Prevalence of neuropathic pain among black African patients suffering from common low back pain

To study the prevalence and semiotic characteristics of neuropathic pain in the common low back pain to the Black African subject. This was a prospective cross-sectional survey carried on from April 1 2009 to August 31 2009 in consultations of rheumatology, neurology, and neurosurgery at the University Hospital Yalgado Ouédraogo in Ouagadougou (Burkina Faso). All patients with a low back pain or a common lomboradiculalgie were included. DN4 questionnaire was used for the diagnosis of neuropathic pain. One hundred and seven patients have been recruited during the study period; Sixty-four (59.80%) were female (sex ratio M/F: 0.67). The average age was 34.11?±?13.46?years of age with extremes of 20 and 79. The average duration of disease was 48.53?months with extremes of 10?days and 50?years. Eighty-seven patients (81.31%) had a disease duration, which was 3?months longer. Sixty-six patients (61.70%) had a predominant lomboradiculalgie; among the remaining 41, low back pain predominated. Average intensity of pain was 62.81?±?22.43 (on a scale of 100). A sign of Lasèque was present in the 41 (38.30%) patients. Fifty-three (49.5%) patients had a neuropathic pain. The prevalence of neuropathy signs according to the DN4 questionnaire was as follows: burning (n?=?37; 34.58%), painful cold (n?=?13; 12.15%), electric shocks (n?=?31; 38.97%), pins and needles (n?=?34; 31.77%), tingling (n?=?35; 32.71%), numbness (n?=?45; 42.05%), itching (n?=?18; 16.82%), touch hypoesthesia (n?=?35; 32.71%), pinprick (n?=?33; 30.84%), and tactile allodynia (n?=?21; 19.62%). Among the studied variables, the presence of a radiculalgy was statistically associated with neuropathic pain. The lomboradiculalgie of the Black African subject associates neuropathic pain observed in half of patients. Treatment must therefore always take account of this association. However, further studies are needed before any definitive conclusion.     

Closing the gap on drug-induced liver injury

Drug-induced liver injury (DILI) limits the development and application of many therapeutic compounds and presents major challenges to the pharmaceutical industry and clinical medicine. Acetaminophen-containing compounds are among the most frequently prescribed drugs and are also the most common cause of DILI. Here we describe a pharmacological strategy that targets gap junction communication to prevent amplification of fulminant hepatic failure and acetaminophen-induced hepatotoxicity. We demonstrate that connexin 32 (Cx32), a key hepatic gap junction protein, is an essential mediator of DILI by showing that mice deficient in Cx32 are protected against liver damage, acute inflammation and death caused by liver-toxic drugs. We identify a small-molecule inhibitor of Cx32 that protects against liver failure and death in wild-type mice when co-administered with known hepatotoxic drugs. These findings indicate that gap junction inhibition could provide a pharmaceutical strategy to limit DILI and improve drug safety. (HEPATOLOGY 2012;).     

Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial

Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment. CONCLUSIONS: Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.     

Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease

The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 ± 1, body mass index = 34.1 ± 0.3 kg/m(2) ) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IR(i) = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IR(i) quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[(3) H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). CONCLUSION: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population.