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Biomedical subjects

J H Stewart

Publications and source records attributed to J H Stewart.

At least 19 recordsLinked to original sources

Cancer incidence among semiconductor and electronic storage device workers.

AIMS: To evaluate cancer incidence among workers at two facilities in the USA that made semiconductors and electronic storage devices. METHODS: 89 054 men and women employed by International Business Machines (IBM) were included in the study. We compared employees' incidence rates with general population rates and examined incidence patterns by facility, duration of employment, time since first employment, manufacturing era, potential for exposure to workplace environments other than offices and work activity. RESULTS: For employees at the semiconductor manufacturing facility, the standardised incidence ratio (SIR) for all cancers combined was 81 (1541 observed cases, 95% confidence interval (CI) 77 to 85) and for those at the storage device manufacturing facility the SIR was 87 (1319 observed cases, 95% CI 82 to 92). The subgroups of employees with > or =15 years since hiring and > or =5 years worked had 6-16% fewer total incidents than expected. SIRs were increased for several cancers in certain employee subgroups, but analyses of incidence patterns by potential exposure and by years spent and time since starting in specific work activities did not clearly indicate that the excesses were due to occupational exposure. CONCLUSIONS: This study did not provide strong or consistent evidence of causal associations with employment factors. Data on employees with long potential induction time and many years worked were limited. Further follow-up will allow a more informative analysis of cancer incidence that might be plausibly related to workplace exposures in the cohort.

Adult↗

Geographic, ethnic, age-related and temporal variation in the incidence of end-stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002.

BACKGROUND: Only unbiased estimates of end-stage renal disease (ESRD) incidence and trends are useful for disease control-identification of risk factors and measuring the effect of intervention. METHODS: Age- and sex-standardized incidences (with trends) were calculated for all-cause and diabetic/non-diabetic ESRD for persons aged 0-14, 15-29, 30-44 and 45-64 years in 13 populations identified geographically, and six populations identified by ethnicity. RESULTS: The incidence of ESRD varied most with age, ethnicity and prevalence of diabetes. All non-Europid populations had excess ESRD, chiefly due to rates of type 2 diabetic ESRD that were greater than accounted for by community prevalences of diabetes. Their rates of non-diabetic ESRD also were raised, with contributions from most common primary renal diseases except type 1 diabetic nephropathy and polycystic kidney disease. The ESRD rates generally were low, and more similar than different, in Europid populations, except for variable contributions from type 1 (high in Finland, Sweden, Denmark and Canada) and type 2 (high in Austria and Canada) diabetes. In Europid populations during 1998-2002, all-cause ESRD declined by 2% per year in persons aged 0-44 years, and all non-diabetic ESRD by a similar amount in persons aged 45-64 years, in whom diabetic ESRD had increased by 3% per year. CONCLUSIONS: Increased susceptibility to type 2 diabetes and to kidney disease progression characterizes excess ESRD in non-Europid peoples. The decline in all-cause ESRD in young persons, and non-diabetic ESRD in the middle-aged, probably reflects improving management of progressive renal disease.

Adolescent↗

Divergent trends in the incidence of end-stage renal disease due to Type 1 and Type 2 diabetes in Europe, Canada and Australia during 1998-2002.

AIMS: To describe the variation in geographical distribution of end-stage renal disease (ESRD) due to Type 1 and Type 2 diabetes, and to calculate recent trends in incidence in predominantly white populations. METHODS: Estimation of age- and sex-standardized incidence of ESRD by type of diabetes, and temporal trends, in population-based data for persons aged 30-44, 45-54 or 55-64 years newly treated for ESRD during 1998-2002 in eight countries or regions of Europe, and Non-Indigenous Canadians and Australians. RESULTS: The incidence of ESRD due to Type 1 diabetes at age 30-44 years correlated with published rates of childhood-onset insulin dependent diabetes mellitus (P = 0.0025). ESRD due to Type 2 diabetes was uncommon before 45 years of age; in older persons, the highest rates (in Canada and Austria) were five times the lowest rates (in Norway and the Basque region). Rates of ESRD due to Type 1 diabetes fell, per year, by 6.4%[95% confidence interval (CI): 2.1-10.6%) in persons aged 30-44 years, and by 7.7% (95% CI: 2.4-12.7%] in those aged 45-54 years. In contrast, rates of ESRD due to Type 2 diabetes increased annually by 16% (95% CI: 5-28%) in the 30-44-year age group, 11% (95% CI: 6-16%) at 45-54 years, and 9% (95% CI: 5-14%) at 55-64 years. CONCLUSIONS: Modern prevention has reduced progression of nephropathy to ESRD due to Type 1 diabetes, but the continuing rise of ESRD due to Type 2 diabetes represents a failure of current disease control measures that has serious public health implications.

