tbuckley/cabot-search huggingface dataset:
Hepatocarcinogenesis in Female Mice With Mosaic Expression of Connexin32
Authors: Oliver Moennikes, Albrecht Buchmann, Klaus Willecke, Otto Traub, Michael Schwarz
Journal: Hepatology (2000)

Mice deficient for connexin32 (Cx32), the major gap junction forming protein in liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is located on the X-chromosome, heterozygous females show mosaicism with respect to Cx32 expression; this enables their use in studying the effect of Cx32-deficiency in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice (Cx32 +/+ ) were crossed with Cx32-deficient C57BL/129Sv males (Cx32 Y/- ) to yield F1 females heterozygous with respect to Cx32 (Cx32 +/− ). Patches of hepatocytes were observed in normal liver that either expressed Cx32 or failed to express the protein. The mean fraction of Cx32-negative tissue in liver was about 60% and did not change significantly with age of mice. Neoplastic liver lesions, induced in weanling mice, were identified in serial liver sections by their deficiency in glucose-6-phosphatase staining. Parallel sections were used for immunohistochemical demonstration of Cx32 protein. Smaller lesions were either homogenously Cx32-negative or showed unchanged to slightly elevated levels of Cx32 protein. There were no major differences in number and size distribution between lesions of these 2 phenotypes. In addition, larger lesions were mostly Cx32-negative but often contained embedded patches of Cx32-positive cells. Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal significant differences between Cx32-negative and Cx32-positive hepatocytes in Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation of tumor cells does not negatively regulate their growth nor does it seem to affect the proliferation of their directly neighboring Cx32-negative counterparts.
TCT-851 A Propensity Score Analysis of Venous Access Closure Using Extravascular Closure Device In High Risk Patients
Authors: Divya Ratan Verma, Nick Lee, Anwar Tandar, Troy Badger, Elizabeth Dranow, Renee M. Neuharth, Joseph B. Muhlestein, Rodney S. Badger
Journal: Journal of the American College of Cardiology (2014)
Vasodilation for Vasospastic Hypertension
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1973)

Accelerated or malignant hypertension is a progressive vasospastic disease characterized by rapidly increasing peripheral vascular resistance. Arterial pressure must be quickly and effectively reduced to halt arteriolar deterioration and to prevent advancing renal damage, hemorrhagic complications, or hypertensive encephalopathy. In most patients this decrease can be accomplished with a variety of antihypertensive drugs or drug combinations. Only a few cases of accelerated hypertension fail or cease to respond satisfactorily to the commonly employed agents. Such cases have been labeled "refractory" hypertension, and some have been treated with bilateral nephrectomies.Lack of adequate response to the usual antihypertensive drugs should not . . .
Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury
Authors: Thomas V. Adamkiewicz, Miguel R. Abboud, Carole Paley, Nancy Olivieri, Melanie Kirby-Allen, Elliott Vichinsky, James F. Casella, Ofelia A. Alvarez, Julio C. Barredo, Margaret T. Lee, Rathi V. Iyer, Abdullah Kutlar, Kathleen M. McKie, Virgil McKie, Nadine Odo, Beatrice Gee, Janet L. Kwiatkowski, Gerald M. Woods, Thomas Coates, Winfred Wang, Robert J. Adams
Journal: Blood (2009)
Treatment of Acne-Reply
Authors: Leonard J. Swinyer
Journal: JAMA (1981)

<h3>In Reply.—</h3> First, a comment on Dr Voron's initial statement concerning Table 2. The average for each degree of dryness is weighted in the statistical analysis according to the number of patients in that category. The dryness score of 3 contained only four subjects, which meant that the percent improvement of 49% weighted much less in the final statistical analysis than did the dryness score of 2 that contained 12 subjects with an average percent improvement of 41%. A superficial scan of this table clearly shows that dryness scores of 0 to 1 indicated that those subjects who had minimally dry skin showed improvement of 60+%, and those who had drier skin (with scores of 2 or 3) had only a 40+% improvement at 16 weeks. The most important argument against Dr Voron's first point, however, is that the statistical analysis showed an inverse correlation between dryness and clearing of
Increasing mortality from thrombotic thrombocytopenic purpura in the United States—analysis of national mortality data, 1968–1991
Authors: Thomas J. Török, Robert C. Holman, Terence L. Chorba
Journal: American Journal of Hematology (1995)

