tbuckley/cabot-search huggingface dataset:
Glucokinase Activators for Diabetes Therapy
Authors: Franz M. Matschinsky, Bogumil Zelent, Nicolai Doliba, Changhong Li, Jane M. Vanderkooi, Ali Naji, Ramakanth Sarabu, Joseph Grimsby
Journal: Diabetes Care (2011)

Type 2 diabetes is characterized by elevated blood glucose levels resulting from a pancreatic β-cell secretory insufficiency combined with insulin resistance, most significantly manifested in skeletal muscle and liver (1). If untreated, diabetic complications develop that cause loss of vision, peripheral neuropathy, impaired kidney function, heart disease, and stroke. The disease has a polygenic basis because numerous genes (the latest count exceeding 20) participate in its pathogenesis, but modern lifestyle characterized by limited physical activity and excessive caloric intake are critical precipitating factors for the current epidemic of type 2 diabetes worldwide (2). It appears that available treatments, including attempts at lifestyle alterations and drug therapies including insulin, are insufficient to stem the tide. Therefore, new approaches, including the development of therapeutic agents with novel mechanisms of action, are needed.

Selection of new drug targets to treat type 2 diabetes has to be guided primarily by consideration of established physiological chemistry of glucose homeostasis and of prevailing views about the pathophysiology of type 2 diabetes because the genetics of the disease that could serve as another guiding principle remain prohibitively perplexing. The glucose-phosphorylating enzyme glucokinase (GK) was identified as an outstanding drug target for developing antidiabetic medicines because it has an exceptionally high impact on glucose homeostasis because of its glucose sensor role in pancreatic β-cells and as a rate-controlling enzyme for hepatic glucose clearance and glycogen synthesis, both processes that are impaired in type 2 diabetes (3). Milestones in the 45-year history of GK research are listed in Supplementary Table 1 (Supplementary References S1–S27). In the mid-1990s, Hoffmann La-Roche scientists conducted a high-throughput screen in search of small molecules that could reverse the inhibition of GK by its regulatory protein (GKRP, see further discussion below) and identified a hit molecule that reversed GKRP inhibition by directly stimulating GK (4 …
On-demand analgesia equipment.
Authors: W D White, D J Pearce, J Norman
Journal: BMJ (1979)

In February 1978 the patient went skiing with his school colleagues, and being afraid of taking drugs in the presence of his friends he stopped taking his immunosuppressive therapy for two weeks.Seen again at the end of March 1978 he was azotaemic, with a plasma creatinine of 884 ,umol/l (10-0 mg/100 ml).An open biopsy of the transplant showed the signs of an acute interstitial graft rejection.Under high-dose steroids administered in addition to his continuous immunosuppressive regimen the graft function improved again, and since June 1978 the plasma creatinine is stable at about 256 tmol/l (2 9 mg/100 ml).
Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases from renal cell carcinoma: Comparison between France, Germany, and the United Kingdom
Authors: M. F. Botteman, S. Kaura
Journal: Journal of Clinical Oncology (2009)

