tbuckley/cabot-search huggingface dataset:
Drug points: Prolonged cholestasis associated with irbesartan
Authors: R Hariraj, E Stoner, S Jader, D M Preston
Journal: BMJ (2000)

increases the risk of gestational diabetes.In women who weighed less than 3500 g at birth, weight for gestational age may provide additional predictive information on risk.No other birth characteristics were predictive of gestational diabetes.The non-significant raised risk in women weighing 4500 g or more at birth could indicate undiagnosed or unrecorded maternal diabetes.Low birth weight and low weight for gestational age may be common risk factors for gestational diabetes and non-insulin dependent diabetes.The results are compatible with the fetal origins of disease hypothesis.Future studies combining birth information with risk factors in adulthood may improve predictive models for identifying women at risk of gestational diabetes.Barbro Mork Emblem was instrumental in linking the generational birth information and in setting up the generational analytical database.Contributors: GE had the idea for the study, conducted analyses, and wrote the report.RS provided guidance in using the registry, discussed core ideas and study design, and edited the report.LI supervised data collection, discussed core ideas and study design, and edited the report.
Cardiac Resuscitation
Authors: Stephen B. Shohet, Roger H. Sweet
Journal: New England Journal of Medicine (1962)

THE technics of external electric cardiac stimulation1 and defibrillation2 have found considerable application in cardiac emergencies. Most recently the technic of external cardiac massage has also been advocated for use in similar emergencies.3 , 4 In the following case all three procedures were employed, and all three were apparently indispensable for the successful cardiac resuscitation.Case ReportH.M. (B.I.H. M141204), a previously well 60-year-old postal worker, entered the Emergency Ward on November 20, 1961, with a chief complaint of chest pain of 3 hours' duration.When first seen, he was sweating slightly, the lungs were clear, the heart was not enlarged, and . . .
Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis
Authors: Evangelos J. Giamarellos-Bourboulis, Spyridon Zakynthinos, Fotini Baziaka, Evangelos Papadomichelakis, Simona Virtzili, Pantelis Koutoukas, Apostolos Armaganidis, Helen Giamarellou, Charis Roussos
Journal: Intensive Care Medicine (2006)
Physical and Biological Considerations Militating against the Use of Endoscopically Applied High-frequency Current in the Abdomen
Authors: K. Semm
Journal: Endoscopy (1983)

In general surgery, high-frequency current is a routine method of producing destructive heat for hemostasis. The so-called "skin effect" prohibits any electric reactions into the human nervous or muscle tissue. When using high-frequency current in the closed abdominal cavity, the nature of the current forces is to go unpredictable ways. This fact provokes unforeseen damage (bowel, ureter, skin burns) which are method-induced and cannot be excluded even with extreme care in the handling of the high-frequency current during tubal sterilization or other endoscopic haemostasis procedures. All biological and physical data are presented that support the demand that high-frequency current must be excluded from pelviscopy e.g. laparoscopy, and a new technique called "endocoagulation" is described, which can replace the intraabdominal use of high-frequency current during pelviscopy.
Triacetyloleandomycin with Triple Sulfa
Authors: Grayson Carroll
Journal: JAMA (1960)

Effects of treatment were studied in 277 patients with infections of the urinary tract, 113 of these infections being either staphylococcic or streptococcic. The treatment consisted of the oral administration of two tablets, each containing triacetyloleandomycin, 75 mg.; sulfadiazine, 111 mg.; sulfamerazine, 111 mg.; and sulfamethazine, 111 mg.; thrice daily for five days. The choice of drugs was intended to decrease the likelihood of difficulty with drug-resistant mutations and was based on evidence that tests of sensitivity of infecting organisms to sulfa drugs in vitro are not reliable in predicting therapeutic effectiveness. Of 86 patients who had staphylococcus infections, 64 (74%) recovered. Of 27 patients with streptococcus infections, 17 (63%) recovered. Six patients developed a rash or diarrhea as side-effects, but these were not sufficiently severe to necessitate interruption of the treatment.
Community oriented primary care
Authors: A. M Pollock, F A. Majeed
Journal: BMJ (1995)

Over 9000 general practitioners, covering more than a third of the population of England and Wales, have opted to become fundholders.1 They have taken the responsibility for managing budgets for staff, premises, and prescribing and for some hospital and community health services. The remaining 21000 non-fundholding general practitioners are also taking greater responsibility for commissioning health services, either as part of commissioning groups or through locality purchasing. To become effective commissioners of health services, fundholding general practitioners will need skills in disciplines that are usually seen as the remit of public health specialists and health service planners, such as epidemiology, needs assessment, and health service planning. In short, fundholders are expected to take on many of the roles of district health authorities and family health services authorities but at a practice level.