Adult↗

The Health Status Questionnaire: achieving concordance with published disability criteria.

AIM: To compare the Health Status Questionnaire with established methods of assessing disability in preterm and very low birthweight infants. METHOD: All survivors of gestational age <31 weeks or birth weight <1500 g, born in 1994 to women resident in Wales were identified. Assessments were by a single observer at a median corrected age of 28.3 months and included the Health Status Questionnaire and a Griffiths developmental test. Outcome was also described according to criteria for disability used in three published studies. RESULTS: There were 297 survivors of which 279 (94%) were assessed. Using the Health Status Questionnaire, severe disability was found in 12.9% of cases compared to 8.2%, 2.9%, and 3.6% using the Northern, Victorian, and Mersey outcome criteria respectively. Following the simple modifications of removing the growth criteria from the Health Status Questionnaire and reclassifying the severe disability group in the Victorian and Mersey criteria, comparable severe disability rates ranging from 7.9% to 9.3% were found. CONCLUSION: The Health Status Questionnaire requires no formal training, is rapid to perform, and with simple modifications provides comparable results to established methods of assessing disability. Its use in the follow up of preterm and very low birthweight infants should be encouraged.

Child, Preschool↗

Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis.

BACKGROUND: It has previously been demonstrated that 17-allylamino geldanamycin (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular endothelial factor expression in non-small cell lung cancer. This project was designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude mice. METHODS: In vitro cytotoxic drug combination effects were evaluated by (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation assays. The combinations of 17-AAG and paclitaxel were administered intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were measured weekly. Tumor expression of erbB2, vascular endothelial cell growth factor, von Willebrand factor (tumor microvasculature), and activated caspase 3 (apoptosis) were determined by immunohistochemistry. RESULTS: Five- to 22-fold enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG combination that was paralleled with marked induction of apoptosis. This combination treatment profoundly suppressed tumor growth and significantly prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining of tumor tissues indicated profound reduction of vascular endothelial cell growth factor expression associated with reduction of microvasculature in tumors treated with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG + paclitaxel than in those treated with 17-AAG or paclitaxel alone. CONCLUSIONS: Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in supraadditive growth inhibition effects in vitro and in vivo. Analysis of molecular markers of tumor tissues indicated that therapeutic drug levels could be achieved with this chemotherapy regimen leading to significant biological responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell growth factor production by tumor cells may contribute to the antitumor effects of this drug combination in vivo.

Allylamine↗

Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases.

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.

Adult↗

Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study.

This report notes the differences in the classification of the primary renal disease (PRD) used in different renal dialysis and transplant registries worldwide. The heterogeneity of coding systems complicates the comparative analysis of end-stage renal disease from different regions. Using data collected over two decades in the United States, Europe, and Australia/New Zealand, we present a method for reorganization of the classes of PRD that allows a straightforward comparison of retrospective data from these registries.

Adult↗

Morphologic evidence that analgesic-induced kidney pathology contributes to the progression of tumors of the renal pelvis.

