Biomedical subjects
A H Smith
Publications and source records attributed to A H Smith.
Arsenic ingestion and internal cancers: a review.
Inorganic arsenic is known to cause skin cancer by ingestion and lung cancer by inhalation. However, whether arsenic ingestion causes internal cancers is still a matter of debate. This paper has reviewed the epidemiologic literature that bears on this question. Published studies of populations who have ingested arsenic in medicines, wine substitutes, or water supplies, as well as workers exposed to arsenic by inhalation, were considered in terms of whether the observed associations might be explained by the presence of biases, the consistency of the evidence, and the biologic plausibility of the associations. Many studies were found to be uninformative because of low statistical power or potential biases. The most informative studies, which were from Taiwan and Japan, involved exposure to arsenic in drinking water. These studies strongly suggest that ingested inorganic arsenic does cause cancers of the bladder, kidney, lung, and liver, and possibly other sites. However, confirmatory studies are needed.
Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their implication for cancer hypotheses.
BACKGROUND: The phenoxyherbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) has been widely used by professional pesticide applicators in New Zealand since before 1950. Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals. PURPOSE: The objective of this study was to determine whether the blood serum levels of TCDD in a group of professional 2,4,5-T applicators in New Zealand were greater than those of a matched control group not involved in 2,4,5-T spraying. METHODS: Of 548 men employed as professional pesticide applicators in New Zealand from 1979 through 1982, nine were selected who had sprayed pesticides, although not necessarily 2,4,5-T, for at least 180 months. These applicators had sprayed 2,4,5-T for a range of 83-372 months. We measured the blood serum levels of polychlorinated dibenzo-p-dioxins and dibenzofurans, which were substituted with chlorine at the 2,3,7,8 position, in the nine pesticide applicators and in a matched group of nine control subjects. RESULTS: The average serum level of TCDD for applicators was almost 10 times that for the matched control subjects, while the average levels of all other congeners and isomers measured in the two groups did not differ substantially. TCDD levels in eight of the nine applicators were higher than those in the control subjects (mean difference, 47.7 parts per trilion). The variation in TCDD levels among the applicators was related to their duration of work exposure to 2,4,5-T. CONCLUSIONS: On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyherbicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks.
Long-term followup of infants with gross vesicoureteral reflux.
The majority of children (1 year old or less) with gross vesicoureteral reflux already have renal damage at the time of presentation or reflux nephropathy develops during the first few years of life. We report the long-term followup of 31 patients (16 boys) presenting in infancy with gross vesicoureteral reflux (Rolleston classification) between 1952 and 1970. They had a total of 44 grossly refluxing ureters (13 bilateral, 18 unilateral) and presented between ages 1 day and 48 weeks (mean 15.3 weeks). Of the 31 infants 5 died within the first year of life, 4 were followed for up to 11 years before being lost to followup and 1 was killed in a motor vehicle accident after 19.5 years of followup. The remaining 21 patients have been followed for 16 to 37 years (mean 23.9 years); 4 have normal kidneys, and 13 have unilateral and 4 have bilateral reflux nephropathy. Of those patients with unilateral reflux nephropathy proteinuria, hypertension and renal failure developed in 1 born with a single kidney and he is now on hemodialysis, while 2 others have a diastolic blood pressure of 90 mm. Hg or greater. Of the 4 patients with bilateral reflux nephropathy 2 have proteinuria and renal insufficiency, with 1 progressing towards end stage renal failure. Infants who present with gross vesicoureteral reflux within the first year of life appear to do well if free of severe bilateral reflux nephropathy at presentation. Patients with reflux nephropathy should remain under regular nephrological supervision with particular attention given to proteinuria, renal function and blood pressure.
Can glycogen be measured by in vivo neutron activation analysis?
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Synergism between occupational arsenic exposure and smoking in the induction of lung cancer.