The King's Fund has recently suggested community oriented primary care as one method of teaching and applying public health skills in a primary care setting.2 Originally developed in Israel, community oriented primary care has several requirements. These include a primary care practice based in the community; an identifiable population or community for which the practice assumes responsibility for improving its health status; a planning, monitoring, and evaluation process for identifying and resolving health problems; and liaison and collaboration with local community leaders.3 Readers might be forgiven for mistaking this as a description of the work done by their local health authority (which to all intents and purposes it is).

Community oriented primary care was started in Israel because of concerns about the lack of coordination of health …
Oral Bisphosphonate and Breast Cancer: Prospective Results from the Women's Health Initiative (WHI).
Authors: R. Chlebowski, Z. Chen, J. Cauley, R. Rodabough, A. McTiernan, D. Lane, J. Manson, L. Snetselaar, S. Yasmeen, M. O'Sullivan, M. Stafford, S. Hendrix, R. Wallace
Journal: Cancer Research (2009)

Abstract Background: Emerging clinical evidence suggest intravenous bisphosphonates may directly inhibit breast cancer (Gnant SABCS 2008) while oral bisphosphonates in US clinical practice have received limited evaluation regarding breast cancer influence.Methods: To investigate associations between oral bisphosphonates and invasive breast cancer we examined data for 151,592 postmenopausal women enrolled in the WHI. Information was collected on breast cancer risk factors and oral bisphosphonate use. To control for bone mineral density (BMD) we employed a published hip fracture prediction model which did not incorporate BMD (Robbins 2007) against the 10,296 WHI participants who had baseline total hip BMD determination. Breast cancers were centrally adjudicated by pathology report review. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).Results: Of the 151,592 participants, 2,216 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). An analysis comparing hip fracture risk score to BMD in those with both found a significant correlation (regression line = .79-.0478 log predicted hip fracture, r=0.43). As a result, the hip fracture risk score was used to control for potential BMD group differences. HRs for invasive breast cancer by bisphosphonate use are outlined below after 7.8 (1.7) mean years (SD). Bisphosphonate Use NoYesBreast Cancer Incidence ** Invasive Breast CancerNRate*NRateHR95% CIP-valueTotal50924.38643.290.68(0.52-0.89)&amp;lt; .01ER positive38293.28502.560.70(0.52-0.95)0.02ER negative7170.6180.410.66(0.31-1.39)0.27 * Rate/1000 women years of follow-up**Cox proportional hazards analyses adjusted for age, ethnicity, smoking, alcohol use, physical activity, BMI, mammograms, prior hormone use, calcium, vitamin D, hip fracture risk score, Gail risk score and stratified on WHI trial randomization arm.Conclusion: There was a statistically significant association between oral bisphosphonate use and lower invasive breast cancer incidence with fewer ER positive breast cancers and a non-significant trend for ER negative breast cancers in bisphosphonate users. This result suggests oral bisphosphonates may have direct inhibiting effects on breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 21.
Remote control of induced dopaminergic neurons in parkinsonian rats
Authors: Maria Teresa Dell’Anno, Massimiliano Caiazzo, Damiana Leo, Elena Dvoretskova, Lucian Medrihan, Gaia Colasante, Serena Giannelli, Ilda Theka, Giovanni Russo, Liudmila Mus, Gianni Pezzoli, Raul R. Gainetdinov, Fabio Benfenati, Stefano Taverna, Alexander Dityatev, Vania Broccoli
Journal: Journal of Clinical Investigation (2014)