BACKGROUND: Whether phenacetin-containing analgesics cause renal pelvic tumors by virtue of the weak mutagenicity of phenacetin, or indirectly through local effects of analgesic-induced renal papillary scarring, is debated. Because phenacetin consumption ceased in New South Wales, Australia in 1975, cases of renal pelvic carcinoma seen 14-15 years later (many of which were associated with long-standing analgesic-induced renal papillary pathology) provided an opportunity to examine the temporal relation between phenacetin exposure and those histologic characteristics of the tumors and adjacent renal tissue that may implicate analgesics in their etiology. METHODS: The authors conducted a "blinded" histopathologic review of tumors of the renal pelvis and adjacent noncancerous renal tissue from 100 cases for which epidemiologic data regarding risk factor exposure (specifically phenacetin-containing analgesics, tobacco, infection, and kidney stones) had been obtained in a population-based case-control study from New South Wales in 1989 and 1990. RESULTS: A history of consumption of phenacetin-containing analgesics was associated strongly with the presence and severity of diffuse renal papillary scarring, and less strongly with papillary calcification. The histologic grade of the renal pelvic tumors tended to rise significantly with consumption of phenacetin-containing analgesics in a dose-dependent fashion and with the degree of papillary scarring, but was not related to smoking. In multivariate analysis it was the degree of papillary scarring (to a greater extent than the amount of phenacetin consumption) that was associated significantly and strongly with a higher histologic grade. Only diffuse papillary calcification was associated significantly with squamous change in the renal pelvic tumors. CONCLUSIONS: Based on the results of the current study, the authors conclude that 1) in phenacetin-related tumors of the renal pelvis, the presence and severity of analgesic-induced renal papillary scarring correlates with tumor progression and 2) papillary calcification is a risk factor for squamous change in renal pelvic urothelioma.

Age Factors↗

Cancer in patients on dialysis for end-stage renal disease: an international collaborative study.

BACKGROUND: Previous studies have suggested that the frequency of cancer is higher in patients with end-stage renal disease (ESRD) than in the general population, but have not established whether this increase is confined to certain cancers or to certain categories of ESRD patients. The aim of this study was to examine the risk of cancer in a large cohort of patients treated by dialysis but not transplantation. METHODS: We assembled a cohort of 831,804 patients who received dialysis during the period 1980-94 for ESRD in the USA, Europe, Australia, or New Zealand. We compared the observed frequency of cancer among these patients during 2,045,035 person-years of follow-up with the frequency of cancer in the respective background populations. FINDINGS: During average follow-up of 2.5 years, 25,044 (3%) of 831,804 patients developed cancer compared with an expected number of 21,185 (standardised incidence ratio 1.18 [95% CI 1.17-1.20]). We observed a higher risk of cancer in patients younger than 35 years (3.68 [3.39-3.99]), and the risk gradually decreased with increasing age. High risks were observed for cancer of the kidney (3.60 [3.45-3.76]), bladder (1.50 [1.42-1.57]), and thyroid and other endocrine organs (2.28 [2.03-2.54]). Excess cancers appeared in several organs for which viruses have been suspected as causative agents, whereas cancers of the lung, colorectum, prostate, breast, and stomach were not consistently increased. INTERPRETATION: The overall risk of cancer is increased in patients with ESRD, and the distribution of tumour types resembles the pattern seen after transplantation (although we have no data to make the comparison with skin cancer). The excess risk can largely be ascribed to effects of underlying renal or urinary-tract disease, or of loss of renal function, on the kidney and bladder, and to increased susceptibility to viral carcinogenesis. The relative risk, which is especially high in younger patients, gradually diminishes with age.

Adolescent↗

Corporal punishment by American parents: national data on prevalence, chronicity, severity, and duration, in relation to child and family characteristics.

We present data on corporal punishment (CP) by a nationally representative sample of 991 American parents interviewed in 1995. Six types of CP were examined: slaps on the hand or leg, spanking on the buttocks, pinching, shaking, hitting on the buttocks with a belt or paddle, and slapping in the face. The overall prevalence rate (the percentage of parents using any of these types of CP during the previous year) was 35% for infants and reached a peak of 94% at ages 3 and 4. Despite rapid decline after age 5, just over half of American parents hit children at age 12, a third at age 14, and 13% at age 17. Analysis of chronicity found that parents who hit teenage children did so an average of about six times during the year. Severity, as measured by hitting the child with a belt or paddle, was greatest for children age 5-12 (28% of such children). CP was more prevalent among African American and low socioeconomic status parents, in the South, for boys, and by mothers. The pervasiveness of CP reported in this article, and the harmful side effects of CP shown by recent longitudinal research, indicates a need for psychology and sociology textbooks to reverse the current tendency to almost ignore CP and instead treat it as a major aspect of the socialization experience of American children; and for developmental psychologists to be cognizant of the likelihood that parents are using CP far more often than even advocates of CP recommend, and to inform parents about the risks involved.

Adolescent↗

Maternal cigarette smoking and pregnancy outcome.