5106 Background: Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients (pts) with bone metastases from RCC. This study assessed and compared the cost-effectiveness of ZOL in pts with RCC from French, German, and United Kingdom (UK) societal perspectives. Methods: This analysis was based on a retrospective analysis of RCC pts with bone metastases who were enrolled in a 9-mo trial of ZOL or placebo (PBO) plus concomitant antineoplastic therapy. A model was developed to simulate costs and quality-adjusted life-years (QALYs) experienced by study pts. The model included data and assumptions regarding SRE incidence, mortality, drug and administration costs, SRE costs, reduced quality of life (QOL) because of SREs and bone pain, and therapy duration. SRE costs were estimated using diagnosis-related group tariff information and published literature. Consistent with similar economic analyses, it was assumed that QOL decreased 20% to 80% (depending on SRE type) for 1 mo after each SRE experienced. Sensitivity analyses were performed to test the effects of alternate assumptions, with &lt; 30,000/QALY considered cost-effective. Results: Compared with PBO-treated pts (n = 19), ZOL-treated pts (n = 27) experienced 1.07 fewer SREs/pt and gained discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among pts treated with ZOL vs PBO (-4,196 in France, -3,880 in Germany, and -3,355 in the UK). After including drug therapy costs, ZOL saved 1,358, 1,223, and 719 per pt in France, Germany, and the UK, respectively. In multivariate sensitivity analyses, ZOL saved costs in 67% to 77% of cases, depending on the country. ZOL resulted in a cost per QALY gained &lt; 30,000 in approximately 93% of cases. Conclusions: Treatment with ZOL reduces SREs, improves QOL, and lowers health-related costs compared with PBO in French, German, and UK pts with bone metastases from RCC. Use of ZOL in these populations therefore provides health-related cost savings and is a cost-effective use of healthcare resources. [Table: see text]
Bromocriptine for severe mastalgia.
Authors: B V Palmer, J C Monteiro
Journal: BMJ (1977)

sites must be affected by some secondary mechanism (for example, allergy) it is likely that the intestinal lesions are of like origin rather than simple irritation.It is not easy to date onset.Cases observed in depth show symptoms in childhood which in retrospect can be ascribed to Crohn's disease.Thus it could well be that patients with "preclinical" Crohn's disease find cornflakes more acceptable than other cereals.Likewise, the cornflake hypothesis does not account for cases in my knowledge with florid features before the introduction (about 1920) of cornflakes.I would rather put my money on refined sugar-though in my observation alcohol can provoke acute exacerbations.
HYSTERO-EPILEPSY IN A CHILD.
Authors: THEODORE LE BOUTILLIER
Journal: JAMA (1907)

As there are comparatively few recorded cases of hystero-epilepsy in children, it was thought worth while to record this instance. <h3>History.</h3> —Beatrice L., aged 15, was first seen in consultation in New York, Aug. 8, 1906. Parents are healthy and have five other children of normal health. The patient is the second child, the oldest being a boy, aged 18. One child died when four months old of some intestinal disorder. There was a miscarriage ten years ago. There is no history on either side of venereal disease, hysteria, epilepsy or insanity. On the maternal side two sisters died of phthisis before reaching adult life; the grandfather of pneumonia at 53 years of age and the grandmother at 42 years of age of unknown causes. On the paternal side, the grandfather died of lead poisoning at 55 years of age, while the grandmother is in good health at 67 years.
Case of Simple Fracture and Dislocation of the Greater Portion of the Right Astragalus, Forwards and Outwards
Authors: E. J. Spry
Journal: BMJ (1847)

vaysore The seee pain in the back pased off at t time..New and larger spots were noticed on the 28th, whilst the old ones had faded; they were confined to the, upper pan of the body on this occasion.No futther bleeding occurred, so that it had lasted during four days.Three or feur days later little trace
Hypercytokinemia with 2009 pandemic H1N1 (pH1N1) influenza successfully treated with polymyxin B-immobilized fiber column hemoperfusion
Authors: Shinhiro Takeda, Ryo Munakata, Shinji Abe, Seiji Mii, Manabu Suzuki, Takeru Kashiwada, Arata Azuma, Takeshi Yamamoto, Akihiko Gemma, Keiji Tanaka
Journal: Intensive Care Medicine (2010)
Ketoconazole to Reduce the Need for Cyclosporine after Cardiac Transplantation
Authors: Anne Keogh, Phillip Spratt, Cate McCosker, Peter Macdonald, Julie Mundy, Annemarie Kaan
Journal: New England Journal of Medicine (1995)

Because ketoconazole can markedly reduce the need for cyclosporine and because it also has antimicrobial properties, it may offer benefits in the treatment of patients after cardiac transplantation.
Pathology of the Head and Neck: Armed Forces Institute of Pathology
Authors: John F. Madden
Journal: JAMA (1994)

