Interferon administered orally: protection of neonatal mice from lethal virus challenge.

Interferon was identified in the milk of mice injected with an interferon inducer. The kinetics of interferon appearance in serum and in milk were similar, but maximum concentrations in milk were 10 to 20 percent of those in serum. Interferon administered orally to neonatal mice was detected in their serums. Significantly more newborns survived an oral challenge with vesicular stomatitis virus when interferon had been induced in the lactating mothers.

Carbocyclic arabinofuranosyladenine (cyclaradine): efficacy against genital herpes in guinea pigs.

Carbocyclic arabinofuranosyladenine (cyclaradine), a novel nucleoside analog with such desired features as hydrolytic and enzymatic stability, adenosine deaminase resistance, and low systemic toxicity, inhibited the replication of herpes simplex virus types 1 and 2. The 5'-methoxyacetate prodrug form exhibited significant efficacy in the topical treatment of genital infections by herpes simplex virus type 2.

Cutaneous herpes simplex virus infection of guinea pigs as a model for antiviral chemotherapy.

The kinetics of Herpesvirus hominis (Type 1) replication and lesion development in guinea pig skin were determined. The data indicate that lesion scores did not always reflect virus content. Virus replication was detected prior to appearance of lesions and maximum virus content preceded maximum lesion score. Lesions resolved slowly while virus content declined rapidly to an undetectable level. The utility of the guinea pig skin-herpesvirus model for the evaluation of ara-A and kethoxal was studied. Ara-A treatment at three dose levels suppressed lesion development and at the two highest dose levels lesion development was delayed. Lesion virus content, when determined during the period of maximum virus replication, was not affected by treatment. Kethoxal markedly suppressed lesion development and virus growth. Aspects of this experimental model typify cutaneous herpes simplex disease of man. Studies designed to further assess its utility for evaluating antiviral drugs seem warranted.

Argon plasma coagulation for the treatment of colonic varices.

Various individually tailored endoscopic treatment modalities have been described for bleeding colorectal varices. We describe a case of a 65-year-old man, in whom argon plasma coagulation successfully eradicated ectopic varices at the ileocolonic anastomosis; bleeding could be stopped.

Endoscopic management of bile duct stones.

The advantages of endoscopic retrograde cholangiopancreatography (ERCP) over open surgery make it the predominant method of treating choledocholithiasis. Today, technologic advances such as magnetic resonance cholangiopancreatography and laparoscopic surgery are challenging ERCP's primacy in the management of common bile duct (CBD) stones. This article reviews the current status of endoscopic treatment of biliary stones and examines this in relation to laparoscopic management. The techniques and safety of endoscopic sphincterotomy and balloon sphincteroplasty are reviewed. Balloon sphincteroplasty should be limited to study protocols because of safety questions and inherent limitations. After sphincterotomy, 85% to 90% of CBD stones can be removed with a Dormia basket or balloon catheter. These techniques are described as having both advantages and disadvantages. Methods for managing "difficult stones" include mechanical lithotripsy, intraductal shock wave lithotripsy, extracorporeal shock wave lithotripsy, chemical dissolution, and biliary stenting. These approaches are presented along with data supporting their use in specific situations. Laparoscopic cholecystectomy has emerged as the preferred alternative to open cholecystectomy. Parallel advances in the endoscopic and laparoscopic management of CBD stones have made the issue regarding the optimal treatment strategy complex. Three approaches to the management of choledocholithiasis in the laparoscopic era are presented as follows: strict therapeutic splitting, flexible therapeutic splitting, and strict laparoscopic management. The optimal approach needs to be defined in prospective comparative trials. For now, preoperative endoscopic stone extraction should still be recommended as the approach of choice in patients suspected to have CBD stones based on clinical, biochemical, and imaging parameters. Primary laparoscopic evaluation and management is reasonable in patients who have a low-to-moderate probability of having CBD stones.

Gastrointestinal complications of schistosomiasis.

Schistosomiasis is an important disease in many parts of the world and has affected the course of human history many times over. The parasitic infection is acquired during contact with infected water. A chronic inflammatory response to schistosome eggs, mediated by both cellular and humoral mechanisms, is the root of the pathology seen in schistosomiasis. Hepatosplenic disease results in intrahepatic presinusoidal portal hypertension. The resultant esophageal and gastric varices are an important cause of morbidity and mortality. Standard treatment guidelines for managing varices can be applied to patients with schistosomiasis. Coinfection with viral hepatitis results in liver disease that progresses more rapidly and is more difficult to treat. Intestinal schistosomiasis may be confused with other disease states and can be an important cause of morbidity, especially in heavily infected patients. Diagnosis relies on demonstration of schistosome eggs in feces or tissue. Praziquantel is the treatment of choice. The development of a vaccine for schistosomiasis is an important goal in the attempt to control this disease.

