Biomedical subjects
Publications and source records attributed to Z Trizna.
We report a case of a 28-year-old human immunodeficiency virus-positive man. He presented with confluent verrucous papules and nodules on his scrotum that were due to herpes simplex infection.
Vohwinkel's syndrome or keratoderma hereditaria mutilans is a diffuse, honeycombed, palmar, and plantar keratosis usually accompanied by pseudoainhum near the distal interphalangeal creases. The mutilating keratoderma associated with sensorineural hearing loss is thought to have an etiologic basis, resting on a mutation of the GJB2 gene, which encodes the gap junction protein connexin26 (Cx26). This specific mutation results in impaired epidermal differentiation as well as inner ear function. We describe a patient with Vohwinkel's syndrome accompanied by high-frequency sensorineural hearing loss whose mother and son were similarly affected.
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Griscelli syndrome (GS) is a rare inherited disease characterized by immunodeficiency and partial albinism. The microscopic findings of the skin and hair are highly suggestive of the disease. The GS locus colocalizes on chromosome 15q21 with the myosin-Va gene (MYO5a), and mutations have been identified in few patients. We describe a 2-month-old Hispanic girl with severe pancytopenia secondary to hemophagocytosis. Even though a mutation at the Griscelli locus had not been identified, her clinical features and outcome were typical of GS. The purpose of this article is to alert physicians to the association between GS and hemophagocytosis. We suggest that GS should be considered in infants with hemophagocytosis because the features of partial albinism can be subtle. The relevant literature is summarized.
A case of a cutaneous tumor caused by atypical mycobacterial infection (Mycobacterium kansasii) in a patient with hairy cell leukemia is reported. Surgical removal of the lesion and subsequent combination antituberculotic treatment led to a cure of this infection. Remission of the leukemia was achieved with interferon alfa.
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Explore the source record for details and available documents.
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Pediatric dermatologic disease that have specific therapies and/or specific prophylactic measures are reviewed. Herpes simplex virus and varicella-zoster virus infections, human papillomavirus infections, and molluscum contagiosum infections are discussed with special emphasis on recent advances of therapy and prophylaxis.
BACKGROUND: Interferon (IFN) alpha and IFN gamma have synergistic in vitro and in vivo effects and have each been used in the treatment of anogenital condylomata acuminata. STUDY GOALS: To compare the efficacy and safety of regional 3 x 10(6) U IFN alpha (Group A), 3 x 10(6) U IFN gamma (Group B), 1.5 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group C), and 3 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group D) in the treatment of recalcitrant anogenital condylomata acuminata. STUDY DESIGN: Six-week courses of regional IFNs were administered in a randomized, double-blind, multicenter study. Response was assessed as change in the total area affected by condylomata. RESULTS: The treatments of Groups A, B, and C were similarly effective (complete response in 13.6%, 18.5%, and 16.0%, respectively). Group D had the lowest rate of complete response (3.8%), but this combination was the most effective when partial and complete responses were combined (73.0%). CONCLUSION: Regional IFN is a moderately effective and safe treatment in patients with recalcitrant anogenital condylomata acuminata. Combinations of IFNs alpha and gamma were not superior to IFN monotherapy.
The role of genetic polymorphisms in modulating susceptibility to carcinogenic exposures has been well explored for tobacco-related neoplasms but not for other neoplasms including gliomas. It is relevant to explore these polymorphisms because certain carcinogenic exposures such as nitrosamines are implicated in the risk of gliomas. We therefore conducted a pilot case-control study to examine the role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with glioma were ascertained as part of an ongoing genetic epidemiological study and were age, gender, and race matched with 90 healthy controls. We used PCR based methodology to determine the prevalence of the above genetic polymorphisms using sequences and PCR conditions directly adapted from studies reported previously. We calculated univariate odds ratios and performed multiple logistic regression to assess interactions between polymorphisms. We found no statistically significant associations between the null genotypes of GSTM1 and GSTT1, and CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2 acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate, and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any single polymorphism is sufficiently predictive of risk, and a panel of markers integrated with epidemiological data should be conducted on a large number of study subjects to fully understand the role of genetic polymorphisms and brain tumor risk.
Mutagen sensitivity, as measured by an in vitro assay, has been described as a risk factor for the development of several tobacco-related epithelial cancers. In vitro studies have indicated that sensitivity to the clastogenic effects of bleomycin on chromosomes was reduced with the introduction of ascorbic acid in a dose-dependent relationship. We report the results of a randomized clinical trial to determine whether increasing levels of oral ascorbic acid could reduce the levels of mutagen sensitivity. For this study, we recruited 228 healthy smokers from 21 centers around the country through the Clinical Community Oncology Program. Each individual was randomly assigned to one of four daily regimens: placebo, 1 g of ascorbic acid, 2 g of ascorbic acid, or 4 g of ascorbic acid. Treatments were administered for 16 weeks. Assessment of mutagen sensitivity was made at baseline and at weeks 4, 16, and 20 (4 weeks after cessation of treatment). Serum ascorbic acid levels were measured at baseline and at weeks 4 and 16. Demographic and risk factor data were collected at baseline and at each-measurement point. Analyses measured the differences of mutagen sensitivity levels across the four treatment arms, as well as investigating the correlation between serum ascorbic acid level and mutagen sensitivity levels in individuals. We did not find a dose-response relationship between ascorbic acid intake and mutagen sensitivity. Additionally, we did not find an association between serum ascorbic acid levels and mutagen sensitivity.