Maternal smoking rates in pregnancy have declined, particularly in the non-manual social classes, and perinatal mortality rates have fallen over the last 20 years. We have therefore re-evaluated the relationship between maternal cigarette smoking and pregnancy outcome against this background. A total of 608 stillbirths and 634 infant deaths were identified using the All Wales Perinatal Survey. The cause of death was classified using the clinicopathological system. Maternal smoking rates and social class groupings were compared with those in a cohort of 16047 survivors born to women resident in South Glamorgan. The smoking rate was 37.8% in mothers of babies who died compared with 27.2% in mothers of survivors, an odds ratio (OR) of 1.63 [95% CI 1.44, 1.84]. The OR for unexplained stillbirth was 1.72 [95% CI 1.38, 2.13], placental abruption 2.07 [95% CI 1.29, 3.31], infection 3.70 [95% CI 2.23, 6.13] and sudden infant death syndrome 4.84 [95% CI 3.05, 7.69]. Maternal smoking was not associated with death due to prematurity or a congenital anomaly. Despite changes in smoking habits and the causes of perinatal death, smoking during pregnancy continues to be strongly associated with fetal and infant mortality. It is important that health promotion activities are effective in reducing smoking during pregnancy.

Adult↗

Confidential enquiry into deaths due to prematurity.

The aim of this study was to audit the management of neonatal respiratory distress syndrome (RDS) in a geographically defined population using a retrospective peer review of case notes. The subjects were 49 infants of 24-36 wk gestation with a birthweight >499 g, and dying as a consequence of prematurity at <1 y of age in Wales during 1996. Forty-four infants (90%) were delivered in a unit with staff experienced in the management of preterm birth. Of the 30 infants <30 weeks' gestation, 29 (97%) received neonatal intensive care on a (sub)regional unit. Predelivery corticosteroids were indicated in 34 cases and administered in 31 (91%). Resuscitation at birth was indicated in 47 infants and conducted satisfactorily in 42 (89%). Temperature on admission to the neonatal unit was not recorded in 7 infants; in the other 42 it was >35.5 degrees C in 21 (50%). Early surfactant therapy was administered to 31/34 (91%) infants still intubated 120 min after birth, but was given within 30 min to only 8 (24%). Mechanical ventilation was assessed in 41 infants and considered to be good in 23 (56%). Cardiovascular therapy was evaluated in 40 infants requiring active support and considered to be good in 31 (78%). We concluded that neonatal RDS was generally well managed, thermal care during resuscitation was poor, surfactant should be administered more promptly, and deficiencies in the management of ventilation were common and related mainly to poor anticipation and a slow response to problems.

Adrenal Cortex Hormones↗

Numbers of deaths related to intrapartum asphyxia and timing of birth in all Wales perinatal survey, 1993-5.

OBJECTIVES: To investigate the relation between the timing of birth and the occurrence of death related to an intrapartum event. DESIGN: Analysis of 107,206 births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of neonatal death identified in the all Wales perinatal survey, the cause of death classified with the clinicopathological system. SUBJECTS: 79 normally formed babies stillborn or who died in the neonatal period, birth weight > 1499 g, for whom cause of death was related to an intrapartum event. MAIN OUTCOME MEASURES: Relative risk of death due to an intrapartum event according to the hour, day, and month of birth. RESULTS: Mortality was higher in babies born between 9.00 pm and 8.59 am than in those born between 9.00 am and 8.59 pm; relative risk (95% confidence interval) 2.18 (1.37 to 3.47). July and August births also had a higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23). Weekened births had a higher death rate but it was not significant. CONCLUSIONS: The excess of deaths at night and during months when annual leave is popular may indicate an overreliance on inexperienced staff at these times. Errors of judgement may also be related to physical and mental fatigue, demanding a more disciplined systematic approach at night. Mistakes may be ameliorated by increasing shiftwork, but shifts should be carefully designed to avoid undue disruption of circardian rhythms. In addition, greater supervision by senior staff may be required at night and during summer months.

Asphyxia Neonatorum↗

Improving the quality of perinatal and infant necropsy examinations: a follow up study.

