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Biomedical subjects

R Whitley

Publications and source records attributed to R Whitley.

At least 19 recordsLinked to original sources
PubMed2006

New approaches to the therapy of HSV infections.

Two recent studies have demonstrated single-day regimens of high-dose antiviral therapy (famciclovir 1000 mg twice daily for genital herpes, and famciclovir 1500 mg single dose for herpes labialis) to be effective episodic treatment strategies. Both have the potential to improve patient compliance and therapeutic satisfaction. Patient-initiated episodic therapy (PIE) regimens such as these may improve the time to treatment initiation, which can halt lesion development: PIE allows antiviral drugs to be administered in the narrow therapeutic window that occurs early in the course of a herpes simplex virus (HSV) infection episode. This review article discusses short-course antiviral therapy, which may offer an effective alternative to traditional episodic or suppressive antiviral regimens for HSV-related disease outbreaks.

2-Aminopurine↗
PubMed2005

Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic.

BACKGROUND/OBJECTIVES: While nearly one in four Americans has antibodies to HSV-2, only one of 40 reports a history of genital herpes (GH). The goal of this study was to correlate questions designed to elicit a GH history with serological evidence of HSV-2 in male STD clinic attendees. METHODS: Consecutive males were enrolled in a study of the epidemiology of GH. Consenting men answered questionnaires regarding their histories of possible GH and underwent serological testing for HSV-1 and HSV-2. Association statistics between response to each question and HSV-2 serological status were calculated. RESULTS: Of 328 men enrolled, 148 (46%) had HSV-2 antibodies. 14 (4.3%) reported a history of GH when queried as part of a list of other STD (sensitivity (S) 0.08). 17 (5.2%) reported a history of GH when asked directly "Do you have genital herpes?" (S 0.09). 75 (21.1%) participants reported a history of a recurring genital sore, ulcer, or zipper cut (S 0.32). Overall, 64.2% of HSV-2 seropositive men answered "no" to all three questions. A "yes" response to any of the questions was only 36% sensitive for predicting HSV-2 infection. CONCLUSION: Few HSV-2 infected men report either a history of GH or are aware that they are infected. Asking about a history of recurrent genital sores was a more sensitive historical marker of HSV-2 infection than asking about a history of "genital herpes."

Adult↗
PubMed2001

Phase specific analysis of herpes zoster associated pain data: a new statistical approach.

Herpes zoster or shingles is a frequent occurrence in both elderly individuals and immunocompromised hosts. The pain associated with herpes zoster is the most debilitating complication of the disease. It can be described as acute pain and post-herpetic neuralgia or zoster associated pain (ZAP). The latter definition encompasses pain from the onset of disease through its resolution and provides a convenient analytic tool for evaluation of antiviral therapy. A heuristic examination of ZAP historical data suggests the existence of three phases of pain resolution: the acute, subacute and chronic phases. The subacute and chronic phases comprise the post-herpetic neuralgia (PHN) stage. Common analytic methods, such as a Kaplan-Meier survival function or a Cox's model, have been used to assess the pain. However, such approaches do not adequately allow for phase comparison. Notably, in the clinical trial setting the comparison of specific treatment effects on the latter stages of pain are of the greatest medical relevance since this is the most debilitating phase of the illness. In order to incorporate the phase-specific information in the modelling of time to cessation of ZAP, we assumed the hazard function was a stepwise constant. Utilizing the full likelihood function, we obtained the maximum likelihood estimate for the transition times (that is, change-points), and other parameters of medical importance. The standard error of the change-point estimates were obtained through a bootstrapping method. The asymptotic properties of the parameter estimates are also discussed. Hence, the rates of pain resolution across all phases can be examined in order to precisely define the existence of multiple phases. In addition, the covariates effect can be examined across phases and populations, thereby allowing us to translate potential efficacy of a standard therapy to different populations. These results can be utilized in the design of clinical trials or in targeting the outcome for a specific phase while controlling for the effect of other variables.

Acute Disease↗
PubMed1998

Molecular epidemiology of p53 protein mutations in workers exposed to vinyl chloride.

