tbuckley/cabot-search huggingface dataset:
Coronary Heart Disease
Authors: David H. Spodick
Journal: JAMA (1971)

At last, a symposium really worth publishing! Most of the 83 distinguished participants have avoided that cardinal sin of so many symposia—offering tired contributions to justify a junket to the oral sessions. In the present volume we have a series of well-written and appropriately illustrated papers, relatively short, and superbly organized. They amply cover coronary disease, including anatomy, physiology, epidemiology, diagnosis, and every form of modern treatment. Panel discussions, illuminating and often witty, effectively clarify most topics and develop further controversial points. Significant areas are considered in timely, authoritative presentations whose authorship accurately proclaims their quality, notably: Keys on cholesterol and allied culprits; a well-balanced exposition of the pathogenetic role of behavior patterns by Rosenman and Friedman; Raab's learned polemic on metabolic vs "coronary" [sic] etiology of myocardial necrosis; Kannel, Castelli, and colleagues on risk factors—the best statistical distillate from the Framingham Study; Texon on the hydraulic induction of atheroma;
<i>Pseudomonas aeruginosa</i>Resistant to Carbenicillin and Gentamicin
Authors: WILLIAM H. GREENE
Journal: Annals of Internal Medicine (1973)

Since November 1969 the Baltimore Cancer Research Center has used the combination of carbenicillin (C) and gentamicin (G), with or without cephalothin, as therapy for granulocytopenic patients with severe Gram-negative bacillary infection, especially Pseudomonas aeruginosa. Since 1971 an increasing percentage of isolates have been resistant to carbenicillin or gentamicin, or both, by disc-susceptibility testing. Measurements of minimum inhibitory concentrations showed that, during 11 months, 14 patients, 8 with acute leukemia, had developed resistant strains. From these 14 patients, 40 distinct serotypes or resistance patterns of P. aeruginosa could be delineated: 15 were C- and G-susceptible; 12, C-resistant and G-susceptible; 5, G-resistant and C-susceptible; and 8, C- and G-resistant. The appearance of resistant organisms correlated significantly with the administration of carbenicillin or gentamicin, or both. The induction of gentamicin resistance was particularly associated with oral G intake. Carbenicillin resistant variants and strains susceptible to carbenicillin and gentamicin were virulent, but those with gentamicin resistance seemed to be less invasive.
The President's Emergency Plan for AIDS Relief — Is the Emergency Over?
Authors: Wafaa M. El-Sadr, David Hoos
Journal: New England Journal of Medicine (2008)

On July 16, the Senate approved legislation that would increase the funding for the President's Emergency Plan for AIDS Relief (PEPFAR) to $48 billion for the next 5 years. Drs. Wafaa El-Sadr and David Hoos examine PEPFAR's achievements, limitations, and lessons for the future. Dr. Wafaa El-Sadr discusses PEPFAR's successes in addressing the HIV epidemic in the developing world, its broader effect on health care systems, and common criticisms of the program. Dr. El-Sadr is the director of the International Center for AIDS Care and Treatment Programs and a professor of clinical medicine and epidemiology at Columbia University, New York.
Update on Pulmonary Hypertension 2009
Authors: Mark T. Gladwin, Hossein-Ardeschir Ghofrani
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

This article reviews selected studies published in 2009 covering advances in the pulmonary hypertension field. Material covered includes the recent changes in the classification of pulmonary hypertension and the completion of new phase III clinical trials of combination therapy, as well as new studies on the epidemiology, clinical course, and advances in the diagnosis of pulmonary hypertension. We conclude with a survey of studies examining new basic mechanisms of disease and novel therapeutic agents. This summary is necessarily limited and we encourage the reader to obtain the primary manuscripts and related work to examine in more detail.

