James C. Overall

The natural history of recurrent herpes simplex labialis. Implications for antiviral therapy.

We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.

Nosocomial infections in a newborn intensive-care unit. Results of forty-one months of surveillance.

We detected a 24.6 per cent nosocomial infection rate (222 infections in 138 infants) among 904 infants hospitalized for over 48 hours in a regional newborn intensive-care during 41 months of surveillance. Surface infections accounted for 40.1 per cent of the total, pneumonia for 29.3 per cent, bacteremia for 14.0 per cent, surgical-wound infection for 8.1 per cent, urinary-tract infection for 4.5 per cent, and meningitis for 4.0 per cent. Staphylococcus aureus (47.3 per cent) and gram-negative enteric bacilli (45.1 per cent) were the most common organisms recovered. Nosocomial infection rates were significantly higher in infants with a birth weight less than 1500 g (P less than 0.001). The mortality rate in infants with any nosocomial infection was 33 per cent in contrast to 14 per cent in non-infected babies (P less than 0.001). Nosocomial infections are a major problem in newborn intensive-care units.

Neonatal bacterial meningitis: Analysis of predisposing factors and outcome compared with matched control subjects

Twenty-five cases of neonatal meningitis were identified among 54,535 live births in the Collaborative Perinatal Research Study. Low-birth-weight infants had a significantly higher incidence of meningitis, as well as a higher mortality rate from the disease. Gram-negative enteric bacteria were the most frequent etiologic agents. Predisposing factors significantly associated with meningitis were complications during labor and delivery, maternal peripartum infection, and chorioamnionitis. In the majority of maternal infections, the same organism was isolated from mother and infant. The case fatality rate of neonatal meningitis was 60 per cent. The presence of coma, abnormal Moro reflex, or opisthotonus correlated significantly with the mortality rate. Sequelae were present on follow-up examinations in five of the ten survivors, compared with four of twenty matched control subjects.

Treatment of experimental herpesvirus infections with phosphonoformate and some comparisons with phosphonoacetate.

Phosphonoformate (PF) at a concentration of 5 to 10 μg/ml inhibited the growth of type 1 strains of herpes simplex virus (HSV) in tissue culture, whereas 20 to 30 μg/ml was required for inhibition of type 2 strains and about 50 μg/ml was required for murine cytomegalovirus. In mice inoculated intraperitoneally or intracerebrally with HSV or intraperitoneally with murine cytomegalovirus, treatment with 250 to 400 mg of PF per kg twice daily for 5 days had only minimal effectiveness. When mice were inoculated intravaginally (i.vg.) with HSV type 2 and treated i.vg. with 10% PF beginning 3 h after viral inoculation, treatment was effective in completely inhibiting viral replication in the genital tract. If i.vg. therapy was initiated 24 h after infection, when the mice had a mean virus titer of 105 plaque-forming units in vaginal secretions, a significant reduction in the mean virus titer was observed on days 3, 5, and 7 after infection as compared with control animals. In guinea pigs treated i.vg. with 10% PF beginning 6 h after i.vg. inoculation with HSV type 2 there was also complete inhibition of viral replication in the genital tract, and no extenal lesions developed. When therapy was initiated 24 h after infection there was a 4 to 5-log decrease in viral titers on days 3, 5, and 7 of the infection and a slight delay in the development of external lesions.

Dietary vitamins A, C, and E and selenium as risk factors for cervical cancer.

The relation between cervical cancer and dietary intake of vitamins A, C, and E, beta-carotene, and selenium was examined in a population-based case-control study in Utah. Cervical cancer cases (n = 266) and population-based controls (n = 408) were interviewed between 1984 and 1987. Protective effects were observed for vitamins A, C, and E and beta-carotene but were attenuated by age, level of education, and lifetime cigarette use. Associated risk (comparing highest with lowest quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted) for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E; and from 0.95 (crude) to 0.70 (adjusted) for selenium. Adjustment for number of sex partners and church attendance, factors significantly related to cervical cancer risk, only slightly attenuated these adjusted risk estimates.

Determining the Efficacy of a Resiliency Training Approach in Adults With Type 2 Diabetes

PURPOSE The purpose of this randomized clinical study was to test the efficacy of a resiliency training approach for people with diabetes who have previously received standard diabetes self-education. METHODS A single-blinded, randomized design was employed with repeated measures (baseline, 3 months, 6 months) with 67 participants assigned to either treatment as usual (n = 37) or the resiliency classes (n = 30). Outcome variables included physiological measures (glycosylated hemoglobin, waist measurement, eating and exercise habits) and psychosocial measures (self-efficacy, locus of control, social support, and purpose in life). RESULTS Analyses of variance indicated that the intervention group had higher levels of resiliency as reported by knowing positive ways of coping with diabetes-related stress, knowing enough about themselves to make right diabetes choices, having fun in life, eating healthier, and increasing physical activity compared with the control group at 3 months (P < .05). Glycosylated hemoglobin and waist measurement improved but not significantly. CONCLUSIONS Interventions to foster resilience among people with diabetes have the potential to make an important contribution to increasing positive life outcomes. Diabetes educators using the resiliency approach in tandem with standard diabetes education programs can assist their patients to become more self-directed in their diabetes care.

Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir.

To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), maximum lesion area (42 mm2), vesicle or ulcer formation (91%), and maximum lesion virus titer (4.8 log10 PFU) in the drug recipients were not reduced in comparison with those who received the vehicle (5.2 days, 30 mm2, 75%, and 4.5 log10 PFU, respectively). Topical acyclovir in polyethylene glycol was ineffective for the treatment of herpes labialis despite an optimum therapeutic opportunity.

Recurrent Genital Herpes Simplex Virus Infection in Guinea Pigs

After recovery from initial genital herpes simplex virus (HSV) infections, female guinea pigs developed spontaneous recurrent infections characterized by discrete erythematous or vesicular herpetic lesions on the external genital skin. HSV type 2 (HSV2) caused significantly more recurrent infections in guinea pigs than did HSV type 1 (HSV1). HSV2-infected animals demonstrated a significant decline in frequency of recurrences over time. The viral nature of the recurrent lesions was confirmed by recovery of infectious HSV, detection of HSV antigen, and histologic examination. Latent HSV2 could be demonstrated in dorsal root ganglia and external genital skin after recovery from the primary infection. Recurrent genital HSV infection in the guinea pig shares many features with recurrent genital herpes in humans and provides a model for studying the relationship between latency and recurrences and for exploring methods for control of recurrent disease.

Antiviral Activity of Extracts from Marine Algae

Extracts of two species of marine algae, Constantinea simplex and Farlowia mollis, were tested for antiviral activity in tissue culture and in experimental infections of mice. Treatment of confluent mouse embryo fibroblast cell monolayers with either compound before viral inoculation was effective in inhibiting the replication of herpes simplex virus type 1 and type 2, vaccinia virus, and vesicular stomatitis virus, but not encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus. Prophylactic administration of these extracts was effective in reducing final mortality or prolonging the mean day of death of animals inoculated by the intraperitoneal, intracerebral, or intranasal routes with herpes simplex virus type 2. When therapy was initiated after viral inoculation or at a site other than that of viral inoculation, no significant effect on mortality or on mean day of death was observed. Neither preparation was effective in mice inoculated intraperitoneally with encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus or in animals infected intravaginally with herpes simplex virus type 2. The prophylactic but not therapeutic antiviral activity of these preparations seriously limits their potential use in human herpes simplex virus infections.

Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.