The histopathological effects of reabsorbable polyethylene glycol hydrogel (Coseal) on epidural fibrosis in an experimental postlaminectomy model in rats

Background/aimTo investigate the histopathological effects of reabsorbable polyethylene glycol hydrogel (RPGH, Coseal) on epidural fibrosis (EF) following laminectomy in rats.Materials and methodsA total of 24 rats were equally divided into three groups. In the first group, no treatment was applied after laminectomy (control group, Group 1). In the second group, hemostasis was achieved after laminectomy, and 2 mm absorbable gelatin sponge soaked in saline was placed over the epidural space and the wound was closed (Group 2). In the third group, hemostasis was achieved following laminectomy, and 0.5 mL RPGH (Coseal, Group 3) was squeezed over the dura mater, and the wound was closed. A histopathological examination was undertaken to evaluate arachnoidal invasion and EF.ResultsThe results of EF in the Group 2 and Group 3 were significantly lower compared to the Group 1 (p = 0.023 and p = 0.002, respectively). No statistically significant difference was found between the Group 2 and Group 3 in terms of EF (p = 0.957). There was also no statistically significant difference between the mean arachnoidal invasion of the three groups (p > 0.171). However, the rate of arachnoidal invasion was the lowest in the Group 3.ConclusionIntraoperative Coseal, a polyethylene glycol polymer, tends to reduce the risk of epidural fibrosis, although this is not statistically significant.     

Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids

The adverse effect of disease and chronic corticosteroid therapy on bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) has been reported in several studies of Caucasian populations. As the factors controlling bone homeostasis may be different in Asian populations, we measured BMD in 52 pre-menopausal Chinese women (mean age 34.1 +/- 8.0 yr) with SLE (mean disease duration 6.4 +/- 4.5 yr) treated with prednisone (mean daily dose 11.4 +/- 10.8 mg/day). Lumbar spine, hip (total and subregions) and total body BMDs were measured in the SLE patients using dual-energy X-ray absorptiometry (DEXA), and compared with those from healthy controls matched for age, sex and body mass index. Compared to controls, SLE patients were found to have lower BMD (g/cm2) at several sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72 vs 0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs 0.82, P = 0.05). There was no correlation between BMD at any region and duration of disease, activity of disease or prednisone therapy (mean daily dose, cumulative dose or treatment duration). When BMDs were compared between controls and SLE patients, subgrouped according to those not on calcium and those arbitrarily receiving calcium supplements (1 g/day), significantly lower BMDs were found in those not on calcium compared to both controls and SLE patients on calcium. BMDs in SLE patients on calcium were not different from those in controls. The low prevalence of osteoporosis in our SLE patients (4-6%) suggests significant loss of BMD in Chinese SLE patients on corticosteroid therapy is less than that reported in Caucasians (12-18%).      

Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay

An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT- 1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI- 1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.     

von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene [published erratum appears in Blood 1995 Sep 15;86(6):2461]

An animal model for human type I von Willebrand disease (vWD) has been previously described in the inbred mouse strain RIIIS/J. Murine vWD is characterized by a prolonged bleeding time, normal von Willebrand factor (vWF) multimer distribution, autosomal dominant inheritance, and proportionately decreased plasma vWF antigen, ristocetin cofactor, and factor VIII (FVIII) activities. To study the molecular genetics of murine vWD, a portion of the vWF gene surrounding exon 28 was cloned, sequenced, and used to develop two informative DNA sequence polymorphisms for rapid genotyping by DNA polymerase chain reaction. RIIIS/J mice were crossed with PWK/Ph mice, an inbred line of Mus musculus musculus, and the F1 progeny backcrossed to the parental PWK/Ph strain. vWF antigen levels in F1 mice were not significantly different from the parental RIIIS/J strain but were markedly decreased compared with the parental PWK/Ph mice. Genetic linkage analysis of 104 backcross progeny showed no correlation between vWF antigen level and vWF genotype. These data indicate that murine vWD is caused by a defect at a novel genetic locus, distinct from the murine vWF gene. The distribution of vWF antigen levels among backcross progeny suggests the presence of one major dominant vWD gene in the RIIIS/J mouse with possible modifying contributions from one or more additional minor loci. These observations may provide new insights into the molecular basis and variable expressivity of human vWD.     

Mortality is influenced by locality in a major HIV/AIDS epidemic

Objectives

The aim of the study was to compare the risks of death among HIV‐infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users.

Methods

We compared the clinical and socioeconomic characteristics of HIV‐infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan–Meier methods were used to estimate the cumulative mortality rates. Results We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV‐experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24].

Conclusions

A threefold increase was observed in the risk of death among HIV‐infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.