AIM: To compare the quality of perinatal and infant necropsy examinations in 1996 with those performed in 1993. METHODS: Cohort analysis, with data from the All Wales Perinatal Survey, of 1027 deaths (540 in 1993; 487 in 1996) of babies between 20 weeks' gestation and one year of age. The quality of the necropsy was assessed by scoring aspects identified as being part of the investigation. RESULTS: Necropsy was performed in 335 cases (62%) in 1993 and in 320 cases (66%) in 1996. The proportion done in a regional centre increased significantly from 39% (131/335) in 1993 to 76% (243/320) in 1996 (p < 0.0001). The quality of necropsy was above the minimum standard in 54% of cases in 1993 (171/314) compared with 93% in 1996 (289/312) (p < 0.0001). Improvement occurred in all categories. For stillbirths, 35% (46/133) were above the minimum standard in 1993 compared with 90% (104/116) in 1996 (p < 0.0001); for cases not classified as sudden unexpected death in infancy (SUDI), the improvement was from 62% in 1993 (40/65) to 97% in 1996 (73/75) (p < 0.0001); and for SUDI cases, the improvement was from 32% in 1993 (10/31) to 91% in 1996 (21/23) (p < 0.0001). The quality of both non-regional and regional necropsies improved. For non-regional cases, the score was above the minimum standard in 28% (51/183) in 1993 compared with 69% (52/75) in 1996 (p < 0.0001); for regional cases it improved from 92% (120/131) in 1993 to 100% (237/237) in 1996 (p < 0.0001). CONCLUSIONS: The quality of perinatal and infant necropsies improved considerably between 1993 and 1996, reflecting better awareness of the importance of good quality examination and an increase in referrals to paediatric centres.

Autopsy↗

Survival of very low birthweight and very preterm infants in a geographically defined population.

OBJECTIVE: To determine in a geographically defined population 1 year survival of infants with a birthweight of less than 1500 g or gestational age less than 32 weeks, and to establish the effect of postnatal age on predicted survival. DESIGN: Cohort analysis of 72,427 births to Welsh residents in 1993-94. Deaths were identified using the All Wales Perinatal Survey, a population-based surveillance of mortality between 20 weeks of gestation and 1 year of age. MAIN OUTCOME MEASURES: Birthweight- and gestation-specific infant mortality, and the effect of postnatal age, gender, and multiple pregnancy on predicted survival. RESULTS: In normally formed infants 1 year survival at 24-25 weeks gestation was 35%, compared to 75% at 27-28 weeks, and 95% at 30-31 weeks. In infants with a birthweight of 500-699 g 1 year survival was 18% compared to 70% at 800-999 g, and 97% at 1300-1499 g. The chances of survival improved markedly with increasing postanatal age; at 24-25 weeks gestation it was 35% at birth, 50% at 12 h. 66% at 7 days and 78% at 4 weeks. Infant mortality was higher in males, but multiple pregnancy had no effect. CONCLUSIONS: Up-to-date birthweight- and gestation-specific survival rates are essential for predicting the outcome of a newborn infant. The rapid change in the chances of survival with increasing postnatal age emphasises especially the importance of revising the prediction as the infant gets older, particularly during the first few days of life.

Cohort Studies↗

International renal-cell-cancer study. VI. the role of medical and family history.

A number of medical conditions have been linked with renal-cell cancer, although the evidence is not consistent in every case. In a large international case-control study of renal-cell cancer, we examined, among other hypotheses, associations with a personal history of certain medical conditions and a family history of cancer of the kidney or thyroid. Relative risks (RR), adjusted for the effects of age, gender, body-mass index, tobacco smoking and study centre, were significantly increased by a history of kidney stones or thyroid or kidney disease. The RR were not altered by additional adjustment for hypertension, or when diagnoses were restricted to those made at least 5 or 10 years before 1987 (the usual "cut-off" date). The link with kidney injury is particularly likely to be affected by recall bias. Increased RR of borderline significance were found for kidney infection (RR, 1.2) and diabetes (RR, 1.4). Having one first-degree relative with kidney cancer was associated with a significantly increased risk of renal-cell cancer (RR, 1.6; 95% Cl, 1.1-2.4). Seven cases reported 2 first-degree relatives with kidney cancer. No controls had first-degree relatives with kidney cancer. None of our participants reported having von Hippel-Lindau disease. The data suggests that a few conditions of the kidney are strongly associated with renal-cell cancer and that heredity plays a role in a small proportion of cases.

Adult↗