The diagnostic surgical pathologist must assimilate myriad images of various histopathologic processes into visual memory and then gauge the similarity of each new gross specimen or microscopic slide to this array of remembered morphological benchmarks. The daily practice of pathology brings repeated exposure to images of common diseases. But training the eye to recognize unusual entities requires the use of study sets—a limited commodity—or, more often, recourse to a few representative photomicrographs reproduced in a textbook or journal article.  The pathology titles in the Imagedisc Library series produced by Image Premastering Services attempt to overcome the space and cost limitations of traditional print reproduction by using laser disk technology to provide access to thousands of color video images in a convenient package. Pathology of the Head and Neck , authored by staff members of the Armed Forces Institute of Pathology, has the stated goal of providing access to the Institute's comprehensive
Sexual Behaviors and Reproductive Health Outcomes
Authors: Sandra L. Martin, Brian Kilgallen, Amy Ong Tsui, Kuhu Maitra, Kaushalendra Kumar Singh, Lawrence L. Kupper
Journal: JAMA (1999)

Wife abuse has been associated with a variety of health concerns. Associations between abuse and reproductive health in India are not well known.To examine relationships between men's reports of wife abuse and reproductive health issues in northern India.Structured face-to-face interviews were conducted as part of the male reproductive health supplement of the PERFORM System of Indicators Survey, a systematic multistage survey conducted in 1995-1996.The northern state of Uttar Pradesh, one of the least developed states in India.A total of 6632 married men aged 15 to 65 years who lived with their wives and completed all survey questions for the study variables reported here.Physically and sexually abusive behaviors toward wives, sexual activities outside marriage, sexually transmitted disease (STD) symptoms, contraception use, unplanned pregnancies, and sociodemographic characteristics.Fifty-four percent of men reported not abusing their wives, while 17% reported physically but not sexually abusing their wives, 22% reported sexual abuse without physical force, and 7% reported sexual abuse with physical force. Abuse was more common among men who had extramarital sex (for sexual abuse using force: odds ratio [OR], 6.22; 95% confidence interval [CI], 3.98-9.72). Similarly, men who had STD symptoms were more likely to abuse their wives (with current symptoms: OR, 2.43; 95% CI, 1.73-3.42). Unplanned pregnancies were significantly more common among wives of abusive men, especially sexually abusive men who used force (OR, 2.62; 95% CI, 1.91-3.60).Wife abuse appears to be fairly common in northern India. Our findings that abusive men were more likely to engage in extramarital sex and have STD symptoms suggest that these men may be acquiring STDs from their extramarital relationships, thereby placing their wives at risk for STD acquisition, sometimes via sexual abuse. These abusive sexual behaviors also may result in an elevated rate of unplanned pregnancies.
Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines
Authors: Lorenza Cannarile, Francesca Fallarino, Massimiliano Agostini, Salvatore Cuzzocrea, Emanuela Mazzon, Carmine Vacca, Tiziana Genovese, Graziella Migliorati, Emira Ayroldi, Carlo Riccardi
Journal: Blood (2005)
Treatment of children with chronic hepatitis C with recombinant interferon-α: A pilot study
Authors: Mercedes Ruiz-Moreno, Maria José Rua, Inmaculada Castillo, Maria Dolores García-Novo, Maravillas Santos, Sonia Navas, Vicente Carreño
Journal: Hepatology (1992)

Twelve children with chronic non-A, non-B hepatitis were entered in a pilot trial of recombinant interferon-alpha. Although all the children had hepatitis C virus RNA in serum, only five had antibodies against this virus. Children received 3 MU/m2 body surface area interferon-alpha 3 times/wk for 6 mo; they were followed for 24 mo, including the therapy period. One child was dropped from the study, so the results are from the 11 children who completed the study. At the end of the therapy period, 36% of the children had normal ALT levels; this percentage increased to 90% at mo 15 of follow-up. Thereafter, relapse occurred in five children; thus ALT normalization was observed in 5 of 11 children at the 24th month. Moreover, two different ALT patterns were found: HCV antibody-negative children had significant peaks of ALT levels with respect to the basal samples (p less than 0.05) until the third month of the therapy; these levels later decreased. In contrast, HCV antibody-positive children had slight fluctuations of ALT until normal levels were reached. At the end of treatment, three children had HCV RNA; one demonstrated a rebound in ALT levels. Finally, histological activity had decreased significantly in the second liver biopsy specimen in all children. In summary, interferon treatment in children with chronic hepatitis C may be helpful, although these results should be confirmed in controlled trials.
Sunset for Statins after AURORA?
Authors: Giovanni F.M. Strippoli, Jonathan C. Craig
Journal: New England Journal of Medicine (2009)

