Nuclear industry family study:methods and description of a United Kingdom study linking occupational information held by employers to reproduction and child health

OBJECTION: To describe the methods used in the nuclear industry family study for which a comprehensive database has been assembled that links employment in the nuclear industry and dosimetry records to information on employees'' reproductive health and the health of their children. To discuss the response rates and characteristics of the study population. METHODS: Occupational cohort design leading to a retrospective cohort study of reproductive outcomes reported by 46 396 current and former employees of both sexes in the nuclear industry. Employees of nuclear establishments in the United Kingdom operated by the Atomic Energy Authority, the Atomic Weapons Establishment, and British Nuclear Fuels were surveyed with postal questionnaires ot collect information on pregnancies, children,and periods of infertility. Information on employment and monitoring for ionising radiation was supplied by the employing nuclear authority and was linked to pregnancies and periods of infertility with unique personal identification numbers. RESULTS: The design and completion of this study resulted in high quality data on a representative population of the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels workforces. The response to the survey was extremely good (82% for male workers and 88% for female workers, excluding undelivered questionnaires), and a unique relational database has been created which will enable infertility, pregnancy, and child health outcomes to be examined with respect to the employment and radiation monitoring characteristics of parents. CONCLUSION: This is the first United Kingdom study to link detailed reproductive history data to occupational information held by employers. The methods developed for the study were found to be feasible and successful. The design can be adapted for other investigations of reproductive hazards to men and women in the workplace and is currently in use to survey over 100 000 armed forces personnel in an investigation of reproductive outcome among veterans of the Gulf war.       

Women's occupation and cancer: preliminary analysis of cancer registrations in England and Wales, 1971-1990.

BACKGROUND: In recent years increasing attention has been paid to examining the relation between women's health and their own occupation. The findings presented here relate to an analysis of 381,915 cancers in women registered in England and Wales over the 20-year period 1971-1990. METHODS: To explore the value of the data for epidemiological research, five sites (pleura, bladder, stomach, lung, and breast) and two occupations (agriculture and textile) were selected. Associations between cancer and occupation were evaluated using age and social class adjusted proportional registration ratios (PRRs) and 95% confidence intervals (CI). RESULTS: Pleural cancer risk was increased in a range of occupations with a potential for asbestos exposure (e.g., PRR 608, 95% CI 381-921 for craft and other production process workers), and the well-established link between bladder cancer and employment in the rubber industry was confirmed (PRR 303, 95% CI 188-464). Associations between "dusty" occupations and stomach cancer were noted (e.g., PRR 198, 95% CI 126-298 for ceramic decorators and finishers), and possible links with lung cancer and smoke in the work environment were highlighted (e.g., PRR 167, 95% CI 147-189 for publicans). As a group, agricultural workers were found to be at increased risk of non-Hodgkin's lymphoma (PRR 164, 95% CI 126-211), and textile workers at increased risk of pleural cancer (PRR 145, 95% CI 111-185). No evidence for an occupational aetiology for breast cancer was found within these data. CONCLUSIONS: Occupational information collected at cancer registration in the United Kingdom can be reliably used to identify groups that may be at increased risk of disease.     

Regional dissemination and control of epidemic methicillin-resistant Staphylococcus aureus. Manitoba Chapter of CHICA-Canada.

A methicillin-resistant Staphylococcus aureus (MRSA) strain introduced into the largest tertiary-care teaching hospital in Manitoba in 1993 led to a sustained outbreak with secondary outbreaks at one community hospital, two large long-term-care facilities, and nosocomial transmission at a second teaching hospital. Control measures were consistent at each institution and were coordinated on a province-wide basis. MRSA is not currently endemic in any facility in the province.     