The year 2009 saw remarkable advances to the pulmonary hypertension field. These studies reported on new basic mechanisms of disease, advances in diagnostics, the discovery of novel therapeutic agents, and the completion of new phase III clinical trials. A PubMed search using the term “pulmonary hypertension” and restricted to the year 2009 yields an astounding 963 new publications. Although this current review is not intended to cover all publications in this rapidly growing field, we will highlight recent changes in the classification and updates on major clinical trial results and review important advances in diagnostic studies and basic science mechanisms.
Effects of Chenodeoxycholate and a Bile Acid Sequestrant, Colesevelam, on Intestinal Transit and Bowel Function
Authors: Suwebatu T. Odunsi–Shiyanbade, Michael Camilleri, Sanna McKinzie, Duane Burton, Paula Carlson, Irene A. Busciglio, Jesse Lamsam, Ravinder Singh, Alan R. Zinsmeister
Journal: Clinical Gastroenterology and Hepatology (2009)
HAPTEN-SANDWICH LABELING
Authors: L. Wofsy, P. C. Baker, K. Thompson, J. Goodman, J. Kimura, C. Henry
Journal: The Journal of Experimental Medicine (1974)

A hapten-sandwich procedure has been developed for specific labeling of cell surface antigens for fluorescence or electron microscopy. Haptens are azo-coupled to immunoglobulins specific for a cell surface antigen; the hapten-modified cell-bound antibodies can then be visualized by adding fluorescent antihapten antibody, or by adding antihapten antibody followed by hapten-modified markers for electron microscopy. Virus or high molecular weight protein markers are lightly cross-linked before conjugation with hapten to prevent their disruption. Such stable hapten-modified markers, and the accessibility of many different purified anti-azophenyl-hapten antibodies, make it feasible to distinguish more than one membrane antigen in a given labeling experiment. When mouse lymphoid cell populations are labeled with separate markers for Ig and for thymus-associated antigens, many cells exhibit the Ig marker exclusively or the thymic marker predominantly, and some cells are completely free of label.
HERPES ZOSTER WITH MOTOR PARALYSIS
Authors: H. M. Juergens
Journal: JAMA (1924)

Bloedorn and Roberts<sup>1</sup>recently reviewed the literature on abdominal muscle paralysis associated with herpes zoster, and reported a case. I am able to add another case: <h3>REPORT OF CASE</h3> E. S., a man, aged 66, a retired farmer, seen, Feb. 14, 1924, had a typical eruption of herpes zoster of the skin supplied by the fibers of the tenth right thoracic nerve trunk. The eruption had been present for two weeks before I saw him, but as the pain became severe, he sought medical attention. Physical examination showed marked pyorrhea alveolaris, but otherwise was negative, except that the patient had had constipation for years, which seemed to be made worse by the herpes zoster. He was given local treatment for the eruption. One week later I was again called because of a "tumor" of the abdomen and to relieve the constipation. At this time a protrusion of the right
QUANTITATIVE STUDIES OF SULFONAMIDE RESISTANCE
Authors: William M. M. Kirby, Lowell A. Rantz
Journal: The Journal of Experimental Medicine (1943)

1. In vitro experiments were performed with E. coli, using a method designed for the quantitative study of various aspects of sulfonamide resistance. 2. Resistance was found to be a gradually developing process, and was demonstrated for all four drugs tested, sulfanilamide, sulfapyridine, sulfathiazole, and sulfadiazine. 3. It was shown that the degree of resistance developed was correlated with the bacteriostatic potency of the sulfonamides, and that organisms resistant to certain bacteriostatic concentrations of one sulfonamide were equally resistant to similar bacteriostatic concentrations of the other sulfonamides. 4. These observations were interpreted as indicating that the development of sulfonamide resistance represents an interaction between the organisms and the one common structural unit of all the sulfonamides, namely, the p-amino nucleus. It is also suggested that this interaction may involve the same enzyme system (or systems) as those concerned in the antagonism of the sulfonamides by para-aminobenzoic acid. 5. The relation of these findings to the broader aspects of sulfonamide resistance is discussed, and it is postulated that, despite reports to the contrary, all organisms susceptible to the bacteriostatic action of the sulfonamides are capable of becoming resistant to all of the sulfonamides.
AN ATTEMPT TO ISOLATE A FILTER-PASSING VIRUS IN EPIDEMIC INFLUENZA
Authors: Herbert K. Detweiler, W. Ray Hodge
Journal: The Journal of Experimental Medicine (1924)

