Biomedical subjects

A H Smith

Publications and source records attributed to A H Smith.

At least 37 records · Page 2Linked to original sources

PubMed2000

Contamination of drinking-water by arsenic in Bangladesh: a public health emergency.

The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 micrograms of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic.

Arsenic↗

PubMed1999

Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity.

Focal segmental glomerulosclerosis (FSGS) is a pathological entity characterized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD). Recently, familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite markers. Linkage, multipoint analysis, and tests for heterogeneity were performed on the subsequent results. In addition, three small families were used for haplotype analysis. Evidence for linkage was found on chromosome 11q21-q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or to a previously described locus on chromosome 19q13. There were no shared haplotypes among affected individuals in the three smaller families. Our findings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes that cause familial FSGS will provide valuable insights into the molecular basis and pathophysiology of FSGS.

Adolescent↗

PubMed1999

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis. International Collaborative Group for the Study of Familial Focal Segmental Glomerulosclerosis.

BACKGROUND: Familial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530). METHODS: Families were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test. RESULTS: Linkage was excluded at a distance of +/- 5 to 10 CM for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60 CM interval in this area of chromosome 19q via multipoint analysis. CONCLUSIONS: FSGS has been called the "final common pathway" of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS.

Adolescent↗

PubMed1999

NO modulates myocardial O2 consumption in the nonhuman primate: an additional mechanism of action of amlodipine.

Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso-N-acetylpenicillamine (SNAP; 10(-7)-10(-4) M), bradykinin (10(-7)-10(-4) M), ramiprilat (10(-7)-10(-4) M), and amlodipine (10(-7)-10(-5) M). SNAP (-38 +/- 5.8%), bradykinin (-19 +/- 3.9%), ramiprilat (-28 +/- 2.3%), and amlodipine (-23 +/- 4.5%) each caused significant (P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-L-arginine methyl ester (10(-4) M) blunted the effects of bradykinin (-5.4 +/- 3.2%), ramiprilat (-4.8 +/- 5.0%), and amlodipine (-5.3 +/- 5.0%) but had no effect on the tissue response to SNAP (-38 +/- 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism.

Amlodipine↗

PubMed1999

Treatment of adolescent sex offenders with intellectual disabilities.

The problems of male adolescent sex offenders with intellectual disabilities were described and issues for treatment reviewed. A group treatment based on cognitive therapy was offered. Treatment methods and assessment of attitudes related to commission of sexual offenses were described. Four case studies of teenage male adolescent sex offenders with intellectual disabilities were presented. All subjects responded to treatment. Their individual differences related to their responses were discussed in the context of the type of denial exhibited by each subject. At the time of this study, 3 years had elapsed for 2 subjects and 4 years for the other 2 without a recurrence of an offense.

Adolescent↗

PubMed1999

Can centrifugation at increased G be used to predict results of 0G?

Can physiologic research on the effects of weightlessness be conducted using a centrifuge providing an increased G environment? The answer to this question, if affirmative can have extraordinary implications regarding physiologic research in space that now begs the answer to the more general and basic question, what is the 'best environment' to differentiate the biological effects of mass from weight? In considering the best environment, there are several important factors in support of conducting human and animal physiologic 'gravitational' research on centrifuges here on Earth. Increased G research using a centrifuge can be conducted for a small fraction of the cost of research in space. It can be made available to more scientists as the number of centrifuges for this type of research increases. There are far less-detailed and therefore much easier preparation requirements for animal and human studies on a centrifuge compared with space research.

Acceleration↗

PubMed1998

Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water.

Studies in Taiwan and Argentina suggest that ingestion of inorganic arsenic from drinking water results in increased risks of internal cancers, particularly bladder and lung cancer. The authors investigated cancer mortality in a population of around 400,000 people in a region of Northern Chile (Region II) exposed to high arsenic levels in drinking water in past years. Arsenic concentrations from 1950 to the present were obtained. Population-weighted average arsenic levels reached 570 microg/liter between 1955 to 1969, and decreased to less than 100 microg/liter by 1980. Standardized mortality ratios (SMRs) were calculated for the years 1989 to 1993. Increased mortality was found for bladder, lung, kidney, and skin cancer. Bladder cancer mortality was markedly elevated (men, SMR = 6.0 (95% confidence interval (CI) 4.8-7.4); women, SMR = 8.2 (95% CI 6.3-10.5)) as was lung cancer mortality (men, SMR = 3.8 (95% CI 3.5-4.1); women, SMR = 3.1 (95% CI 2.7-3.7)). Smoking survey data and mortality rates from chronic obstructive pulmonary disease provided evidence that smoking did not contribute to the increased mortality from these cancers. The findings provide additional evidence that ingestion of inorganic arsenic in drinking water is indeed a cause of bladder and lung cancer. It was estimated that arsenic might account for 7% of all deaths among those aged 30 years and over. If so, the impact of arsenic on the population mortality in Region II of Chile is greater than that reported anywhere to date from environmental exposure to a carcinogen in a major population.