We assembled data from numerous studies to examine whether active smoking and occupational exposure to arsenic act synergistically (more than additively) to increase the risk of lung cancer. Although several smaller studies lacked the power to reject simple additive relations, the joint effect from both exposures consistently exceeded the sum of the separate effects by about 70 to 130%. The only study not showing a greater than additive effect appeared to have inadequate data to address this question. We calculated the excess fractions for the synergism; these showed that a minimum of between 30% and 54% of lung cancer cases among those with both exposures could not be attributed to either one or the other exposure alone. Previous authors addressing the synergism between arsenic exposure and smoking have evaluated deviations from a multiplicative model, which is inappropriate for this purpose. Reports of no interaction or "negative" interaction have therefore been misleading. Taken as a whole, the evidence is compelling that arsenic and smoking act in a synergistic manner to produce lung cancer. Substantial reductions in the lung cancer burden of smokers occupationally exposed to arsenic could be achieved by reductions in either exposure. The mechanism for the synergism is unclear.
Confidence limit analyses should replace power calculations in the interpretation of epidemiologic studies.
Frequently, after an epidemiologic study is completed, statistical power to detect a relative risk of interest is recalculated using data obtained during the course of the study. A negative study may then be dismissed on the grounds that its power was too low. However, post hoc power calculations ignore the actual relative estimate and its variance, which are by then known. We present evidence that post-study power calculations have little value and should be replaced by a more informative method using the upper (1 - alpha)% confidence limit of the point estimate that touches the value of the relative risk of interest.
Hepatic perfusion index: a multicentre trial.
The reproducibility and accuracy of the hepatic perfusion index (HPI) was examined by consideration of in vitro and in vivo factors. A phantom was used to simulate liver blood flow and data acquired on nine gamma cameras. Dynamic hepatic scintigraphy was undertaken on 28 patients at two centres and values obtained for the HPI. Results from the phantom study showed good agreement between the nine cameras and also with the HPI values predicted from the measured phantom flow rates. The results of the patient study indicated a high degree of conformity between observers (r = 0.95, S.E = 0.03) but poorer correlation between the HPI values from the two centres (r = 0.67, S.E. = 0.09). These results imply that centres wishing to use HPI clinically should establish their own range of normality.
Cancer risks from arsenic in drinking water.
Ingestion of arsenic, both from water supplies and medicinal preparations, is known to cause skin cancer. The evidence assessed here indicates that arsenic can also cause liver, lung, kidney, and bladder cancer and that the population cancer risks due to arsenic in U.S. water supplies may be comparable to those from environmental tobacco smoke and radon in homes. Large population studies in an area of Taiwan with high arsenic levels in well water (170-800 micrograms/L) were used to establish dose-response relationships between cancer risks and the concentration of inorganic arsenic naturally present in water supplies. It was estimated that at the current EPA standard of 50 micrograms/L, the lifetime risk of dying from cancer of the liver, lung, kidney, or bladder from drinking 1 L/day of water could be as high as 13 per 1000 persons. It has been estimated that more than 350,000 people in the United States may be supplied with water containing more than 50 micrograms/L arsenic, and more than 2.5 million people may be supplied with water with levels above 25 micrograms/L. For average arsenic levels and water consumption patterns in the United States, the risk estimate was around 1/1000. Although further research is needed to validate these findings, measures to reduce arsenic levels in water supplies should be considered.
Serum beta-carotene in persons with cancer and their immediate families.
