Cutaneous disorders and viral gene expression in HIV-1 transgenic mice.

Patients infected with HIV-1 experience several hyperproliferative skin disorders, including seborrheic dermatitis, ichthyosis, and psoriasis. Transgenic mice carrying a subgenomic HIV-1 proviral construct lacking the gag and pol genes were found to develop proliferative epidermal lesions, manifested as diffuse epidermal hyperplasia in homozygous transgenic mice and benign papillomas in heterozygous transgenic mice. Nonpapillomatous skin from both homozygotes and heterozygotes expressed viral RNA, and the viral envelope protein gp120 was localized to the suprabasal keratinocyte. Papillomas contained increased amounts of both viral mRNA and envelope glycoprotein. Exposure of transgenic mice to doses of ultraviolet B (UV-B) irradiation that induced cutaneous injury increased viral gene expression and resulted in the development of papillomas within 14-21 days. Cutaneous injury induced by phenol and liquid nitrogen had similar effects. These data support a role for HIV-1 gene products in the pathogenesis of proliferative epidermal disorders associated with HIV-1 infection. Further, they suggest that the process of wound repair increases HIV-1 gene expression in this transgenic mouse model.

Double-blind comparison of weekend and daily regimens of oral acyclovir for suppression of recurrent genital herpes.

The potential utility of intermittent regimens of oral acyclovir for suppression of recurrent genital herpes depends on how long the suppressive effect of the drug persists during pauses in treatment. To study this question, we admitted 38 patients in a double-blind controlled trial comparing the results of daily acyclovir treatment (200 mg t.i.d.) with treatment on weekend days only (400 mg t.i.d. on Saturday and Sunday) for suppression of recurrent genital herpes. Of the 35 patients completing the study, significantly more failures occurred in the weekend group (13/17) than in the daily group (3/18, P less than 0.001). Failures on the weekend regimen were more frequent as the week progressed (P = 0.005). The findings suggest a short-term persistence of suppression by acyclovir and hence that intermittent regimens with more closely spaced periods of treatment may be more effective than the regimen we studied. Most virus isolates studied, including all of those isolated from the patients during treatment, were sensitive to acyclovir.

Sports and clean living: a useful myth?

The effects of athletics upon participants' concern for physical health and community norms were investigated through a correlational analysis of sports participation and use of mood-altering drugs among high school seniors. Five hypotheses were tested: (1) the greater the number of sports participated in, the lower the rate of illegal substance use; (2) the greater the number of sports participated in, the lower the rate of alcohol use; (3) the greater the number of sports participated in, the lower the rate of cigarette use; (4) participation in out-of-school sports is associated with a greater diminishment of illegal substance use, alcohol use, and cigarette use than is participation in university sports or intramural sports; (5) the greater the number of sports participated in, the fewer the number of problems resulting from substance use. Only hypothesis 4 regarding diminished use of cigarettes was upheld but the correlations for hypothesis 4 are small, accounting for less than 3% of the variance. It is concluded that participation in all types of sports has very little effect on the use of mood-altering drugs. Athletics as a social institution, however, can continue to symbolize goodness, fun and fair play irrespective of the private behavior of the participants.

Perceived differences of standards for alcohol use among American youth.

Students perceive the greatest degree of similarity of standards for beer use with their close friends. An increase in liberality of personal standards and the perception of liberality as well as any dissimilarity of standards among close friends are associated with an increase in alcohol-related problems.

A clinical trial of temazepam, a sleep inducer, in hospital patients.

Temazepam, a common metabolite of diazepam and oxazepam, was evaluated as a sleep inducer. A dose of 20 mg, in a Scherer capsule formulation, was compared with 200 mg of amylobarbitone sodium in a between-patients, randomized study. Patient and staff assessments were used. No statistically significant difference as to onset of sleep, duration or quality of sleep or morning drowsiness was found using the patients' assessments. The staff recorded significantly less daytime dozing and morning hangover in patients receiving temazepam. Side-effects were mild and confined mainly to drowsiness on awakening. Two patients, both on amylobarbitone sodium, withdrew from the study because of increasing confusion.

Life stage differences in resident coping with restart of the Three Mile Island nuclear generating facility.

