Thirty cases of bronchial asthma associated with exposure to pet hamsters.

BACKGROUND: The identification, isolation, and elimination of allergen(s) causing bronchial asthma are the most efficient form of treatment. The pet industry has diversified recently, increasing the risk of exposure of pet owners to many unknown antigens. We clinically studied the characteristics of asthma associated with exposure to pet hamsters. METHODS: The study group comprised 30 adults in whom the onset, recurrence, or exacerbation of asthma was triggered by contact with pet hamsters. Clinical characteristics such as sex, age, period required for symptom onset, species of hamster, treatment and disease course, smoking status, and hamster-specific IgE antibodies in serum were studied. RESULTS: The male: female ratio of the study group was 1:1.3, and mean age was 37.7 years. Patients with no previous history of asthma initially presented with cough, progressing to episodes of asthma. Asthmatic symptoms were associated with hamster contact and ranged in severity from mild to severe. Three patients required hospital admission for treatment. The mean period from the start of hamster exposure to the onset of asthmatic episodes was 15.7 months. Dwarf hamsters were responsible for most cases. The CAP-RAST score for hamster-specific IgE antibodies was 1 to 4 in 22 patients and 0 in 8 patients. Eight patients with a score of 1 or higher for hamster-specific IgE antibodies had a CAP-RAST score of 0 for mite antigen. In these patients, terminating hamster contact resulted in a rapid improvement in symptoms, with no need for further treatment. Twenty-three of the 30 subjects (76.7%) were smokers. CONCLUSION: Exposure to pet hamsters is an important risk factor for the onset, recurrence, or exacerbation of asthma. Smoking may also increase the risk of asthmatic symptoms in patients exposed to hamsters.

Clinical evaluation of response to long-term treatment with Pranlukast in patients with bronchial asthma.

BACKGROUND: Short-term treatment with pranlukast, a leukotriene receptor antagonist, has shown to be effective for the management of asthma. The effectiveness and safety of long-term treatment with pranlukast remains to be established. OBJECTIVES: The aim of this study was to determine the effects of pranlukast on morning peak expiratory flow rates (PEFRs), the diurnal variation of these values, and disease severity. METHODS: Fifteen men with bronchial asthma were studied for 5 years. During the first year, the subjects were treated with a bronchodilator; some also received inhaled and oral corticosteroids. During the next 4 years, the subjects received pranlukast in addition. RESULTS: Mean PEFR increased after the start of treatment with pranlukast. The increase in PEFR occurred later in subjects with more severe disease. Diurnal variation of PEFR was unchanged, but subsequently decreased. The condition of all subjects improved, but the greatest improvement was obtained in patients with mild to moderate asthma. CONCLUSIONS: Long-term treatment with pranlukast is effective for the management of bronchial asthma, particularly in patients with mild to moderate disease. Our results suggest that the effectiveness of antiasthmatic drugs should be evaluated over a period of years, rather than on a short-term basis.

Occupational cancer genetics: infrequent ras oncogenes point mutations in lung cancer samples from chromate workers.

BACKGROUND: Chromium carcinogenicity and mutagenicity are no longer disputed. However, although chromium has various genetic effects that induce cancer, its mechanism of inducing lung cancer in humans is still not fully understood. p53, a tumor suppressor gene, was found to be infrequently mutated in samples of lung cancer in workers with long occupational exposure to chromium, suggesting other cancer-related genes to be targeted in such tumors. METHODS: To assess the contribution of the ras oncogenes in the pathogenesis of chromate-related lung cancer, we studied point mutations at the critical positions of codons 12, 13, and 61 of the Ha-ras and Ki-ras oncogenes in 38 lung cancer samples derived from Japanese patients who worked in the chromate industry for long periods. We used both radioactive isotope and non-radioisotope PCR-SSCP techniques. RESULTS: The results of this study demonstrated that activation of ras genes due to point mutations in chromate-related lung cancer is a rare event. CONCLUSIONS: Ras oncogenes activated by point mutations do not have a major role in the process of tumorigenesis of chromate-related lung cancer.

Familial isolated primary hyperparathyroidism with parathyroid carcinomas: clinical and molecular features.

