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Biomedical subjects

D J Thomas

Publications and source records attributed to D J Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2001

Brain CT infarction in patients with carotid atheroma. Does it predict a future event?

BACKGROUND: The aim of the present study was to investigate the predictive value for subsequent stroke of different patterns of brain CT infarction in patients with carotid atheroma. METHODS: Prospective study on 138 patients, with 138 carotid plaques, having, on presentation, a greater than 50 percent stenosis on duplex scanning and associated with an ipsilateral (to the plaque) amaurosis fugax (AF), hemispheric transient ischaemic attack (HTIA) or which were asymptomatic. This carotid artery defined the side of interest. All patients had a brain CT scan on presentation and subsequently were followed for a period of 1-5 years (mean 3.14). The baseline CT neurovascular findings on the side of interest were classified as pattern A (discrete subcortical and cortical infarctions), pattern B (haemodynamic infarctions, widespread white matter lesions, basal ganglia infarctions and lacunae) and normal CT. RESULTS: On follow-up, 5/27 (18.5 percent) of patients with pattern A, 4/38 (10.5 percent) with pattern B and 3/73 (4.1 percent) with normal CT appearance developed stroke in the hemisphere of interest (Cox regression: p=0.02). CONCLUSIONS: Pattern A confers an unfavourable prognosis in patients with carotid atheroma who are either asymptomatic or presented with amaurosis fugax or hemispheric transient ischaemic attacks.

Adult↗
PubMed2000

Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells.

Biomethylation is considered a major detoxification pathway for inorganic arsenicals (iAs). According to the postulated metabolic scheme, the methylation of iAs yields methylated metabolites in which arsenic is present in both pentavalent and trivalent forms. Pentavalent mono- and dimethylated arsenicals are less acutely toxic than iAs. However, little is known about the toxicity of trivalent methylated species. In the work reported here the toxicities of iAs and trivalent and pentavalent methylated arsenicals were examined in cultured human cells derived from tissues that are considered a major site for iAs methylation (liver) or targets for carcinogenic effects associated with exposure to iAs (skin, urinary bladder, and lung). To characterize the role of methylation in the protection against toxicity of arsenicals, the capacities of cells to produce methylated metabolites were also examined. In addition to human cells, primary rat hepatocytes were used as methylating controls. Among the arsenicals examined, trivalent monomethylated species were the most cytotoxic in all cell types. Trivalent dimethylated arsenicals were at least as cytotoxic as trivalent iAs (arsenite) for most cell types. Pentavalent arsenicals were significantly less cytotoxic than their trivalent analogs. Among the cell types examined, primary rat hepatocytes exhibited the greatest methylation capacity for iAs followed by primary human hepatocytes, epidermal keratinocytes, and bronchial epithelial cells. Cells derived from human bladder did not methylate iAs. There was no apparent correlation between susceptibility of cells to arsenic toxicity and their capacity to methylate iAs. These results suggest that (1) trivalent methylated arsenicals, intermediary products of arsenic methylation, may significantly contribute to the adverse effects associated with exposure to iAs, and (2) high methylation capacity does not protect cells from the acute toxicity of trivalent arsenicals.

Aged↗
PubMed2000

Patterns of cerebrovascular symptomatology associated with carotid atheroma.

The aim of this study was to identify ultrasonic tissue characteristics and stenosis of carotid plaques that correspond to amaurosis fugax, hemispheric transient ischaemic attack, and stroke. At total of 146 symptomatic carotid plaques (136 patients) associated with amaurosis fugax, hemispheric transient ischaemic attack, stroke, and having 50-99% stenosis on duplex, were studied. These plaques were imaged on duplex, captured in a computer and their grey scale median was evaluated to distinguish the dark (low grey scale median) from the bright (high grey scale median) plaques. Stenosis was assessed on duplex. The amaurosis fugax group corresponded to carotid plaques with low grey scale median and severe stenosis, as contrasted with the other two groups (hemispheric transient ischaemic attack and stroke) (P < 0.05). These results suggested that amaurosis fugax was dependent only on the instability of carotid plaques, whereas hemispheric transient ischaemic attack and stroke were both dependent on carotid plaques and other pathogenetic factors.

Adult↗
PubMed2000

Peripheral neuropathy associated with common variable immunodeficiency.

We report a patient with common variable immunodeficiency (CVID) who developed an axonal sensorimotor polyneuropathy, a hitherto unreported association to our knowledge. These conditions may be linked at the pathogenetic level, since some CVID patients are prone to the development of autoimmune disease.

Common Variable Immunodeficiency↗
PubMed2000

Factors influencing single mother's employment status.

