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Biomedical subjects

A H Smith

Publications and source records attributed to A H Smith.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of lacidipine, a dihydropyridine calcium antagonist on renal function of hypertensive patients with renal insufficiency.

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.

Adult↗
PubMed1997

The Chief Scientist reports... A controlled investigation of changes following a programme of community living, skills training and the validation of these changes through relocation.

Fifty-seven adults with mild to moderate learning disabilities served as subjects in a community living skills training project. Twenty-nine subjects were trained using in vivo techniques, 13 were taught using classroom techniques and 15 subjects acted as a no-treatment control group. The effects of the training programme were assessed using videotaped assessments rated by independent observers and the in vivo techniques were found to be significantly superior to the teaching and no-treatment control conditions. These effects were still evident at one year and two year follow-up assessments. Two years after the final follow-up, eventual relocation was examined and the in vivo group were found to have significantly more independent living circumstances than either of the two control groups.

Activities of Daily Living↗
PubMed1997

Decrease in bladder cell micronucleus prevalence after intervention to lower the concentration of arsenic in drinking water.

Epidemiological studies performed in Taiwan, Argentina, and Chile suggest that ingestion of arsenic (As) may cause bladder cancer. Because of these findings, we previously investigated the relationship between As ingestion and genetic damage to the urothelium in two cross-sectional biomarker studies, one in Nevada and one in Chile. In both studies, we found that increased levels of micronucleated cells (MNCs) in exfoliated bladder cells were associated with elevated concentrations of As in drinking water, suggesting that As induces genetic damage to bladder cells. To further investigate this relationship, we conducted an intervention study in a subset of highly exposed men (n = 34) from the cross-sectional study in Chile. Subjects whose usual source of water contained about 600 micrograms/liter As were supplied with water lower in As (45 micrograms/liter) for 8 weeks, allowing ample opportunity for renewal and exfoliation of bladder epithelial cells. Mean urinary As levels decreased during the intervention from 742 to 225 micrograms/liter. Bladder MNC prevalence also decreased from 2.63 MNCs/1000 cells preintervention to 1.79 MNCs/1000 cells postintervention (P < 0.05). When the analysis was limited to individuals previously having subcytotoxic urinary As levels (< 700 micrograms/liter), the change between pre- and postintervention MNC was more pronounced: the level decreased from 3.54 to 1.47 MNCs/1000 cells, respectively (P = 0.002). Among smokers, MNC prevalences decreased from 4.45 MNCs/1000 cells preintervention to 1.44 MNCs/1000 cells postintervention (P = 0.002). Among nonsmokers, the decrease was much smaller: 2.04 MNCs/1000 cells preintervention to 1.90 MNCs/1000 cells postintervention (P = 0.25), suggesting that smoker's bladder cells could be more susceptible to genotoxic damage caused by As. The reduction in bladder MNC prevalence with reduction in As intake provides further evidence that As is genotoxic to bladder cells.

Adult↗
PubMed1996

Audit of the outcome of patients with renal failure presenting to a regional nephrology service.

AIM: To assess the outcome of patients with renal failure presenting to a regional nephrology unit. METHODS: The records of patients with plasma creatinine concentration > or = 0.30 mmol/L who presented between 1 January 1988 and 31 December 1993, or were already under follow up, were studied. RESULTS: The outcome of 491 patients (293 males) aged from 4.8 to 88.8 years, 123 of whom had acute renal failure, was assessed at 30 June 1994. Thirty seven (30%) of the patients with acute renal failure had died. Of the 372 patients with chronic renal failure 139 had started regular dialysis treatment and 95 were dead, including 27 patients, with a mean age of 71 years, who died of untreated end-stage renal failure (ESRF). For 11 (40%) of these patients the patient and/or family made the decision not to start dialysis treatment. The rates of treatment of ESRF are lower in Canterbury and Westland than those in the Auckland region. The latter can be explained partly by the differences in the demography of the respective populations. CONCLUSION: Death from untreated ESRF is uncommon in Canterbury and Westland. The rates of treatment of ESRF with regular dialysis are lower than in the Auckland region.

Acute Kidney Injury↗
PubMed1996

Chrysotile asbestos is the main cause of pleural mesothelioma.

