Interferon alpha-2b in the treatment of chronic hepatitis C: early experience

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic Hepatitis C in multi-ethnic patients to prevent viral replication and chronic liver damage. Three million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 9 active Hepatitis C patients. A clinical response was defined as normalization of serum ALT values. Serum was frozen and stored for Hepatitis C viral assays. Four patients normalized their liver functions. When viral levels were measured only two patients had unmeasurable levels of HCV RNA after treatment. Therapeutic results were observed and much work needs to be done to improve therapy because a serious epidemic is predicted for the future.     

Nitric oxide is present in exhaled breath in humans: direct GC-MS confirmation

The physiological role of nitric oxide (NO) is being investigated in many experimental and clinical settings. There is considerable evidence that NO is involved in the regulation of lung vascular function. In addition there are many studies reporting the beneficial effect of NO inhalation. NO formed from L-Arginine has been detected in exhaled breath using indirect mass spectrometry and chemiluminescence. Both methods provided good evidence for the presence of NO in breath samples but were not unequivocal. We therefore developed a method using gas-chromatography-mass spectrometry which allowed us to measure trace levels of NO in air and breath. Eight healthy volunteers supplied numerous breath samples for analysis. A clear peak for nitric oxide was observed in seven volunteers. The mean level was 13ppb (n = 7, range < 2 to 19ppb). This data is in good agreement with our previous data and unequivocally confirms the presence of nitric oxide in human breath.     

A comparative evaluation of halo pin designs in an immature skull model

To design an improved halo pin for use in pediatric patients, three commonly used halo pins were evaluated with a mechanical testing apparatus and segments of prepared fetal calf skull. The pins were driven through the bone segments while the load at the bone-pin interface was measured. New pins were designed with respect to pin tip and flange width and similarly compared. Mean maximum loads to penetration, normalized for bone segment thickness, were 55.6 N/mm for the PMT Corporation pin, 61.5 N/mm for the Bremer pin, and 73.6 N/mm for the Ace pin. Four new, short tipped pins were designed and compared with the Ace pin, and there was no significant difference. Finally, four new pins were designed with varying flange widths. Mean maximum loads, normalized for bone segment thickness, were 68.9 N/mm for the 4.2 mm flange, 72.2 N/mm for the 4.7 mm flange, 92.9 N/mm for the 5.2 mm flange, and 96.4 N/mm for the 5.7 mm flange. The findings of this investigation are clinically important because they may help to explain the variability in the complication rates seen with the use of different halo systems in children. The three halo pins currently on the market have different pin designs, including tip lengths and flange distances, which contribute to the difference in load to penetration for each pin. The new, wide flanged, short tipped halo pin design might decrease the complication rate of halo use in children by providing an improved capacity to resist penetration despite increased loads of application.     

Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.     

Therapy of dislocated calcaneus joint fracture with the AO calcaneus plate

From August 1992 to March 1997, 66 patients with 71 displaced intraarticular calcaneal fractures were prospectively examined after an operative treatment using an extended lateral approach and the ASIF calcaneal plate followed by early functional postoperative treatment (mean follow-up 25 months, retrieval rate 96%). To classify the type of fracture and to verify the results of reduction and of retention CT scans in the coronal and transverse plane were performed pre- and postoperatively and on the day of assessment. The Zwipp Score was used for clinical evaluation. After fractures with 5 to 8 points according to the calcaneal fracture scale, 97% of the patients had an anatomical or near anatomical reduction of the posterior facet and the clinical outcome in 82% of the patients was graded as good or excellent. In 70% of patients with a fracture rated 9 to 10 points a good reduction was demonstrated and clinically there were 67% good or excellent results. But in the fractures with 11 to 12 points, despite 40% good reductions, the clinical outcome was graded as good in 10% of the patients only. However, if the post-operative displacement of the posterior facet was more than 2 mm no patient had a good result independent of the type of fracture. Due to restoration of the geometry of the most comminuted fracture types and the immediate partial weight bearing secondary soft tissue problems could be minimized without any loss of articular reduction. Anatomical reduction and stable internal fixation together with adequate physical therapy are apparently preconditions but not a guarantee for a good clinical result after displaced calcaneal fractures.     

Effects of estrogen on tight junctional resistance in cultured human umbilical vein endothelial cells

OBJECTIVE: To study the effects of estrogen on transendothelial paracellular permeability in women. METHODS: Human umbilical vein endothelial cells (HUVEC) obtained from women were grown on filters. The paracellular permeability characteristics were determined in terms of changes in the permeability to the polar acid pyranine (Ppyr) and as changes in the transendothelial electrical resistance (RTE). Tight junctional resistance characteristics were assayed by lowering luminal NaCl and measuring the dilution potential, and were expressed as the ratio of monoion mobility uCl/uNa (cation selectivity). RESULTS: Low extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The former but not the latter condition abolished the endothelium-specific cation selectivity. Treatment with 10 nM of estradiol-17 beta had no effect on RTE, but it increased the cation selectivity. The effect of estradiol required 1-6 hours' incubation with the hormone; it was dose dependent and saturable, with a median effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not estriol, could mimic the effect of estradiol, and the estrogen receptor antagonist ICI-182, 780 blocked it. CONCLUSION: Cultured HUVEC cells form patent tight junctions. Estrogens increase the cation selectivity across HUVEC cultures. The effect of estrogen may be mediated by an estrogen receptor. These effects may be important for vasculoprotection in cases of sudden changes in ions levels across the capillary wall, such as ischemia or reperfusion.     

Population structure and physiological changes within a hot spring microbial mat community following disturbance

The influence of disturbance on a hot spring cyanobacterial mat community was investigated by physically removing the top 3.0 mm, which included the entire cyanobacterial layer. Changes in 16S rRNA-defined populations were monitored by denaturing gradient gel electrophoresis analysis of PCR-amplified 16S rRNA gene segments. Some previously absent cyanobacterial populations colonized the disturbed areas, while some populations which were present before the disturbance remained absent for up to 40 days. Changes in physiological activity were measured by oxygen microelectrode analyses and by 14CO2 incorporation into cyanobacterial molecular components. These investigations indicated substantial differences between the disturbed and undisturbed mats, including an unexplained light-induced oxygen consumption in the freshly exposed mat, increased carbon partitioning by phototrophs into growth-related macromolecules, bimodal vertical photosynthesis profiles, and delayed recovery of respiration relative to photosynthesis.