Adult↗

PubMed1998

Comparison of in-vivo body composition using two Lunar dual-energy X-ray absorptiometers.

OBJECTIVE: To compare in-vivo composition analysis between two dual energy X-ray absorptiometers, a DPX and a DPX/L, from the same manufacturer (LUNAR), pre(Study A) and post(Study B) hardware changes on both absorptiometers. DESIGN: Comparison of (1) quality assurance (QA) data: air-counts low (38 keV), air-counts high (70 keV), air-counts ratio, percent spillover, R-delrin; and (2) total body compartments: total body tissue (TBTISS), total body fat (TBF), percent total body fat (%TBF), total body lean (TBLEAN), total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD), between the two absorptiometers. SETTING: Centre for Bone and Body Composition Research, University of Leeds. SUBJECTS: Study A, 14 normal subjects and Study B, a different cohort of 19 normal subjects, were scanned on both machines on the same day. RESULTS: In Study A, large significant differences were observed in the QA parameters between the two machines. The DPX, air-counts low and air-counts high, being 25% and 22% lower than the DPX/L. The Bland Altman method of analysis indicated that the DPX was significantly higher for TBTISS (0.3 kg), %TBF (2%) and TBF ( 1.4 kg) and correspondingly lower for TBLEAN (-1.0 kg). No significant difference was observed in TBBMC. After the hardware changes (Study B) a marked reduction in the differences in QA air-counts was observed. The DPX air-counts low was now 1% higher and air-counts high 8% lower than the DPX/L. The DPX had now only small significant negative differences for %TBF (-0.6%) and TBF (-0.4 kg) and a small significant positive difference for TBLEAN (0.4 kg), compared to the DPX/L. TBBMC difference although slightly increased, was still non-significant. CONCLUSIONS: The closer agreement observed in the QA parameters after the hardware changes was associated with a reduction in the mean differences, 95%CI of the mean differences and limits of agreement of the comparison of body composition analysis from the Lunar machines using the Bland-Altman method. The study indicates that the QA limits set for bone mineral analysis may require more stringent limits for body composition.

Absorptiometry, Photon↗

PubMed1998

Responses to treatment for sex offenders with intellectual disability: a comparison of men with 1- and 2-year probation sentences.

The present study compares the responses to treatment of sex offenders with intellectual disability receiving 1- and 2-year probationary sentences. There were seven subjects in each group. There were no differences between subjects with regard to age, IQ or previous offences. All subjects received group treatment which addressed issues of: denial, minimization and responsibility for the offence; harm done to the victim; behaviour consistent with offending; and victim awareness and confidentiality. The subjects were assessed on a standard questionnaire designed to assess attitudes consistent with sex offending. All subjects were convicted of either indecent exposure or offences against children. There was a significant difference between the groups at the end of the probation period with subjects sentenced to 2 years' probation showing greater improvement. Subjects receiving 1 years' probation retained a number of attitudes consistent with denial and minimization of their offence. Furthermore, follow-up data underlined the poorer response to treatment for the 1-year probation group in terms of re-offending rates and assessment of attitudes consistent with sex offending. The authors recommend that a court order for a 1-year period of probation with treatment is of little value when dealing with sex offenders with intellectual disability. Rather, a period of at least 2 years' probation with a treatment recommendation is suggested.

Adult↗

PubMed1998

Lung and kidney cancer mortality associated with arsenic in drinking water in Córdoba, Argentina.

BACKGROUND: Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Córdoba, Argentina, which has a well-documented history of arsenic exposure from drinking water. METHODS: Mortality from lung, kidney, liver and skin cancers during the period 1986-1991 in Córdoba's 26 counties was investigated, expanding the authors' previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population. RESULTS: We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group. CONCLUSIONS: The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear.

Argentina↗

PubMed1998

Arsenic levels in drinking water and the prevalence of skin lesions in West Bengal, India.

