San Diego, California shares the world’s busiest land border crossing with Tijuana, Mexico—a city where 95 % of injection drug users (IDUs) test hepatitis C virus (HCV) antibody-positive. Yet, little ...is known about the prevalence and risk behaviors for HCV among IDUs in San Diego. In 2009–2010, 18–40-year-old IDUs in San Diego County completed a risk assessment interview and serologic testing for HCV and HIV infection. Recruitment involved respondent-driven sampling, venue-based sampling at a syringe exchange program, and convenience sampling. Correlates of HCV infection were identified by multivariable logistic regression. Among 510 current IDUs, 26.9 % (95 % CI 23.0–30.7 %) and 4.2 % (95 % CI 2.4–5.9 %) had been infected with HCV and HIV, respectively. Overall, median age was 28 years; 74 % were male; 60 % white and 29 % Hispanic; and 96 % were born in the U.S. Median years of injecting was 6; 41 % injected daily; 60 % injected heroin most often; 49 % receptively shared syringes and 68 % shared other injection paraphernalia; and only 22 % reported always using new syringes in the past 3 months. Two thirds had ever traveled to Mexico and 19 % injected in Mexico. HCV infection was independently associated with sharing injection paraphernalia (adjusted odds ratio AOR = 1.69) and SEP use (AOR = 2.17) in the previous 3 months, lifetime history of drug overdose (AOR = 2.66), and increased years of injecting (AOR = 2.82, all
P
values <0.05). Controlling for recruitment method did not alter results. HCV infection prevalence among IDUs in San Diego was modest compared to other US cities and much lower than Tijuana. Given that known individual-level HCV risk factors were common in San Diego, the city’s lower HCV prevalence might be due to differences in social and structural factors between the cities.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder and is characterized by significant clinical and genetic heterogeneity. Recently, mutations in both the small ...heat shock protein 27 (HSP27 or HSPB1) and 22 (HSP22 or HSPB8) genes have been reported to cause autosomal dominant CMT with minimal sensory involvement (CMT 2F/CMT2L) and autosomal dominant distal hereditary motor neuropathy type II (dHMN II).
We analyzed the HSPB1 and HSPB8 genes in a large clinically well-characterized series of dHMN and CMT type 2 (CMT2) cases and families using linkage analysis and direct sequencing of these genes.
We identified a novel homozygous mutation in the alpha-crystallin domain of HSPB1 segregating in an autosomal recessive fashion in a family with distal HMN/CMT2. A further four heterozygous HSPB1 mutations were identified in four autosomal dominant families dHMN/CMT2, and two sporadic cases were identified with probable de novo mutations. In the autosomal dominant and autosomal recessive families, there were no clinical sensory findings, but reduced sural nerve action potential amplitudes were found in some affected individuals, indicating that long sensory axons are mildly affected in this predominantly motor disorder.
This extends the clinical and electrophysiologic spectrum of HSPB1 mutations and identifies four unreported dominant HSPB1 mutations and the first family where the HSPB1 mutation acts in a recessive way to cause distal HMN.
BACKGROUND.Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 ...mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age.
METHODS.This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms for ≤36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication).
FINDINGS.A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P < 0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B.
CONCLUSIONS.Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.
BACKGROUND : Accurately predicting the outcomes of peripheral blood stem cell harvests is important because unproductive collections are expensive and subject the donor to unnecessary toxicity.
STUDY ...DESIGN AND METHODS : Predictive factors for stem cell mobilization and collection by a retrospective review of 104 consecutive donors were evaluated.
RESULTS
: Of several previously suggested measures, the peripheral CD34+ cell concentration on the day of harvest (pCD34
DH
) correlated best with total numbers of CD34+ collected (r = 0.88). This was followed by the pCD34 on the day before harvest (pCD34
Day –1
) (r = 0.74). The peripheral WBC count on the day of harvest (pWBC) was inferior (r = 0.39). When ratios of potential predictive factors divided by the previous day's value were examined, pWBC ratio was found to be a significant independent predictive factor for cells collected (r = 0.45). Furthermore, the predictive value of both the pCD34
Day –1 and the pWBC can be improved by combining with the pWBC ratio. To examine whether the chosen collection starting days were optimal, serial pCD34 obtained daily during the harvest procedures was examined. Poorly mobilizing donors, who required several days of collection, did not reach maximal harvest yields until the fourth collection day.
