tbuckley/cabot-search huggingface dataset:
Six-Week Versus Twelve-Week Antibiotic Therapy for Nonsurgically Treated Diabetic Foot Osteomyelitis: A Multicenter Open-Label Controlled Randomized Study
Authors: Alina Tone, Sophie Nguyen, Fabrice Devemy, Hélène Topolinski, Michel Valette, Marie Cazaubiel, Armelle Fayard, Éric Beltrand, Christine Lemaire, Éric Senneville
Journal: Diabetes Care (2014)

OBJECTIVE Little is known about the optimal duration of antibiotic therapy for diabetic foot osteomyelitis (DFO). This study sought to compare the effectiveness of 6 versus 12 weeks of antibiotic therapy in patients with DFO treated nonsurgically (i.e., antibiotics alone). RESEARCH DESIGN AND METHODS This was a prospective randomized trial comparing 6- versus 12-week duration of antibiotic treatment. Remission of osteomyelitis during the monitoring period was defined as complete and persistent (&amp;gt;4 weeks) healing of the wound (if present initially), absence of recurrent infection at the initial site or that of adjacent rays, and no need for surgical bone resection or amputation at the end of a follow-up period of at least 12 months after completion of antibiotic treatment. RESULTS Forty patients followed at five French general hospitals were randomized between January 2007 and January 2009, with 20 treated for 6 weeks and 20 treated for 12 weeks with antibiotics. The two groups were comparable for all variables recorded at inclusion in the study. Remission was obtained in 26 (65%) patients, with no significant differences between patients treated for 6 versus 12 weeks (12/20 vs. 14/20, respectively; P = 0.50). We did not identify any significant parameters associated with patient outcome. Fewer patients treated for 6 weeks experienced gastrointestinal adverse events related to antimicrobial therapy compared with patients treated for 12 weeks (respectively, 15 vs. 45%; P = 0.04). CONCLUSIONS The present multicenter prospective randomized study provides data suggesting that 6-week duration of antibiotic therapy may be sufficient in patients with DFO for whom nonsurgical treatment is considered.
Variations in number of births and perinatal mortality by day of week in England and Wales.
Authors: A MacFarlane
Journal: BMJ (1978)

Analysis of the births that occurred in England and Wales during 1970-6 showed that they followed a seven-day cycle, being concentrated from Tuesdays to Fridays and least numerous on Sundays. This pattern became increasingly pronounced during the period examined. Relatively few births occurred on bank holidays, especially Christmas Day and Boxing Day. In general perinatal mortality was higher among babies born at weekends than among those born on weekdays. It is likely that the pattern seen in the numbers of births is associated to a large extent with elective intervention. It is not possible to draw any conclusions about the pattern seen in perinatal mortality as so far the analysis has been confined to crude rates.
Effects of deep and shallow water running on spinal shrinkage.
Authors: C N Dowzer, T Reilly, N T Cable
Journal: British Journal of Sports Medicine (1998)

OBJECTIVES: Running in water has the potential to decrease the compressive forces on the spine as the body is supported. The aim of the study was to determine the magnitude of this loss in stature compared with running on land. METHODS: Fourteen runners completed three 30 minute runs on separate days in deep water, shallow water, and on a motor driven treadmill. During the three conditions, runners exercised at 80% of their exercise mode specific peak oxygen consumption. Subjects rested in the Fowler position for 20 minutes before and after exercise. Measurements of changes in stature were taken before resting, before running, after 15 minutes of running, after 30 minutes of running, and after the post-exercise rest in the Fowler position. Changes in stature were recorded using a stadiometer accurate to 0.01 mm. RESULTS: Loss of stature values were 4.59 (1.48), 5.51 (2.18), and 2.92 (1.7) mm (means (SD)) for running on the treadmill, and in shallow and deep water respectively. Running in deep water caused significantly lower creep than in the other trials (p&lt;0.05), with no difference between the shallow water and treadmill conditions. Loss of stature was greater in the first half of the run for all conditions (p&lt;0.05). Ratings of perceived exertion did not differ between the three exercise conditions. CONCLUSION: Results support the use of deep water running for decreasing the compressive load on the spine.
TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons
Authors: Robert J Gasperini, Xu Hou, Helena Parkington, Harry Coleman, David W Klaver, Adele J Vincent, Lisa C Foa, David H Small
Journal: Molecular Neurodegeneration (2011)