BACKGROUND: A cross-sectional survey was conducted between April 1995 and March 1996 to investigate arsenic-associated skin lesions of keratosis and hyperpigmentation in West Bengal, India, and to determine their relationship to arsenic water levels. METHODS: In all, 7683 participants were examined and interviewed, and the arsenic levels in their drinking water measured. RESULTS: Although water concentrations ranged up to 3400 microg/l of arsenic, over 80% of participants were consuming water containing <500 microg/l. The age-adjusted prevalence of keratosis was strongly related to water arsenic levels, rising from zero in the lowest exposure level (<50 microg/l) to 8.3 per 100 for females drinking water containing >800 microg/l, and increasing from 0.2 per 100 in the lowest exposure category to 10.7 per 100 for males in the highest exposure level (> or =800 microg/l). However, 12 cases with keratosis (2 females and 10 males) were drinking water containing <100 microg/l of arsenic. Findings were similar for hyperpigmentation, with strong dose-response relationships. Among those with hyperpigmentation, 29 cases were exposed to drinking water containing <100 microg/l. Calculation by dose per body weight showed that men had roughly two to three times the prevalence of both keratosis and hyperpigmentation compared to women apparently ingesting the same dose of arsenic from drinking water. Subjects who were below 80% of the standard body weight for their age and sex had a 1.6 fold increase in the prevalence of keratoses, suggesting that malnutrition may play a small role in increasing susceptibility. CONCLUSION: The surprising finding of cases who had arsenic-associated skin lesions with apparently low exposure to arsenic in drinking water needs to be confirmed in studies with more detailed exposure assessment. Further research is also needed concerning susceptibility factors which might be present in the exposed population.

Adolescent↗

PubMed1998

The treatment of six men with a learning disability convicted of sex offences with children.

This paper describes a cognitive therapy for men with a learning disability convicted of sex offences against children. Methods are described which focus the session, emphasize confidentiality, ensure that the patient accepts responsibility for the offence, and deal with issues of intent, harm done to the victim and sequences of offending behaviour. Methods for producing cognitive change are described. Patients were assessed regularly and data are presented in detail. While all six men showed improvement, there were several variables which interfered with the course of treatment. The study attempts to address two major problems in work with sex offenders: the difficulty of employing a controlled treatment design and the importance of a long follow-up period.

Adult↗

PubMed1998

Changes following community living skills training: a controlled study.

Fifty-seven adults with mild to moderate learning disability served as participants in a community living skills training programme. Twenty-nine were trained using in vivo techniques, 13 were taught using classroom techniques and 15 acted as a no treatment control group. Assessments of community living skills and adaptive behaviour found those receiving in vivo training performed significantly better than the other groups. Eventual placement in the community reflected this superiority.

Activities of Daily Living↗

PubMed1998

Diesel exhaust exposure and lung cancer.

We evaluated the relation between occupational exposure to diesel exhaust and cancer of the lung in a meta-analysis of 29 published cohort and case-control studies. Twenty-one of the 23 studies meeting the inclusion criteria had observed relative risk estimates greater than one. Pooled effect measures weighted by study precision indicated an increased relative risk (RR) for lung cancer from occupational exposure to diesel exhaust [RR = 1.33; 95% confidence interval (CI) = 1.24-1.44]. Subanalysis of case-control (RR = 1.33; 95% CI = 1.18-1.51) vs cohort studies (RR = 1.33; 95% CI = 1.21-1.47) and of studies that controlled for smoking (RR = 1.35; 95% CI = 1.20-1.52) vs those that did not (RR = 1.33; 95% CI = 1.20-1.47) produced results that did not differ from those of the overall analysis. On the other hand, cohort studies using internal comparisons (RR = 1.43; 95% CI = 1.29-1.58) showed higher relative risks than those using external comparisons (RR = 1.22; 95% CI = 1.04-1.44). Heterogeneity between studies was reduced when we stratified studies by the occupational setting in which exposure occurred. A positive duration-response relation was evident in those studies that were stratified by employment duration. This meta-analysis supports a causal association between increased risks for lung cancer and exposure to diesel exhaust.

Case-Control Studies↗

PubMed1997

Use of radioactive phosphorus in haematology.

