tbuckley/cabot-search huggingface dataset:
Urban-Rural Differences in the Prevalence of Foot Complications in South-Indian Diabetic Patients
Authors: Vijay Viswanathan, Sivagami Madhavan, Seena Rajasekar, Snehalatha Chamukuttan, Ramachandran Ambady
Journal: Diabetes Care (2006)

Diabetes is recognized to be common in Asian Indians. The number of people with diabetes in the world is expected to double between 2000 and 2030. The greatest absolute increase in the number of people with diabetes will be in India (1).

Regional studies from urban areas of India have shown a several-fold increase in the prevalence of diabetes in the last 2 decades (2). In a national survey reported in 2001, a concomitant increase in prevalence of impaired glucose tolerance (IGT) was noted (3). In four of six cities, the ratio of IGT to diabetes was greater than one, implying the possibility of a future conversion of IGT subjects to diabetes. An urban-rural difference in the prevalence rate was found, indicating that the environmental factors related to urbanization had a significant role in increasing the prevalence of diabetes (4). It was shown that diabetes had increased threefold over a span of 14 years in a rural population in southern India (5). The prevalence of diabetes in the urbanizing rural population was found to be midway between the rural and urban population (6).

In India, diabetic foot infection is a common cause for hospital admission among diabetic patients and is caused by a number of sociocultural practices (7). The economic and emotional consequences for the patient and the family can be enormous (8).

There is not much comparative data on the occurrence of foot complications between urban and rural populations. This study was therefore done in an …
P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome
Authors: R. Diz-Kucukkaya, M. Inanc, V. Afshar-Kharghan, Q E. Zhang, J. A Lopez, Y. Pekcelen
Journal: Annals of the Rheumatic Diseases (2007)

Antiphospholipid antibodies (aPLA) have been shown to enhance thrombus formation by increasing the expression of adhesive receptors such as P-selectin on endothelial cells. The P-selectin counter-receptor on leucocytes is P-selectin glycoprotein ligand-1 (PSGL-1). We have previously described a variable number of tandem repeats (VNTR) polymorphism in the mucin-like region of PSGL-1, with three alleles: allele A, 16 repeats; allele B, 15 repeats; and allele C, 14 repeats.We compared the PSGL-1 VNTR allele and genotype frequencies in 90 patients with antiphospholipid syndrome (APS) with thrombosis, 39 patients with persistent aPLA positivity without thrombosis, and 203 healthy controls.The frequency of the B allele was significantly higher in patients with APS with thrombosis compared with patients without thrombosis (p = 0.023). When we compared the groups by genotype frequencies, we found a markedly higher frequency of the AB genotype in patients with APS with thrombosis than in aPLA-positive patients without thrombosis (38.9% vs 10.3%, p = 0.001) or in normal population (38.9% vs 22.2%, p<0.01).We suggest that the VNTR polymorphism of PSGL-1 is a significant determinant of thrombotic predisposition in patients with APS. Furthermore, risk appears to correlate best with the combination of alleles inherited rather than with the presence of any particular allele.
A 3-year-old female with cough, dyspnoea and low-grade fever
Authors: J. V. Been, S. G. Robben, T. Delhaas, P. Theunissen, E. Dompeling, Q. Jöbsis
Journal: European Respiratory Journal (2009)

CASE REPORTA 3-yr-old female presented at the emergency dept with a 24-h history of dyspnoea, productive cough, bilious vomiting and a low-grade fever.At physical examination, nasal flaring and mild chest retractions were noted.No stridor or wheezing was present and oxygen saturation was normal.Heart rate was 120 bpm in the presence of a low-grade fever (38.6uC).Decreased breath sounds were heard over the right hemithorax, while no asymmetry was noted on either chest inspection or percussion.Otherwise, the findings of physical examination were normal.Laboratory investigation showed no signs of infection.A chest radiograph was performed (fig.1).As a result of the dyspnoea, the patient was admitted and azithromycin was commenced to cover possible Mycoplasma pneumoniae.However, serological screening for Mycoplasma antibodies was negative.Furthermore, no pathogen was cultured from either blood or pharynx.
Accidental ingestion of methadone by children in Merseyside
Authors: J M Binchy, E M Molyneux, J Manning
Journal: BMJ (1994)

