Severity of experimentally reactivated herpetic eye disease is related to the neurovirulence of the latent virus

The authors examined the eye diseases produced during acute and experimentally reactivated infections of rabbits intranasally inoculated with high and low neurovirulent strains of herpes simplex virus, type-1 (HSV-1). Experimental reactivation of latent trigeminal ganglionic infection was accomplished by an injection of cyclophosphamide followed by one injection of dexamethasone the next day. Neither drug, when given as a single injection, reactivated latent HSV-1 infection. During acute and reactivated phases of high neurovirulent HSV-1 strain infection, many rabbits developed very severe conjunctivitis and keratitis. Some rabbits developed hemorrhagic corneal lesions, and a few became blind. Only a few rabbits with acute and reactivated low neurovirulent virus strain infections developed mild conjunctivitis. The high neurovirulent strain was recovered from tear film more frequently than the low neurovirulent strain during reactivated infections. By use of 3H-labelled DNA prepared from purified virus to probe trigeminal ganglionic tissues in situ, both strains of virus were found to establish ganglionic latency to about the same degree. Reactivation correlated with an increase in the amount of HSV-1 RNA per ganglionic neuron and a change in subcellular location. These studies indicate that the relative neurovirulence of the infecting strain determines the ease with which it can be reactivated from latency and the severity of the reactivated ocular disease produced.     

Immunohistochemical demonstration of spread of Aujeszky''s disease virus to the porcine central nervous system after intestinal inoculation

The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.     

Borna disease virus infection in animals and humans

Tomographic reconstructions of biological specimens are now routinely being generated in our high voltage electron microscope by tilting the specimen around two orthogonal axes. Separate tomograms are computed from each tilt series. The two tomograms are aligned to each other with general 3-D linear transformations that can correct for distortions between the two tomograms, thus preserving the inherent resolution of the reconstruction throughout its volume. The 3-D Fourier transforms of the two tomograms are then selectively combined to achieve a single tomogram. Unlike a single-axis tomogram, a dual-axis tomogram shows good resolution for extended features at any orientation in the plane of the specimen; it also has improved resolution in the depth of the specimen. Calculations indicate that the improvements available from double tilting and from tilting to higher angles are largely additive. Actual and model data were used to assess whether varying the increment between tilted views in proportion to the cosine of the tilt angle would allow a reduction in the number of pictures required to achieve a given resolution of reconstruction. Analysis by Fourier sector correlation indicated that the variable tilt increment improved the reconstruction in some respects but degraded it in others. A varying tilt increment thus does not give an unqualified improvement, at least when using back-projection algorithms for the reconstruction.     

Granulomatous epididymitis related to Rhodotorula glutinis infection in a dog

A 4-year-old, male Great Dane dog developed severe swelling of the scrotum on 9 December 1991, and the testes and epididymides were removed surgically on 12 December 1992. The cut surface of the epididymides consisted of hard connective tissue and several small abcesses with slight hemorrhage. Histopathologically, the seminiferous tubules in the testes had only a few spermatogenic cells, but Sertoli cells were well preserved. Both epididymides consisted entirely of a proliferation of fibrous connective tissue, and only a few ducts deferens containing cell debris, neutrophils, and macrophages in the lumina were present. In all lesions of the epididymides, the macrophages contained periodic acid-Schiff- and Grocott's silver-positive round granules, 5-8 microns in diameter. Microbiologically, smooth salmon-pink colonies consisting of ovoidal yeast, about 10 microns in diameter, were isolated from the samples of epididymides but not from those of the testes. The isolated yeast had microbiological characteristics of Rhodotorula glutinis. From these observations, we diagnosed the present case as granulomatous epididymitis due to Rhodotorula infection.     

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.     

Hodgkin's disease in the setting of human immunodeficiency virus infection

Although Hodgkin's disease (HD) is not usually associated with congenital or acquired immunodeficiency disorders, recent evidence would suggest a statistically significant increase in HD among individuals infected with human immunodeficiency virus (HIV). In the setting of underlying HIV infection, clinical and pathologic characteristics of HD may differ from usual expectations. Thus, 70%-100% of HIV-infected patients with HD present with systemic "B" symptoms. Likewise, disseminated, stage III or IV disease is reported in approximately 75%-90%. Bone marrow is a common site of extranodal HD, occurring in 40%-50%. Complete response rates after multiagent chemotherapy range from approximately 45% to 70%, although median survival has been only in the range of approximately 18 months. Hematologic toxicity from multiagent chemotherapy may be substantial, even with the use of hematopoietic growth factor support. It is apparent that new strategies of therapeutic intervention must be explored.     