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare disease and the epidemiologic features have been incompletely characterized. Because of the historically high case‐fatality rate for TTP, we analyzed U.S. multiple cause‐of‐death mortality data with TTP listed on the death record for the period 1968–1991, in order to estimate the incidence of TTP, to characterize demographic features of the decedents, and to determine if trends in mortality correlate with findings from clinical studies showing improved survival in recent years. There were 4,523 TTP‐associated deaths during the 24‐year study period. The annual age‐adjusted mortality rate decreased initially and reached its lowest point at 0.4 per 1,000,000 residents for the years 1970 through 1973, and then increased steadily to 1.1 during the last 4 years of the study period, 1988 through 1991. We estimate the current incidence of TTP to be approximately 3.7 cases per 1,000,000 residents. Deaths were rare below the age of 20 years, but the age‐specific mortality rate for those 20 years and older increased steadily with increasing age. Regardless of age, females were affected more often than males, and the overall female‐to‐male age‐adjusted rate ratio was 1.9 (95% confidence interval (Cl), 1.8 to 2.0). The greatest age‐specific difference was between females and males in their twenties (rate ratio 3.2; 95% Cl, 2.6 to 3.9). The mortality rate for blacks, and especially black females, was higher than the mortality rate for whites (black‐to‐white age‐adjusted rate ratio 3.4; 95% Cl, 3.2 to 3.6; black female‐to‐white female age‐adjusted rate ratio 3.6; 95% Cl, 3.3 to 3.9), although the majority of deaths were among whites (71.5%). Infection with the human immunodeficiency virus (HIV) or an HIV‐related diagnosis was reported in 61 (1.3%) decedents overall and in 51 (4.4%) decedents from 1988 through 1991. The TTP mortality rate has increased over time despite reports of significant improvement in survival associated with clinical use of plasma infusion and plasma exchange. This trend in mortality suggests that the incidence of TTP is increasing. Blacks, and black females in particular, are affected at a disproportionately high rate. The increased incidence of HIV infection and related disease may have contributed to some of the increase in TTP mortality in recent years, but it does not explain the majority of the increase, which began before the onset of the HIV epidemic.
Effect of Intensive Versus Standard Blood Pressure Control on Depression and Health-Related Quality of Life in Type 2 Diabetes
Authors: Patrick J. O’Connor, K.M. Venkat Narayan, Roger Anderson, Patricia Feeney, Larry Fine, Mohammed K. Ali, Debra L. Simmons, Don G. Hire, JoAnn M. Sperl-Hillen, Lois Anne Katz, Karen L. Margolis, Mark D. Sullivan
Journal: Diabetes Care (2012)

We tested the hypothesis that intensive (systolic blood pressure [SBP] <120 mmHg) rather than standard (SBP 130-139 mmHg) blood pressure (BP) control improves health-related quality of life (HRQL) in those with type 2 diabetes.
New surgical procedures: can we minimise the learning curve?
Authors: A Hasan
Journal: BMJ (2000)

The Ross procedure for aortic valve replacement was introduced at two paediatric cardiac centres (Freeman Hospital, Newcastle, and Royal Liverpool Children's Hospital) where surgeons had no previous experience of this technique. A structured programme of training and cooperation between the two centres enabled surgeons to minimise the learning curve for this procedure. We share our experience and suggest options for surgeons who wish to undertake new procedures in the current era of surgical practice and clinical governance. Issues of informed consent and risk stratification remain.

#### Summary points

Surgeons have always recognised the concept of a learning curve when undertaking a new procedure

Recent events mean that there is a lack of professional and public tolerance for suboptimal results due to a learning curve

Learning a new technique, even for an established consultant, requires some sort of learning curve

Introducing a new procedure in a structured way that incorporates formal training courses, cadaveric resection, and assistance from expert practitioners can reduce the learning curve

The recent General Medical Council (GMC) inquiry into the Bristol Paediatric Cardiac Surgical Unit highlighted many concerns common to all surgical specialties. At the end of the judgment, the president of the GMC listed 13 issues that the professions should address, and the senate of surgery recently published its response.1 The concept of a learning curve, which has long been recognised by surgeons, was of particular consequence. However, the senate responded that “there should be no learning curve as far as patient safety is concerned.”1 To learn to perform a new procedure without having a learning curve is a dilemma that we, as established consultants in paediatric cardiac surgery, faced when we wanted to introduce the Ross procedure into our surgical practice.