Familial amyloidotic polyneuropathy (FAP) is a peripheral neuropathy caused by the extracellular accumulation and deposition of insoluble transthyretin (TTR) aggregates. However the molecular mechanism that underlies TTR toxicity in peripheral nerves is unclear. Previous studies have suggested that amyloidogenic proteins can aggregate into oligomers which disrupt intracellular calcium homeostasis by increasing the permeability of the plasma membrane to extracellular calcium. The aim of the present study was to examine the effect of TTR on calcium influx in dorsal root ganglion neurons.Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Nav1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.These data suggest that activation of TRPM8 channels triggers the activation of Nav1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.
Coordinated Induction by IL15 of a TCR-Independent NKG2D Signaling Pathway Converts CTL into Lymphokine-Activated Killer Cells in Celiac Disease
Authors: Bertrand Meresse, Zhangguo Chen, Cezary Ciszewski, Maria Tretiakova, Govind Bhagat, Thomas N. Krausz, David H. Raulet, Lewis L. Lanier, Veronika Groh, Thomas Spies, Ellen C. Ebert, Peter H. Green, Bana Jabri
Journal: Immunity (2004)
ACETYLCHOLINE IN TOBACCO AMBLYOPIA
Authors: H. C. Orr
Journal: BMJ (1936)

M~~~~~~~~~~-NEDICAL JOURN4ALwidest part of the forearm.There was no pitting..The axillary vein was stil palpable and cord-like.The superficial veins were mnore prominent on -the right shoulder than on the left. SummaryThe aetiology of primary thrombosis of the axillary vein is discussed.One case is described, and in the appended bibliography twenty-three others are collected since the exhaustive study made in 1928 by Pearce Gould and Patey on eight of their own cases and on the thirty- one other cases reported in the literature previous to this.It is suggested that pressure on the axillary vein by constriction of a pyjama sleeve at night may cause the onset of the thrombosis in certain cases.We are indebted to Professor H.
Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease
Authors: S. Kajander, E. Joutsiniemi, M. Saraste, M. Pietilä, H. Ukkonen, A. Saraste, H.T. Sipilä, M. Teräs, M. Mäki, J. Airaksinen, J. Hartiala, J. Knuuti
Journal: Circulation (2010)

Background— Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. Methods and Results— We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with 15 O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients) with spiral CT. Conclusion— Cardiac hybrid PET/CT imaging allows accurate noninvasive detection of coronary artery disease in a symptomatic population. The method is feasible and can be performed routinely with &lt;10 mSv in most patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172.
Adverse Life Events and Cognitive-Personality Characteristics in the Prediction of Major Depression and Antidepressant Response
Authors: C M Mazure, M L Bruce, P K Maciejewski, S C Jacobs
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Stressful life events are known to precipitate major depression. However, it remains unclear why some individuals who experience adverse events develop depression whereas others do not, and how the occurrence of life events affects treatment outcome. Emerging models posit that the effect of adverse life events varies by cognitive-personality style. This study examines the direct and interactive effects of stressful life events and cognitive-personality style in predicting 1) episode onset in patients with DSM-IV unipolar depression versus community comparison subjects and 2) depressive symptom severity at the completion of a 6-week standard antidepressant regimen.METHOD: Multivariate models were used to test the effects of adverse life events, cognitive-personality style, and the congruence of event type (interpersonal versus achievement) with cognitive-personality style on depressive onset and treatment outcome in 43 patients with major depression and 43 healthy comparison subjects. Cognitive-personality characteristics were assessed by using Beck's measures of sociotropy (interpersonal dependency) and autonomy (need for independence and control).RESULTS: Adverse life events, sociotropy, and an autonomy factor need for control were each significantly related to depressive onset and predicted group status for 88% of the subjects. Event types affected outcome differently, and specific life event types interacted with cognitive-personality styles in predicting response to treatment. A multivariate model accounted for 65% of the variance in predicting outcome.CONCLUSIONS: Adverse life events are a potent factor in predicting depression. However, cognitive-personality characteristics also confer susceptibility to depression. Better outcome is associated with occurrence of adverse interpersonal events (e.g., death of a loved one) rather than adverse achievement events (e.g., loss of job) and occurs when the event type is congruent with cognitive-personality style.
HCV Treatment — No More Room for Interferonologists?
Authors: Joost P.H. Drenth
Journal: New England Journal of Medicine (2013)