method of cataract surgery (309 general practitioners), followed by extracapsular extraction (301).Forty seven general practitioners were familiar with phacoemulsification, 26 were unaware of any of the methods used, and 43 were familiar with all three methods.Only 69 general practitioners expressed a preference for which method was used.The intracapsular technique was often preferred, and few of those expressing a preference chose phacoemulsification (table ).When referring patients with cataracts, only 32 general practitioners said that their choice of consultant was influenced by the surgical method they used.Methods ofcataract surgery preferred by generalpractitioners No of general practitioners Preferred method (n=367) None 298Phacoemulsification or extracapsular extraction 3
Biology and chemistry of the inhibition of nitric oxide synthases by pteridine‐derivatives as therapeutic agents
Authors: Hans Matter, Peter Kotsonis
Journal: Medicinal Research Reviews (2004)

Abstract Inhibitors of the family of nitric oxide synthases (NOS‐I–III; EC 1.14.13.39) are of interest as pharmacological agents to modulate pathologically high nitric oxide (NO) levels in inflammation, sepsis, and stroke. In this article, we discuss the approach for targeting the unique ( 6R )‐5,6,7,8‐tetrahydro‐ l ‐biopterin (H 4 Bip) binding site of NOS by appropriate inhibitors. This binding site maximally increases enzyme activity and NO production from the substrate l ‐arginine upon cofactor binding. The first generation of H 4 Bip‐based NOS inhibitors was based on 4‐amino H 4 Bip derivatives in analogy to anti‐folates such as methotrexate. In addition, we discuss the structure–activity relationship of a related series of 4‐oxo‐pteridine derivatives. Furthermore, molecular modeling studies provide an understanding of pterin antagonism on a structural level based on favorable and unfavorable interactions between protein binding site and ligands. These techniques include 3D‐QSAR (CoMFA, CoMSIA) to understand ligand affinity and GRID/consensus principal component analysis (CPCA) to learn about selectivity requirements. Collectively these approaches, in combination with the presented SAR and structural data, provide useful information for the design of novel NOS inhibitors with increased isoform selectivity. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 5, 662–684, 2004
Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial
Authors: Thierry Conroy, Marie-Pierre Galais, Jean-Luc Raoul, Olivier Bouché, Sophie Gourgou-Bourgade, Jean-Yves Douillard, Pierre-Luc Etienne, Valérie Boige, Isabelle Martel-Lafay, Pierre Michel, Carmen Llacer-Moscardo, Eric François, Gilles Créhange, Meher Ben Abdelghani, Beata Juzyna, Laurent Bedenne, Antoine Adenis
Journal: The Lancet Oncology (2014)
Electrophysiologic Characterization of an Organic Anion Transporter Cloned from Winter Flounder Kidney (fROAT)
Authors: BIRGITTA CHRISTINA BURCKHARDT, NATASCHA A. WOLFF, GERHARD BURCKHARDT
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The two-electrode voltage clamp technique was used to demonstrate translocation of p -aminohippurate (PAH) and related compounds such as loop diuretics in Xenopus laevis oocytes expressing the renal organic anion transporter from winter flounder kidney (fROAT). In fROAT-expressing oocytes, PAH (0.1 mM) induced a depolarization of 4.2 ± 0.4 mV and at a holding potential of -60 mV an inward current of -22.6 ± 3.5 nA. PAH-induced current and the current calculated from [ 3 H]-PAH uptake were of similar magnitude. Depolarization, inward current, and current-to-uptake relation indicated exchange of the monovalent PAH with a divalent anion, possibly α-ketoglutarate (α-KG), causing net efflux of one negative charge. The kinetic analysis of PAH-induced currents revealed that translocation is dependent on membrane potential, saturable with an apparent K m of 58 ± 8 μM, and sensitive to probenecid and furosemide. In contrast to probenecid and furosemide, the loop diuretics bumetanide, ethacrynic acid, and tienilic acid and the nephrotoxic mycotoxin ochratoxin A elicited inward currents indicating translocation through fROAT. Substrate-dependent currents provide a tool to elucidate the structure/function relationship of the renal organic anion transporter.
Calcineurin Inhibitors Modulate CXCR3 Splice Variant Expression and Mediate Renal Cancer Progression
Authors: Dipak Datta, Alan G. Contreras, Martin Grimm, Ana Maria Waaga-Gasser, David M. Briscoe, Soumitro Pal
Journal: Journal of the American Society of Nephrology (2008)