Sensitivity of rhinoviruses to human leukocyte and fibroblast interferons.

Rhinoviruses were tested for sensitivity to human interferon from two sources: human leukosytes induced with Sendai virus and human diploid fibroblasts induced with polyriboinosinic-polyribocytidylic acid. Twenty-five serotypes of rhinovirus were tested against fibroblast interferon in HeLa cells, and five serotypes were evaluated in fibroblast cultures against fibroblast and leukocyte interferons. Sensitivity varied widely in the HeLa cell assay; rhinovirus type 10 was inhibited by approximately 20-40 units of interferon, whereas rhinovirus type 15 was not inhibited by 5,120 units; the significance of this observation is unclear. In contrast, when fibroblast cultures were used in the assay system, five selected serotypes, including rhinovirus types 10 and 15, had similar levels of sensitivity (0.5-5.0 units) to fibroblast or leukocyte interferon.

Influence of vehicle on topical efficacy of 2-acetylpyridine thiosemicarbazone and related derivatives on in vivo type 2 herpes simplex virus infections.

2-Acetylpyridine semicarbazone (APSC), 2-acetylpyridine thiosemicarbazone (APTSC) and 2-acetylpyridine-4-methyl-3-thiosemicarbazonoe (APMTSC) were evaluated against type-2 herpes simplex virus (HSV-2)-induced genitalis and encephalitis in mice and guinea pigs. The antiviral activity of these compounds was compared with that of acyclovir. With 1,3-butanediol as a topical treatment vehicle, 1% APSC and APTSC showed significant activity against the genital infection in mice, as evidenced by increased survivors and decreased severity of vaginal lesions. Reduced titers of virus recovered from the lesions were also observed with APTSC treatments. Eight different commercially available vehicles were compared to determine in which topically administered 1% APTSC would be most efficacious against the vaginal disease induced in mice. Significant results were observed with Squibb cream base, Eucerin base, and K-Y jelly; these effects were essentially equivalent to using 1,3-butanediol Unibase, Aquaphor, polyethylene glycol, polyvinyl alcohol and petrolatum were less effective as carrier vehicles. The herpesvirus genital infection in guinea pigs was treated with 1% APMTSC and APTSC comparing Squibb cream, Eucerin and K-Y jelly bases; while neither compound exerted striking effects against this infection in any vehicle, 1% APMTSC in Squibb cream was effective in increasing mean survival time and reducing lesion score and titers of recoverable virus. In this experiment, treatments with 1 and 5% acyclovir in polyethylene glycol base were effective in reducing titers of virus from the vaginal area. Orally administered APTSC (12.5, 25, 50 mg/kg/day given twice daily for 7 days) caused moderate prevention of death of mice infected intraperitoneally with HSV-2; subcutaneous injection of the compound was markedly effective with efficacy comparable to that of acyclovir at 120 mg/kg/day.

Effect of antiviral agents in equine abortion virus-infected hamsters.

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-beta-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2'-deoxyuridine, distamycin A, and N-ethylisatin beta-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group.

Evaluation of gentamicin for use in virology and tissue culture.

Data are presented comparing gentamicin to penicillin and streptomycin (Pen-Strep) in tissue culture medium with respect to a number of parameters associated with virology and tissue culture. Unlike Pen-Strep, gentamicin was stable at pH 2 to 10 for 15 days at 37 C in tissue culture medium, and its activity was unaffected by the presence of serum. Moreover, it was stable to autoclaving. Twenty cell types replicated normally at the suggested concentration of 50 mug/ml, and all cells were unaffected by 20 times this concentration. Evidence for its practical use in virus studies was demonstrated in that (i) it was not viricidal to ribonucleic acid or deoxyribonucleic acid viruses at 40 times the suggested concentration at 37 C, (ii) the size and number of plaques were not affected by 20 times the suggested concentration, (iii) interferon assays and production were unaffected by 20 times the suggested concentrations. Gentamicin may be uniquely useful for shipment of clinical specimens and long-term tissue culture and virus studies.