A unique case-control study design including family members of cases and controls was used to assess the association between serum beta-carotene and cancer. The cases (n = 389) were incident cancer cases diagnosed between 1981 and 1984 in Wellington, New Zealand, and the controls (n = 391) were hospital patients without cancer. Both cases and controls were on a home diet at the time beta-carotene levels were measured. Since findings concerning patients who have already been diagnosed with cancer may reflect changes that occurred subsequent to development of cancer, family members of cancer patients (n = 618) and control patients (n = 675) were included, giving a total of 2,073 study participants. Low levels of beta-carotene were observed for individuals with a number of cancers, including cancers of the lung stomach, esophagus, small intestine, cervix, and uterus. Low levels of beta-carotene were also found in the relatives of these cancer patients. These differences persisted after stratification by current cigarette smoking. The strongest findings were those for lung cancer. Excluding adenocarcinoma, lung cancer patients had average serum beta-carotene levels of 40.2 micrograms/dl, 25.9 micrograms/dl lower than those of controls, adjusted for age, sex, and length of sample storage (p less than 0.01). Family members of the lung cancer patients also had lower values than family members of control patients, with an adjusted difference of 10.8 micrograms/dl (p less than 0.01). Odds ratio estimates for lung cancer by quartiles of beta-carotene residuals ranged from 3.6 (90% confidence interval (CI) 1.1-12.2) for the second-highest quartile to 6.6 (90% CI 1.9-23.0) for the lowest quartile (test for trend, p less than 0.001). Patients with cancers of the breast, colon, prostate, and skin did not have lower levels of serum beta-carotene than expected. Family members of individuals with these cancers also did not have lower levels of serum beta-carotene. The cancer sites that were associated with serum beta-carotene are, in general, sites for which smoking is a strong risk factor, and the sites that were not associated with beta-carotene do not have smoking as a risk factor.
Inelastic scattering of pulsed 14.4 MeV neutrons as a function of depth in tissue and the half-life for radiative capture.
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Gravitational fields and aging.
Alteration of the ambient gravitational field and aging are both accompanied by a variety of physiological changes, but at present it is not possible to estimate how aging and alteration of gravitational fields would interact. The time will undoubtedly come when it will be advantageous to expose individuals of older ages to the altered gravitational fields. Consequently it is timely to know in advance the limitations and special maintenance requirements, if any, that may apply. The importance of such studies has been recognized by Comfort (3) in a chapter entitled "A special application: Aerospace Gerontology." Initially there should be a series of experiments in which animals of increasing ages are exposed to the weightlessness of spaceflight, and to increased fields provided by centrifugation. Also of interest would be the study of the effects of long-term exposure to moderately increased acceleration fields (1/2-1 G) to determine the gravitational effects on the aging process. In addition to its application toward improving the maintenance of aging astronauts/cosmonauts, such information also should contribute to the general understanding of gravitational physiology. Conversely, the effects exposure to the unconventional stress of altered gravitational fields, and the nature of any counter-measure developed, would be valuable contributions to the understanding of aging and the management of the elderly. It appears only logical that at least as much attention be given to gravitational fields and aging, as is given to gravitational fields and development.
Hepatic perfusion index: colloid lung retention.
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Influence of race, tobacco use, and caffeine use on the relation between blood pressure and blood lead concentration.
A number of studies have suggested a small to moderate positive relation between blood pressure and blood lead concentration in males (2-4 mmHg/In(microgram/dl]. However, this 1986 study of San Francisco bus drivers suggests larger relations in black males (n = 132) for both systolic pressure (7.5 mmHg/In(microgram/dl] and diastolic pressure (4.7 mmHg/In(microgram/dl] at very low blood lead concentrations (2-21 micrograms/dl). This increase appears to result from negative confounding, particularly after taking into account tobacco use. Relations are even larger in blacks who infrequently use caffeine (16.7 and 10.4 mmHg/In(microgram/dl) for systolic and diastolic pressure, respectively). In contrast, a negative relation between systolic pressure and blood lead concentration (-5.7 mmHg/In(microgram/dl] is suggested in nonblack males (n = 117). These findings indicate that race, lead accumulation, and physiologic effects related to caffeine use (e.g., catecholamine effects) may interact to produce marked differences in effect on blood pressure.
Epidemiological evidence indicates asbestos causes laryngeal cancer.
