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The acute toxic effects of hydrogen sulfide have been known for decades. However, studies investigating the adverse health effects from chronic, low-level exposure to this chemical are limited. In this study, the authors compared symptoms of adverse health effects, reported by residents of two communities exposed mainly to chronic, low-levels of industrial sources of hydrogen sulfide, to health effects reported by residents in three reference communities in which there were no known industrial sources of hydrogen sulfide. Trained interviewers used a specially created, menu-driven computer questionnaire to conduct a multi-symptom health survey. The data-collection process and questions were essentially the same in the reference and exposed communities. The two exposed communities responded very similarly to questions about the major categories. When the authors compared responses of the exposed communities with those of the reference communities, 9 of the 12 symptom categories had iterated odds ratios greater than 3.0. The symptoms related to the central nervous system had the highest iterated odds ratio (i.e., 12.7; 95% confidence interval = 7.59, 22.09), followed by the respiratory category (odds ratio = 11.92; 95% confidence interval = 6.03, 25.72), and the blood category (odds ratio = 8.07; 95% confidence interval = 3.64, 21.18). Within the broader health categories, individual symptoms were also elevated significantly. This study, like all community-based studies, had several inherent limitations. Limitations, and the procedures the authors used to minimize their effects on the study outcomes, are discussed. The results of this study emphasize the need for further studies on the adverse health effects related to long-term, chronic exposure to hydrogen sulfide.

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Stevens-Johnson syndrome (SJS) is an acute mucocutaneous disorder that can be associated with considerable morbidity. Several previous reports, all involving either adults with acquired immunodeficiency syndrome or children, suggest that intravenous immunoglobulin may be an effective treatment for SJS. We report a case of SJS in an immunocompetent adult whose condition improved dramatically after therapy with intravenous immunoglobulin.

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Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.

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Using an intramolecular [2 + 2] photocyclization, 2,4-methanopyrrolidine-2,4-dicarboxylate was prepared as a conformationally locked analogue of glutamate. This compound, in combination with two other pyrrolidine dicarboxylates, has been used to define the structural elements that differentiate substrate and nonsubstrate inhibitors of a high-affinity, sodium-dependent glutamate transporter.

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Cement kilns are major sources of toxic air emissions. Regulations based on demonstrated concentrations of specific chemicals, and risk assessments with inherent limitations and uncertainties, are the current methods of preventing exposure to 'unsafe' emission levels. Monitoring data are frequently incomplete. These limitations mandate that residents residing near cement kilns be evaluated for adverse health effects. This study reports findings from a symptom survey conducted in Midlothian, Texas, which adds to the limited but growing body of knowledge showing that persons living near cement kilns are experiencing increased respiratory effects. This cross-sectional study uses randomized sampling and an extensive health questionnaire, covering 12 physiological systems, to determine differences in reported health symptoms between the study community (Midlothian, Texas, n = 58) and the reference community (Waxahachie, Texas, n = 54). Findings indicate significant elevations in reported respiratory symptoms in the study community (p-value 0.002). Although the comparatively small sample size is a limitation, the fact that only 'respiratory effects' were highly significant supports the efficacy of this investigation. Respiratory effects would be the major anticipated outcome from the known exposures under investigation. This specificity of response (i.e., elevation in respiratory symptoms only), indicates that 'response bias' was not a significant factor in this study.

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Inter-arytenoid glottic bar is a rare complication of prolonged endotracheal intubation. We present two such cases and their treatment. The aetiology of this complication is multifactorial and involves local factors--local trauma, movement of the endotracheal tube within the larynx, infection, and anatomical influences--together with systemic factors such as in our two cases. The relative importance of these factors is discussed. A comment is also made on the use of a pre-operative topogram and the importance of an ENT assessment in patients with airway problems following prolonged intubation.

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We describe four patients with a benign hepatic malformation most consistent with the rarely described anomaly known as corset liver. Three of these patients were extensively evaluated to rule out a malignancy because of an abdominal mass. These patients illustrate several features which may help in making the diagnosis and avoiding unnecessary surgery.

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Streptozotocin was administered at a dose of 500 mg/m2/day by continuous infusion for 120 hours to 14 patients with advanced malignant melanoma. No responses were observed in this group of patients and the median survival for the entire group was 2 months. At the dose and schedule delivered, streptozotocin is inactive against malignant melanoma.

