Evaluation and assessment of the efficacy of an abatement strategy in a former lead smelter community, Boolaroo, Australia.

This study examines the recent soil Lead Abatement Strategy (LAS) in Boolaroo, New South Wales, Australia, that was designed to "achieve a reduction in human exposure to lead dust contamination in surface soils". The abatement programme addressed legacy contamination of residential areas following closure of lead smelting operations in 2003 at the Pasminco Cockle Creek Smelter (PCCS). The principal objective of the LAS was to "cap and cover" lead-contaminated soils within the urban environment surrounding the PCCS. Soil lead concentrations of 2500-5000 mg/kg were scheduled for removal and replacement, while concentrations between 1500 and 2500 mg/kg were replaced only under limited circumstances. To date, there has been no industry, government or independent assessment of the clean-up programme that involved >2000 homes in the township of Boolaroo. Thus, by measuring post-abatement soil lead concentrations in Boolaroo, this study addresses this knowledge gap and evaluates the effectiveness of the LAS for reducing the potential for lead exposure. Soil lead concentrations above the Australian residential soil health investigation level value for residential soils (300 mg/kg) were identified at all but one of the residential properties examined (n = 19). Vacuum dust samples (n = 17) from the same homes had a mean lead concentration of 495 mg/kg (median 380 mg/kg). Bio-accessibility testing revealed that lead in household vacuum dust was readily accessible (% bio-accessible) (mean = 92 %, median = 90 %), demonstrating that the risk of exposure via this pathway remains. Assessment of a limited number of properties (n = 8) where pre-abatement soil lead levels were available for comparison showed they were not statistically different to post-abatement. Although the LAS did not include treatment of non-residential properties, sampling of community areas including public sports fields, playgrounds and schools (n = 32) was undertaken to determine the contamination legacy in these areas. Elevated mean soil lead concentrations were found across public lands: sports fields = 5130 mg/kg (median = 1275 mg/kg), playgrounds and schools = 812 mg/kg (median = 920 mg/kg) and open space = 778 mg/kg (median = 620 mg/kg). Overall, the study results show that the LAS programme that was dominated by a "cap and cover" approach to address widespread lead contamination was inadequate for mitigating current and future risk of lead exposures.

A phase I clinical and pharmacokinetic study of Brequinar sodium, DUP 785 (NSC 368390), using a weekly and a biweekly schedule.

Brequinar, DUP 785, is a substituted 4-quinoline carboxylic acid derivative which in preclinical studies has shown broad antitumor activity. It is a novel antimetabolite blocking pyrimidine nucleotide synthesis. In a clinical phase I study, 83 patients were treated on a weekly schedule and 18 patients on a biweekly schedule. The drug was given intravenously as a short infusion. Three patients were entered on each dose level from a starting dose of 6 mg/m2 up to 2600 mg/m2 weekly. The dose ranges on a biweekly schedule were 500-850 mg/m2. There was no dose escalation in individual patients. Pharmacokinetic studies were performed in 19 patients on a weekly schedule and in two patients on a biweekly schedule. A biphasic decay in plasma was observed with a median half life of 10 h (5.1-23.4). The main dose-limiting toxicity was thrombocytopenia. Of non-hematologic side-effects, stomatitis/mucositis occurred frequently. Skin eruptions occurred rarely, but were a major problem when found. All side-effects were fully reversible; there were no signs of cumulative toxicity. Antitumor activity was observed in one patient with a lung metastasis from a bladder cancer and in a patient with an unknown primary tumor. The recommended doses for phase II trials with DUP 785 are: 1500-2000 mg/m2 on a weekly schedule and 500-750 mg/m2 on a biweekly schedule dependent on status before treatment.

Effect of change in particle number on pulmonary clearance of aerosolized 99mTc-DTPA.

Pulmonary clearance (PCl) of inhaled aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA) across the alveolocapillary membrane is diffusion limited. Therefore, if the mixing of the 99mTc-DTPA in the aqueous hypophase underlying surfactant is slow or incomplete or if there were no hypophase, an increase in the alveolar surface area occupied by 99mTc-DTPA particles would increase the absorption rate. The aim of this study was to examine whether there is an effect on PCl of changing the number of inhaled particles. The change in particle number was accomplished by a setup of four parallel jet nebulizers feeding a central delivery chamber of 400 cm3. We performed two kinds of experiments in eight healthy nonsmokers between 28 and 52 yr of age. In the first experiment, 99mTc-DTPA in saline was nebulized in one nebulizer, while saline was nebulized in the other three. In the second experiment the number of inhaled particles containing 99mTc-DTPA was increased by a factor of four by nebulizing 99mTc-DTPA in saline in all four nebulizers simultaneously. Increasing the number of inhaled 99mTc-DTPA particles caused an increase in PCl of 24.2% (P less than 0.01). We conclude that there is a slight but significant effect of changing the number of DTPA particles on PCl and that this is probably due to an uneven mixing of the 99mTc-DTPA in the aqueous hypophase underlying the surfactant lining and the alveoli.

A phase I evaluation of N10-propargyl-5,8-dideazafolic acid.

The quianazoline antifolate N10-propargyl-5,8-dideazafolic acid (ICI 155,387), an inhibitor of thymidylate synthetase (TS), was evaluated for clinical toxicity in a phase I trial. The compound was given once every week as a bolus injection. Fourteen patients with advanced cancer were treated at doses of 10-30 mg/m3. Four patients from the lowest to the highest dose developed severe renal toxicity, detected by a reversible decrease in the Cr-EDTA clearance. Hepatotoxicity was observed with transient elevations of alanine aminotransferase (ALT) in 10 patients and alkaline phosphatase in nine patients. Neither the incidence nor the severity of these toxicities was dose related. Two patients developed feelings of fatigue, which in one patient coincided with a decrease in Cr-EDTA clearance. No myelotoxicity, dermatological, gastrointestinal toxicity or mucositis was seen. No tumour responses due to ICI 155,387 occurred. The severity and the erratic nature of the renal side-effects suggest that this schedule cannot be recommended for further development of this compound in Phase II trials.

Primary squamous-cell carcinoma of the endometrium.

Primary squamous cell carcinoma of the endometrium is an extremely rare condition. The 23rd case of this lesion is presented and a short review of the pathogenesis is given.

Carcinoembryonic antigen: physician attitudes, patterns of use, and impact upon patient care.

Recent data would limit indications for serum CEA measurement primarily to follow-up of resected colonic malignancy, yet physician attitude and usage patterns may lag far behind current findings. This discrepancy was investigated at our institution, where more than 1100 CEAs costing $71,000 are ordered each year. Of 45 physicians (all MDs ordering a CEA test during a preselected month), over 50% believed the test to be worthwhile in initial detection of colonic cancer, and 69% thought an elevated CEA to be an adequate reason to begin an aggressive workup to rule out cancer of the colon in a nonsmoking, previously healthy patient. Impressions of cost were less than or equal to $30 (50% of true cost) in nearly half of MDs and less than 20% of true cost in a tenth of MDs. Analysis of the medical record revealed that indications of questionable validity (initial detection of cancer together with follow-up of noncolonic malignancy) accounted for the majority of requested CEAs and included the attempted detection or monitoring of 12 different tumor types in addition to its use as a "general cancer screen." Patient benefit was realized in none in a random sample of 106 cases (beta = 0.11, power = 0.89 for an assumed benefit of 2%), while management was altered in only one patient as a direct result of the CEA value. It is important that we continue to inform and educate our colleagues about relatively expensive tests that have only limited and specific application.