Malignant mesothelioma from neighborhood exposure to anthophyllite asbestos

BACKGROUND: Anthophyllite asbestos has been reported to cause asbestosis, lung cancer, mesothelioma, and pleural plaques in occupationally exposed workers. Anthophyllite has also been associated with pleural plaques in Finland and Japan among those who live near mines and mills and have neighborhood or environmental exposure. METHODS: We evaluated a 38-year-old patient with pleural mesothelioma who lived, attended school, and delivered newspapers near a manufacturing facility that used exclusively anthophyllite asbestos fiber from ages 8-17 years. He had no work exposure to asbestos. RESULTS: The pleural mesothelioma was an epithelial type with tubulopapillary structures and was treated with an extrapleural pneumonectomy followed by radiation therapy. The malignant cells were positive by immunohistochemistry for cytokeratin but negative for carcinoembryonic antigen, S100, B72.3, and leu M1 antigen. Anthophyllite fibers were > 5 microm in length in lung tissue compared to 3 microm from a general population study. CONCLUSIONS: Anthophyllite asbestos has been associated with neighborhood environmental exposure and pleural plaques; we now report a neighborhood exposure and pleural mesothelioma.     

Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy

Purpose: The purpose of this study was to examine the relationship between overall survival and prognostic factors in carcinoma of the cervix treated with radiation therapy. A clinicopathologic study was performed on 24 patients.

Methods and Materials: Formalin-fixed, paraffin-embedded tumor biopsies were stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53. Clinical factors such as stage, grade, tumor size, pre- and post-treatment hemoglobin level, and radiotherapy dose were also evaluated.

Results: Median follow-up was 75 months for living patients. The only immunohistochemical or clinical factor that was associated with improved survival was decreased COX-2 distribution staining. High COX-2 distribution staining was associated with decreased overall survival (p = 0.021) and decreased disease-free survival (p = 0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall survival rates for tumors with low vs. high COX-2 distribution values were 75% and 35%, respectively. COX-2 staining intensity was found to correlate positively with tumor size (p = 0.022).

Conclusion: These findings indicate that increased expression of COX-2 portends a diminished survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early-response gene involved in angiogenesis and inducible by different stimuli, these data may indicate opportunity to intervene with specific inhibitors of COX-2 in carcinoma of the cervix.     

Methods for animal satellite cell culture under a variety of conditions

Primary and clonal culture systems have been devised and refined for animal-derived satellite cells. Satellite cell (SC) culture development includes efficient cell isolation techniques, establishment of effective plating and growth conditions, formulation of media requirements and thorough evaluation of experimental limitations. As the field of muscle cell culture has expanded, the number of animal species from which satellite cells have been isolated has increased. The focus of this paper is to compare and contrast SC culture conditions presently used by a variety of researchers and to introduce a new source of SC from wapiti (elk).     

The serum carnitine status of cancer patients

Carnitine is necessary for the translocation of fatty acids into the mitochondria, and the relative concentration of carnitine and acylcarnitine in the serum are known to reflect metabolic states. A survey of serum carnitine concentrations was made in 54 cancer and 81 noncancer patients for the purpose of determining the carnitine profile. The total carnitine, nonesterified carnitine, and acid-insoluble acylcarnitine concentrations of cancer patients were similar to noncancer patients and within the normal range; however, the acid-soluble acylcarnitine concentration was significantly lower in cancer patients than in controls (6.7 vs 11.5 nmol/ml). When percentages and ratios were calculated for the relative proportions of acylcarnitines, large variations were found to occur among cancer types. The acylcarnitine ratio (the sum of acid-soluble and acid-insoluble acylcarnitine divided by nonesterified carnitine) ranged from 0.17 in leukemia to 0.30 in breast cancer cases. Since the acylcarnitine concentration and ratio are reflective of the metabolic state, the depressed acylcarnitine ratio in cancer patients may be due to decreased production, increased utilization, or increased excretion of acid-soluble acylcarnitine. Elevated concentrations of nonesterified carnitine and total carnitine were observed in two patients, and some of the lowest acylcarnitine concentrations and ratios were observed in advanced cancer cases. The therapeutic regimen and/or the neoplastic process itself may be responsible for the observed differences in the serum carnitine profile.     

Delayed hepatic CT scanning: increased confidence and improved detection of hepatic metastases

Fifty oncologic patients with suspected hepatic metastases were prospectively evaluated by dynamic sequential hepatic computed tomography (DSHCT) and by delayed iodine hepatic computed tomography (DICT) scanning. DICT scanning was performed 4-6 hours following administration of 60 g of intravenous iodine. Both techniques were evaluated for lesion definition relative to the adjacent hepatic parenchyma and for numbers of metastases detected. Metastases were detected by both techniques in 26 patients. Fifteen patients (58%) had lesions better defined by DICT. DICT scanning detected more metastases in seven of these 15 patients. In eight patients (31%), there was no difference between the two techniques in numbers of masses detected or lesion definition. In three cases (11%), metastases were more confidently identified on the initial or DSHCT scan. DICT scanning, as described, is useful in defining and detecting hepatic metastases, especially where there is questionable hepatic involvement or better quantification of size is necessary.     