Human immunodeficiency virus infection: knowledge of the disease and attitudes toward related issues and policies among health care workers in a low-incidence nonurban hospital

We compared the knowledge and attitudes regarding human immunodeficiency virus (HIV) infection among employees in a tertiary care teaching hospital in a nonurban southeastern city with a relatively low incidence of acquired immunodeficiency syndrome (AIDS). All 260 physicians and a random sample of 240 other employees were asked to complete a 59-item anonymous mail survey. All groups of respondents, including physicians, showed a lack of understanding of critical aspects of AIDS, particularly transmission. Negative attitudes such as victim blaming and not liking to care for persons with HIV infection were common, especially among house staff and respondents who do not give hands-on care. Misinformation, aversion, fear, and lack of compassion were evidenced by a substantial proportion of the respondents, particularly house staff. The attitudes expressed suggest that there is more focus on the rights of the caregiver than on the welfare of patients. These findings show that there is a need for medical education that focuses on both knowledge and affective issues of HIV infection.     

Bilateral putaminal hemorrhage related to methanol poisoning: a complication of hemodialysis? Case report

A case of acute methanol intoxication is presented, in which bilateral putaminal hemorrhage developed after hemodialysis. Even though the patient was initially comatose and profoundly acidotic, favorable outcome was achieved, with long-term neurologic impairments essentially restricted to mild crural paraparesis, retrograde amnesia, and marked visual deficit. A comparative literature review is evaluated.     

Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship

BACKGROUND: Fibromyalgia syndrome (FS) is a common disorder of diffuse pain in the muscles or joints accompanied by tenderness at specific tender points and a constellation of related symptoms. The potential role of infections in the pathogenesis of FS has only recently been investigated. OBJECTIVES: To evaluate the prevalence of FS and to assess tenderness thresholds in patients infected with hepatitis C virus (HCV). METHODS: The study included 90 patients with HCV, 128 healthy, anti-HCV-negative controls, and 32 patients with non-HCV-related cirrhosis. Tenderness was measured by manual palpation (18 tender points) and with a dolorimeter. Fibromyalgia syndrome was diagnosed according to the 1990 American College of Rheumatology criteria. RESULTS: The diagnosis of FS was established in 14 patients (16%) with HCV, in 1 patient (3%) with non-HCV-related cirrhosis, and in none of the healthy controls (P < .001). Thirteen of the HCV-positive patients with FS were women. The patients with HCV had significantly (P < .01) more tender points (mean [+/- SD] 3.6 +/- 5.3) than the healthy controls (0.1 +/- 0.5) and the patients with non-HCV-related cirrhosis (1.2 +/- 2.7). Specifically, the patients with cirrhosis were most tender on both tenderness measures owing to the high proportion of women in this group. Patients with FS were significantly more tender than those without FS: their dolorimetry thresholds were 2.9 kg vs 6.0 kg (P < .001). CONCLUSIONS: A high prevalence of FS was observed in patients infected with HCV, especially women. Recognizing FS in patients with HCV will prevent misinterpretation of FS symptoms as part of the liver disease and will enable the physician to reassure the patient about these symptoms and to alleviate them.     

Bilateral medial bulbar infarct related to dolichoectasia of the vertebral artery

INTRODUCTION AND CLINICAL CASE: A 58-year-old hypertensive man presented with the sudden onset of quadriplegia and inability to protrude the tongue. Magnetic resonance imaging showed a bilateral medial medullary infarction associated with an abnormally dilated and partially occluded vertebral artery. CONCLUSION: This is the first clinicoradiological report of a bilateral medial medullary infarction related to vertebral artery dolichoectasia.     

Variations in response of four lines of ring-necked pheasants to infection with marble spleen disease virus

This study evaluated the response and susceptibility of four lines of ring-necked pheasants to infection with marble spleen disease (MSD) virus. Fifteen birds of the following lines were used: the standard ring-necked gamebird, the highly inbred jumbo white, the Sichuan, and the first-generation cross of the Sichuan and the standard gamebird. Baseline immune responses were assessed at 6 weeks of age by lymphoblastogenesis assays. All birds were orally challenged at 7 weeks of age with cell -culture-propagated MSD virus. Eight birds of each group were necropsied at 6-7 days post-inoculation (PI), and gross splenic lesions were recorded. Appropriate tissue sections were collected, fixed in 10% buffered formalin, and routinely processed for microscopic evaluation. The remaining birds were bled weekly from week 2 through week 8 Pl. Serum was tested for antibodies to MSD virus using a commercial enzyme-linked immunosorbent assay kit. Results of the lymphoblastogenesis assays and the gross and microscopic lesion incidences indicated that variations did exist between several lines evaluated. The jumbo white pheasant had significantly higher lymphoblastogenesis stimulation index and was more resistant to developing gross and histologic lesions than was the standard ring-necked gamebird.     