1. Six cases of epidemic influenza in various stages of disease were investigated. 2. Suspicious cultures of bodies resembling Bacterium pneumosintes were obtained in three cases, twice from the lung filtrates of inoculated animals and once from the filtrate of nasopharyngeal washings direct. 3. In these instances material was obtained within 36 hours of the acute onset, thus confirming the observations of Olitsky and Gates. 4. Macroscopic and microscopic findings in the lungs of inoculated animals were uniformly negative.
Development of glucagon sensitivity in neonatal rat liver.
Authors: F Vinicor, G Higdon, J F Clark, C M Clark
Journal: Journal of Clinical Investigation (1976)

The ontogenesis of the hepatic glucagon-sensitive adenylate cyclase system has been studied in the rat. With a partially purified liver membrane preparation, fetal adenylate cyclase was less responsive to glucagon than the enzyme from neonatal or adult livers. Similar results were obtained in gently prepared liver homogenates, suggesting that destruction of essential components of the fetal liver membrane did not account for the relative unresponsiveness of the adenylate cyclase enzyme to glucagon. Investigation of other factors that might account for diminished fetal hepatic responsiveness to glucagon indicate (a) minimal glucagon degradation by fetal membranes relative to 8-day or adult tissue; and (b) available adenylate cyclase enzyme, as suggested by a 13-fold increase over basal cyclic AMP formation with NaF in fetal liver membranes. These results indicate that neither enhanced glucagon degradation nor adenylate cyclase enzyme deficiency accounts for the relative insensitivity of the fetal hepatic adenylate cyclase system to glucagon. In early neonatal life, hepatic adenylate cyclase responsiveness to glucagon rapidly developed and was maximal 6 days after birth. These changes were closely paralleled by a fivefold increase in glucagon binding and the kinetically determined Vmax for cyclic AMP formation. These observations suggest that (a) fetal hepatic unresponsiveness to glucagon may be explained by a limited number of glucagon receptor sites; (b) during the neonatal period, the development of glucagon binding is expressed primarily as an increase in adenylate cyclase Vmax; (c) the ontogenesis of hepatic responsiveness to glucagon may be important in the resolution of neonatal hypoglycemia.
Chelsea Postgraduate Medical Centre
Authors: D. M. Wallace
Journal: BMJ (1966)

Research over the past decade on the link between depression and coronary artery disease (CAD) has moved from establishing the epidemiologic association between depression and CAD to a focus on whether and how treating depression in patients with CAD benefits these patients. Evidence to date indicates that depression therapy does improve depression, albeit somewhat modestly, in CAD patients. The effect of depression therapy on CAD outcomes is less clear, although there is enough positive evidence to encourage further research. The effects of depression treatment on mechanisms mediating increased CAD risk in depressed patients are variable. Future research should perhaps focus on targeting treatment at intermediary mechanisms as well as at depression itself.
Vitamin E. An inhibitor of the platelet release reaction.
Authors: M Steiner, J Anastasi
Journal: Journal of Clinical Investigation (1976)

Formation of lipid peroxides rises sharply when platelets undergo the release reaction. In this study the in vitro effect of vitamin E on platelet aggregation was investigated. alpha-Tocopherol, an anitoxidant of known inhibitory action on lipid peroxidation, was added to platelet suspensions in concentrations up to 1.5 mM. A dose-dependent reduction in platelet aggregation was observed, with complete inhibition of the secondary wave of aggregation at greater than or equal to 0.9 mM alpha-tocopherol. The inhibitory effect of alpha-tocopherol on the platelet release reaction was further documented by the decrease in aggregation-induced release of [14C]5-hydroxytryptamine from prelabeled platelets and by the reduction of N-acetylglucosaminidase activity released into the medium. The sharp rise in lipid peroxides normally associated with platelet aggregation was markedly reduced by alpha-tocopherol and also by acetylsalicylic acid, a known inhibitor of the platelet release reaction. In vivo studies examined the effect of oral vitamin E administration (1,200-2,400 IU daily) on plasma and platelet levels of alpha-tocopherol. Up to 1,800 IU daily, increasing dosages of vitamin E resulted in increasing concentrations of alpha-tocopherol in plasma and platelets, but intake of vitamin E in excess of this dosage failed to show any further increase in plasma or platelet levels.
Campylobacter Infection Associated With Raw Milk
Authors: Bruce S. Klein, James M. Vergeront, Martin J. Blaser, Paul Edmonds, Don J. Brenner, David Janssen, Jeffrey P. Davis
Journal: JAMA (1986)