In contrast to amphibole forms of asbestos, chrysotile asbestos is often claimed to be only a minor cause of malignant pleural mesothelioma, a highly fatal cancer of the lining of the thoracic cavity. In this article we examine the evidence from animal and human studies that relates to this issue. Reported data do not support widely quoted views regarding the relative inertness of chrysotile fibers in mesothelioma causation. In fact, examination of all pertinent studies makes it clear that chrysotile asbestos is similar in potency to amphibole asbestos. Since asbestos is the major cause of mesothelioma, and chrysotile constitutes 95% of all asbestos use world wide, it can be concluded that chrysotile asbestos is the main cause of pleural mesothelioma in humans.

Air Pollutants, Occupational↗
PubMed1996

Use of the fluorescent micronucleus assay to detect the genotoxic effects of radiation and arsenic exposure in exfoliated human epithelial cells.

The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN-) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. We also applied the assay to exfoliated bladder cells of 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 micrograms As/L) and 18 matched controls (average level, 16 micrograms As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN-) and those containing whole chromosomes (MN+) both increased (1.65-fold, P = 0.07, and 1.37-fold, P = 0.15, respectively), suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN- frequency increased 2.06-fold (P = 0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN- and MN+ were positively associated with urinary arsenic and its metabolites. However, the association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can now be determined in epithelial tissues.

Adult↗
PubMed1996

Intraocular melanoma linked to occupations and chemical exposures.

We conducted a case-control study in the western United States to determine the relation between occupations or chemical exposures and increased risk of uveal melanoma. Among men (221 patients, 447 controls), we found increased risks for occupational groups who had intense exposure to ultraviolet light [odds ratio (OR) = 3.0; 95% confidence interval (CI) = 1.2-7.8], welding exposure (OR = 2.2; 95% CI = 1.3-3.5), and asbestos exposure (OR = 2.4; 95% CI = 1.5-3.9 for most likely exposed). The highest odds ratio was for the small number of men (nine cases, three controls) who were chemists, chemical engineers, and chemical technicians (OR = 5.9; 95% CI = 1.6-22.7). Odds ratios also were elevated for exposures to antifreeze, formaldehyde, pesticides, and carbon tetrachloride, but these findings, based on recall of specific chemical exposures, are more subject to recall bias than the findings based on occupational groups.

Asbestos↗
PubMed1996

Bladder cancer mortality associated with arsenic in drinking water in Argentina.

Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan.

Adolescent↗
PubMed1996

Elevated symptom prevalence associated with ventilation type in office buildings.

The California Healthy Building Study was designed to assess relations between ventilation system type and office worker symptoms in a set of U.S. buildings selected without regard to worker complaints. Twelve public office buildings in northern California meeting specific eligibility criteria were studied in the summer of 1990: three naturally ventilated, three mechanically ventilated (without air conditioning), and six air-conditioned buildings. Questionnaire data were collected from 880 workers in selected spaces within the study buildings. We adjusted effect estimates for various ventilation types for personal, job, and work place factors using logistic regression, and alternatively, using a mixed effects model (SAS/GLIMMIX) to adjust for correlated responses within study spaces. Higher adjusted prevalences of most symptom outcomes were associated with both mechanical and air-conditioned ventilation, relative to natural. With a conservative adjustment for problem building status, the highest adjusted prevalence odds ratios from logistic regression models were for dry or itchy skin [mechanical: odds ratio (OR) = 6.0, 95% confidence interval (CI) = 1.6-22; air-conditioned: OR = 6.0, 95% CI = 1.7-21] and lower respiratory symptoms (mechanical: OR = 2.9, 95% CI = 0.7-11; air-conditioned: OR = 4.0, 95% CI = 1.1-15). GLIMMIX estimates were similar, with slightly wider confidence intervals. Reporting bias was small. These findings of symptom increases within mechanically ventilated and air-conditioned U.S. buildings support previous findings available only from European buildings.

Adult↗
PubMed1996

Consideration of background exposures in the management of hazardous waste sites: a new approach to risk assessment.