Following the development of the cyclotron in 1932, radio-isotopes became available for use in medicine both as tracer substances and therapeutic agents. The father of nuclear medicine, Dr J. H. Lawrence, pioneered their use in a range of disease states and found that radio-isotopes were of enormous value in the diagnosis and treatment of haemopoetic disease, particularly the myeloproliferative disorders. Radioactive phosphorus 32P emerged as the radio-isotope of choice for the myelosuppressive treatment of myeloproliferative disorders. This article also describes the use of radio-isotopes in the treatment of other disorders: chronic myeloid leukaemia, chronic lymphocytic leukaemia and myeloma, work that is now largely forgotten. All myeloproliferative disorders may evolve without treatment into myelodysplastic syndrome or blast-cell transformation. It is accepted that life is prolonged in myeloproliferative disorders treated with 32P or alkylating agents, yet both are leukaemogenic. The ideal form of treatment for polycythaemia vera is unknown and will remain so, for patients with this disorder often outlive their physician and achieve 90% of normal life expectation. 32P remains the treatment of choice for elderly patients with polycythaemia vera.

Animals↗

PubMed1997

Relationship of urinary arsenic to intake estimates and a biomarker of effect, bladder cell micronuclei.

The purpose of this study was to investigate methods for ascertaining arsenic exposure for use in biomarker studies. Urinary arsenic concentration is considered a good measure of recent arsenic exposure and is commonly used to monitor exposure in environmental and occupational settings. However, measurements reflect exposure only in the last few days. To cover longer time periods exposure can be estimated using arsenic intake data, calculated by combining measures of environmental arsenic and inhalation/ingestion rates. We compared these different exposure assessment approaches in a population chronically exposed to arsenic in drinking water in northern Chile. The study group consisted of 232 people, some drinking water low in arsenic (15 micrograms/l) and others drinking water with high arsenic concentrations (up to 670 micrograms/l). First morning urine samples and questionnaire data, including fluid intake information, were collected from all participants. Exfoliated bladder cells were collected from male participants for the bladder cell micronuclei assay. Eight different indices of exposure were generated, six based on urinary arsenic (microgram As/l urine; microgram As/g creatinine; microgram InAs/l urine; microgram MMA/l urine; microgram DMA/l urine; microgram As/h, excreted), and two on fluid intake data (microgram As/day, ingested; microgram As/l fluid ingested-day). The relationship between the different exposure indices was explored using correlation analysis. In men, exposure indices were also related to a biomarker of effect, bladder cell micronuclei. While creatinine-adjusted urinary arsenic concentrations had the strongest correlations with the two intake estimates (r = 0.76, r = 0.81), unadjusted urinary arsenic showed the strongest relationship with bladder cell micronuclei. These data suggest that, in the case of the bladder, unadjusted urinary arsenic concentrations better reflect the effective target organ dose compared to other exposure measures for biomarker studies.

Adolescent↗

PubMed1997

Increased chronic acceleration exposure enhances work capacity.

Adult male chickens adapted to 1.75 or 2.5 G from long term centrifugation, were maximally exercised on an animal treadmill at 1 g (Earth's gravity) and compared with the exercise capacities of control chickens raised at 1 g. The increased-G birds had statistically significantly greater exercise capacities than the controls during the first 3 weeks of the study after the initial exercise exposure. Thereafter however for the following two months of the study, there was no difference in either group's exercise capacities. This early increased work capacity was attributed to the increased-G birds improved ability to maximize their muscular strength with neurological adaptation. The increased-G birds lost body mass at a 31% greater rate during exercise than the controls although this difference was not statistically significant. This increased body mass loss was considered to have resulted from increased use of glycogen during exercise.

Acceleration↗

PubMed1997

Micronuclei in exfoliated bladder cells among individuals chronically exposed to arsenic in drinking water.

Inorganic arsenic is an established cause of lung and skin cancer. Epidemiological evidence from Taiwan suggests that arsenic causes more fatal internal cancers, with the highest relative risks reported for bladder cancer. We conducted a cross-sectional biomarker study in a Chilean male population chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in their drinking water (average concentrations, 600 and 15 micrograms As/liter, respectively). A fluorescent version of the exfoliated bladder cell micronucleus (MN) assay was used employing fluorescence in situ hybridization with a centromeric probe to identify the presence (MN+) or absence (MN-) of whole chromosomes within micronuclei, thereby determining the mechanism of arsenic-induced genotoxicity in vivo. We divided the study population into quintiles by urinary arsenic levels and found an exposure-dependent increase in micronucleated cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The largest increase appeared when quintile 4 was compared to quintile 1 [prevalence ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+ increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN-increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that chromosome breakage was the major cause of MN formation. Prevalences of total MN, MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894 micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add additional weight to the hypothesis that ingesting arsenic-contaminated water enhances bladder cancer risk and suggest that arsenic induces genetic damage to bladder cells at drinking water levels close to the current United States Maximum Contaminant Level of 50 micrograms/liter for arsenic.

Adult↗