Although tobacco and alcohol use are the major determinants of upper aerodigestive tract carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens. One explanation may be differences in mutagen sensitivity (as measured by the in vitro bleomycin-induced mutagen sensitivity assay) in patients with squamous cell carcinoma of the upper aerodigestive tract. Antioxidant supplementation has also been shown to decrease DNA damage and thus may also inhibit carcinogenesis. In this study, we examined whether smoking, alcohol intake, and dietary antioxidant intake were correlated with mutagen sensitivity. The 612 patients evaluated are part of an ongoing multicenter Phase III trial of 13-cis retinoic acid for the prevention of second primary tumors. We found that patients with pharyngeal cancers were more likely than patients with oral cavity or larynx cancers to be mutagen sensitive. There were no significant differences in the distribution of mutagen sensitivity by sex or alcohol use. Never smokers were significantly more likely (61.1%) to be mutagen sensitive than current smokers (35.6%). Dietary consumption of the micronutrients alpha-carotene, beta-carotene, lutein, lycopene, and vitamin C was not correlated with mutagen sensitivity. Therefore, we suggest that mutagen sensitivity is an independent marker of cancer risk not affected by other known risk factors.
Currently, there are two systems in use for recording chromatid breaks, either spontaneously occurring or induced by mutagens: The International System for Human Cytogenetic Nomenclature (ISCN) and the Chatham Barrs Inn Conference (CBIC) recommendation. The former system considers that a chromatid break is recognized only when the chromatid fragment is displaced to the other side of its sister chromatid, while all others, regardless of the distance between the two broken ends, are called chromatid gaps. The CBIC system recognizes a chromatid break when the intervening achromatic segment is longer than or equal to the diameter of the chromatid, whether the fragment is displaced or not. Minor lesions are called chromatid gaps. We conducted experiments using bleomycin treatment of human cells (primary cultures or lymphoblastoid cell lines) and read the chromatid lesions both ways. We conclude that the CBIC system appears to have more direct biologic relevance than the ISCN system.
In vitro mutagen hypersensitivity, determined with the bleomycin assay, has been found to be an independent risk factor for developing primary upper aerodigestive tract cancers, lung cancers, and second malignant tumors. The average number of chromatid breaks per cell (b/c) is derived from evaluating an arbitrarily set number of metaphases (usually 50) in each sample. The reliability of such an approach is of key importance in large-scale epidemiological studies. Because evaluating metaphases is a time-consuming task, it is desirable to know the minimum number of readings needed to reach an acceptable reliability. Statistical analyses were performed in 160 observations for which b/c values were determined by the same observer scoring 100 consecutive metaphases per sample. The b/c values were between 0.14 and 1.30 (mean, 0.61). The b/c values were separately calculated for the first and second sets of 50 metaphases. There was essentially no difference in the mean b/c values between the first and second 50 readings (difference, -0.002). The correlation between the two sets of readings was 0.72. The SE of the b/c values, based on scoring 50 metaphases, was 0.15. When scoring 100 metaphases, the SE decreased to 0.11. After evaluating the first 50 metaphases, the theoretical gain in reducing the SE was <1% with each additional reading. When 0.8 was used to dichotomize the mean b/c value into bleomycin-resistant or bleomycin-hypersensitive groups, sensitivity and specificity of reading 50 metaphases were above 75% and 95% when compared to 100 readings. A simulated case control study showed that there is a 15% attenuation in estimating the odds ratio with 50 readings. The findings suggest that the conventional method of reading 50 metaphases can yield an acceptable reliability in our setting and may be applied to other cancer epidemiology studies.
BACKGROUND: Several enzymatic systems, including glutathione S-transferases, are involved in the metabolism of environmental agents. The absence of glutathione S-transferases mu (GSTM1) and theta (GSTT1) results in decreased detoxification of carcinogens, for example, chemicals in cigarette smoke. These metabolic deficiencies may predispose individuals to the development of smoking-related tumors, such as cancers of the lung, head and neck, and bladder. METHODS: The glutathione S-transferase genotypes of 186 previously untreated patients with squamous cell carcinoma of the head and neck and 42 healthy controls were determined with polymerase chain reaction (PCR) methodologies. Lymphocytes separated from heparinized peripheral blood or whole blood extracts served as sources of genomic DNA. The presence or absence of the gene-specific PCR products revealed the positive or negative genotypes, respectively. RESULTS: The absence of the GSTM1 genotype conferred an odds ratio of 2.37, and the 95% confidence interval (CI) was 1.20 to 4.67. The absence of the GSTT1 gene conferred an odds ratio of 1.47 (CI 0.71 to 3.02). In the population of 42 patients and their matched 42 controls, the absence of the GSTM1 and GSTT1 genotypes conferred odds ratios of 3.10 (CI 1.24 to 7.75) and 2.18 (CI 0.91 to 5.23), respectively. CONCLUSIONS: Despite the small study size, our preliminary data suggest that genetically determined factors of carcinogen metabolism may be associated with increased risk for head and neck cancer.