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is a rare hereditary disorder. We present four patients from a single family with FIHP, and genetic analysis of their parathyroid adenomas and parathyroid carcinoma. DESIGN: DNA was extracted from tumours resected at surgery. Tumours were examined for loss of heterozygosity (LOH) with microsatellite polymorphic markers. PATIENTS: The 27-year-old proband (Patient 1) died of parathyroid carcinoma with metastases to the lungs and chest wall. Sixteen years later, his 34-year-old sister (Patient 2) presented with a neck tumour and primary hyperparathyroidism. Family screening revealed parathyroid tumours in his 36-year-old sister (Patient 3) and 29-year-old cousin (Patient 4). Histological examination of resected tumours showed parathyroid carcinoma and adenoma in Patient 2, a parathyroid adenoma in Patient 3, and an atypical parathyroid adenoma in Patient 4. Autopsy of the proband ruled out multiple endocrine neoplasia (MEN) type 1, and the three patients who underwent parathyroidectomy did not exhibit any abnormalities in the pancreas or the pituitary gland. RESULTS: Analysis of tumour DNA from one parathyroid carcinoma (Patient 2), the atypical parathyroid adenoma (Patient 4), and two parathyroid adenomas (Patients 2 and 3) showed limited LOH on chromosomes 13q12.3-q32 in an adenoma of Patient 2 and 9p21-p22 and 13q12.3-q32 in an adenoma of Patient 3. CONCLUSION: These results suggest the possible contribution of tumour suppressor genes including the retinoblastoma gene and the hereditary breast cancer susceptibility gene (BRCA2) on 13q to parathyroid tumours in this family.

Mutations of the p53 gene in human lung cancer from chromate-exposed workers.

We examined p53 mutations in 20 cancer samples from 19 chromate workers with lung cancer by Polymerase chain reaction-Single strand conformation polymorphism analysis and direct sequencing. Six missense mutations were identified in 4 (20%) of the 20 chromate lung cancer samples. Fewer mutations were found in the patients with lung cancers who had been exposed to chromate than in those who had not. However, the pattern of p53 mutations in lung cancer patients exposed to chromate differed from that of common lung cancers in 3 respects. There were no apparent G to T transversions, which are common base changes in lung cancers. Half of the mutational sites (3/ 6) had changes of AT base-pairs, and 2 of 4 mutational tumor samples had double missense mutations. Our results suggested that chromate exposure may induce point mutation of the p53 gene.

Atypical glomus tumor in the mediastinum: a case report with immunohistochemical and ultrastructural studies.

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small "glomoid" cells arranged in organoid and hemangiopericytomalike patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.

Point mutations of ras and Gs alpha subunit genes in thyroid tumors.

We studied 43 thyroid tumors including 5 adenomatous goiters, 7 follicular adenomas, 22 papillary carcinomas, and 9 medullary carcinomas with regard to the presence of point mutations in the genes of Gs alpha subunit (Gs alpha), Gi2 alpha subunit (Gi2 alpha), H-ras, K-ras, and N-ras by a polymerase chain reaction-direct sequencing method. An adenomatous goiter and a follicular adenoma showed double mutations at codon 227 and 231, and 4 papillary carcinomas showed mutation at codon 231 of the Gs alpha gene. An adenomatous goiter, a follicular adenoma, and a papillary carcinoma showed a missense mutation in codon 13 of the K-ras gene. There were no such missense mutations of these G-protein or ras genes in medullary carcinomas. These data indicate that the genetic events involved in the oncogenesis of parafollicular C-cells are different from those of thyroid follicular cells, in which missense mutations of Gs alpha and ras genes seem to play important roles in tumorigenesis.

[Prevalence of hepatitis C virus infection among chronic hemodialysis patients].

A high prevalence of HCV (hepatitis C virus) antibodies have been reported in chronic hemodialysis (HD) patients. In this study, sera from 584 hemodialysis patients (378 males and 206 females) were examined for the 2nd generation HCV antibody by enzyme immunoassay (EIA) and for HCV-RNA by the reverse transcription-polymerase chain reaction (RT-PCR) method. The positive rates of HCV antibody and HCV-RNA were 22.0% (129/584) and 12.3% (72/584), respectively. In HD patients, HCV infections were considered to be caused by the contact with contaminated blood samples, the main cause of which is blood transfusions. However, a high prevalence of HCV markers even in HD patients without a history of blood transfusions indicates that there may be other ways of HCV transmission other than blood transfusions. While HCV-RNA was detected in about 50% of the HD patients with the HCV antibody, this rate was lower than that found in the general population with the HCV antibody. And the abnormality rate of serum alanine aminotransferase (ALT) in HD patients with HCV-RNA was lower than that of the general population with HCV-RNA. On the other hand, the amounts of HCV-RNA which were semiquantified by RT-PCR using the end-point dilution method showed a correlation with serum ALT levels in both HD patients and chronic HCV infections. Moreover, HCV-RNA titers measured immediately after hemodialysis showed a marked decrease compared with those measured before hemodialysis. These results suggest that HCV was eliminated to certain extent with hemodialysis and that it might also be the cause of the low abnormality rate of serum ALT in HD patients with HCV-RNA.

