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Biomedical subjects

J C Overall

Publications and source records attributed to J C Overall.

At least 19 recordsLinked to original sources

Tsukamurella paurometabolum: a novel pathogen causing catheter-related bacteremia in patients with cancer.

Tsukamurella paurometabolum is a weakly acid-fast, pleomorphic gram-positive bacterium found in soil. Human infection due to this organism has rarely been described, and there are no published accounts of bacteremia. Three cases of bacteremia due to T. paurometabolum and related to long-term use of a central venous catheter in patients with cancer who were receiving chemotherapy are described.

Actinomycetales

Is vaginal douching related to cervical carcinoma?

The association between cervical carcinoma and vaginal douching was examined in a population-based case-control study conducted in the low-risk population of Utah between 1984 and 1987. The authors compared 266 cases of in situ and invasive cervical carcinoma with 408 group-matched controls by vaginal douching behavior, controlled for age, lifetime number of sex partners, cigarette smoking history, religious activity, and educational level. Essentially no association was found in women who douched once per week or less, but in those who douched more than once per week, a consistent relation was demonstrated (adjusted odds ratio = 4.7, 95% confidence interval 1.9-11). Few differences were found with type of douching preparation used. The authors hypothesize that frequent douching alters the vaginal chemical environment, making the cervix more susceptible to pathologic change.

Carcinoma

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.

Adult

Cross contamination of viral specimens related to shell vial caps.

A cluster of poliovirus type 3-positive specimens cultured in shell vials led to the discovery of significant cross contamination between vials related to the type of vial cap. Simulated testing with colored media in the shell vials indicated that the most contamination occurred with the plastic snap cap and that the least occurred with the screw cap. Measures to prevent cross contamination in clinical virology laboratories are discussed.

Centrifugation

Cigarette smoking and exposure to passive smoke are risk factors for cervical cancer.

Personal cigarette smoking and exposure to passive smoke as risk factors for cervical cancer were examined in a population-based, case-control study conducted in Utah. Personal cigarette smoking was found to increase the risk of cervical cancer, after adjusting for age, educational level, church attendance, and sexual activity. The adjusted risk estimate associated with being a current smoker was 3.42 (95% confidence interval [Cl], 2.10 to 5.57); for having smoked for 5 or more pack-years, it was 2.81 (95% Cl, 1.73 to 4.55); and for having smoked at least 100 lifetime cigarettes, it was 2.21 (95% Cl, 1.44 to 3.39). The adjusted risk estimate (also adjusted for actual cigarettes smoked) associated with passive smoke exposure for 3 or more hours per day was 2.96 (95% Cl, 1.25 to 7.03). Risk from passive smoking was greater in women who were not smokers (odds ratio, 3.43; 95% Cl, 1.23 to 9.54) than in women who smoked (odds ratio, 2.59; 95% Cl, 0.23 to 29.24).

Adult

Sexual activity, contraception, genital infections, and cervical cancer: support for a sexually transmitted disease hypothesis.

A case-control study was conducted in Utah between 1984 and 1987 to examine risk factors for cervical cancer. Interviews were completed with 266 histologically confirmed carcinoma in situ and invasive squamous cell cervical cancer cases who were categorically matched by age to 408 controls. Among the factors identified as altering risk for cervical cancer, after adjustment for age, education, church attendance, and cigarette smoking, were: having numerous sex partners (odds ratio (OR) = 8.99 for 10 or more partners); the current mate having several sex partners (adjusted OR for 10 or more partners = 8.62); using foam or jelly as a contraceptive method (OR, adjusted for number of sex partners, = 0.44); reported Trichomonas infection (OR, adjusted for number of sex partners, = 2.10); and herpes simplex virus type 2 infection as determined by 2:1 neutralization index values above 100 (OR = 2.70). A protective effect was noted from the use of diaphragms (OR = 0.67) or condoms (OR = 0.53) in women who reported more than one sex partner. These data support the hypothesis that cervical cancer is a sexually transmitted disease.

Adult

Acyclovir treatment of disseminated herpes simplex virus type 2 infection in weanling mice: alteration of mortality and pathogenesis.

Intranasal inoculation of weanling mice with herpes simplex virus type 2 (HSV-2) provides an experimental infection that closely resembles disseminated and central nervous system HSV infections of human neonates. Intraperitoneal treatment with acyclovir (ACV) successfully reduced mortality even when therapy was begun as late as 2 days and oral therapy as late as 4 days after viral challenge. Treatment with ACV beginning on day 1 completely inhibited HSV-2 replication in lung, spleen, kidney, olfactory lobe, and cerebrum and decreased viral titers in the pons by 2-3 logs. Comparison of these data with our previous experiments using adenine arabinoside and adenine arabinoside 5' monophosphate indicates that ACV is more effective in the murine model of neonatal disease and suggests that ACV may also be more effective in treating the disease in humans.

Acyclovir

Rapid detection of herpes simplex virus in clinical specimens by centrifugation and immunoperoxidase staining.

The effect of immunoperoxidase staining and centrifugation on the sensitivity and rapidity of herpes simplex virus detection in mink lung cell cultures was determined with 730 clinical specimens. In standard tube cultures, the use of immunoperoxidase staining resulted in detection of 31 (91%) of 34 positive cultures after overnight incubation, compared with 25 (74%) detected without the stain (P less than 0.05). The effect of centrifugation of specimens onto the monolayer followed by overnight incubation and immunoperoxidase staining was studied with 431 specimens. Of 107 positive specimens, 103 (96%) were detected by this method, compared with 91 (85%) detected in standard cell cultures observed for 5 days (P less than 0.02). Standard cell cultures that were examined after overnight incubation detected only 62 (58%) of the 107 positive specimens (P less than 0.001). Centrifugation of clinical specimens onto cell monolayers followed by overnight incubation and immunoperoxidase staining is more rapid and sensitive than are standard cell culture techniques for the laboratory diagnosis of herpes simplex virus infection.