Direct lineage reprogramming through genetic-based strategies enables the conversion of differentiated somatic cells into functional neurons and distinct neuronal subtypes. Induced dopaminergic (iDA) neurons can be generated by direct conversion of skin fibroblasts; however, their in vivo phenotypic and functional properties remain incompletely understood, leaving their impact on Parkinson's disease (PD) cell therapy and modeling uncertain. Here, we determined that iDA neurons retain a transgene-independent stable phenotype in culture and in animal models. Furthermore, transplanted iDA neurons functionally integrated into host neuronal tissue, exhibiting electrically excitable membranes, synaptic currents, dopamine release, and substantial reduction of motor symptoms in a PD animal model. Neuronal cell replacement approaches will benefit from a system that allows the activity of transplanted neurons to be controlled remotely and enables modulation depending on the physiological needs of the recipient; therefore, we adapted a DREADD (designer receptor exclusively activated by designer drug) technology for remote and real-time control of grafted iDA neuronal activity in living animals. Remote DREADD-dependent iDA neuron activation markedly enhanced the beneficial effects in transplanted PD animals. These data suggest that iDA neurons have therapeutic potential as a cell replacement approach for PD and highlight the applicability of pharmacogenetics for enhancing cellular signaling in reprogrammed cell-based approaches.
Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man?
Authors: J A Kanis, T Cundy, M Bartlett, R Smith, G Heynen, G T Warner, R G Russell
Journal: BMJ (1978)

Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.
Kidney lite: four doctors with only four kidneys
Authors: A. Ferriman
Journal: BMJ (2015)

<h3>Aim</h3> To examine whether intraocular pressure (IOP) reduction by latanoprost correlates with single nucleotide polymorphisms (SNPs) of the prostaglandin F2α (FP) receptor gene in patients with glaucoma and ocular hypertension (OH). <h3>Methods</h3> The genotype of nine SNPs in the FP receptor gene was determined by direct DNA sequencing, or other techniques, in 82 patients with glaucoma or OH who were treated with latanoprost monotherapy in one eye. The IOP reduction was evaluated by the percent IOP reduction (%ΔIOP), estimated by subtracting IOP fluctuations in the untreated fellow eye. Subjects were classified by %ΔIOP into low responders (%ΔIOP&lt;10%) and others (%ΔIOP ≥10%). The correlation between %ΔIOP and SNPs in the FP receptor gene was analysed. <h3>Results</h3> Multiple regression analysis demonstrated that the rs12093097 was the only significant factor that correlated with %ΔIOP (p=0.039). Among estimated haplotypes, one haplotype that contained the minor allele only in rs3753380, was significantly correlated with low responders even after correction for multiple test (permutation test, p=0.037). <h3>Conclusions</h3> An association was found between SNPs of the FP receptor gene and the response to latanoprost in patients with glaucoma or OH. The FP receptor genetic polymorphism may influence the degree of IOP reduction by latanoprost in these patients.
Lymphomatoid papulosis with a natural killer-cell phenotype.
Authors: M.W. Bekkenk, P.M. Kluin, P.M. Jansen, C.J.L.M. Meijer, R. Willemze
Journal: British Journal of Dermatology (2001)

Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the atypical cells expressed a CD3-, CD4-, CD8-, CD30+, CD56+ phenotype. Detailed phenotypic and genotypic analysis confirmed that these cells had a natural killer (NK)-cell phenotype. Lymphomas with an NK-cell phenotype usually have a poor prognosis. However, the waxing and waning of papular lesions for more than 20 years and the excellent response to low-dose oral methotrexate in this patient suggest similar clinical behaviour to LyP cases with a T-cell phenotype.
Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
Authors: Marco Gobbi, Francesca Re, Mara Canovi, Marten Beeg, Maria Gregori, Silvia Sesana, Sandro Sonnino, Doriano Brogioli, Claudia Musicanti, Paolo Gasco, Mario Salmona, Massimo E. Masserini
Journal: Biomaterials (2010)
A Role for Hydroxy-Methylglutaryl Coenzyme A Reductase in Pulmonary Inflammation and Host Defense
Authors: Michael B. Fessler, Scott K. Young, Samithamby Jeyaseelan, Jonathan G. Lieber, Patrick G. Arndt, Jerry A. Nick, G. Scott Worthen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: A growing literature indicates that hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) modulate proinflammatory cellular signaling and functions. No studies to date, however, have addressed whether statins modulate pulmonary inflammation triggered by aerogenic stimuli or whether they affect host defense. Objectives: To test whether lovastatin modulates LPS-induced pulmonary inflammation and antibacterial host defense. Methods: To address these questions, and to confirm any effect of statins as dependent on inhibition of hydroxy-methylglutaryl coenzyme A reductase, we treated C57Bl/6 mice with three oral doses of 10 mg/kg lovastatin (or vehicle) and three intraperitoneal doses of 10 mg/kg mevalonic acid (or saline), and then exposed them to the following: (1) aerosolized LPS, (2) intratracheal keratinocyte-derived chemokine (KC), or (3) intratracheal Klebsiella pneumoniae. Measurements and main results: LPS- and KC-induced airspace neutrophils were reduced by lovastatin, an effect that was blocked by mevalonic acid cotreatment. Lovastatin was also associated with reduced parenchymal myeloperoxidase and microvascular permeability, and altered airspace and serum cytokines after LPS. Native pulmonary clearance of K. pneumoniae was inhibited by lovastatin and extrapulmonary dissemination was enhanced, both reversibly with mevalonic acid. Ex vivo studies of neutrophils isolated from lovastatin-treated mice confirmed inhibitory effects on Rac activation, actin polymerization, chemotaxis, and bacterial killing. Conclusion: Lovastatin attenuates pulmonary inflammation induced by aerosolized LPS and impairs host defense.
Gastric acid secretion and gastrin production in the short bowel syndrome.
Authors: N S Williams, P Evans, R F King
Journal: Gut (1985)

Excess gastric acid secretion and gastrin production may occur in patients with the short bowel syndrome but the two measurements have never been made simultaneously in man in response to a food stimulus. Using the technique of intragastric titration, this was carried out in eight patients after extensive small bowel resection resulting mainly from vascular occlusion and in eight matched normal control subjects. Basal acid output and peak acid output in response to pentagastrin was also measured separately. Although peak and integrated serum gastrin concentrations were significantly greater in patients (450 +/- SE 109 pg/ml; 113 +/- 2.9X10(-3) pg/ml/min) compared with control subjects (174 +/- 98 pg/ml; 6.1 +/- 2.0X10(-3) pg/ml/min p less than 0.05), no concomitant increase in acid secretion was shown either during intragastric titration or in response to pentagastrin. These findings indicate that there is no rationale for treating these patients with long term anti-ulcer therapy.
Human serum proinsulin
Authors: F. Melani, A. H. Rubenstein, D. F. Steiner
Journal: Journal of Clinical Investigation (1970)

Gel filtration of human serum extracts on Bio-Gel P-30 columns produced two peaks of material reactive with insulin antisera. The earlier eluting fraction appeared at the elution position of proinsulin (serum proinsulin-like component, PLC) while the second fraction corresponded in elution volume to insulin. In assays using porcine insulin-(131)I and an antiserum against porcine insulin, human pancreatic proinsulin was less reactive than human insulin. Serial dilutions of the serum PLC in the immunoassay showed immunological identity with the human proinsulin standard. Partial tryptic digestion of the serum PLC yielded products with increased immunological reactivity as estimated with insulin as the standard. With larger amounts of trypsin, all the serum PLC was converted to insulin-like components (desthreonine and desoctapeptide insulin). On the basis of these results we conclude that the earlier eluting fraction of human serum extracts is proinsulin. The fasting values of proinsulin in normal subjects ranged between 0.05 and 0.4 ng/ml, representing from 5 to 48% of the insulin concentration. In one subject the values of proinsulin were higher than those of insulin. After oral administration of 100 g of glucose, the proinsulin levels tended to rise similarly to insulin. Three obese patients with hyperinsulinemia had higher fasting levels of proinsulin and a greater increase after glucose than the normal subjects. As the high levels of proinsulin coexisted with raised insulin concentration in these obese subjects, the relative proportions of the two hormones were in the same range observed in the normal group. Thus hyperinsulinemia in these obese subjects was not accompanied by an increase in the fraction of serum proinsulin. When the values for serum proinsulin were expressed as percentage of the insulin levels, there was a decrease in the per cent proinsulin in the first hour of the glucose tolerance test. After the second hour, the per cent tended to rise towards the fasting levels.
Abstract 4982: N-myc downstream-regulated gene 1/Cap43 expression promotes cell differentiation of human osteosarcoma cells
Authors: Nobuhiro Fukushima, Michihisa Zenmyo, Koji Hiraoka, Takanori Shoda, Toru Matsugaki, Setsuro Komiya, Mayumi Ono, Michihiko Kuwano, Kensei Nagata
Journal: Cancer Research (2010)