No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys

BACKGROUND: The xenotransplantation of organs and tissues, in particular those from pigs, is viewed as a means to alleviate the shortage of human donor organs and cells available for transplantation and also as a therapy for other diseases. The potential microbiological hazards of xenotransplantation have recently attracted much attention. One concern is over pig endogenous retroviruses (PERV). Until the possible consequences of infection by PERV are better understood it is unlikely that a significant number of porcine xenotransplants will proceed. However, a small number of patients have already been treated with or exposed to living porcine cells or tissue, and investigation of these patients may provide valuable information. METHODS: We took serial blood samples from two renal dialysis patients whose circulation had been linked extracorporeally to pig kidneys and tested them for pig DNA and PERV DNA by nested PCR. The patients' plasma was also tested for neutralising antibodies to two anthropotropic PERV strains. FINDINGS: Having established that the nested PCRs could detect single molecules of target sequence, we analysed DNA isolated from patients' peripheral blood mononuclear cells. We found no evidence of pig or PERV DNA in either patient, even in samples taken as early as 6 h after the perfusion. Furthermore, we found no evidence of seroconversion for PERV-specific antibodies. INTERPRETATION: The absence of porcine cells in the circulation of both patients, even in the samples taken soon after the perfusion experiment, suggests that any porcine cells dislodged from the kidney became rapidly sequestered from the circulation. Since cell-to-cell contact increases the efficiency of infection of PERV this removal of porcine cells may increase the risk of transmission of PERV to the xenograft recipient. We did not, however, detect indications of infection by PERV by PCR or neutralisation assay. The genetic and serological methods described here will be useful for detection of possible PERV infection in other patients.     

Tissue specific distribution of the herpes simplex virus type 1 latency-associated transcripts on polyribosomes during latent infection

Certain natural products and Asian herbal remedies have been used in Asia to attenuate neurodegenerative diseases, including senile dementia. We have examined derivatives of several natural products for potential neuroprotective activity in an in vitro test system. In the present study, we assayed a number of compounds that were isolated from Panax ginseng C.A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rb1 and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was reduced significantly by pretreatment with Rb1 and Rg3. Ginsenosides Rb1 and Rg3 inhibited the overproduction of nitric oxide, which routinely follows glutamate neurotoxicity, and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound that is produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rb1 and Rg3 exerted significant neuroprotective effects on cultured cortical cells. Therefore, these compounds may be efficacious in protecting neurons from oxidative damage that is produced by exposure to excess glutamate.     

Impact of hepatitis C virus infection on schistosomal liver disease

BACKGROUND/AIMS: This study was conducted to determine whether Hepatitis C virus infection has a role in patients with schistosomal liver disease. METHODOLOGY: Sixty patients with hepatosplenic schistosomiasis and evidence of portal hypertension were seen at the Armed Forces Hospital Riyadh, Saudi Arabia over 5 years. The impact of Hepatitis C virus infection on chronic schistosomal liver disease was studied in 30 of these patients (group one) who were Hepatitis C virus positive and compared with the other 30 patients (group two) who were Hepatitis C virus negative (control group). RESULTS: Hepatitis C virus may be an important factor contributing to deterioration of liver function for patients with hepatosplenic schistosomiasis. Liver functions showed elevated ALT in 83.3% in group one compared to 23.4% in group two. Liver biopsy in 19 patients (group one) and 16 patients (group two) showed evidence of schistosomiasis and in patients of group one, liver biopsy also showed chronic active hepatitis together with Schistosoma in 57.9%, and cirrhosis in 31.6%. None of group two patients had cirrhosis. Alpha-fetoprotein levels were elevated in 16 patients (group one) and 3 of these patients had hepatocellular carcinoma. None of the control group had radiological or histological evidence of hepatocellular carcinoma. CONCLUSION: The mean age of HCV positive patients was less than the HCV negative patients, which may indicate that Hepatitis C virus infection leads to decompensation of liver function earlier in patients with Schistosoma and severe liver disease may be promoted at a younger age in Schistosoma patients with hepatitis C.