Animals

Synergism between recombinant human interferon and nucleoside antiviral agents against herpes simplex virus: examination with an automated microtiter plate assay.

An automated, quantitative, cytopathic effect (CPE) inhibition assay with human fibroblasts in 96-well microtiter plates was used to examine the combination of recombinant human interferon-alpha (rIFN-alpha A) and acyclovir, vidarabine, or dihydroxypropoxymethyl guanine against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) in vitro. Fifty percent CPE (CPE50) end points, calculated from optical density readings of crystal violet-stained monolayers in an automated spectrophotometer, represented 1.7 log reduction in viral yield (50-fold or 98% decrease). Using CPE50 end points of drugs alone and in combination, we defined synergism, additivism, or antagonism with an isobologram plot and a combination index equation. The combinations of rIFN-alpha A plus acyclovir and rIFN-alpha A plus dihydroxypropoxymethyl guanine were highly synergistic against both HSV-1 and HSV-2, whereas the combination of rIFN-alpha A plus vidarabine was additive to mildly synergistic. Combinations of antiviral agents synergistic in cell cultures should be pursued with further studies in animal models of human viral disease and potentially in clinical trials.

Acyclovir

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.

Animals

Ineffectiveness of topical adenine arabinoside 5'-monophosphate in the treatment of recurrent herpes simplex labialis.

The ability of topical 10 per cent adenine arabinoside 5'-monophosphate to decrease the severity and frequency of recurrent herpes simplex labialis was evaluated in a double-blind, randomized study of 233 patients at three collaborating institutions. Nine clinical and four virologic measurements were used to evaluate drug efficacy during a single episode. No statistically significant improvement in any measurement was seen in the drug-treated patients. Analyses according to institution and age, stage and size of lesion before therapy also indicated no benefit attributable to the drug. There was no effect of the drug on the rate of recurrence of herpes simplex labialis. We conclude that, despite activity against herpes simplex virus infection in tissue culture and in some laboratory animal models, topical use of the drug is ineffective against recurrent herpes simplex labialis. This may be due to failure of the drug to penetrate the skin.

Arabinonucleotides

Infectious mononucleosis and Epstein-Barr virus. 1. Epidemiology, pathogenesis, immune response.

The evidence linking Epstein-Barr virus causally with infectious mononucleosis is compelling. The disease occurs only in persons who lack antibody to this virus, and serologic findings during the acute illness provide almost certain evidence for its etiologic association. Additional evidence is derived from transformation studies using lymphocytes from persons infected with Epstein-Barr virus. Epidemiologic studies have related the need for close contact with salivary secretions to the low communicability of infectious mononucleosis. The clinically relevant antibodies which develop during the disease, other than heterophile antibody, are those against the viral capsid antigen. Part 2 of this article considers the clinical picture, diagnosis, and management and begins on page 95.

Acute Disease

Infectious mononucleosis and Epstein-Barr virus. 2. Clinical picture, diagnosis, management.

The diagnosis of infectious mononucleosis is confirmed by hematologic, biochemical, and serologic data. An absolute increase in peripheral mononuclear cells to at least 4,500/cu mm is an essential feature. The serologic hallmark of the disease is the presence of heterophile antibody. The age of the patient may affect the clinical presentation and laboratory findings. Therapy is largely supportive, with steroids being used only in the presence of certain severe complications.

Adolescent

Treatment of recurrent herpes simplex labialis with levamisole.

Because deficient immune responses may play a contributory role in recurrent herpes simplex labialis, an immunomodulating agent, levamisole, has been advocated for therapy. Forty-two patients with a high frequency of recurrent herpes simplex labialis were followed for a mean of 7.8 months (range 4 to 12) and treated for 3 days at the onset of each episode of herpes with one of three different doses of levamisole or placebo in a randomized, double-blind study. Statistical analysis revealed that as the dosage increased, so did the frequency of recurrences (P = 0.007). Conversely, duration of the lesions and lesion pain decreased with increasing dosage (P = 0.05 and 0.03). These results indicate that levamisole is not an appropriate drug for the management of recurrent herpes simplex labialis. The paradoxical response to an immunomodulator (increased frequency, decreased severity) provides evidence that altered host responses may contribute to the pathogenesis of the disease.

Adult

Clinical and virologic course of herpes simplex genitalis.

The clinical and virologic course of herpes simplex genitalis in women and men was examined in order to identify measurements useful in antiviral trials. Factors influencing the clinical course included initial disease versus recurrent disease, wet-skin versus dry-skin lesions, female versus male sex. Women with initial genital herpes had higher mean peak lesion virus titers than those with recurrent disease (10(4.5) pfu compared with 10(2.5) pfu) and excreted virus longer (13 to 15 days compared with 6 to 8 days). Men with recurrent lesions had higher mean peak virus titers than women (10(4.0) pfu compared with 10(2.5) pfu), but the duration of virus excretion was shorter (three to four days compared with six to eight days). There was pronounced variation in the clinical and virologic course of recurrent lesions among different patients and even within the same patient. These observations indicate several difficulties that must be considered in conducting careful antiviral trials in patients with herpes simplex genitalis.

Adolescent