The landscape of therapy for hepatitis C virus (HCV) infection is changing rapidly. Until recently, the standard of care for HCV infection was a combination of peginterferon and ribavirin. Our increased understanding of the basic biology of HCV led to the identification of specific proteins involved in the replication of the virus. These proteins can be targeted by protease and polymerase inhibitors.Two years ago, the advent of protease inhibitors, such as telaprevir and boceprevir, profoundly affected the field.1,2 These agents improved the likelihood of cure but came with a number of inherent limitations. Protease inhibitors do not have . . .
Multidrug resistant pulmonary TB: Characteristics of drug resistance profiles of MBT in Ukraine
Authors: Irina Liskina, Svetlana Kuzovkova
Journal: European Respiratory Journal (2011)

About 9% of newly diagnosed pulmonary (P) TB is accompanied by MDR, and among patients with chronic forms that level is 30-70%. Knowledge of drug resistance (DR) is important for treatment and to forecasting the outcome.  Aim: The aim was to determine the current DR profiles and their prevalence among PTB pts in Ukraine.  Materials and methods: Medical records, results of microbiological examination of pts for a year.  Results: 224 cases of verified MDR-PTB were established, 142 men and 82 women, average age – 32,54±3,9 years. The initial or secondary resistance were determined. It was in 59 (21,33%) and in 165 (73,66%) pts respectively. To analyze the DR profiles all patients were divided into 2 groups: the 1st included 59 (26,33%) pts with DR only to first-line drugs, and the 2nd - 165 (73,67%) pts with additional DR to second-line drugs (s). Profiles formed on the base of first-line drugs. We have identified 7 profiles in 1st group: HR, HRS, HRE, HRZ, HRSE, HRSZ, HRSZE; and 7 in 2nd: HR+s, HRS+s, HRE+s, HRZ+s, HRSE+s, HRSZ+s, HRSZE+s. The most common in 1st was HRS profile – 28 (46,67) pts. Less common are HRSE and HRSZ (21,67% and 10,0% respectively). The predominance of HRS and HRSZ profiles was found in the 2-d group – 71 (31,69%) pts and 41 (25,0%), respectively. Totally HRS profile was in 99 (44,19%) pts. The smallest spread has HRE and HRZ (1,79% and 3,57% respectively).  Conclusion: The majority of cases (73,66%) has secondary MDR and simultaneously DR to first-line drugs and to s. Most common is HRS profile – as with maintaining sensitivity to s, and in presence of additional resistance to the different number s. The smallest spreads have HRE and HRZ-profile.
Cinacalcet Reduces the Set Point of the PTH-Calcium Curve
Authors: Casimiro Valle, Mariano Rodriguez, Rafael Santamaría, Yolanda Almaden, Maria E Rodriguez, Sagrario Cañadillas, Alejandro Martin-Malo, Pedro Aljama
Journal: Journal of the American Society of Nephrology (2008)

The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium-sensing receptor to calcium and therefore should produce a decrease in the set point of the parathyroid hormone (PTH)-calcium curve. For investigation of this hypothesis, nine long-term hemodialysis patients with secondary hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a protocol based on intact PTH and plasma calcium concentrations. Dialysis against low- and high-calcium (0.75 and 1.75 mM) dialysate was used to generate curves describing the relationship between PTH and calcium. Compared with precinacalcet levels, cinacalcet significantly reduced mean serum calcium, intact PTH and whole PTH (wPTH; all <i>P</i> &lt; 0.001). The set points for PTH-calcium curves were significantly reduced, and both maximum and minimum levels of PTH (intact and whole) were significantly decreased. The calcium-mediated inhibition of PTH secretion was more marked after cinacalcet treatment. In addition, cinacalcet shifted the inverse sigmoidal curve of wPTH/non-wPTH ratio <i>versus</i> calcium to the left (<i>i.e</i>., less calcium was required to reduce the wPTH/non-wPTH ratio). In conclusion, cinacalcet increases the sensitivity of the parathyroids to calcium, causing a marked reduction in the set point of the PTH-calcium curve, in hemodialysis patients with secondary hyperparathyroidism.
Cholesterol feeding increases low density lipoprotein synthesis.
Authors: C J Packard, L McKinney, K Carr, J Shepherd
Journal: Journal of Clinical Investigation (1983)