Calcineurin inhibitors (CNI) are used to prevent inflammatory diseases and allograft rejection. However, little is known about the mechanism(s) underlying their ability to promote the development and recurrence of cancer. Recent studies suggested that the chemokine receptor CXCR3 may play important roles in tumorigenesis. CXCR3 has two splice variants with opposite functions: CXCR3-A promotes cell proliferation, and CXCR3-B inhibits cell growth. Here, we explored the effects of CNI on the expression and function of CXCR3 splice variants. Compared with normal renal tissues and renal epithelial cells, human renal cancer tissues and renal cancer cell lines demonstrated higher expression of CXCR3-A and markedly lower expression of CXCR3-B. In human renal cancer cells (786-0 and Caki-1) and renal epithelial cells, CNI markedly downregulated the expression of CXCR3-B, whereas expression of CXCR3-A was unchanged. This CNI-mediated downregulation of CXCR3-B resulted in increased proliferation and migration of renal cancer cells; CNI-mediated cell proliferation involved signaling through G(i) proteins, perhaps via CXCR3-A. Finally, it was observed that CNI treatment increased the growth of human renal tumors in vivo, and the expression of CXCR3-B was significantly decreased in these tumors. In summary, these observations suggest that CNI may mediate the progression of human renal cancer by downregulating CXCR3-B and by promoting proliferative signals, likely through CXCR3-A. Targeting CXCR3 splice variants or the signaling pathways downstream of CXCR3 receptors may provide a therapeutic strategy for the prevention of CNI-mediated renal cancer progression.
Effects of the Antifertility Drug Enovid in Five Strains of Mice, With Particular Regard to Carcinogenesis
Authors: W. E. Heston, G. Vlahakis, B. Desmukes
Journal: JNCI Journal of the National Cancer Institute (1973)

The antifertility drug, Enovid, was tested for possible carcinogenicity in female mice of 5 specially selected strains: BALB/c, C3H, C3HfB, A, and C57BI. Enovid was chosen for testing since it is one of the most widely used oral contraceptives. The 5 strains of mice provided maximum genetic variation in the test animals. The drug was fed at 3 dose levels: 5 mcg/gm, 10 mcg/gm and 20 mcg/gm of food. The lowest dose did not prevent reproduction. The 10 mcg dose prevented some females from reproducing. The 20 mcg dose prevented all females from reproducing. The strains of mice differed in their response to Enovid. Weight gain was reduced in all strains. Effect on life-span varied, partly because of the tumors. Cervical and vaginal lesions showed invasion of the epithelium into the stroma but was limited, with few exceptions to the BALB/c females. In the BALB/c strain these lesions occurred in controls as well, but showed more progression and a higher incidence with the highest dose of Enovid. None of these lesions appeared grossly as tumors and none had extended beyond the vaginal wall or metastasized. They were observed only on histologic sections. Neither ovarian nor mammary gland tumors were increased in any strain. In the C3H strain such tumors seemed to be inhibited. In the C3HfB strain there was some inhibition of hepatomas and in the BALB/c strain some inhibition of adrenocortical adenoma. Chromophobe adenomas of the hypophysis were significantly increased in old C57BI females treated with the highest dose of Enovid. Offspring of Enovid-treated females showed no abnormalities. Enovid increased the occurrence and may have advanced the progression of epithelial lesions of the cervix and vagina of old BALB/c females. A study of the lesions in untreated females of this strain might help the understanding of carcinoma in situ in women and possibly the appearance of adeno-carcinoma of the vagina of young women whose mothers had been treated with stilbestrol during the first trimester to maintain pregnancy. Other neoplasms in this strain were not increased by the Enovid therapy. In the C3H strain mammary tumors were reduced by the Enovid and those that did occur were found later than in controls. Results from experimental animals should be applied to humans with care. Such results are of greatest value in directing attention to certain areas for investigation.
Transbronchial biopsy without fluoroscopy: a five year experience in outpatients.
Authors: O de Fenoyl, F Capron, B Lebeau, J Rochemaure
Journal: Thorax (1989)

