Coinfection with hepatitis C virus,oxidative stress and antioxidant status in HIV‐positive drug users in Miami*

Background

The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV‐coinfected and HIV‐monoinfected adults.

Methods

Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB‐4) markers were calculated.

Results

Significant differences were found between HIV/HCV‐coinfected and HIV‐monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P<0.001), APRI (0.52±0.37 vs. 0.255±0.145; P=0.0001), FIB‐4 (1.64±.0.91 vs. 1.03±0.11; P=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52 g/dL; P=0.038). There were no significant differences in CD4 cell count, HIV viral load or antiretroviral therapy (ART) between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344± 0.223 nmol/mL, respectively; P=0.006) and plasma antioxidant concentrations were significantly lower [vitamin A, 39.5 ± 14.1 vs. 52.4±16.2 μg/dL, respectively (P=0.0004); vitamin E, 8.29±2.1 vs. 9.89±4.5 μg/mL (P=0.043); zinc, 0.61±0.14 vs. 0.67±0.15 mg/L (P=0.016)] in the HIV/HCV‐coinfected participants than in the HIV‐monoinfected participants, and these differences remained significant after adjusting for age, gender, CD4 cell count, HIV viral load, injecting drug use and race. There were no significant differences in glutathione peroxidase concentration, selenium concentration, body mass index (BMI), alcohol use or tobacco use between groups. Glutathione peroxidase concentration significantly increased as liver disease advanced, as measured by APRI (β=0.00118; P=0.0082) and FIB‐4 (β=0.0029; P=0.0177). Vitamin A concentration significantly decreased (β=?0.00581; P=0.0417) as APRI increased.

Conclusion

HIV/HCV coinfection is associated with increased oxidative stress and decreased plasma antioxidant concentrations compared with HIV monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV coinfection.

     

Clinical and echocardiographic survey of the Ehlers-Danlos syndrome

Cardiac abnormalities such as mitral valve prolapse (MVP) are reported to be common features of the Ehlers Danlos syndrome (EDS), and it has been suggested that the majority of patients with type IV EDS will have cardiac involvement and vascular aneurysms. However, the evidence for valve lesions is inconsistent and often based on early clinical studies using mainly M-mode echo. We studied 33 patients (six male, 27 female; median age 35 yr) with EDS (30 type I, II or III, three type IV) and 30 age- and sex-matched controls. The study assessed skin stretch and joint hypermobility using Beighton and Contompasis scores. Echocardiographic examination included standard two-dimensional views from the parasternal and apical windows, and measurement of the aorta at four sites (annulus, sinotubular junction, arch and abdominal aorta). Echocardiographic abnormalities were found in four patients (12.1%) (one atrial septal aneurysm, one tricuspid prolapse, two MVP) and two controls (6.7%). MVP was found in 6.1% of EDS patients and 7% of controls. Seven patients had previously been diagnosed as having MVP; only two were shown to have true MVP using current criteria. None of those with type IV EDS had any echocardiographic abnormality. No patients with EDS had mean aortic dimensions outside the normal range at any of the points tested. Cardiac symptoms were more frequent amongst the patients than controls (atypical chest pain 48%, P = 0.0001; palpitation 39%, P = 0.001; exertional dyspnoea 30%). A wide range of rheumatological complaints were reported (current arthralgia 75%; recent back pain 72%, P = 0.005; recurrent dislocation 72%). Contrary to earlier published observations, we have not found an increased incidence of cardiac abnormalities in EDS. This syndrome may be relatively more benign, from the cardiac point of view, than was previously thought.      

Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti‐thrombotic drugs

Background and Aim: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti‐thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. Methods: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti‐thrombotic therapy. VCE studies were re‐evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti‐thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti‐thrombotic therapy was resumed before the VCE study. Results: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty‐two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti‐thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20–60.42, P = 0.032). Conclusions: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti‐thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.     

The role of torovirus in nosocomial viral gastroenteritis at a large tertiary pediatric centre

OBJECTIVE:

To describe the viral etiology and epidemiology of nosocomial viral gastroenteritis (NVG) at a tertiary care pediatric hospital and identify any changes over the past two decades.

METHODS:

Retrospective review of all patients with laboratory-confirmed NVG at The Hospital for Sick Children (Toronto, Ontario), from January 1, 2004, to December 31, 2005.

RESULTS:

One hundred forty-two episodes of NVG were found among 133 patients, occurring in 0.48 of 100 admissions. The median age was two years; 42% were <1 year of age and 41% were immunocompromised. The most commonly detected pathogen was torovirus (67% of episodes), followed by rotavirus (19%) and adenovirus (9%). Seventy-five cases (53%) were epidemiologically linked in 32 separate clusters (median cluster size two, range two to four). The NVG rate fell from 0.63 of 100 to 0.22 of 100 admissions after March 2005 (P<0.001) when enhanced infection control precautions were instituted in response to an outbreak of vancomycin-resistant Enterococcus.

CONCLUSIONS:

Torovirus remains the most commonly identified cause of NVG at The Hospital for Sick Children. Most NVG cases were epidemiologically linked, and a significant reduction in cases occurred after the institution of enhanced infection control practices following an outbreak of vancomycin-resistant Enterococcus. Improved education and surveillance for NVG should lead to further reduction in this problem.     

Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48-72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.     

Management of oral Kaposi's sarcoma and a proposal for clinical staging

Kaposi's sarcoma (KS) is the most common neoplastic disease in patients with disease due to human immunodeficiency virus (HIV), and oral KS (OKS) is the commonest oral neoplasia. OKS has been managed by local excision, intralesional chemotherapy regional radiotherapy, and systemic chemotherapy. Comparison between studies is difficult as the severity of oral involvement is not well defined in most studies. This paper reviews the approach to the management of OKS and also presents a proposal for the clinical staging of OKS. Clinical staging of OKS will facilitate comparisons of outcomes of treatment of OKS and improve our understanding of the natural history of the neoplasia, which has varied presentation and rates of progression.     

Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension

Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency.     

Hyperinflation and expiratory muscle recruitment during NREM sleep in humans

The purpose of this study was to determine the effect of hyperinflation on expiratory muscle recruitment during NREM sleep in healthy humans. Hyperinflation was produced by negative pressure in a tank ventilator or application of positive end-expiratory pressure (PEEP). Expiratory and inspiratory electromyograms (EMGexp and EMGinsp) were measured using transcutaneously implanted wire and surface electrodes, respectively. During wakefulness, sustained hyperinflation (3-5 min, +0.72 +/- 0.31 L) in the tank respirator caused augmentation of EMGexp (+77%, P less than 0.05) and EMGinsp (+27%, P less than 0.05) in all subjects. Brief hyperinflation with PEEP (5 breaths, +0.53 +/- 0.32 L) augmented EMGexp in 3 of 6 subjects and EMGinsp in 5 of 5 subjects (+98%, P less than 0.05). During NREM sleep, sustained hyperinflation (+0.54 +/- 0.17 L) in the tank respirator caused no change in EMGexp and a small increase in EMGinsp (+9%, P less than 0.001). Brief hyperinflation with PEEP (0.29 +/- 0.10 L) caused no change in EMGexp or EMGinsp. Sustained hyperinflation with PEEP activated EMGexp only in subjects whose end-tidal CO2 increased. We concluded that moderate hyperinflation does not recruit expiratory muscles during NREM sleep as it does during wakefulness.