We discussed strategies which we hoped would reduce the steepness of our learning curve, and …
Metabolic Consequences of p300 Gene Deletion in Human Colon Cancer Cells
Authors: Jacob G. Bundy, N. Gopalakrishna Iyer, Michelle S. Gentile, De-En Hu, Mikko Kettunen, Ana-Teresa Maia, Natalie P. Thorne, James D. Brenton, Carlos Caldas, Kevin M. Brindle
Journal: Cancer Research (2006)

Abstract Metabolite profiling using 1H nuclear magnetic resonance (NMR) spectroscopy was used to investigate the metabolic changes associated with deletion of the gene for the transcriptional coactivator p300 in the human colon carcinoma cell line HCT116. Multivariate statistical methods were used to distinguish between metabolite patterns that were dependent on cell growth conditions and those that were specifically associated with loss of p300 function. In the absence of serum, wild-type cells showed slower growth, which was accompanied by a marked decrease in phosphocholine concentration, which was not observed in otherwise isogenic cell lines lacking p300. In the presence of serum, several metabolites were identified as being significantly different between the two cell types, including glutamate and glutamine, a nicotinamide-related compound and glycerophosphocholine (GPC). However, in the absence of serum, these metabolites, with the exception of GPC, were not significantly different, leading us to conclude that most of these changes were context dependent. Transcript profiling, using DNA microarrays, showed changes in the levels of transcripts for several enzymes involved in choline metabolism, which might explain the change in GPC concentration. Localized in vivo 1H NMR measurements on the tumors formed following s.c. implantation of these cells into mice showed an increase in the intensity of the peak from choline-containing compounds in the p300− tumors. These data show that NMR-based metabolite profiling has sufficient sensitivity to identify the metabolic consequences of p300 gene deletion in tumor cells in vitro and in vivo. (Cancer Res 2006; 66(15): 7606-14)
Chloromycetin in the Treatment of Salmonella Enteritis
Authors: Sidney Ross, Frederic G. Burke, E. Clarence Rice, John A. Washington, Sara Stevens
Journal: New England Journal of Medicine (1950)

SALMONELLA infections have shown a singular refractoriness to chemotherapeutic and antibiotic agents thus far. The inability of sulfonamides to affect favorably the course of the disease is now well established.1 During the past year, 8 cases of salmonella enteritis were treated at Children's Hospital, Washington, D. C, with streptomycin in large doses.2 Only 1 patient was rendered permanently free of salmonella; in the other 7 cases, the organism reappeared in the stools after discontinuation of therapy. Seligmann et al.3 have similarly reported a series of 5 cases of salmonella enteritis in infants in whom streptomycin failed to produce a permanent . . .
Surgery in asymptomatic aortic stenosis
Authors: G. P McCann
Journal: BMJ (2004)

Exercise testing is the key investigation 

Aortic stenosis is the commonest valve disease in the developed world that requires surgery. In elderly people its prevalence is approximately 3%.1 Usually a long latent period precedes the cardinal symptoms of the disease.2 Replacement of the aortic valve is an excellent treatment for severe symptomatic aortic stenosis—symptoms improve in most patients and life expectancy approaches that of age matched controls.3 The risks of surgery are declining steadily. In patients who are having their first operation with a mechanical prosthesis and do not require a bypass graft, perioperative mortality is only 2%.4 No randomised controlled trials of aortic valve replacement in symptomatic aortic stenosis have been conducted, yet the level of evidence is regarded as class I because of the dramatic improvement in prognosis with surgery.5

In severe asymptomatic aortic stenosis the risks of perioperative morbidity, mortality, and long term complications related to the prosthesis have to be weighed against the risk of sudden cardiac death and the morbidity and mortality experienced on lengthy surgical waiting lists.6 …
β-Apoprotein Sufficiency and Function
Authors: Antonio Gotto
Journal: New England Journal of Medicine (1969)