Transbronchial biopsy is the technique of choice for obtaining tissue for histological diagnosis in many pulmonary disorders. The procedure has usually been carried out as an inpatient procedure with the use of fluoroscopy, though this policy has recently been questioned. This report concerns a five year experience of 174 transbronchial biopsies performed without fluoroscopy as an outpatient procedure in patients with interstitial lung disease or a suspicion of sarcoidosis. Chest radiography was carried out only if the patient developed symptoms. No major complications were encountered and the overall complication rate was low. Pneumothorax occurred in six patients (3.4%), only one of whom required intercostal intubation, and bleeding of more than 30 ml occurred in two patients. Histological diagnosis was obtained in 154 patients (88%). In the experience of this group transbronchial biopsy has been safe when carried out as an outpatient procedure without fluoroscopic guidance.
YC-1: A Potential Anticancer Drug Targeting Hypoxia-Inducible Factor 1
Authors: E.-J. Yeo, Y.-S. Chun, Y.-S. Cho, J. Kim, J.-C. Lee, M.-S. Kim, J.-W. Park
Journal: JNCI Journal of the National Cancer Institute (2003)

Hypoxia-inducible factor 1 alpha (HIF-1alpha), a component of HIF-1, is expressed in human tumors and renders cells able to survive and grow under hypoxic (low-oxygen) conditions. YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, an agent developed for circulatory disorders that inhibits platelet aggregation and vascular contraction, inhibits HIF-1 activity in vitro. We tested whether YC-1 inhibits HIF-1 and tumor growth in vivo.Hep3B hepatoma, NCI-H87 stomach carcinoma, Caki-1 renal carcinoma, SiHa cervical carcinoma, and SK-N-MC neuroblastoma cells were grown as xenografts in immunodeficient mice (69 mice total). After the tumors were 100-150 mm(3), mice received daily intraperitoneal injections of vehicle or YC-1 (30 microg/g) for 2 weeks. HIF-1 alpha protein levels and vascularity in tumors were assessed by immunohistochemistry, and the expression of HIF-1-inducible genes (vascular endothelial growth factor, aldolase, and enolase) was assessed by reverse transcription-polymerase chain reaction. All statistical tests were two-sided.Compared with tumors from vehicle-treated mice, tumors from YC-1-treated mice were statistically significantly smaller (P<.01 for all comparisons), expressed lower levels of HIF-1 alpha (P<.01 for all comparisons), were less vascularized (P<.01 for all comparisons), and expressed lower levels of HIF-1-inducible genes, regardless of tumor type.The inhibition of HIF-1 alpha activity in tumors from YC-1-treated mice is associated with blocked angiogenesis and an inhibition of tumor growth. YC-1 has the potential to become the first antiangiogenic anticancer agent to target HIF-1 alpha.
Aging Biology and Geriatric Clinical Pharmacology
Authors: Allan J. McLean, David G. Le Couteur
Journal: Pharmacological Reviews (2004)