Raw milk is identified with increasing numbers of outbreaks of gastroenteritis and is an important vehicle for transmission of Campylobacter infection. Unlike Campylobacter jejuni, Campylobacter fetus subsp fetus has not been associated with common-source outbreaks of gastroenteritis. This report describes an outbreak of gastroenteritis involving C jejuni and a thermotolerant strain of C fetus subsp fetus associated with raw milk. Fifteen (39%) of 38 persons who attended a banquet in Wisconsin in June 1982 developed acute gastroenteritis. Stool specimens were obtained from nine ill guests; four yielded C jejuni and three yielded C fetus subsp fetus. The C fetus subsp fetus isolates were identified fortuitously, in part because of unusual thermotolerance (growth at 42 degrees C), permitting isolation at temperature appropriate for C jejuni. Survey results implicated raw milk as the source of the outbreak. Findings provide evidence of a potentially emergent milkborne pathogen contributing to the risk of raw milk consumption and suggest that current diagnostic laboratory techniques may fail to identify significant foodborne agents.
Liraglutide in combination with acitretin for severe recalcitrant psoriasis
Authors: C.T. Reid, A.M. Tobin, T. Ahern, D. O'Shea, B. Kirby
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: B.K. is in receipt of unrestricted research grants from Abbott Ltd, Pfizer and Janssen, and works as an advisor to and consultant for Abbott Ltd, Pfizer and Janssen. Madam, All licensed systemic therapies for psoriasis, except acitretin, have immunosuppressant properties that present a theoretical risk to patients with concomitant malignancies. A 54‐year‐old obese man [weight 138 kg, body mass index (BMI) 42·1 kg m−2] with extensive plaque psoriasis presented with a bleeding erythematous nodule in his natal cleft. This was excised and histopathology revealed an ulcerated nodular amelanotic malignant melanoma with a Breslow thickness of 5 mm and a high mitotic rate. Sentinel node biopsy and subsequent staging did not show metastatic disease. He had commenced adalimumab (40 mg weekly) for severe psoriasis 5 months prior to the diagnosis. Previous treatments included etanercept 50 mg twice weekly and efalizumab 125 mg weekly. Narrowband ultraviolet B, psoralen–ultraviolet A, ciclosporin, methotrexate, acitretin and fumaric acid esters had been tried in turn but none of these medications controlled his psoriasis. Adalimumab was discontinued when melanoma was diagnosed. This case has been reported previously as part of a series reporting the development of malignancies in patients on antitumour necrosis factor α therapies.1
Effects of Metformin on Insulin Resistance, Risk Factors for Cardiovascular Disease, and Plasminogen Activator Inhibitor in NIDDM Subjects: A study of two ethnic groups
Authors: Dinesh K Nagi, John S Yudkin
Journal: Diabetes Care (1993)