CONCLUSIONS
: pCD34
DH
is the optimal predictive factor for harvest yields. If pCD34
DH
is not available, pCD34
Day –1 or pWBC combined with the pWBC ratio may offer the best prediction of harvest outcomes. The best harvest yields on poorly mobilizing donors occur 3 to 4 days after the usual collection starting times.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Job syndrome of hyperimmunoglobulinemia E is defined by markedly elevated serum IgE levels and recurrent sinopulmonary and cutaneous infections. A patient with the syndrome developed lymphoma and ...underwent an allogeneic stem cell transplantation that restored several measures of his immune dysfunction, including the elevated IgE levels.
Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions α and β to the ...carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u , exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of the benzamidin-4-yl moiety with alternative basic groups, elimination of the isoxazoline stereocenter, and reversal of the orientation of the isoxazoline ring resulted in lowered potency and/or duration of action.
Glycerol-3-phosphate acyltransferase (GPAT) controls the first step of triglyceride (TAG) synthesis. Three distinct GPAT activities have been identified, two localized in mitochondria and one in ...microsomes. Mitochondrial GPAT1 (mtGPAT1) is abundantly expressed in the liver and constitutes approximately 50% of total GPAT activities in this organ. Hepatic mtGPAT1 activity is elevated in obese rodents. Mice deficient in mtGPAT1 have an improved lipid profile. To investigate if beneficial effects can result from reduced hepatic expression of mtGPAT1 in adult obese mice, adenoviral vector-based short hairpin RNA interference (shRNA) technology was used to knockdown mtGPAT1 expression in livers of
ob/ob mice. Reduced expression of mtGPAT1 mRNA in liver of
ob/ob mice resulted in dramatic and dose dependent reduction in mtGPAT1 activity. Reduced hepatic TAG, diacylglycerol, and free fatty acid, as well as reduced plasma cholesterol and glucose, were also observed. Fatty acid composition analysis revealed decrease of C16:0 in major lipid species. Our results demonstrate that acute reduction of mtGPAT1 in liver of
ob/ob mice reduces TAG synthesis, which points to a role for mtGPAT1 in the correction of obesity and related disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Currently used antiplatelet drugs, including aspirin and ticlopidine, are effective against certain but not all of the many endogenous platelet activators. Because of their limited efficacy, a ...significant number of serious thromboembolic complications still occur, highlighting the need for a more effective therapy. DMP 728 has been characterized as a potent and specific platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist. The goals of the present study were to determine the oral antiplatelet and antithrombotic efficacies of DMP 728 in various arterial thrombosis models in dogs.
In conscious and anesthetized mongrel dogs, DMP 728 at 0.02 to 1.0 mg/kg PO in gelatin capsules produced dose-dependent antiplatelet effects in inhibiting ex vivo platelet aggregation induced by ADP and prolonging template bleeding time. DMP 728 effects on bleeding time prolongation could be reversed more rapidly than those on platelet aggregation inhibition. A maximal antiplatelet effect for DMP 728 was demonstrated at 1.0 mg/kg PO. DMP 728 demonstrated dose-dependent oral antiplatelet effects with an absolute oral bioavailability of 8% to 12% in dogs. Additionally, the antithrombotic efficacy of DMP 728 was examined after intravenous and oral administration at different doses in various models of arterial thrombosis. In the coronary artery Folts' model in dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01 mg/kg IV and < 0.6 mg/kg PO. Additionally, DMP 728 at 0.1 and 1.0 mg/kg IV or PO demonstrated 60% to 100% prevention of primary thrombosis (P < .01) in an electrolytically induced carotid artery thrombosis model in dogs.
These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic potential as an oral antithrombotic agent in coronary and carotid artery thromboembolic disorders.
Coracoacromial ligament tension in vivo Chambler, A.F.W; Bull, A.M.J; Reilly, P ...
Journal of shoulder and elbow surgery,
07/2003, Volume:
12, Issue:
4
Journal Article
Peer reviewed
Tension in the coracoacromial (CA) ligament has been postulated as the mechanism of acromial spur formation. Five patients (mean age, 58 years) undergoing open rotator cuff repair were recruited. A ...differential variable reluctance transducer (DVRT) was inserted into the CA ligament parallel to the fiber orientation. The DVRT measured linear displacement as the glenohumeral joint was moved through 90° of abduction and full internal/external rotation. The CA ligament was then removed with the DVRT in situ. The specimen was mounted on a material-testing machine. Load was applied in the line of the CA ligament fibers, and the DVRT output recorded. The CA ligament was found to be under tension, which was lowest with the arm adducted (mean, 8.9 N; range, 3.7-22 N) and highest in abduction (mean, 15.7 N; range, 6.5-38 N). This study confirms CA ligament tension in vivo as a possible stimulus for acromial spur formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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