Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Differential modulation of NMDA-stimulated [3H]dopamine release from rat striatum by neuropeptide Y and sigma receptor ligands

Although the identity of the endogenous ligands for sigma (sigma) receptors is unknown, neuropeptide Y (NPY) has been named as a possible candidate for a natural transmitter at these receptors. Using a superfusion system, we compared the effect of NPY on NMDA-stimulated [3H]dopamine release in rat striatum to that of the sigma agonists (+)-pentazocine and BD737. In contrast to (+)-pentazocine- or BD737-mediated inhibition of release, NPY enhanced release. However, the same sigma antagonists (BD1008, DuP734, haloperidol and DTG) that reverse (+)-pentazocine- or BD737-mediated inhibition, as well as a Y receptor antagonist, PYX-1, all reversed the enhancement. PYX-1 also reversed the (+)-pentazocine- and BD737-mediated inhibition of release. Peptide YY (PYY) and [Leu31,Pro34]NPY did not mimic the effect of NPY. NPY13-36 enhanced release to the same extent as NPY but the effect was not reversed by sigma antagonists. Our findings are consistent with the potential role of NPY as an endogenous ligand for a subtype of sigma receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-1.     

A carcinoembryonic antigen polynucleotide vaccine for human clinical use

Congenital cataract, type Volkmann (McKusick no 115665, gene symbol CCV) is an autosomal dominant eye disease. The disease is characterized by a progressive, central and zonular cataract, with opacities both in the embryonic, fetal and juvenile nucleus and around the anterior and posterior Y-suture. We examined blood samples from 91 members of a Danish pedigree comprising 426 members, by using highly informative short tandem repeat polymorphisms and found the closest linkage of the disease gene (CCV) to a (CA)n dinucleotide repeat polymorphism at locus D1S243 (Zmax = 14.04 at theta M = 0.025 theta F = 0.000), at a penetrance of 0.90. Using two additional chromosome 1 markers, we were able to map the CCV gene in the sequence 1pter-(CCV, D1S243)-D1S468-D1S214. The (enolase 1) gene has been mapped to this area; however, a mutation described in this gene did not give eye disease.     

Basilar membrane nonlinearity and loudness

Loudness matching functions for tones for persons with one shifted-threshold ear (hearing loss and noise-shifted thresholds) and one ear within normal limits were used to derive the presumed basilar membrane (BM) input-output (I/O) function in a normal ear. The comparison was made by assuming that the BM I/O function for the ear with the cochlear threshold shift has a slope of one (a linearized cochlea). The function for the normal ear was derived from the loudness matching function based on this assumption. Comparisons were made for archival basilar membrane data [M. A. Ruggero, N. C. Rich, A. Recio, S. S. Narayan, and L. Robles, J. Acoust. Soc. Am. 101, 2151-2163 (1997)] for chinchilla and archival loudness matches for long-duration tones for persons with various degrees of cochlear hearing loss [F. Miskolczy-Fodor, J. Acoust Soc. Am. 32, 486-492 (1960)]. Comparisons were made also between BM I/O functions and ones derived from loudness matches for persons with unilateral hearing loss simulated by broadband noise. The results show a close resemblance between the basilar membrane I/O function and the function derived from loudness matches for long-duration tones, even though the comparison was between human and chinchilla data. As the degree of threshold shift increases from 40 to 80 dB, the derived BM I/O functions become shallower, with slopes for losses of 60 dB or more falling in the range of values reported for physiological data. Additional measures with short-duration tones in noise show that the slope of the loudness function and the slope of the derived basilar membrane I/O function are associated with the behavioral threshold for the tone. The results for long-duration tones suggest a correspondence between BM displacement and loudness perception in cases of recruitment, but the relation between the degree of loss and the amount of BM compression and the relation between signal duration and compression suggests that other factors, such as the neural population response, may play a role.     