A study of residents who remained in the vicinity of Three Mile Island (TMI) immediately following the restart of the nuclear generating plant revealed that older residents employed a more emotion-focused coping style in the face of this event than did younger residents. Coping style was, however, unrelated to the level of psychological symptoms for these older residents, whereas demographic variables were related. Among younger residents, on the other hand, coping style was related to the level of psychological symptoms, whereas demographic variables were not. Among younger residents, emotion-focused coping was associated with more symptoms and problem-focused coping was associated with fewer symptoms, contradicting previous findings among TMI area residents.

Flurazepam ('Dalmane') in the treatment of insomnia in patients with respiratory disorders.

The effects on subjective aspects of sleep of flurazepam 15 mg and amylobarbitone sodium 100 mg were compared in insomniac patients with chest disease. A double-blind technique was used. The results indicate a significant superiority of flurazepam over the other drug.

The influence of informal control sources upon adolescent alcohol use and problems.

Although the past literature has hypothesized that alcohol consumption on the part of adolescents is influenced by the use patterns and standards of peers, parents, and community, a multivariate analysis of data from high school seniors reveals that only respondent's personal standards and number of close friends who drink exert a major influence on respondents' beer use, while the standards of other students explains an additional small part of the variance. Similarly, only friends' beer use and standards, in addition to the frequency of respondents' beer use, had significant correlations to drinking problems. Use patterns and standards of parents, as well as standards of close friends and of the adult community, had no appreciable relationship to adolescent alcohol use or problems. The greater importance of self-standards among late adolescents is consonant with theories of development of identity and autonomy.

Friendship and disaffiliation among the skid row population.

Personal relationships of skid row men have been described in terms of disaffiliation and replacemtent of friends. Analysis of social relationships of Philadelphia skid row residents upheld the theory of replacement. There was, however, a decline in the number of friends reported after the age of 70, which generally coincided with 20 years residence in the area. The loss of relationships was more closely associated with length of residence in skid row than with age. Qualitative measures of personal relationships indicated no major association between sociability and length of residence in skid row but a small association with advancing age. The proportions of friendless men desiring either friends of casual acquaintances were not related to either age or length of residence. These findings fail to uphold the disaffiliation hypothesis of aging and run counter to Vesliard's postulate of loss of need for meaningful personal relationships with increased exposure to the life of an outcast.

Psychological adaptation among residents following restart of Three Mile Island.

Psychological adaptation is examined in a sample of residents who remained in the vicinity of Three Mile Island following the restart of the nuclear generating facility which had been shut down since the 1979 accident. Findings indicate a lowering of psychological symptoms between 1985 and 1989 in spite of increased lack of control, less faith in experts and increased fear of developing cancer. The suggestion is made that reduced stress might have been related to a process of adaptation whereby a cognition of emergency preparedness was integrated by some of these residents as a modulating cognitive element. Findings also indicate that "loss of faith in experts" is a persistently salient cognition consistent with the "shattered assumptions" theory of victimization.

Delay in seeking help and onset of crisis among Al-Anon wives.

A survey of 123 Al-Anon wives in the Washington, D.C. area revealed that these women delayed an average of more than 7 years after the first occurrence of problem drinking before finally seeking help. The various drinking-related problems antecedent to the wives' seeking help clustered into four time periods composed of similar types of problems; (1) nonthreatening events, such as arrest, occurred 7 years prior to help seeking; (2) acts of physical violence, 5 years; (3) intervention by outside authorities, 3 years; and (4) recognition by significant others that the drinking was out of control, 2 years. The phenomenon of extended delay before recognition of the problem and help seeking is consistent with the paradigm developed from studies of mental patients and their families: pathological behavior becomes defined as a problem only after a long accumulation of bizarre episodes.

Interest in information as a function of worry and perceived control in the aftermath of nuclear disaster.

A survey of residents in the vicinity of the Three Mile Island nuclear generating facility four years after the accident examined level of interest in cancer detection and treatment, radiation monitoring, and epidemiology of cancer as a function of degree of ongoing worry, perceived control and demographic variables. Interest in information was found to be related to worry for all three topics, indicating that residents who had higher degrees of worry were more interested in seeking information than avoiding it. Control expectancy was related to interest in information about epidemiological distribution of cancer. Implications for the dissemination of information in the aftermath of a disaster are discussed.

The automated assessment of the effect of flurazepam and nitrazepam on mood state.