Changes in the welfare system limit the length of time a person can receive welfare benefits, thus mandating employment for many current welfare recipients. Single mothers with young children who do not become employed will lose financial support for housing, food, clothing, and health care and place their own and their children's health and safety at risk. The purpose of this qualitative study was to explore women's experiences of being unemployed and to examine the barriers to employment perceived by single mothers who expressed a desire to be employed. Nine mothers were recruited from a larger sample of single mothers who had participated in a quantitative study about employment conducted 1 to 2 years earlier. Using focus group interviews, mothers were asked what it was like to be a single mother, and then what barriers to their employment they perceived. Two dimensions were identified from the mothers' statements. The first, a sense of obligation, included themes of "being there" for their own and their child's benefit and doing what it takes to optimize the child's growth and development. The second, negotiating the obstacles, referred to problems regarding child care, lack of involvement of the child's father and lack of support from relatives and friends for the mother's efforts toward securing employment. These findings have important implications for welfare reform, namely, that efforts aimed at moving nonemployed single mothers into the workforce will fail if these factors are not considered.

Adaptation, Psychological↗
PubMed2000

A new look at heart failure.

Heart failure is the number one hospital admission for the elderly and a leading client population for home care with numbers expected to rise steadily during the next decade. This article discusses systolic and diastolic heart failure, compensatory mechanisms, pathophysiology, and the signs and symptoms of right and left-sided heart failure. The most current treatment regimen for managing the heart failure patient in the home including medication, diet, activity, and patient education is presented.

Diet↗
PubMed2000

Plasmid transfer between the Bacillus thuringiensis subspecies kurstaki and tenebrionis in laboratory culture and soil and in lepidopteran and coleopteran larvae.

Plasmid transfer between Bacillus thuringiensis subsp. kurstaki HD1 and B. thuringiensis subsp. tenebrionis donor strains and a streptomycin-resistant B. thuringiensis subsp. kurstaki recipient was studied under environmentally relevant laboratory conditions in vitro, in soil, and in insects. Plasmid transfer was detected in vitro at temperatures of 5 to 37 degrees C, at pH 5.9 to 9.0, and at water activities of 0.965 to 0.995, and the highest transfer ratios (up to 10(-1) transconjugant/donor) were detected within 4 h. In contrast, no plasmid transfer was detected in nonsterile soil, and rapid formation of spores by the introduced strains probably contributed most to the lack of plasmid transfer observed. When a B. thuringiensis subsp. kurstaki strain was used as the donor strain, plasmid transfer was detected in killed susceptible lepidopteran insect (Lacanobia oleracea) larvae but not in the nonsusceptible coleopteran insect Phaedon chocleriae. When a B. thuringiensis subsp. tenerbrionis strain was used as the donor strain, no plasmid transfer was detected in either of these insects even when they were killed. These results show that in larger susceptible lepidopteran insects there is a greater opportunity for growth of B. thuringiensis strains, and this finding, combined with decreased competition due to a low initial background bacterial population, can provide suitable conditions for efficient plasmid transfer in the environment.

Animals↗
PubMed2000

The beliefs and practices of traditional birth attendants in the Manxili area of KwaZulu, South Africa: a qualitative study.

The World Health Organization recommends that people be within an hour of the nearest health care facility. In the Manxili region of KwaZulu, South Africa, difficult terrain and tribal fighting make this nearly impossible for pregnant women. Therefore, traditional birth attendants provide much of the midwifery services in this area. They have no medical training, and their beliefs and practices are not well understood. This study, therefore, gathered data on the beliefs and practices of seven attendants, using a case study analysis. Beneficial as well as harmful customs were identified and suggestions made for education of the attendants.

Aged↗
PubMed2000

Comparison of exertional indices following moderate training in collegiate athletes.