The current approach to health risk assessment of toxic waste sites in the U.S. may lead to considerable expenditure of resources without any meaningful reduction in population exposure. Risk assessment methods used generally ignore background exposures and consider only incremental risk estimates for maximally exposed individuals. Such risk estimates do not address true public health risks to which background exposures also contribute. The purpose of this paper is to recommend a new approach to risk assessment and risk management concerning toxic waste sites. Under this new approach, which we have called public health risk assessment, chemical substances would be classified into a level of concern based on the potential health risks associated with typical national and regional background exposures. Site assessment would then be based on the level of concern for the particular pollutants involved and the potential contribution of site contaminants to typical background human exposures. While various problems can be foreseen with this approach, the key advantage is that resources would be allocated to reduce the most important sources of human exposure, and site remediation decisions could be simplified by focussing on exposure assessment rather than questionable risk extrapolations.

Arsenic↗
PubMed1996

Arsenic methylation patterns before and after changing from high to lower concentrations of arsenic in drinking water.

Inorganic arsenic (In-As), an occupational and environmental human carcinogen, undergoes biomethylation to monomethylarsonate (MMA) and dimethylarsinate (DMA). It has been proposed that saturation of methylation capacity at high exposure levels may lead to a threshold for the carcinogenicity of In-As. The relative distribution of urinary In-As, MMA, and DMA is used as a measure of human methylation capacity. The most common pathway for elevated environmental exposure to In-As worldwide is through drinking water. We conducted a biomarker study in northern Chile of a population chronically exposed to water naturally contaminated with high arsenic content (600 micrograms/l). In this paper we present the results of a prospective follow-up of 73 exposed individuals, who were provided with water of lower arsenic content (45 micrograms/l) for 2 months. The proportions of In-As, MMA, and DMA in urine were compared before and after intervention, and the effect of other factors on the distribution of arsenic metabolites was also analyzed. The findings of this study indicate that the decrease in arsenic exposure was associated with a small decrease in the percent In-As in urine (from 17.8% to 14.6%) and in the MMA/DMA ratio (from 0.23 to 0.18). Other factors such as smoking, gender, age, years of residence, and ethnicity were associated mainly with changes in the MMA/DMA ratio, with smoking having the strongest effect. Nevertheless, the factors investigated accounted for only about 20% of the large interindividual variability observed. Genetic polymorphisms in As-methylating enzymes and other co-factors are likely to contribute to some of the unexplained variation. The changes observed in the percent In-As and in the MMA/DMA ratio do not support an exposure-based threshold for arsenic methylation in humans.

Adult↗
PubMed1996

Methylation study of a population environmentally exposed to arsenic in drinking water.

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.

Adolescent↗
PubMed1996

DMSA renal scans in adults with acute pyelonephritis.

The 99mTc-DMSA scan is accepted as the most sensitive imaging modality for detecting areas of renal parenchymal scarring. More recently the DMSA scan has also been shown to be of value in imaging areas of renal parenchymal involvement in both children and adults with acute pyelonephritis. We assessed the acute DMSA scan findings in a consecutive series of 81 patients hospitalized with acute pyelonephritis. Acute pyelonephritis was diagnosed if the patient had a fever of > 37.8 degrees C, loin pain or tenderness and infected urine (99% Escherichia coli). Patients had a blood culture taken (8 positive), as well as a hematological (leukocytosis 75%) and biochemical screen, C-reactive protein (CRP) (increased in 57 of 66 [86%]) and urinary tract ultrasonography. If the initial DMSA scan was abnormal it was repeated after three months and in some instances again at six months. If persisting defects were noted an intravenous urogram was then undertaken. Of the 81 patients, 37 (46%) had an abnormality on the DMSA scan. Nineteen had a single defect, 12 multifocal defects, five features suggestive of pre-existing renal parenchymal scarring (all later shown to have reflux nephropathy) and one a shrunken kidney. Those patients with an abnormal scan had a higher CRP concentration than those with a normal scan. Of the 31 patients who had either a focal or multifocal defect on their initial DMSA scan there was adequate follow-up on 24 patients. In 18 of these the defects had resolved by six months (usually within three months), while of the remainder, three were shown to have reflux nephropathy, one had a large single renal cyst and another an area of parenchymal calcification. Fifty-three of 76 patients (70%) had normal ultrasonography. In adults with acute pyelonephritis, the DMSA scan may prove to be the most useful renal imaging procedure.

Acute Disease↗
PubMed1996

Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.