Beta lipoprotein (βLP) is a large macromolecular complex that transports, in bound form, more than 50 per cent of the cholesterol of human plasma and may be a factor in the genesis of atherosclerotic lesions. The native molecule has a molecular weight of about 2 million and contains protein in association with phospholipid, neutral lipid, water and small amounts of carbohydrate. Since the lipid constituents are not water soluble, it has been assumed that the molecule resembles a micelle with the neutral lipid (esterified cholesterol and triglyceride) forming a hydrophobic core and the protein, phospholipid and possibly unesterified cholesterol partially . . .
Angiographic Findings in Patients With Refractory Unstable Angina According to Troponin T Status
Authors: Christopher Heeschen, Marcel J. van den Brand, Christian W. Hamm, Maarten L. Simoons
Journal: Circulation (1999)

Background —The CAPTURE (C7E3 fab AntiPlatelet Therapy in Unstable REfactory angina) trial enrolled patients with refractory unstable angina and documented a therapeutic benefit for abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, that was particularly evident in patients with elevated troponin T (TnT) levels. In the current study, we related the angiographic data to the TnT status of the CAPTURE patients. Methods and Results —In 853 patients, angiographic data at baseline and 18 to 24 hours after treatment were available and assessed by an Angiographic Committee with respect to TIMI flow, lesion severity, and visibility of thrombus. TnT levels &gt;0.1 μg/L were found in 30.9% of the patients. Before randomization, thrombus was visible in 14.6% of TnT-positive patients (TnT levels &gt;0.1 μg/L) and 4.2% of TnT-negative patients ( P =0.004). Complex lesion characteristics B2+/C (72.0% versus 53.9%; P &lt;0.001) and TIMI flow &lt;2 (15.6% versus 5.1%; P &lt;0.001) were more frequent in TnT-positive patients. Abciximab was effective with respect to reduction of visible thrombus, increase of TIMI flow, and reduction of cardiac events in TnT-positive patients only. Multivariate analysis identified TnT status, but not angiographic findings, as an independent predictor for both outcome and efficacy of treatment with abciximab. Conclusions —Complex lesion characteristics and visible thrombus formation at baseline were significantly linked to TnT elevation. However, TnT status was a more powerful predictor of increased cardiac risk and efficacy of treatment with abciximab than either. Relative to the angiogram, TnT can thus be considered a more sensitive marker for the underlying pathology, identifying patients with unstable angina who will particularly benefit from antiplatelet treatment.
Single Oral Dose Ampicillin-Probenecid Treatment of Gonorrhea in the Male
Authors: Paul A. Kvale, Thomas F. Keys, David W. Johnson, King K. Holmes
Journal: JAMA (1971)

Single oral antibiotic treatments of gonorrhea have not been universally successful. However, in this study of men who acquired gonococcal urethritis in the Philippines, a single oral dose of 3.5 gm of ampicillin with probenecid resulted in only eight failures of 202 patients (4.0%). The same dose of ampicillin without probenecid resulted in 12 failures of 41 patients (29.3%). Furthermore, single oral doses as high as 7.5 gm of phenoxymethyl penicillin were associated with higher failure rates, even with probenecid. In addition, the incidence of post gonococcal urethritis remained high regardless of the dose and duration of treatment. Therefore, a single oral dose of ampicillin with probenecid appears as a reasonable alternative to the standard treatment of acute gonococcal urethritis in men. Phenoxymethyl penicillin, on the other hand, should not be used in the treatment of gonorrhea.
Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.
Authors: S J Krinzman, G T De Sanctis, M Cernadas, D Mark, Y Wang, J Listman, L Kobzik, C Donovan, K Nassr, I Katona, D C Christiani, D L Perkins, P W Finn
Journal: Journal of Clinical Investigation (1996)

Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.
Intraoperative recording of specialized atrioventricular conduction tissue electrograms in 47 patients.
Authors: M Dick, W I Norwood, C Chipman, A R Castaneda
Journal: Circulation (1979)