Some further results on the effects of the two hypnotic drugs, nitrazepam and flurazepam monohydrochloride, on mood state are described. An automated assessment and scoring system, Computer Assisted Psychometric System (C.A.P.S.), was used to assess mood state and showed that both hypnotics had a mild euphoriant effect even when administered to healthy volunteers during the daytime. This was most marked in the case of nitrazepam. It is argued that such euphoriant side effects should be further investigated as they can occur when hypnotics are administered on a long-term nightly basis, and there may therefore be a dependency aspect for those patients who habitually take such hypnotic drugs. The broad scope of the C.A.P.S. system is also discussed.

Transplantation of syngeneic transfected cells to probe the in vivo immune response to viral proteins.

BALB/3T3 cells were transfected with the glycoprotein D (gD) gene of herpes simplex virus (HSV) and a cell line expressing gD on the cell surface was isolated. In vitro, 51Cr release tests showed that the transfected cells were destroyed by anti-HSV antibody in the presence of complement. To investigate in vivo immune response, the gD-transfected cells were transplanted into the footpads of syngeneic HSV-immunized or unimmunized BALB/c mice. In unimmunized mice, transfected cells remained intact for 7 days or longer, and the site of injection showed only slight lymphocyte infiltration. In contrast, in immunized mice, transfected cells elicited massive lymphocyte infiltration and were mostly destroyed by day 4. Analysis of infiltrating cells revealed that they were mainly Thy1+ and CD8+ lymphocytes along with small numbers of CD5+, CD4+, and B lymphocytes. These studies show that transfected murine cells expressing gD can be used to study the in vivo immune response to single viral proteins and they argue that the immune response contributes to the pathogenesis of HSV infection.

Live vaccinia virus recombinants expressing herpes simplex virus genes.

Vaccinia virus recombinants expressing antigens from herpes simplex virus (HSV) have been tested as potential live virus vaccines for prevention of HSV infection. We describe three vaccinia virus/HSV recombinants. The first expresses the HSV-1 glycoprotein D (vaccinia/gD), the second expresses the HSV-1 glycoprotein B (vaccinia/gB), and the third expresses both the HSV-1 glycoprotein D and the influenza A hemagglutinin (vaccinia/HSVgD/influenza). Mice immunized with vaccinia/gD or vaccinia/gB developed antibodies capable of neutralizing HSV in vitro and were protected against both lethal and latent infection with HSV. Protection against HSV challenge persisted for greater than 1 year in mice immunized with vaccinia/gD. The immune response to HSV in mice immunized with vaccinia/gD could be increased by a booster vaccination with vaccinia/gD. However, the immune response to HSV was decreased in animals immunized with a vaccinia recombinant that expressed non-HSV genes before vaccination with vaccinia/gD. In separate experiments, a bivalent vaccinia recombinant, vaccinia/HSVgD/influenza, was constructed and was found to be comparable to the vaccinia/gD single recombinant in immunogenicity and protective efficacy against lethal HSV challenge. We conclude that vaccinia/HSV recombinants can provide protection against HSV infection in mice and that these recombinants may provide an alternative approach in the development of a live virus vaccine against HSV.

Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy.

In a recent phase II clinical study, 13 chronic hepatitis B-infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1-log10 decrease in plasma hepatitis B virus (HBV)-DNA levels. The decline of viral load during therapy displayed a biphasic kinetic profile that was modeled to determine the efficacy of inhibition of viral production, as well as kinetic constants for the clearance of free virus and the loss of infected cells. Viral production was suppressed with an efficacy of 0.993 +/- 0.008, indicating that only 0.7% of viral production persisted during therapy. The initial, faster phase of viral load decline reflects the clearance of HBV particles from plasma with a half-life of 1.1 +/- 0.3 days, translating to a 48% daily turnover of the free virus. The second, slower phase of viral load decline closely mirrors the rate-limiting process of infected cell loss, with a half-life of 18 +/- 7 days. The duration of therapy required to completely eliminate the virus from plasma or suppress it to levels sufficient to induce seroconversion is a function of the half-life of the free virus, the half-life of infected cells, and the efficacy of inhibition of virus production from infected cells. These quantitative analyses provide a more detailed picture of the dynamics of HBV infection and therapy, and can be used to compare the efficacy of various doses and inhibitors of HBV replication for the treatment of HBV infections.