The production of mutations in cellular tumor suppressor genes such as p53 is involved in the development of many human cancers. These mutations result in the expression of mutant forms of the encoded p53 protein which can potentially serve as a biomarker for this carcinogenic process. Workers exposed to vinyl chloride who are at risk for the development of the sentinel neoplasm angiosarcoma of the liver represent a model population for the study of such a mutant p53 biomarker, since vinyl chloride is known to cause specific p53 mutations in persons with angiosarcoma of the liver. To determine the relation between vinyl chloride exposure and this p53 biomarker, the authors examined serum samples collected between 1987 and 1992 from a cohort of 225 French vinyl chloride workers and 111 unexposed controls (matched according to age, sex, race, smoking, and alcohol drinking) for the presence of mutant p53 protein, using an enzyme-linked immunosorbent assay. Stratification of the exposed workers by quartile of vinyl chloride exposure (in estimated ppm-years) yielded a statistically significant trend of increasing odds ratios for p53 biomarker seropositivity with increasing exposure. These results suggest that this serum biomarker for mutant p53 protein is related to vinyl chloride exposure and may be an early indicator of carcinogenic risk in exposed individuals.

Adult↗
PubMed1996

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial.

BACKGROUND: Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS: Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS: Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS: Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Acyclovir↗
PubMed1991

A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS: Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS: After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Acyclovir↗
PubMed1991

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗
PubMed1990

Increased detection of elevated TSH using immunoradiometric assay.

Using a highly sensitive immunoradiometric assay, the authors detected an increased rate of elevated thyrotropin in 2,099 patients vs 1,789 patients examined with radioimmunoassay. Closer scrutiny of mood disorder patients with elevations found confirmatory evidence of thyroid dysfunction in most.

Feeding and Eating Disorders↗
PubMed1988

Treatment of condyloma acuminatum with three different interferons administered intralesionally. A double-blind, placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy and toxicity of intralesionally administered interferons in the treatment of condyloma acuminatum. DESIGN: Randomized, double-blind, and placebo-controlled study. SETTING: Outpatient clinics at university medical centers. PATIENTS: Seventy-nine patients with biopsy-proved condyloma acuminatum that was refractory to conventional therapy were enrolled in the study. INTERVENTIONS: Alpha-2b, alpha-nl-, and beta-interferons were used. One wart on each patients was injected three times per week for 4 weeks with either 1 x 10(6) units of interferon or placebo. MEASUREMENTS AND MAIN RESULTS: Forty-seven percent of warts injected with interferon resolved completely, compared with 22% of placebo-injected warts (P = 0.009). In addition, more recipients of interferon had a complete resolution of uninjected lesions. No differences in rates of response were noted among the different interferon groups. Approximately one third of interferon-injected warts recurred, compared with none of four placebo-injected warts. Intralesionally administered interferon was nontoxic and well tolerated, although transient pain on injection was observed frequently. CONCLUSIONS: Intralesional administration of each of these three interferons appears to be useful in treating condyloma acuminatum. However, the frequent recurrence of disease and the failure of many lesions to resolve indicate that different regimens, such as longer courses of therapy or different routes of administration, should be evaluated to maximize beneficial effects of interferon for treating this common sexually transmitted disease.

Adult↗
PubMed1987

Transfusion-associated viral infections.

Viral infections are a frequent occurrence following transfusion of blood products. While generally benign, these infections are capable of causing significant morbidity and mortality. Therefore, it is prudent to follow several general approaches diligently to reduce the risks of these infections in patients undergoing transfusions of blood products. These suggested measures include the following: 1. Prescribe and administer blood and blood products only when absolutely needed. 2. Use volunteer blood donors only. 3. Avoid use of pooled blood products when possible. 4. Use only blood and blood products that have been appropriately tested for HBsAg and HIV. 5. Use ALT determinations to screen blood products and eliminate those with high level. 6. Avoid the use of clotting-factor concentrates but, if necessary, use only those which have been heat-treated. 7. Limit use of leukocyte transfusion. 8. Use only CMV seronegative blood and blood products or frozen deglycerolized red cells in patients at high risk for posttransfusion CMV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effect of cloned human interferons on protein synthesis and morphogenesis of herpes simplex virus.