BACKGROUND: To better understand the inflammatory response to two divergent training modalities: running and weight training. METHODS EXPERIMENTAL DESIGN: prospective, repeat measures, observational study of subjects over the course of 8-10 weeks of training. Data analysis was consonant with this design and included a repeat measures ANOVA with multiple posthoc comparisons. The level of significance was set at 0.05. SETTING: collegiate athletic training facilities. PATIENTS: twenty-two subjects comprised the study group. These included both male and female collegiate athletes, ages 17-22 years of age with a mean height of 178.6 cm, a mean weight of 77.5 kg and a mean lean body mass of 67.2 kg. Exclusion criteria consisted of hemophilia or chronic conditions requiring anti-inflammatory medication. INTERVENTIONS: training for runners (n=11) consisted of multiple 5-km runs throughout the course of a 60-75 minute workout. For a comparable time period, weight trainers participated in multiple joint, total body strengthening workouts. MEASURES: four exertional indices were examined. These included serum levels of creatine kinase, lactate, Interleukin-6, and C-reactive protein. Assessments of these markers were made immediately before and after each training session. Three sessions were monitored over an 8-10 week period. RESULTS: The data show that moderate exertion is accompanied by modest increases in these markers. Mean serum values did not exceed 125 U/L for serum creatine kinase, 5 mM/I for lactates, and 2.6 pg/ml for IL-6. C-reactive protein was sporadically detectable in weight lifters only. These increases were detected immediately postexercise. Each training modality produced a unique profile for creatine kinase and IL-6, suggestive of a training effect. CONCLUSIONS: Overall, the levels for all exertional markers reported herein are well below those reported for exhaustive exercise. As consistent exhaustive efforts can catalyze overtraining syndromes, periodic assessments of these exertional indices could help to document the appropriateness of the training stimulus.

Adolescent↗
PubMed1999

Strain-dependent disposition of inorganic arsenic in the mouse.

Recent studies have suggested that polymorphisms in the methylation of inorganic arsenic (iAs) exist in animals and humans. Methylation of iAs is an important step in the elimination of arsenic. The objective of this study was to examine whether there are differences in iAs disposition, and hence methylation, between three strains of mice. Ninety-day-old female mice (strains: C3H/HeNCrlBR, C57BL/6NCrlBR, and B6C3F1/CrlBR) were administered [73As]arsenate or [73As]arsenite orally at dose levels of 0.5 or 5.0 mg As/kg. Another group of mice were administered [73As]arsenate (5.0 mg As/kg) intraperitoneally (i.p.). Disposition of [73As] was assessed by whole-body counting, and analysis of urine, feces and tissues for radioactivity. Urine was analyzed by chromatography for arsenic metabolites. Several strain- and dose-related effects in the disposition of [73As] were observed with both arsenicals. After oral administration, the clearance of [73As]arsenate, measured by whole-body counting, was dependent on the strain. However, because there was no strain dependence on clearance of [73As]arsenate administered i.p., the effect after oral administration may be due to a difference in absorption of arsenate between the strains. With increased oral dose of arsenate and arsenite, the clearance of [73As] was slower and there was higher tissue retention of [73As]. The percentage of metabolites excreted in urine also was affected by the administered dose. With increased dose, the percentage of arsenite and monomethylarsonic acid were significantly increased, and dimethylarsinic acid decreased. However, our results suggest there is no overall difference between these strains of mice with respect to disposition of iAs. A better understanding of the role of phenotype in the disposition and toxicity of iAs would reduce the uncertainty in arsenic risk assessment.

Animals↗
PubMed1999

Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples.

BACKGROUND: Prion diseases are associated with the accumulation of an abnormal isoform of cellular prion protein (PrPSc), which is the principal constituent of prions. Prions replicate in lymphoreticular tissues before neuroinvasion, suggesting that lymphoreticular biopsy samples may allow early diagnosis by detection of PrPSc. Variant Creutzfeldt-Jakob disease (variant CJD) is difficult to distinguish from common psychiatric disorders in its early stages and definitive diagnosis has relied on neuropathology. We studied lymphoreticular tissues from a necropsy series and assessed tonsillar biopsy samples as a diagnostic investigation for human prion disease. METHODS: Lymphoreticular tissues (68 tonsils, 64 spleens, and 40 lymph nodes) were obtained at necropsy from patients affected by prion disease and from neurological and normal controls. Tonsil biopsy sampling was done on 20 patients with suspected prion disease. Tissues were analysed by western blot to detect and type PrPSc, by PrP immunohistochemistry, or both. FINDINGS: All lymphoreticular tissues obtained at necropsy from patients with neuropathologically confirmed variant CJD, but not from patients with other prion diseases or controls, were positive for PrPSc. In addition, PrPSc typing revealed a consistent pattern (designated type 4t) different from that seen in variant CJD brain (type 4) or in brain from other CJD subtypes (types 1-3). Tonsil biopsy tissue was positive in all eight patients with an adequate biopsy sample and whose subsequent course has confirmed, or is highly consistent with, a diagnosis of variant CJD and negative in all patients subsequently confirmed to have other diagnoses. INTERPRETATION: We found that if, in the appropriate clinical context, a tonsil biopsy sample was positive for PrPSc, variant CJD could be diagnosed, which obviates the need for a brain biopsy sample to be taken. Our results also show that variant CJD has a different pathogenesis to sporadic CJD.