Immunohistochemical study of estrogen receptor and estradiol on papillary thyroid carcinoma in young patients.

We have immunohistochemically examined estrogen receptors (ER) and estradiol (E2) on papillary thyroid carcinoma in young females under the age of 25 years. The 10 young females in this study were compared with 64 females 30 years of age or older who underwent surgery for treatment of papillary thyroid carcinoma. We did not find any significant difference in the incidences of positive staining for E2 between the two groups. Of the specimens obtained from the young patients, 80% (8/10) showed positive staining for ER; this was significantly higher (P < 0.01) than that observed in patients 30 years of age or older (25%). We think that, especially in youth, estrogen may play an important role as a promoting factor. This indication needs further study.

Loss of heterozygosity on chromosome 1p in thyroid adenoma and medullary carcinoma, but not in papillary carcinoma.

We analyzed 53 loci on 21 chromosomes other than chromosome 4 to detect possible loss of heterozygosity in 31 thyroid tumors using polymorphic DNA markers that detect allelic deletions at specific chromosomal loci. Loss of heterozygosity on chromosomes 1, 7 and 12 was detected in one follicular thyroid adenoma, and on chromosome 1 in two medullary thyroid carcinomas. However, no loss of heterozygosity was detected at any of the loci examined in papillary thyroid carcinomas. These results suggest that chromosomal loss detected in thyroid adenoma is one of the signals for risk of premalignant transformation, and that inactivation of unknown genes on chromosome 1p contributes to tumorigenesis of medullary thyroid carcinoma. Some genetic changes other than chromosomal losses may participate in the tumorigenesis of papillary thyroid carcinoma.

Treatment of chronic non-A, non-B hepatitis with interferon.

The efficacy of interferon therapy (IFN) was investigated in 46 patients with chronic non-A, non-B (NANB) hepatitis, of would 40 (87.0%) were positive for anti-HCV antibody (Ab) (C-100-3). Three kinds of IFN were used; human lymphoblastoid interferon (HLBI), interferon alpha-2b and interferon beta. Total doses of IFN ranged from 1 million units (MU) to 10 MU and treatment duration ranged from 2 weeks to 144 weeks. Of 46 patients 34 (73.9%) responded to IFN. Nine patients have maintained normal ALT levels and 5 patients have maintained near-normal ALT levels for more than 6 months after cessation of IFN treatment. In these cases the titers of anti-HCV Ab had decreased significantly at the end of IFN therapy and 6 months after IFN therapy respectively. The mean age was young and the mean disease duration was short in effective cases. As for doses and treatment duration of IFN, low doses of IFN requires long treatment duration to acquire continuous efficacy and high doses of IFN requires rather short treatment durations. Therefore, early IFN treatment, higher doses and longer periods of IFN treatment may improve the response rate of patients with chronic NANB hepatitis.

Lung cancer in chromate workers: high-risk group for multiple lung cancer.

We diagnosed eight (8.9%) lung cancer patients in 90 workers exposed to chromate compounds. The duration of exposure ranged from 8 to 31 years, with a mean value of 18 +/- 8 years. The histological classification was squamous-cell carcinoma in seven patients and adenocarcinoma in one patient. The site of origin of the primary tumors was located peripherally in two (25%) and centrally in six (75%). All but one of these patients underwent surgery. In three (37.5%) of these patients, lung cancer foci were detected during the postoperative follow-up by sputum cytology and bronchoscopy. Two of these three patients had multicentric cancer foci: double primary early squamous-cell carcinoma in one and early squamous-cell carcinoma + small-cell lung cancer in the other. In a high-risk group such as chromate workers, we should emphasize early detection of lung cancer by serial sputum cytology, chest x-rays, and bronchoscopy. Lung cancer patients with chromate exposure should be treated with due regard to the possibility of synchronous or metachronous cancer.