Population aging evokes doomsday economic and sociological prognostication, despite a minority of older people suffering significant dependency and the potential for advances in therapeutics of age-related disease and primary aging. Biological aging processes are linked mechanistically to altered drug handling, altered physiological reserve, and pharmacodynamic responses. Parenteral loading doses need only be adjusted for body weight as volumes of distribution are little changed, whereas oral loading doses in some cases may require reduction to account for age-related increases in bioavailability. Age-related reduction of hepatic blood flow and hepatocyte mass and primary aging changes in hepatic sinusoidal endothelium with effects on drug transfer and oxygen delivery reduce hepatic drug clearance. Primary renal aging is evident, although renal clearance reduction in older people is predominantly disease-related and is poorly estimated by standard methods. The geriatric dosing axiom, "start low and go slow" is based on pharmacokinetic considerations and concern for adverse drug reactions, not from clinical trial data. In the absence of generalizable dosage guidelines, individualization via effect titration is required. Altered pharmacodynamics are well documented in the cardiovascular system, with changes in the autonomic system, autacoid receptors, drug receptors, and endothelial function to modify baseline cardiovascular tone and responses to stimuli such as postural change and feeding. Adverse drug reactions and polypharmacy represent major linkages to avoidable morbidity and mortality. This, combined with a deficient therapeutic evidence base, suggests that extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid. Even so, therapeutic advances generally may convert healthy longevity from an asset of fortunate individuals into a general social benefit.
Body surface distribution of abnormally low QRST areas in patients with Wolff-Parkinson-White syndrome. Evidence for continuation of repolarization abnormalities before and after catheter ablation.
Authors: M Hirai, N Tsuboi, H Hayashi, M Ito, Y Inden, H Hirayama, T Ito, T Yanagawa, H Sano, T Kondo
Journal: Circulation (1993)

Whether the Wolff-Parkinson-White syndrome (WPW) is associated with repolarization abnormalities is controversial. The QRST isointegral map (I-map) is theoretically independent of the activation sequence and dependent on repolarization properties. There have been no reports concerning the effects of radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization properties analyzed by I-mapping.I-maps were constructed from data recorded in 38 patients with WPW to investigate repolarization properties and their body surface distribution in a physiological state, without pharmacological influences, and in 13 ablated patients to elucidate the effects of RF ablation on repolarization properties. Patients were divided into three groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10 patients with type B (right-sided AP); and group C, 13 patients who were successfully ablated. Group C consisted of three subgroups: subgroup CA, 7 patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I-maps of WPW were highly (r = .87) correlated with the mean normal I-map, the location of the minimum in groups A and B differed significantly from that in normals. The minimum was located over the upper right anterior chest in normal subjects, over the back in 82% of 22 patients with type A WPW including ablated patients (groups A+CA), and over the mid to lower right anterior chest in 62% of 13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA and B+CB had an abnormally low QRST area ("-2SD area") over the back and right anterior chest, respectively. The abnormally located minimum and the "-2SD area" were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After RF ablation, the distribution of the minimum, initially abnormal, became normal over a period of days or weeks, and the "-2SD area" disappeared over 1 week in all 7 patients. Correlation coefficients between I-maps and the mean normal I-map increased after RF ablation.(1) WPW is often associated with abnormalities in repolarization properties. (2) Repolarization abnormalities were located over the back in type A WPW and over the right mid to lower chest in type B WPW: (3) The abnormalities remain immediately after RF ablation and gradually normalize. These findings support the concept that ST-T abnormalities in 12-lead ECGs following RF ablation are attributable to "cardiac memory."
Positron Emission Tomography in Evaluation of Dementia
Authors: Daniel H. S. Silverman, Gary W. Small, Carol Y. Chang, Carolyn S. Lu, Michelle A. Kung de Aburto, Wei Chen, Johannes Czernin, Stanley I. Rapoport, Pietro Pietrini, Gene E. Alexander, Mark B. Schapiro, William J. Jagust, John M. Hoffman, Kathleen A. Welsh-Bohmer, Abass Alavi, Christopher M. Clark, Eric Salmon, Mony J. de Leon, Ruediger Mielke, Jeffrey L. Cummings, Arthur P. Kowell, Sanjiv S. Gambhir, Carl K. Hoh, Michael E. Phelps
Journal: JAMA (2001)

ContextDeficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined.ObjectiveTo assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia.Design, Setting, and PatientsPositron emission tomography (PET) studies of [18F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000.Main Outcome MeasuresRegional distribution of [18F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses.ResultsProgressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P&lt;.001).ConclusionIn patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.