Outcome of Silicone Ring Vertical Gastroplasty in Patients Aged 50 Years and Older

Background: The authors studied the results of silicone ring vertical gastroplasty (SRVG) in patients aged 50 years and older. Methods: The early and late postoperative results in 28 patients aged 50 years or older undergoing SRVG were reviewed retrospectively. The results were compared to those of 370 patients younger than 50 years operated during the same period. Results: There was no postoperative mortality among patients aged 50 years and older. There was a significantly higher incidence of pulmonary embolus and wound infection among patients aged 50 years and older (p < 0.05). The weight loss did not differ significantly between the two studied age groups. Conclusion: SRVG may be performed on patients aged 50 years or older with acceptable complication rate and favourable postoperative results.     

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats

Summary The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 g/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.Deceased February 13, 1979     

In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors

Summary We have developed an in vivo method of measuring the blood-brain transfer constant (K) of iopamidol and the cerebral plasma volume (V_p) in brain tumors using a clinical X-ray CT scanner. In patient studies, Isovue 300 (iopamidol) was injected at a dosage of 1 ml/kg patient body weight. Serial CT scans of the tumor site and arterial blood samples from a radial artery were taken up to 48 min after injection. The leakage of iopamidol into the brain through the blood-brain barrier was modelled as an exchange process between two compartments, the intravascular plasma space and the tissue interstitial space. Using this model and the concentration measurements in blood plasma and tissue, quantitative estimates of K and V_p in brain tumors were obtained. In addition, distribution of the estimated values of K and V_p in tumors were displayed as false colour functional images overlaid on the conventional CT scan.In a study of twelve patients with anaplastic astrocytoma (n = 3), glioblastoma multiforme (n = 4) or metastases (n = 5) the mean K and VP values in tumor were found to be 0.0273 ± 0.0060 ml/min/g and 0.068 ± 0.11 ml/g respectively. These values were significantly higher than those in grey or white matter in the contralateral normal hemisphere (p < 0.05). The functional images showed variations in K and V_p within the tumor which were difficult to perceive in the original contrast enhanced CT scans.     

Mechanisms of proteasome inhibitor PS-341-induced G(2)-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines.

PURPOSE: PS-341 is a novel dipeptide boronic acid proteasome inhibitor with in vitro and in vivo antitumor activity that induces mechanisms of apoptosis by unknown mechanisms. EXPERIMENTAL DESIGN: Human non-small cell lung cancer cell lines were used to investigate effects PS-341 on cell proliferation, cell cycle progression, and the induction of apoptosis. RESULTS: PS-341 was 38-360-fold more cytotoxic against H460 cells when compared with the proteasome inhibitors MG-132 and PSI. Differential PS-341 cytotoxic effects were found with respect to P53 function: H322 cells (p53 mutant) were 6-fold less sensitive as compared with H460 cells (p53 wild type); and H358 cells (p53 null) were 1.6-fold more sensitive as compared with H460 cells (p53 wild type). A concentration- and time-dependent cell cycle blockade at G(2)-M phase was seen for H460 cells without any direct effects on microtubule polymerization or depolymerization. PS-341 exposure in H460 cells led to stabilization of p53, induction of p21(cip/waf-1) and MDM2 expression, an increase in cyclin B and cyclin A, and the activation of cyclin B and cyclin A kinases. MDM2 induction was found only in H460 cells, whereas in H322 and H358 cells, G(2)-M-phase arrest, p21(cip/waf-1) induction, and an increase in cyclin B1 were found. The commitment of G(2)-M-phase cells to apoptosis was verified by the activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in drug-free medium. CONCLUSIONS: Our data suggest that the PS-341-induced G(2)-M-phase arrest may be associated with the inhibition of degradation of cell cycle regulators and that the up-regulation of p21(cip/waf-1) expression may be via p53-dependent and/or -independent pathways. The resulting disturbance of cell cycle progression leads either to growth inhibition or to the initiation of apoptotic pathways.     

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix

: The aim of this work is to invetigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors.

: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m² was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the cofounding effect of the cisplatin.

: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at aproximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The date from the group of patients treated wihout cisplatin is comparable to the date from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison.

: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external irradiation in the head and neck region.