitive episodes of sleep deprivation... do not impair the performance of residents on psychometric tests and, by implication, performance in the provision of patient care. By implication? This is a leap of illogic unsupported in the data or discussion, and the image it conjures up of the physician as a pegboard-punching automaton is misleading and offensive. The key word here is care, which went unmeasured and undiscussed. What sleep deprivation so insidiously and dangerously undermines is
ProNGF Induces p75-Mediated Death of Oligodendrocytes following Spinal Cord Injury
Authors: Michael S Beattie, Anthony W Harrington, Ramee Lee, Ju Young Kim, Sheri L Boyce, Frank M Longo, Jacqueline C Bresnahan, Barbara L Hempstead, Sung Ok Yoon
Journal: Neuron (2002)
Risk factors for the development of prosthetic valve endocarditis.
Authors: S B Calderwood, L A Swinski, C M Waternaux, A W Karchmer, M J Buckley
Journal: Circulation (1985)

Risk factors for the development of prosthetic valve endocarditis (PVE) were analyzed in 2642 patients undergoing initial valve replacement at the Massachusetts General Hospital from 1975 to 1982. Follow-up was available for 2608 patients (98.7%); the mean length of follow-up was 39.8 months. PVE developed in 116 patients (4.4%). The actuarial risk of PVE was 3.1% at 12 months and 5.7% at 60 months. A Cox model was used to identify risk factors for PVE. Recipients of multiple valves had a higher risk of PVE than single valves (p = .01). There was no difference in the risk of PVE for patients receiving aortic valves vs those receiving mitral valves. Recipients of mechanical valves had a higher risk of PVE than recipients of porcine valves in the first 3 months after surgery (p = .02), but the risk of PVE was higher for porcine valve recipients 12 months or more after surgery (p = .004). Despite this difference in the time course of development of PVE, there was no significant difference in the cumulative risk of PVE by 5 years of follow-up between mechanical and porcine valve recipients. Male sex was a risk factor for PVE within 12 months of aortic valve replacement (p = .008) but not thereafter; sex did not influence the risk of PVE after mitral valve replacement. Older patients had a higher risk of late PVE after multiple (p = .04) or mitral valve replacement (p = .08), but not after aortic valve replacement.
Propranolol Infusion After Abdominal Surgery-Reply
Authors: Harold Smulyan
Journal: JAMA (1983)

<h3>In Reply.—</h3> We are grateful to Hug et al for their letter, their interest, and their corroboration of the usefulness of propranolol infusions in patients after surgery. We also want to apologize for failing to cite their previous abstract (their reference 1). Comparison of their protocol with ours shows similar average infusion rates, although their doses were prescribed on a body-weight basis, and we found average doses to work as well. Administration of the usual oral propranolol dose just before surgery, in our hands, obviated the need for a bolus IV dose after surgery before the institution of the constant infusion. However, if 12 hours or more has separated the last oral dose from initiation of constant IV therapy, an IV bolus would be worthwhile, as they point out, to reach equilibrium sooner. They measured plasma propranolol levels several times each hour for four to seven hours. In the interest
Synovial histopathology of behcet's syndrome.
Authors: T Gibson, R Laurent, J Highton, M Wilton, M Dyson, R Millis
Journal: Annals of the Rheumatic Diseases (1981)

Synovial tissue obtained from 7 patients with Behçet9s syndrome and 7 patients with early rheumatoid arthritis could not be distinguished under ordinary light microscopy when examined blind. A wide spectrum of features was seen in both diseases, and it is suggested that these may reflect severity and duration as much as the nature of the arthritis. Electron microscopy also failed to illustrate any distinct features of Behçet9s syndrome, but immunofluorescent studies indicated consistent deposition of IgG.
Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion.
Authors: T F Tse, W E Clutter, S D Shah, P E Cryer
Journal: Journal of Clinical Investigation (1983)

The transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is not solely attributable to dissipation of insulin and, therefore, must also involve factors that actively raise the plasma glucose concentration--glucose counterregulatory factors. We have shown that the secretion of two of these, glucagon and epinephrine, is specific for glucose ingestion and temporally related to the glucose counterregulatory process. To determine the physiologic roles of glucagon and epinephrine in postprandial glucose counterregulation, we produced pharmacologic interventions that resulted in endogenous glucagon deficiency with and without exogenous glucagon replacement, adrenergic blockade, and adrenergic blockade coupled with glucagon deficiency starting 225 min after the ingestion of 75 g of glucose in normal subjects. Also, we assessed the effect of endogenous epinephrine deficiency alone and in combination with glucagon deficiency late after glucose ingestion in bilaterally adrenalectomized subjects. Glucagon deficiency resulted in nadir plasma glucose concentrations that were approximately 30% lower (P less than 0.01) than control values, but did not cause hypoglycemia late after glucose ingestion. This effect was prevented by glucagon replacement. Neither adrenergic blockade nor epinephrine deficiency alone impaired the glucose counterregulatory process. However, combined glucagon and epinephrine deficiencies resulted in a progressive fall in mean plasma glucose to a hypoglycemic level late after glucose ingestion; the final glucose concentration was 40% lower (P less than 0.02) than the control (epinephrine deficient) value in these patients, and was nearly 50% lower (P less than 0.001) than the control value and approximately 30% lower (P less than 0.05) than the glucagon-deficient value in normal subjects. We conclude (a) the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion is the result of the coordinated diminution of insulin secretion and the resumption of glucagon secretion. (b) Epinephrine does not normally play a critical role in this process, but enhanced epinephrine secretion compensates largely and prevents hypoglycemia when glucagon secretion is deficient.
Clinical Prediction Rules
Authors: John H. Wasson, Harold C. Sox, Raymond K. Neff, Lee Goldman
Journal: New England Journal of Medicine (1985)

The objective of clinical prediction rules is to reduce the uncertainty inherent in medical practice by defining how to use clinical findings to make predictions. Clinical prediction rules are derived from systematic clinical observations. They can help physicians identify patients who require diagnostic tests, treatment, or hospitalization. Before adopting a prediction rule, clinicians must evaluate its applicability to their patients. We describe methodological standards that can be used to decide whether a prediction rule is suitable for adoption in a clinician's practice. We applied these standards to 33 reports of prediction rules; 42 per cent of the reports contained an adequate description of the prediction rules, the patients, and the clinical setting. The misclassification rate of the rule was measured in only 34 per cent of reports, and the effects of the rule on patient care were described in only 6 per cent of reports. If the objectives of clinical prediction rules are to be fully achieved, authors and readers need to pay close attention to basic principles of study design.
Electrophysiologic effects of disopyramide phosphate in patients with Wolff-Parkinson-White syndrome.
Authors: C R Kerr, E N Prystowsky, W M Smith, L Cook, J J Gallagher
Journal: Circulation (1982)

We evaluated the electrophysiologic effects of disopyramide phosphate in 12 patients with the Wolff-Parkinson-White syndrome. Electrophysiologic studies were performed during a control period and after administering i.v. disopyramide (four bolus doses of 9.5 mg/kg over 40 minutes superimposed on a continuous infusion at 1.0 mg/kg/hour). All patients were then restudied after 3 days on oral medication in doses of 800-1200 mg/day. In all patients we tried to induce reciprocating tachycardia and atrial fibrillation. The cycle length during reciprocating tachycardia was not changed by i.v. disopyramide, but increased after oral disopyramide, from 331 +/- 53 (+/- SD) to 370 +/- 68 msec (p less than 0.01). This increase occurred predominantly as a result of prolongation of retrograde conduction time in the accessory pathway. Despite prolonging cycle length during reciprocating tachycardia, disopyramide did not prevent its induction. The shortest and mean RR intervals during atrial fibrillation were used to assess antegrade refractoriness of the accessory pathway. Intravenous disopyramide prolonged the shortest RR from 169 +/- 18 to 226 +/- 24 msec (p less than 0.0001) and the mean RR from 255 +/- 58 to 329 +/- 62 msec (p less than 0.005). Oral disopyramide prolonged the shortest RR interval from 169 +/- 18 to 248 +/- 36 msec (p less than 0.0001) and the mean RR from 255 +/- 58 to 360 +/- 93 msec (p less than 0.001). After oral disopyramide, the episodes of atrial fibrillation were shorter and self-terminating. No acute hemodynamic side effects were observed, but five patients developed gastrointestinal or anticholinergic side effects on oral disopyramide. Seven patients elected to have surgical interruption of their accessory pathways and five have been successfully treated with oral disopyramide for 14-33 months. Disopyramide appears to have beneficial electrophysiologic effects in patients with Wolff-Parkinson-White syndrome. Prolongation of refractoriness in the accessory pathway markedly slows the ventricular response during atrial fibrillation and therefore prevents the development of life-threatening arrhythmias.
Balanoposthitis Secondary To Tetracycline Therapy
Authors: Sumner Marshall
Journal: JAMA (1973)