A variety of opinions have been expressed in the literature concerning asbestos and laryngeal cancer. This paper presents an analysis of epidemiological studies based on criteria that prioritized the most heavily exposed cohorts. Emphasis was given to the six cohorts or subcohorts with lung cancer relative risk estimates of 2 or more. The two groups of workers with the highest lung cancer relative risk estimates (4.06 and 3.28) both gave strong support for a causal association of asbestos and laryngeal cancer, with relative risk estimates of 1.91 (90% confidence limits 1.00 to 3.34) and 3.75 (90% confidence limits 1.01 to 9.68), respectively. Confounding with cigarette smoking or alcohol consumption does not explain the findings. Case-control studies gave mixed results, but generally supported the hypothesis. It was concluded that asbestos is a probable cause of laryngeal cancer in view of the reasonable consistency of the studies, the strength of the association in key studies, the evidence for dose-response relationships, and the biological plausibility for asbestos being a cause of laryngeal cancer.
Consistent pattern of elevated symptoms in air-conditioned office buildings: a reanalysis of epidemiologic studies.
Published studies of the relation between type of building ventilation system and work-related symptom prevalence in office workers have been contradictory. A reanalysis was performed of six studies meeting specific eligibility criteria, combining published data with unpublished information obtained from study authors. Five eligible studies were from the United Kingdom, and one was from Denmark. Standardized categories of building ventilation type were created to allow comparison of effects across studies. Within each study, prevalence odds ratios (PORs) were calculated for symptoms in each ventilation category relative to a baseline category of naturally ventilated buildings. Air-conditioned buildings were consistently associated with increased prevalence of work-related headache (POR = 1.3-3.1), lethargy (POR = 1.4-5.1), and upper respiratory/mucus membrane symptoms (POR = 1.3-4.8). Humidification was not a necessary factor for the higher symptom prevalence associated with air-conditioning. Mechanical ventilation without air-conditioning was not associated with higher symptom prevalence. The consistent associations found between type of building ventilation and reported symptom prevalence have potentially important public health and economic implications.
Asbestos and kidney cancer: the evidence supports a causal association.
The role of asbestos in the etiology of lung cancer and of mesothelioma of the pleura and peritoneum has been well documented. The evidence for a causal association between asbestos and other human cancers is not as extensive but suggests that asbestos may be carcinogenic at several different sites. This paper is concerned specifically with a possible causal association between asbestos and human kidney cancer. A review of the evidence to date indicates that only three human studies have sufficient statistical power to detect an excess mortality from kidney cancer among workers exposed to asbestos. All three were occupational cohort studies, and two of these gave strong direct evidence for such an excess; a study of U.S. insulators (kidney cancer SMR = 2.22, 90% CI 1.44-3.30), and a study of U.S. asbestos products company workers (kidney cancer SMR = 2.76, 90% CI 1.29-5.18). The third study, of Italian shipyard workers, reported excess mortality from "cancers of the kidney, urinary bladder, and other urinary organs" (SMR = 1.98, 90% CI 1.42-2.70). Further support for a causal association includes studies finding asbestos fibers in human kidneys and urine, as well as reports of kidney tumors in two animal bioassays. It is concluded that asbestos should be regarded as a probable cause of human kidney cancer.
Preservation of ileocecal junction and entire anal canal in surgery for ulcerative colitis--a "two-sphincter" operation.
Disruption of the terminal ileum and excision of the ileocecal junction during restorative proctocolectomy and formation of a pelvic ileal reservoir may lead to abnormalities of motility, transit, and absorption. We therefore preserved this portion of the gastrointestinal tract in 12 patients who underwent restorative proctocolectomy for ulcerative colitis. In each patient, the entire anal sphincter was preserved without mucosal stripping: the two sphincters were connected by a single loop of ileum without any reservoir. After median follow-up of 12 months, the functional results were similar to those seen with conventional pelvic ileal reservoirs and superior to the results of mucosal proctectomy and straight endoanal ileoanal anastomosis. This operation may be an alternative to standard restorative proctocolectomy for patients with ulcerative colitis.