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A three-drug regimen composed of adriamycin, 50 mg/m2 and cyclophosphamide, 500 mg/m2 administered on day 1; and VP-16-213, 50 mg/m2 days 1-5, with courses repeated at 3-week intervals, was studied in 24 consecutive patients with extensive-stage small cell lung cancer (SCLC). Twelve of 33 patients (36%) evaluable for toxicity developed life-threatening marrow suppression and 12% died of septicemia following the first course of treatment. Eleven of 24 patients (46%) with extensive disease achieved an objective response and only one was classified as a complete response. Survival was related to performance status and metastatic site but was not influenced by tumor response. The present study is distinctive from that of previous reports of the same or similar three-drug regimen in that the response rate is lower and toxicity is substantial. Nonetheless, survival as measured by median duration (7.9 months) and proportion alive at 1 year (35%) is comparable to that of previous reports.

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Thirteen patients with inflammatory bowel disease and a documented allergy to sulfasalazine, manifested by skin rash with or without fever, were enrolled in a sulfasalazine-desensitization protocol. Twelve patients were successfully desensitized by using two concentrations of a liquid suspension of sulfasalazine. Four of thirteen patients developed a rash during the protocol. Although one patient refused further attempts at desensitization, the remainder completed the regimen successfully, despite recurrence of the rash on two occasions in one patient. No predilection to either fast or slow acetylator phenotype was found. This simple and convenient tolerance induction regimen may be used safely to desensitize most patients with sulfasalazine allergy manifested by skin rash with or without fever, despite recurrence of the rash during tolerance induction. Patients with serious reactions to sulfasalazine, such as agranulocytosis, toxic epidermal necrolysis, or fibrosing alveolitis, are not candidates for desensitization.

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One hundred twenty-four patients with metastatic malignancy were treated with four different single agent infusion programs by constant intravenous infusion for 30 or more days. Drug was administered via a tunneled subclavian line by a battery-driven peristaltic pump (Cormed model ML6) on an ambulatory basis. This schedule allowed for increased cumulative drug dose for 5-Fu, decreased tolerated dose for vinblastine, and comparable doses for adriamycin and mitomycin-C relative to that delivered with the standard intermittent bolus schedule. Therapeutic effects were observed for three of four drugs studied: 5-Fu 13/31 colorectal cancer; adriamycin 7/29; and vinblastine 4/12, including 2/4 melanoma. Adverse effects were significantly reduced, particularly with regard to gastrointestinal toxicity, but also in adriamycin-associated cardiac effects and hair loss. Phase III comparative trials of intermittent bolus therapy with protracted infusion therapy are in progress for 5-Fu in advanced colorectal cancer and for adriamycin in specific tumors. Ambulatory pump infusion (API) chemotherapy is technically feasible and has improved patient tolerance to chemotherapy while demonstrating similar, if not comparable, antitumor effects.

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The increasing serum concentrations of various hormones (PTH, PRL, estrogens, and human placental lactogen) are hypothesized to regulate 1,25-dihydroxyvitamin D [1,25(OH)2D] and possibly 24,25-dihydroxyvitamin D [24,25(OH)2D] production during pregnancy. We examined the correlation between the serum levels of 1,25(OH)2D and the pregnancy-related hormones in 25 normal pregnant women, followed throughout gestation and postpartum. Maternal serum levels of 1,25(OH)2D were high during the first trimester (mean +/- SE, 74 +/- 8 pg/ml), remained high until the time of delivery (95 +/- 14 pg/ml), and then fell to almost normal levels (50 +/- 9 pg/ml) on the third postpartum day. The serum levels of 1,25(OH)2D do not correlate with the serum levels of any of the aforementioned hormones. The increase in serum 1,25(OH)2D in pregnancy has been postulated to be related to the stressed calcium homeostatic mechanisms known to occur in the mother. In twin pregnancy, this maternal calcium homeostatic mechanism(s) conceivably may be stressed to a greater extent. However, serum 1,25(OH)2D levels, measured in 27 women with a twin pregnancy in both the second and third trimesters as well as at delivery, did not differ from the levels observed in women with a singleton pregnancy. There were no significant changes in the serum levels of 24,24(OH)2D or 25-hydroxyvitamin D as pregnancy progressed. However, serum 24,25(OH)2D correlated significantly with both serum 1,25(OH)2D (r - 0.51; p less than 0.001, n = 83) and serum 25-hydroxyvitamin D (r = 0.37; P less than 0.001, n = 94). In conclusion, serum levels of 1,25(OH)2D rise early in the first trimester of pregnancy, fall acutely to normal levels soon after delivery, and are similar in singleton and twin pregnancies. The changes in the serum levels of 1,25(OH)2D do not relate to the changes in the serum levels of any of the pregnancy-related hormones.

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Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.

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