To the Editor.—  We have recently seen three cases of balanoposthitis following the use of tetracycline. In all of these cases, the only manifestation of the allergic reaction was marked erythema- and excoriation of the foreskin and glans penis. No other part of the body presented this phenomenon.  Report of Cases.—Case 1.—  A 45-year-old white man with a history of recurrent nonspecific urethritis had been treated on three previous occasions with a ten-day course of tetracycline; no unexpected reaction had appeared. On a fourth occasion, marked edema of his foreskin and glans penis was followed a few hours later by ulceration (Figure). The midstream specimen of urine was free of cells or bacteria. The urethritis gradually responded to erythromycin and the penile lesion healed progressively during the following two weeks.  Case 2.—  A 35-year-old white man was first seen in 1965 with a nonspecific urethritis that cleared rapidly
THE EFFECTS OF THE CARDIAC GLYCOSIDES UPON THE DYNAMICS OF THE CIRCULATION IN CONGESTIVE HEART FAILURE. I. OUABAIN 12
Authors: Richard A. Bloomfield, Bernard Rapoport, J. Pervis Milnor, Walter K. Long, J. Gilmer Mebane, Laurence B. Ellis, M. Rita Lavin
Journal: Journal of Clinical Investigation (1948)
Lack of Association between Azithromycin and Death from Cardiovascular Causes
Authors: Christine M. Khosropour, Jeffrey D. Capizzi, Sean D. Schafer, James B. Kent, Julia C. Dombrowski, Matthew R. Golden
Journal: New England Journal of Medicine (2014)

In this study, treatment of young adults with gonorrhea, chlamydia, or both with a single dose of azithromycin was not associated with an increased risk of death from cardiovascular causes. This finding is reassuring with regard to the use of azithromycin in such patients.
Cholera: The Risk to American Travelers
Authors: EUGENE J. GANGAROSA
Journal: Annals of Internal Medicine (1971)

Cholera has spread widely in the past decade. Although the disease is clinically characterized by severe diarrhea that can lead to cardiovascular collapse and death within a few hours, infection may be mild or subclinical. Appropriate use of intravenous fluids and electrolyte replacement can reduce case-fatality rates to less than 1%. Only four documented cases of cholera in millions of American travelers have occurred in the past decade. Because the risk of cholera is so small, it should not be necessary for anyone to cancel travel plans anywhere in the world. Several factors including personal hygiene and vaccination account for this low risk. Travelers to infected areas should be vaccinated, ideally within 2 months of their planned departure. The risk of cholera spread within the United States is remote because of existing water standards in most areas. Stool cultures should be obtained from travelers returning from infected areas with diarrhea.
Binding of pemphigus vulgaris IgG to antigens in desmosome core domains excludes immune complexes rather than directly splitting desmosomes
Authors: Y. Aoyama, M. Nagai, Y. Kitajima
Journal: British Journal of Dermatology (2010)

Background Pemphigus vulgaris (PV) is characterized by autoantibodies against desmoglein (Dsg) 3 or both Dsg1 and Dsg3, i.e. desmosomal adhesion molecules. Objectives We examined whether or not PV IgG binding to Dsg3 directly impairs the adhesion of desmosomes. Methods For immunofluorescence microscopy, keratinocytes were first incubated with PV IgG for 30 min in low Ca2+ medium, in which no desmosomes were formed, and then for 1 h in high Ca2+ medium to generate desmosomes. For immunoelectron microscopy, after a 30‐min incubation with PV IgG in low Ca2+ medium, cells were incubated with antihuman IgG with 5‐nm gold particles for 5 min; after washing, cells were further incubated in high Ca2+ medium for 1 h. For tracing of PV IgG/Dsg3 immune complexes formed in the desmosomal core domain, cells were first incubated with PV IgG for 5 min to allow PV IgG to bind the desmosomal core domain and were further incubated with PV IgG‐free medium for different times. Results Immunofluorescence microscopy revealed that PV IgG bound in a random‐punctate pattern on the cell surface in low Ca2+ medium was translocated to the cell–cell contacts forming a dotted‐linear distribution, suggesting desmosome generation even in the presence of PV IgG. Immunoelectron microscopy revealed that half‐desmosome‐like structures decorated with gold particles in low Ca2+ keratinocytes coupled to form desmosomes and gold particles were sandwiched in the desmosomal core domain after Ca2+ switch, even though their surfaces were covered with PV IgG/antihuman IgG 5‐nm gold particles. In the tracing experiments, although PV IgG demonstrated a dotted‐linear distribution along the cell–cell contacts colocalized with desmoplakin (DPK) after a 30‐min tracing, it disappeared from cell–cell contacts after a 5‐h tracing, leaving DPK and desmocollin 3. Conclusions These results suggest that the PV IgG/Dsg3 immune complexes are excluded from the desmosomal core domain rather than directly splitting the desmosome.