Abstract N-myc downstream regulated gene 1 (NDRG1)/Cap43 is closely associated with cell differentiation, and its expression is induced by hypoxia and increasing intracellular calcium. Whether NDRG1/Cap43 expression in cancer cells is a predictive marker of good or poor prognosis in patients depends upon tumor types and differentiation status. In this study, we examined whether NDRG1/Cap43 expression was involved in differentiation of osteosarcoma cells, and used three osteosarcoma cell lines, MG63, U2OS, and SaOS2. Its expression in MG63 and U2OS was significantly enhanced by vitamin D3 that also induced production of osteocalcin, a differentiation marker of osteoblasts. Knockdown of NDRG1/Cap43 using siRNA also suppressed the production of osteocalcin and enhanced cell proliferation, accompanying by suppression of p21 expression. Furthermore, acquired invasiveness of osteosarcoma cells during invasion in Matrigel resulted in decreasing expression of NDRG1/Cap43. A possible role of NDRG1/Cap43 in cellular capacity for differentiation and invasion in osteosarcoma cells will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4982.
The Effect of Rosiglitazone on Overweight Subjects With Type 1 Diabetes
Authors: Suzanne M. Strowig, Philip Raskin
Journal: Diabetes Care (2006)

Our report (1) on the effect of rosiglitazone on overweight subjects with type 1 diabetes showed that rosigolitazone-treated subjects with a BMI ≥30 kg/m2 experienced significantly greater improvements in HbA1c (A1C) levels than those with a BMI <30 kg/m2 (−1.4 vs. −0.4%, P = 0.032). In addition, regression analysis showed that BMI, total daily insulin dose, and total, LDL, and HDL cholesterol levels were predictors of improvement in A1C (1). In his letter (2), Orchard raises the intriguing possibility that an estimate …
Medical Nemesis: The Expropriation of Health
Authors: Thomas H. Jobe
Journal: JAMA (1976)

Although Ivan Illich's rhetoric at times suggests otherwise,<i>Medical Nemesis</i>is not primarily an attack against greed for power on the part of physicians nor against "therapeutic greed" on that of patients. The book is rather an extension of Illich's ongoing critique of the impersonal and, to him, inhuman, "sociopolitical system of capital-intensive industrial production," as it applies to health care. (Hospital-based medicine is capital-intensive because it relies on the huge capital outlay of the centralized plant. Illich cites China's "barefoot medicine" as an example of the decentralized labor-intensive form of health care.) Illich focuses his principle of "counterproductivity" on the health care industry to demonstrate how medical technology, through the influence of capital-intensive methods, has burgeoned beyond the point of fulfilling legitimate human health care needs to become a powerful agent of dehumanization. He argues that technological expertise in medicine operates by a self-aggrandizing inner logic to dictate to
First meningitis B vaccine could be available in UK next year
Authors: G. Iacobucci
Journal: BMJ (2012)

The first vaccine for meningitis B is set to become available in the United Kingdom next year after being recommended by the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) has granted marketing authorisation for Bexsero, a new vaccine from Novartis intended to immunise people aged 2 months or older against invasive meningococcal disease caused by Neisseria meningitidis group B.

If accepted, the vaccine could become available in the UK next year, subject to approval from the UK Joint Committee for Vaccination and Immunisation, which is currently assessing the vaccine for inclusion …
Skoda's fool
Authors: D L Sackett
Journal: BMJ (2004)

As the solo intern in charge of a Chicago emergency room one August night in 1960, I was grappling with three dozen former passengers (by then, aspiring personal injury claimants) of a city bus involved in a minor collision. Most had demanded x rays in hope of fracture, and groaned to potential witnesses as they limped about the emergency room.

Into this cacophony …