Pretreatment of human fibroblast cells with 100 U of either cloned human alpha-2 or beta interferon per ml for 24 h reduced the release of infectious herpes simplex virus type 1 by more than 99%. This inhibition in infectivity correlated well with the total number of extracellular virus particles released from treated cells as determined by DNA dot blot hybridization analysis. Electron microscopic observations of interferon-treated human fibroblast cells clearly demonstrated typical assembly of nucleocapsids inside the nucleus, even though very few mature extracellular particles were seen. Analysis of virus-specific proteins by the immunoblot technique showed that neither species of interferon had a significant inhibitory effect on the synthesis of major nucleocapsid proteins. However, the synthesis of specific glycoproteins (D and B) was drastically reduced or delayed in beta-interferon-treated cells. The results presented in this communication suggest that cloned human interferons block herpes simplex virus morphogenesis at a late stage and inhibit the release of particles from the treated cells.

Animals↗
PubMed1982

Mucocutaneous herpes simplex virus infections in immunocompromised patients. A model for evaluation of topical antiviral agents.

Forty-three immunocompromised patients with progressive cutaneous herpes simplex virus infections were studied in a double-blind, placebo-controlled evaluation of topically applied acyclovir. Patients were randomized and 22 received acyclovir and 21 placebo; medications were applied four times daily for 10 days. Both study populations were balanced for all demographic characteristics. Acyclovir therapy resulted in no median differences in time to total healing compared with placebo responses, p = 0.13. However, those patients who received the acyclovir ceased shedding virus more rapidly, p less than 0.001, and lost pain more readily, p = 0.04, than placebo counterparts. Neither group experienced adverse effects. Because of the protracted nature of mucocutaneous herpes simplex infections in these patients, the immunocompromised host provides a good model for evaluation of topical antiviral therapy.

Acyclovir↗
PubMed1982

Vidarabine therapy of varicella in immunosuppressed patients.

In order to assess further the clinical usefulness of vidarabine therapy of chicken pox, a double-blind, placebo-controlled trial was performed in immunocompromised patients. Thirty-four patients entered the trial; 19 received vidarabine and 15 the placebo. All patients had disease less than or equal to 72 hours in duration and 23 had lymphoproliferative malignancies. Both patient populations were balanced for underlying disease, preceding chemotherapy, and duration of chicken pox. No patient received zoster immune globulin. Drug therapy accelerated cessation of new vesicle formation (P = 0.015) and decreased median daily lesion counts (P = 0.06 on days 2 and 3). Fever (greater than or equal to 37.8 degrees C orally) resolved more rapidly in the drug-treated group. By day five, 70% of drug-treated subjects were afebrile in contrast to 35% of placebo recipients (P = 0.066). One drug recipient developed mild pneumonitis during the study which resolved with therapy, whereas eight placebo recipients developed varicella-related complications which led to death in two patients (P less than 0.01). These results were achieved with minimal evidence of laboratory or clinical toxicity related to drug administration. The findings indicate that vidarabine has a good therapeutic index (efficacy/toxicity) for treatment of chicken pox in immunocompromised patients when given early in the course of the infection.

Aspartate Aminotransferases↗
PubMed1981

Rapid detection of viruses in biopsy or autopsy specimens by the pseudoreplica method of electron microscopy.

A rapid pseudoreplica method of electron microscopy (EM) was used to detect viruses in brain tissues obtained from 57 patients suspected of having herpes simplex encephalitis (HSE). Herpesvirus particles were demonstrated in 18 of the 20 (90%) specimens from which herpes simplex virus was isolated in tissue culture. The procedure takes less than 2 hours, as compared to the time (greater than or equal to 2 days) usually required for virus isolation or standard thin-section electron microscopy. Although the immunofluorescence test has comparable rapidity, it was found to be less sensitive and to yield occasionally false-positive reactions. Our findings indicate that, until a brain biopsy can be replaced by less invasive procedures, examination of brain tissue by the pseudoreplica method offers a rapid diagnosis of a herpesvirus encephalitis. Furthermore, the demonstration of viruses in brain, lung and liver specimens obtained by biopsy or at autopsy suggests that this electron-microscopic method would be advantageous for detecting viruses in tissue samples, particularly in the case of viruses which may not be readily demonstrable by conventional methods.

Adult↗