Intraoperative mapping of the specialized atrioventricular conduction system was performed in 47 patients during cardiac surgery. Specialized conduction tissue electrograms were identified in 37, and atrioventricular conduction preserved in 92%. Specialized conduction tissue was identified in 27 patients with atrioventricular canal defect: complete heart block was avoided in 25. Conduction tissue was located in six of 12 patients with complex transpositions; atrioventricular conduction was preserved in all six. Other lesions in which the technique was useful were Ebstein's anomaly and single atrium. Limitations to the technique are 1) deep hypothermia and circulatory arrest; 2) interruption in atrioventricular conduction during mapping; 3) inadequate exposure and access to probable sites of conduction tissue; 4) variation of size and spatial relations of individual malformations; and 5) limited time for identification of unusually located conduction tissue. Indications for use of this technique include patients with both forms of atrioventricular canal, complex transpositions, atrioventricular discordance, single ventricle and single atrium.
Importance and Implementation of Training in Cardiopulmonary Resuscitation and Automated External Defibrillation in Schools
Authors: Diana M. Cave, Tom P. Aufderheide, Jeff Beeson, Alison Ellison, Andrew Gregory, Mary Fran Hazinski, Loren F. Hiratzka, Keith G. Lurie, Laurie J. Morrison, Vincent N. Mosesso, Vinay Nadkarni, Jerald Potts, Ricardo A. Samson, Michael R. Sayre, Stephen M. Schexnayder
Journal: Circulation (2011)
Doctor reprimanded for giving antiretroviral drug to baby who was raped
Authors: P. Sidley
Journal: BMJ (2002)

A second senior public hospital doctor has been reprimanded for supplying the antiretroviral drug zidovudine to a rape victim. When given within two days of the rape, this drug can stop the virus replicating.

What scandalised commentators was that the much publicised rape, in Kimberley in the Northern Cape province, was of a 9 month old baby. She was given the drug as part of extensive treatment after being gang raped by several men.

Dozens of babies in South Africa have been raped, and the crime is on the …
US parents sue psychiatrists for promoting Ritalin
Authors: F. Charatan
Journal: BMJ (2000)

Two lawsuits have been filed in federal courts in the US states of California and New Jersey asserting that the Novartis Pharmaceutical Corporation and the American Psychiatric Association conspired to create a market for methylphenidate (Ritalin), the drug used to treat hyperactive children, and expand its use.

One of the leading lawyers in the class action suits is Richard Scruggs, who won a landmark settlement between state attorneys general and the tobacco industry in 1998. The American Psychiatric Association would not …
Silicone Breast Implants
Authors: Brian D. Kent
Journal: JAMA (1992)

<h3>To the Editor.</h3> —I was disappointed by Marsha F. Goldsmith's article<sup>1</sup>concerning the silicone gel implant controversy. Although her article included information on "both sides" of the issue, it had several disturbing elements. Goldsmith found a plastic surgeon who "won't do an implant unless 'they beg me,'" and documented his personal bias against the operation and those surgeons involved in the research and development of a better product. I doubt that his views are shared by most plastic surgeons. Goldsmith quoted the American College of Rheumatology (ACR): "The ACR strongly endorses the FDA Advisory Panel's recommendation for further research as well as their ruling to limit silicone gel breast implants for augmentation mammoplasty." Although this sentence did appear in a news release dated March 3,1992, their revised (in April) and most recent release on the issue deleted this statement. Goldsmith did not quote the opinion of the Council on Scientific
Efficacy of Hepatobiliary Scintigraphy in Demonstrating Cholangio-Colic Fistulae Is Formation of Internal Biliary Fistula Related to External Leak Closure?
Authors: ASEEM BHATNAGAR, ANUPAM MONDAL, O. P. PATHANIA, RANJU T. DHAWAN, M. K. CHOPRA, C. M. KHANNA
Journal: Clinical Nuclear Medicine (1995)

The authors present four cases of Internal biliary fistulae (IBF) Identified on hepatobiliary scintigraphy. All of the cases share common history of external biliary leak closure. Scintigraphy in all four cases showed a similar pattern of direct visualization of transverse colon without any significant small bowel activity. This suggests an Increased frequency of IBF formation In cases with external fistulous tract closure. Retrospectively, it appears that spontaneous closure of external leak may be pathological consequence of formation of IBF involving hepatic flexure.