OBJECTIVE To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease. RESEARCH DESIGN AND METHODS A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment. RESULTS Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, −3.08 mM, 95% CI −4.12 to −2.04 mM, P &amp;lt; 0.0001) and MCR of glucose (median difference 0.40 ml · kg−1 · min−1, interquartile range −0.10 to 1.30 ml · kg−1 · min−1, P = 0.036). β-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P &amp;lt; 0.001). Total triglyceride (median difference −0.2 mM, interquartile range −0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference −0.52 mM, 95% CI −0.83 to −0.22 mM, P = 0.002), and LDL cholesterol (mean difference −0.40 mM, 95% CI −0.64 to −0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference −5.3 AU/ml, 95% CI −8.2 to −2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference −2.4 μg/min, interquartile range −4.4 to −0.2 μg/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups. CONCLUSIONS These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.
High Expression of <i>CAI2</i>, a <i>9p21</i>-Embedded Long Noncoding RNA, Contributes to Advanced-Stage Neuroblastoma
Authors: Lisa M. Barnhill, Richard T. Williams, Olga Cohen, Youngjin Kim, Ayse Batova, Jenna A. Mielke, Karen Messer, Minya Pu, Lei Bao, Alice L. Yu, Mitchell B. Diccianni
Journal: Cancer Research (2014)

Abstract Neuroblastoma is a pediatric cancer with significant genomic and biologic heterogeneity. p16 and ARF, two important tumor-suppressor genes on chromosome 9p21, are inactivated commonly in most cancers, but paradoxically overexpressed in neuroblastoma. Here, we report that exon γ in p16 is also part of an undescribed long noncoding RNA (lncRNA) that we have termed CAI2 (CDKN2A/ARF Intron 2 lncRNA). CAI2 is a single-exon gene with a poly A signal located in but independent of the p16/ARF exon 3. CAI2 is expressed at very low levels in normal tissue, but is highly expressed in most tumor cell lines with an intact 9p21 locus. Concordant expression of CAI2 with p16 and ARF in normal tissue along with the ability of CAI2 to induce p16 expression suggested that CAI2 may regulate p16 and/or ARF. In neuroblastoma cells transformed by serial passage in vitro, leading to more rapid proliferation, CAI2, p16, and ARF expression all increased dramatically. A similar relationship was also observed in primary neuroblastomas where CAI2 expression was significantly higher in advanced-stage neuroblastoma, independently of MYCN amplification. Consistent with its association with high-risk disease, CAI2 expression was also significantly associated with poor clinical outcomes, although this effect was reduced when adjusted for MYCN amplification. Taken together, our findings suggested that CAI2 contributes to the paradoxical overexpression of p16 in neuroblastoma, where CAI2 may offer a useful biomarker of high-risk disease. Cancer Res; 74(14); 3753–63. ©2014 AACR.
Basement Zone Antibodies in Bullous Pemphigoid
Authors: Robert E. Jordon
Journal: JAMA (1967)

Indirect immunofluorescent (IF) staining revealed that in 14 of 16 patients with active lesions of bullous pemphigoid the sera contained antibodies specific for the basement zone beneath stratified squamous epithelium while the sera from six patients in remission contained no demonstrable antibodies. The sera of 18 patients with dermatitis herpetiformis and 94 patients with various bullous and nonbullous dermatoses yielded negative reactions to the basement zone by indirect IF staining. In four of five skin biopsy specimens from patients with bullous pemphigoid direct IF staining indicated that γ-globulin had been bound in vivo to the basement zone.
Absorption of isophane (NPH) insulin and its clinical implications.
Authors: T Lauritzen, S Pramming, E A Gale, T Deckert, C Binder
Journal: BMJ (1982)

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.
Measuring P50 Suppression and Prepulse Inhibition in a Single Recording Session
Authors: Gregory A. Light, David L. Braff
Journal: American Journal of Psychiatry (2001)

Two distinct measures have been used to assess inhibitory gating deficits in schizophrenia patients: P50 suppression and prepulse inhibition of the startle response. It remains unclear whether both measures can be assessed in a single testing session.Twelve normal subjects underwent testing in a carefully designed combined P50/prepulse inhibition session using stimulus characteristics similar to those described in the existing literature.The levels of both P50 suppression and prepulse inhibition obtained in the combined session were highly similar to those obtained in independent testing of previous cohorts of normal subjects. As in previous experiments, P50 suppression and prepulse inhibition were not significantly correlated.Measuring P50 suppression and prepulse inhibition in a single session is feasible and offers a unique opportunity to assess these two distinct gating measures contemporaneously in cohorts of normal comparison subjects and schizophrenia patients, so that temporal shifts in one or both measures are minimized.