This study examines the effects of increased dietary cholesterol (6 eggs/d) on the metabolism of low density lipoproteins in a group of seven healthy volunteers. Egg supplementation raised high density and low density lipoprotein cholesterol levels by 18 and 40%, respectively. The composition of the low density lipoprotein was unaltered and therefore the number of circulating particles must have increased. Kinetic studies indicated that this was due primarily to a 23% rise in the rate of synthesis of the lipoprotein. Catabolism was also affected. The fractional removal rate of native low density lipoprotein fell by 10% (P less than 0.05). However, the clearance of the 1,2 cyclohexanedione-treated lipoprotein remained unchanged (control fractional clearance rate [FCR] = 0.188 pools/d; cholesterol feeding FCR = 0.183 pools/d). Therefore, the reduction in low density lipoprotein catabolism appeared to be due to a fall in receptor activity. Consequently, an increased sterol load (34.2 mumol/kg per d vs. 27.7 mumol/kg per d in the control phase, P less than 0.02) was channelled into the receptor-independent route during egg feeding.
Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway.
Authors: B S Schwartz, T S Edgington
Journal: The Journal of Experimental Medicine (1981)

It has previously been described that soluble antigen:antibody complexes in antigen excess can induce an increase in the procoagulant activity of human peripheral blood mononuclear cells. It has been proposed that this response may explain the presence of fibrin in immune complex-mediated tissue lesions. In the present study we define cellular participants and their roles in the procoagulant response to soluble immune complexes. Monocytes were shown by cell fractionation and by a direct cytologic assay to be the cell of origin of the procoagulant activity; and virtually all monocytes were able to participate in the response. Monocytes, however, required the presence of lymphocytes to respond. The procoagulant response required cell cooperation, and this collaborative interaction between lymphocytes and monocytes appeared to be unidirectional. Lymphocytes once triggered by immune complexes induced monocytes to synthesize the procoagulant product. Intact viable lymphocytes were required to present instructions to monocytes; no soluble mediator could be found to subserve this function. Indeed, all that appeared necessary to induce monocytes to produce procoagulant activity was an encounter with lymphocytes that had previously been in contact with soluble immune complexes. The optimum cellular ratio for this interaction was four lymphocytes per monocyte, about half the ratio in peripheral blood. The procoagulant response was rapid, reaching a maximum within 6 h after exposure to antigen:antibody complexes. The procoagulant activity was consistent with tissue factor because Factors VII and X and prothrombin were required for clotting of fibrinogen. WE propose that this pathway differs from a number of others involving cells of the immune system. Elucidation of the pathway may clarify the role of this lymphocyte-instructed monocyte response in the Shwartzman phenomenon and other thrombohemorrhagic events associated with immune cell function and the formation of immune complexes.
Hemoglobin Variability and Mortality in ESRD
Authors: Wei Yang, Rubeen K. Israni, Steven M. Brunelli, Marshall M. Joffe, Steven Fishbane, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2007)

Hemoglobin levels vary substantially over time in hemodialysis patients, and this variability may portend poor outcomes. For a given patient, hemoglobin concentration over time can be described by absolute levels, rate of change, or by the difference between observed level and expected level based on the preceding trend (i.e., seemingly random variability). We investigated the independent associations of these different methods of describing hemoglobin over time with mortality in a retrospective cohort of 34,963 hemodialysis patients. Hemoglobin concentration over time was modeled with linear regression for each subject, and the model was then used to define the subject's absolute level of hemoglobin (intercept), temporal trend in hemoglobin (slope), and hemoglobin variability (residual standard deviation). Survival analyses indicated that each 1g/dl increase in the residual standard deviation was associated with a 33% increase in rate of death, even after adjusting for multiple covariates. Patient characteristics accounted for very little of the variation in our hemoglobin variability metric (R2 = 0.019). We conclude that greater hemoglobin variability is independently associated with higher mortality.
Randomized Efficacy Trial of Early Preconception Counseling for Diabetic Teens (READY-Girls)
Authors: Denise Charron-Prochownik, Margaret Ferons-Hannan, Susan Sereika, Dorothy Becker
Journal: Diabetes Care (2008)

To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls).A total of 53 adolescent females with type 1 diabetes between 16 and 19.9 years of age were randomized into groups receiving a CD-ROM, a book, or standard care (control) and given one comprehensive session. Outcomes were assessed at baseline, immediately after, and at 3 months.Teens who received the CD and those who received the book demonstrated significant (P < or = 0.05) sustained improvement (over 3 months) in knowledge, perceived benefits of both receiving preconception counseling and using effective family planning, and perceived more support with reproductive health issues.Clinical feasibility of the program was demonstrated. Both the CD and the book appeared to be efficacious formats for the short term. Future studies should examine repeated boosters of a CD and a book, which are not meant to replace but rather to reinforce and supplement health professional education.