Reducing mortality from cardiovascular disease among patients undergoing dialysis is a global public health challenge. The past 10 years have seen trials of many interventions designed to improve survival and cardiovascular outcomes in these patients.14 Unfortunately, none of these interventions have been shown to be effective, despite beneficial effects in surrogate markers.5,6 It appears that statins have now joined this group of "promising but ineffective" interventions.In this issue of the Journal, Fellström et al.7 report on the results of A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and . . .
Cerebrovascular Thrombosis in Patients with Buerger's Disease
Authors: HEINZ I. LIPPMANN
Journal: Circulation (1952)

Nine cases of cerebrovascular thromboangiitis obliterans were observed among 1700 cases of peripheral thromboangiitis obliterans. These, with 30 acceptable cases from the literature, are analyzed. Smoking appears to activate the disease, which is characterized by, recurrences and remissions of focal cortical signs due to thrombosis of cerebral arteries and cortical granular atrophy. Of my patients, one died. Eight have been followed for 35 to 3 years, and with one exception all are ambulatory. Cessation of smoking is necessary. No other effective treatment is known.
P380Cardiac autonomic nervous system function in early period after radiofrequency ablation-induced destruction of paraganglionic nervous plexuses
Authors: V Evtushenko, K Petlin, K Smyshlyaev, YU Saushkina
Journal: Cardiovascular Research (2014)

Purpose: The aim of the study was to evaluate the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive methods. Materials and Methods: The study included 19 patients with NYHA functional class III/IV heart failure (mean age: 60 ± 9.4 years). All patients underwent surgical treatment of valvular diseases. Patients were assigned to two groups: group 1: 11 patients with AF who underwent RF maze procedure with destruction of paraganglionic nervous plexuses; group 2: 8 patients with SR without denervation. All patients received examination of cardiac sympathetic tone by scintigraphy using 123I- metaiodobenzylguanidine (123I-MIBG). Results: Before surgery, patients with AF had significantly lower heart-to-mediastinum (H/M) ratio (1.64 ± 0.21 vs. 1.9 ± 0.27; p < 0.05) and significantly higher indicator washout rate (30.21 ± 10.43% vs. 21.94 ± 15.01%; p < 0.05) compared with group of patients with sinus rhythm. According to data of regional sympathetic activity evaluation, patients of both groups had similar defects in accumulation of 123I-MIBG before surgery (11.1 ± 5.6% vs. 8.9 ± 5.0%; p = 0.057). Patients with cardiac denervation showed a significant decrease in H/M indexes compared with the corresponding values before surgery (1.64 ± 0.21 vs. 1.42 ± 0.18; p < 0.05). Defect of accumulation significantly increased (11.1 ± 5.6% vs. 24.9 ± 7.56; p < 0.05). Patients without denervation had statistically significant decrease only in H/M index (1.9 ± 0.27 vs. 1.63 ± 0.24; p < 0.5). The study showed that washout rate of 123I-MIBG significantly changed after surgery (36 ± 13.38% vs. 25.14 ± 9.96%; p < 0.05). Patients with AF had significantly lower H/M index compared with group of patients with sinus rhythm (1.42 ± 0.18 vs. 1.63 ± 0.24; p < 0.05). Evaluation of regional sympathetic activity showed that 123I-MIBG accumulation defect was significantly larger in patients with cardiac denervation compared with group of patients without it (24.9% ± 7.56% vs. 13.7 ± 5.81%; p < 0.05). Conclusions: Data of the study showed that patients who underwent destruction of paraganglionic nervous plexuses had statistically significant increase of 123I-MIBG washout rate, decrease of H/M index on early and delayed scintigrams, and increase of 123I-MIBG accumulation defect suggesting that this method may be used for the quality evaluation of cardiac sympathetic denervation in the postoperative period.
CEREBRAL SYPHILIS IN CHILDREN.
Authors: ARTHUR WILLARD FAIRBANKS
Journal: JAMA (1907)

