Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

INTRODUCTION Under physiological conditions, interferon-α (IFN-α) is a key cytokine produced by virtually all cells in the mammalian organism in response to a variety of bacterial and viral stimuli. In response to viral infection, IFN-α produced by the infected target cells induces a number of cellular genes involved in inhibition of viral replication. In addition, IFN-α is secreted by stimulated NK-cells and T-cells and exerts a multitude of immune stimulatory effects of innate a…     

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.     

Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

Features of the metabolic syndrome of "hypertriglyceridemic waist" and transplant coronary artery disease.

BACKGROUND: This study evaluated the prevalence of the atherogenic metabolic triad and the hypothesis that waist circumference and fasting triglyceride concentrations could be used as screening tools for identification of the atherogenic metabolic triad in a population of heart transplant men. It also evaluated the relationship between the atherogenic metabolic triad and coronary artery disease (CAD). METHODS: In the study group of 83 consecutive male heart transplant patients having their routine annual coronarography, 23 patients (28%) were characterized by the atherogenic metabolic triad defined by the presence of elevated fasting insulin and apolipoprotein B concentrations and by small low-density lipoprotein (LDL) particles. RESULTS: Seventy-seven per cent of patients with waist circumference values >/= 90 cm and with elevated triglyceride levels (>/=2.0 mmol/liter) were characterized by this atherogenic metabolic triad. Patients with the atherogenic metabolic triad were at markedly increased risk of CAD (odds ratio of 25.3, 95% CI: 1.11-577.3, p < 0.04) compared to heart transplant patients without the atherogenic metabolic triad. CONCLUSIONS: About 30% of heart transplant patients showed the features of the atherogenic metabolic triad. Measurement and interpretation of waist circumference and fasting triglycerides could be used among heart transplant patients to early identify men characterized by the presence of elevated fasting insulin and apolipoprotein B concentrations and small LDL particles. The presence of the atherogenic metabolic triad identified patients at high risk of CAD even in the heart transplant population.     

Screening for type 2 diabetes mellitus in children and adolescents: attitudes, barriers, and practices among pediatric clinicians.

OBJECTIVE: The American Diabetes Association (ADA) recommends screening children at risk for type 2 diabetes with a fasting plasma glucose test or an oral glucose tolerance test. The purpose of this study was to describe attitudes, barriers, and practices related to type 2 diabetes screening in children among pediatric clinicians. METHODS: Pediatricians, nurse practitioners and physician assistants from a multispecialty, group practice in Eastern Massachusetts completed a mailed survey. To assess screening practice, three vignettes were presented representing pediatric patients with low, moderately high, and high risk for type 2 diabetes. The moderately high-risk and high-risk patients met ADA criteria for screening. ADA-consistent practice was defined as only screening the moderately high-risk and high-risk patients; lower-threshold practice was defined as also screening the low-risk patient; and higher threshold practice was screening only the high-risk patient. RESULTS: Sixty-two of 90 clinicians responded (69%). Based on intent to screen in the 3 vignettes, 21% of respondents reported ADA-consistent screening practice, 39% lower-threshold, and 35% higher-threshold screening practice. Five percent had incomplete or nonclassifiable responses. Many clinicians ordered screening tests other than those recommended by the ADA; few (< or =8% in any vignette) ordered only an ADA-recommended test. Preferences for nonfasting tests were influenced by nonmedical factors such as access to or cost of transportation. Inadequate patient education materials and unclear recommendations for appropriate screening methods were the most frequently reported moderate/strong barriers to screening. CONCLUSIONS: Most respondents reported type 2 diabetes screening practices that differed from current ADA recommendations. Our findings suggest that type 2 diabetes screening tests must be practical for clinicians and patients if they are to be used in pediatric practice. Further study of the benefits and cost-effectiveness of type 2 diabetes screening in children is warranted to clarify the role and optimal methods for screening in pediatric primary care.     

Ungewöhnliche Strahlenreaktion nach Röntgenweichstrahltherapie bei einer Patientin mit Pemphigus vulgaris

Zusammenfassung Bei einer 71j?hrigen Frau trat nach R?ntgenweichstrahltherapie an der Nase (Gesamtdosis 28 Gy, Gewebehalbwerttiefe 10,5–11,5 mm) eine ausgepr?gte Strahlenerosion auf. Diese zeigte 5 Wochen nach Ende der Bestrahlung noch keine Tendenz zur Abheilung. Ursache dieses ungew?hnlichen Verlaufes war ein gleichzeitig bestehender Pemphigus vulgaris. Dieser hatte sich nach der Strahlentherapie, vermutlich als Folge einer Freisetzung epidermaler Antigene, verschlimmert. Da? der Pemphigus in diesem Fall durch die Bestrahlung ausgel?st wurde – wie mehrfach in der Literatur berichtet – ist unwahrscheinlich, aber nicht sicher auszuschlie?en. Eingegangen am 11. April 1994 Angenommen am 10. Juni 1994     

Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation     

Urogenitale Infektionen beim Mann – können sie die Fertilität beeinflussen?

Urogenital infections are established as hazards to male fertility. Various pathophysiological hypotheses have evolved from experimental and clinical studies, facilitating explanation of the effects of bacteria and immunological events on reproductive tissues. Numerous current studies have identified and evaluated infectious mediators accounting for specific molecular events in urogenital infections. Valuable studies can be expected to appear in the future due to improvements in diagnostic procedures and new classifications of urogenital infections.