Aminoglycosides are drugs of choice for severe gram-negative urinary tract sepsis. Recent evidence suggests that they are just as efficacious, but less nephrotoxic and ototoxic, if given as a single daily dose rather than in divided doses. We considered that a single, large dose of an aminoglycoside followed by oral therapy with a different antibiotic might be equally effective and possibly less toxic. This randomized, controlled study compared a single large i.v. dose (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the treatment of patients with suspected acute pyelonephritis requiring hospitalization for parenteral antibiotic treatment. All patients were switched to oral ciprofloxacin either four hours after the S dose or when clinically appropriate in the M regimen. For all patients the total duration of treatment was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled. Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm were cured bacteriologically (sterile urine 7-10 days after treatment). In 41 patients high tone audiometry was carried out before or very soon after the start of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were mild and not different between groups. Substantial cost savings occurred in the S group. In summary, a large single dose of gentamicin was comparable in efficacy and toxicity to a standard regimen, but cheaper and more convenient to use.

Acute Disease↗
PubMed1995

Case-control study of bladder cancer and arsenic in drinking water.

Mortality from several cancers, including bladder cancer, is elevated in a Taiwanese population exposed to high levels of arsenic in drinking water. Data from the Utah respondents to the National Bladder Cancer Study conducted in 1978 were used to evaluate these associations in a US population exposed to measurable, but much lower, levels of drinking water arsenic. Two indices of cumulative arsenic exposure were used, one representing total cumulative exposure (index 1) and the other, intake concentration (index 2). Overall, there was no association of bladder cancer with either measure; however, among smokers, but not among nonsmokers, positive trends in risk were found for exposures estimated for decade-long time periods, especially in the 30- to 39-year period prior to diagnosis. Exposures were in the range 0.5-160 micrograms/liter (mean, 5.0 micrograms/liter). The data raise the possibility that smoking potentiates the effect of arsenic on risk of bladder cancer. However, the risk estimates obtained are much higher than predicted on the basis of the results of the Taiwanese studies, raising concerns about bias or the role of chance. Confirmatory studies are needed.

Adult↗
PubMed1995

Enteric absorption of ciprofloxacin during the immediate postoperative period.

We studied the enteric absorption of ciprofloxacin immediately following major abdominal surgery to determine if this drug could replace parenteral agents. Nine critically ill subjects received ciprofloxacin, 750 mg, every 12 h for 48 h via nasogastric tube. Drug concentrations were measured after the first and fourth doses. There was insignificant absorption after the initial dose, Cmax = 0.6 +/- 0.6 (mg/L) and AUC0-12 = 3.5 +/- 3.2 (mg.h/L). Unfortunately, serum ciprofloxacin concentrations were also minimally detectable in three of nine subjects after the fourth dose. Enteric absorption of ciprofloxacin, therefore, was erratic and unpredictable in critically ill patients following major abdominal surgery.

Abdomen↗
PubMed1995

Meta-analysis of studies of lung cancer among silicotics.

The relation between exposure to crystalline silica and lung cancer has been a controversial topic, and findings have appeared inconsistent. In this paper, we focus on lung cancer risks in epidemiologic studies of silicotics. We abstracted data from 29 studies for quantitative evaluation. We identified several studies that suffered from biases due to competing risks of different causes of death--in particular, death due to silicosis itself. After adjustment for competing risks, all 29 studies demonstrated lung cancer relative risk (RR) estimates greater than one. The pooled RR estimate for the 23 studies that could be combined was 2.2, with a 95% confidence-interval (CI) of 2.1-2.4. The pooled estimates by study design were 2.0 (95% CI = 1.8-2.3) for cohort studies and 2.5 (95% CI = 1.8-3.3) for case-control studies. The proportional mortality studies combined gave a summary RR of 2.0 (95% CI = 1.7-2.4), whereas the studies of cancer incidence gave a summary RR of 2.7 (95% CI = 2.3-3.2). Although statistical tests demonstrated heterogeneity between studies, and the confidence intervals given above may therefore be a little too narrow, the overall findings could not be attributed to chance, confounding by smoking, or other sources of bias. We conclude that the association between silicosis and lung cancer is causal, either due to silicosis itself, or due to a direct effect of the underlying exposure to silica.

Bias↗