P-selectin blockade is beneficial after uncontrolled hemorrhagic shock

OBJECTIVE: Increased intra-abdominal pressure (IAP) compromises cardiopulmonary function and visceral perfusion. Our goal was to characterize acute changes in these subsystems associated with operative abdominal decompression. PATIENT POPULATION: A series of 11 consecutive injured patients monitored with a pulmonary artery catheter and nasogastric tonometer in whom operative decompression was performed. Indications for decompression included oliguria or progressive acidosis despite aggressive resuscitation in the presence of elevated IAP (>25 mm Hg). MAIN OUTCOME MEASURES: Studied hemodynamic variables included pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic volume index (RVEDVI), and cardiac index (CI). Pulmonary variables included shunt fraction (Qs/Qt) and dynamic compliance (Cdyn). Visceral perfusion was assessed using hourly urine output 4 hours before and after decompression (UOP) and gastric intramucosal pH (pHi). Mean values before and after decompression were compared using the paired t test. Linear regression and Fisher's z transformation were used to evaluate the relationships between RVEDVI, PAOP, CI, and IAP. IAP was transduced via bladder pressures. Significance was defined as p < 0.05. Data are expressed as means+/-SD. RESULTS: IAP decreased with decompression (49+/-11 to 19+/-6.8 mm Hg; p < 0.0001). RVEDVI improved independent of CI and correlated better (p < 0.01) with CI (r =0.49, p=0.04) than PAOP did (r=-0.36, p=0.09). PAOP correlated significantly with IAP (r=0.45, p=0.04). Decompression resulted in significant improvements in Qs/Qt, Cdyn, UOP, and pHi. CONCLUSION: Abdominal decompression in patients with increased IAP improves preload, pulmonary function, and visceral perfusion. Elevated IAP has important effects on PAOP, which makes the PAOP an unreliable index of preload in these patients.     

Effects of hydrotherapy on pressure ulcer healing

We have earlier reported a higher Fcgamma-receptor (FcgammaR)-mediated generation of reactive oxygen species, measured as luminol-enhanced chemiluminescence (CL) from peripheral neutrophils in adult periodontitis patients. The aims of this study were to confirm our previous results and to elucidate the mechanism of this phenomenon by measuring CL in parallel with the intracellular production of hydrogen peroxide, after stimulation with opsonized bacteria. To determine whether the higher CL was associated with altered responsiveness to priming, the cells were preincubated with tumor necrosis factor alpha (TNFalpha) and lipopolysaccharide (LPS). While CL was significantly higher in subjects with periodontitis, there was no difference in hydrogen peroxide production between the patients and the controls, indicating that the hyperreactivity is related to the generation of other oxygen species than H2O2 and/or to processes in the outer cell membrane. The responsiveness to priming with LPS on CL was slightly but not significantly higher in the periodontitis group, suggesting that priming could be of value for distinguishing subjects with periodontitis. When assaying intracellular production of H2O2, TNFalpha and LPS had both a priming and an activating effect. There were no significant differences between the two groups. In conclusion, this study shows a higher FcgammaR-mediated CL of peripheral neutrophils from adult patients with periodontitis, thus confirming our earlier results. The hyperreactivity seems to be related to the outer cell membrane or to oxygen species other than H2O2.     

Smith-Lemli-Opitz syndrome: phenotypic extreme with minimal clinical findings

The effect of spine venom from the crown-of-thorns starfish (Acanthaster planci) on drug-metabolizing enzymes in rat liver was studied. The spine venom was prepared by saturation of spine homogenate with ammonium sulfate and the protein fraction precipitating 50% saturation was used as venom B. Venom A was the protein precipitated between 50 and 100% saturation. When venom B (100-200 mg/kg) was given to rats, liver microsomal GSH S-transferase and cytochrome P450 activities decreased while cytosolic GSH S-transferase activity was not changed. The decrease in these microsomal enzyme activities was seen from 12 hr to 24 hr after giving 100 mg/kg of venom B. Rats given venom A died, suggesting an involvement of the lethal factor in venom A. The data showed that the spine venom B from A. planci depressed microsomal GSH S-transferase and cytochrome P450 activities in rat liver and that this venom was distinct from the lethal factor of the spine venom.