Cervical cancer: women aged 35 and younger compared to women aged 36 and older

One hundred fifty-three patients with invasive cervical cancer were evaluated and treated at one of the two teaching hospitals of the Intergrated Ob-Gyn Residency Program of Wright State University, Dayton, Ohio, from 1 July 1983 to 30 June 1989. Sixteen patients with recurrent cervical cancer who initially had received their treatment elsewhere were excluded. Forty-one of the 137 newly diagnosed patients with cervical cancer were aged 35 years or less. This review was undertaken because of frequent reports of the increasing incidence of cervical cancer in women aged 35 and under. Some reports also reveal a worse prognosis for the younger age group. This investigation provided the opportunity to evaluate cervical cancer patients aged 35 and under and compare the results to the evaluations of women aged 36 and over. Evaluation of age, stage, presenting symptoms, number of positive lymph nodes, pap smear history, pregnancy within 1 year of diagnosis, treatment, and survival was carried out in patients aged 35 years and less and compared to their older counterparts aged 36 and over with cervical cancer.     

Standardized visual evoked potentials for telematic electrodiagnosis from five laboratories in three European countries.

The pattern-reversal visual evoked potential (PR VEP) is an electrodiagnostic test which uses an alternating checkerboard pattern as the visual stimulus. To validate the performance of an automated testing system, the equipment was installed in five locations in three countries (the UK, Greece and Cyprus). PR VEPs require accurate control of stimulus size, luminance, contrast, timing, multichannel recordings and various modes of signal processing. Recordings were obtained from 70 subjects, 18-34 years old (seven male and seven female in each laboratory). The data were transmitted by telephone line to the central station in Bristol. Only in Bristol were the operators experienced. There were no significant differences between laboratories in latency or amplitude of the N70 and P100 components. There were no significant differences between eyes. There were significant differences between the sexes but this was related to head size. Decreased square size used in stimulation produced an increased latency in both components. The amplitude of the N70 component increased while that of the P100 decreased with reduced square size. The results confirmed the ability of the automated system to produce standardized PR VEP recordings comparable to those obtainable in advanced laboratories. The system performed well in different locations using inexperienced operators. The system is suitable for multicentre research studies and telemedicine.     

Medical conditions underlying retinal vein occlusion in patients with glaucoma or ocular hypertension.

Forty-three patients with glaucoma and 24 patients with ocular hypertension presenting with a retinal vein occlusion were medically assessed. The prevalence of systemic hypertension was 60.5% in those with glaucoma and 66.6% with ocular hypertension. The prevalence of hyperlipidaemia was 38.1% in those with glaucoma and 37.5% in those with ocular hypertension. These findings were compared with those from a carefully age-sex matched group of patients presenting with a retinal vein occlusion without evidence of glaucoma or ocular hypertension. There were no statistical differences between any of the groups (52.2% had systemic hypertension and 28.8% had hyperlipidaemia). There was also a strikingly high prevalence of systemic hypertension (89%) and hyperlipidaemia (55.5%) in nine of the patients who had evidence of a recurrent retinal vein occlusion associated with glaucoma, and these prevalence rates were strikingly similar to the rates in patients with recurrence but without glaucoma. The data suggest that glaucoma or ocular hypertension has a less prominent aetiological role in the development of a retinal vein occlusion than underlying medical causes and that full medical assessment is worthwhile.     

Imparied glutathione biosynthesis in cultured human ataxia-telangiectasia cells

Cell lines established from donors with the inherited disorder ataxia-telangiectasia (A-T) exhibit exceptional sensitivity to ionizing radiation and chemicals known to produce increased levels of intracellular H2O2, suggesting a deficiency in glutathione-dependent detoxication reactions. Glutathione (GSH) biosynthesis in fibroblast and lymphoblast cultures derived from individuals known to be clinically unaffected, homozygous, or heterozygous for A-T was assessed. Following GSH depletion by diethylmaleate, fibroblasts (GM 3492) from a clinically unaffected individual resynthesized GSH at a rate approximately twice that observed in fibroblasts from known heterozygotes (GM 3488 and GM 3489). Unrelated A-T homozygote fibroblast lines GM 3487B and GM 5823 resynthesized GSH only very slowly. GM 3492 cells repleted intracellular GSH by 6 h after depletion, the heterozygote lines by 18 h. The A-T homozygotes replaced only 30% of the intracellular GSH pool by 24 h. A lymphoblast cell line from the A-T homozygote (GM 3189) also exhibited slow resynthesis after depletion. However, if these cells were permeabilized by treatment with digitonin, GSH synthesis proceeded at a rate exceeding synthesis in permeabilized or untreated normal lymphoblasts (GM 3323). The first enzyme in GSH synthesis, gamma-glutamylcysteine synthetase, was found to be elevated about 2.7-fold in A-T homozygote fibroblasts, suggesting that a substrate for GSH synthesis may be rate limiting. A-T homozygote lymphoblasts contained about 2-fold more gamma-cystathionase activity over other cell lines tested suggesting increased flux through the transsulfuration pathway for cysteine production in response to reduced cysteine supply. Transport of cysteine and cystine was found to be 8- and 5-fold slower in A-T homozygotes that did not affect fibroblasts while glutamate and methionine transport Vmax did not differ among the cell lines tested. These experiments demonstrate that cells from A-T homozygotes are deficient in cysteine transport, thus limiting GSH resynthesis after a depleting challenge such as radiation or GSH-depleting xenobiotic compounds.