In part, this paper is based on the study of somewhat over 100 cases of undoubted syphilitic cerebral disease in children from the literature. A large number of other cases, undoubtedly of similar character, have been excluded merely because unequivocal evidence of syphilitic infection was wanting, or postmortem examination had not been made. The paper is really a consideration of hereditary cerebral syphilis, but it is thought best to employ the broader title in deference to the opinion of certain well-known observers who believe that many cases of syphilis developing late in childhood are instances of acquired and not of congenital infection. A study of a large number of cases from the literature does not indicate that there is much ground for this belief. Certainly, the great majority of the cases are undoubted instances of inherited disease. There is no reason, however, why cerebral symptoms of presumptive specific character, appearing
Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease
Authors: Colomba Falcone, Maria Paola Buzzi, Catherine Klersy, Peter J. Schwartz
Journal: Circulation (2005)

We previously demonstrated that reduced vagal activity and/or increased sympathetic activity identify post-myocardial infarction patients at high risk for cardiac mortality. Simple and inexpensive autonomic markers are necessary to perform autonomic screening in large populations. We tested our hypothesis that abnormally elevated heart rate (HR) responses at the onset of an exercise stress test, which imply rapid vagal withdrawal immediately preceding sympathetic activation, might predict adverse cardiac events in patients with documented coronary artery disease.The HR increase during the first minute (DeltaHR1 minute) of a symptom-limited exercise stress test was quantified in 458 patients with documented coronary artery disease. During a 6-year (interquartile range 3.7 to 9.0 years) follow-up, 71 patients experienced adverse cardiac events (21 cardiac deaths, 56 nonfatal myocardial infarctions). In univariate analysis, DeltaHR1 minute > or =12 bpm (above the median value of its distribution) predicted both adverse outcome and cardiac death with a hazard ratio of 5.0 (95% CI 2.7 to 9.1; P<0.0001) and of 15.6 (95% CI 2.0 to 118.7; P<0.001), respectively. After adjustment for potential confounders, DeltaHR1 minute remained predictive for both combined end points and for cardiac death.A marked HR increase at the onset of a standard exercise stress test is a novel and easily available parameter that could be clinically useful as an independent predictor of adverse cardiac events, including death, among patients with documented coronary artery disease.
Multiclinic controlled trial of bethanidine and guanethidine in severe hypertension.
Authors: E A Ramirez, L Elson, A S Gear, J R Oster, F N Talmers, J R Thomas
Journal: Circulation (1977)

One hundred and eight patients with initial diastolic blood pressure in the range of 100-124 mm Hg while taking hydrochlorothiazide were assigned randomly and double-blind to hydrochlorothiazide plus either bethanidine or guanethidine. The average reduction of the fifth and sixth months' diastolic blood pressure was 18.4 mm Hg for guanethidine and 13.6 mm Hg for bethanidine (P less than 0.01). The distribution of the individual values was such that 68.8% of guanethidine treated patients achieved a diastolic level below 90 mm Hg, compared to only 45.5% of the bethanidine treated group (P less than 0.025). The degree of orthostatic fall in blood pressure was greater with bethanidine than with guanethidine (P less than 0.05). The diurnal variation of blood pressure was slightly greater with bethanidine than with guanethidine. The results significantly favor guanethidine. This study failed to demonstrate that the shorter action of bethanidine confers significantly better control of blood pressure than the longer action of guanethidine.