Adolescent↗
PubMed1999

Signal selection in high-resolution NMR by pulsed field gradients.

We describe a new and powerful computer program called TRIPLE GRADIENT which calculates optimized pulsed field gradient sequences for specific coherence pathway selection or rejection. Sequences can be computed for gradient coils acting along one, two, or three perpendicular axes. The program is based on the computational minimization of a penalty function formed from the summed amplitudes of the unwanted signals. The underlying mathematical analysis makes use of a vectorial representation of the way in which a gradient sequence suppresses different signals. It is argued that experiments using well-calculated gradient sequences are quicker and generally perform better than those using extensive phase cycling, especially when suppressing extremely strong solvent signals, and it is shown that in many cases gradient experiments of optimal signal-to-noise ratio can be performed. These claims are illustrated by spectra obtained from an HQQC experiment.

Algorithms↗
PubMed1999

Metabolism of arsenic in primary cultures of human and rat hepatocytes.

The liver is considered a major site for methylation of inorganic arsenic (iAs). However, there is little data on the capacity of human liver to methylate iAs. This work examined the metabolism of arsenite (iAs(III)), arsenate (iAs(V)), methylarsine oxide (MAs(III)O), methylarsonic acid (MAs(V)), dimethylarsinous acid (DMAs(III)), and dimethylarsinic acid (DMAs(V)) in primary cultures of normal human hepatocytes. Primary rat hepatocytes were used as methylating controls. iAs(III) and MAs(III)O were metabolized more extensively than iAs(V) and MAs(V) by either cell type. Neither human nor rat hepatocytes metabolized DMAs(III) or DMAs(V). Methylation of iAs(III) by human hepatocytes yielded methylarsenic (MAs) and dimethylarsenic (DMAs) species; MAs(III)O was converted to DMAs. The total methylation yield (MAs and DMAs) increased over the range of 0.1 to 4 microM iAs(III). However, DMAs production was inhibited by iAs(III) in a concentration-dependent manner, and the DMAs/MAs ratio decreased. iAs(III) (10 and 20 microM) inhibited both methylation reactions. Inhibition of DMAs synthesis resulted in accumulation of iAs and MAs in human hepatocytes, suggesting that dimethylation is required for iAs clearance from cells. Methylation capacities of human hepatocytes obtained from four donors ranged from 3.1 to 35.7 pmol of iAs(III) per 10(6) cells per hour and were substantially lower than the methylation capacity of rat hepatocytes (387 pmol of iAs(III) per 10(6) cells per hour). The maximal methylation rates for either rat or human hepatocytes were attained between 0.4 and 4 microM iAs(III). In summary, (i) human hepatocytes methylate iAs, (ii) the capacities for iAs methylation vary among individuals and are saturable, and (iii) moderate concentrations of iAs inhibit DMAs synthesis, resulting in an accumulation of iAs and MAs in cells.

Animals↗
PubMed1999

Methylarsenicals and arsinothiols are potent inhibitors of mouse liver thioredoxin reductase.

Thioredoxin reductase (TR, EC 1.6.4.5) was purified 5800-fold from the livers of adult male B6C3F1 mice. The estimated molecular mass of the purified protein was about 57 kDa. The activity of the purified enzyme was monitored by the NADPH-dependent reduction of 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB); this activity was fully inhibited by 1 microM aurothioglucose. Arsenicals and arsinothiols, complexes of As(III)-containing compounds with L-cysteine or glutathione, were tested as inhibitors of the DTNB reductase activity of the purified enzyme. Pentavalent arsenicals were much less potent inhibitors than trivalent arsenicals. Among all the arsenicals, CH(3)As(III) was the most potent inhibitor of TR. CH(3)As(III) was found to be a competitive inhibitor of the reduction of DTNB (K(i) approximately 100 nM) and a noncompetitive inhibitor of the oxidation of NADPH. The inhibition of TR by CH(3)As(III) was time-dependent and could not be reversed by the addition of a dithiol-containing molecule, 2,3-dimercaptosuccinic acid, to the reaction mixture. The inhibition of TR by CH(3)As(III) required the simultaneous presence of NADPH in the reaction mixture. However, unlike other pyridine nucleotide disulfide oxidoreductases, there was no evidence that mouse liver TR was inactivated by exposure to NADPH. Treatment with CH(3)As(III) did not increase the NADPH oxidase activity of the purified enzyme. Thus, CH(3)As(III), a putative intermediate in the pathway for the biomethylation of As, is a potent and irreversible inhibitor of an enzyme involved in the response of the cell to oxidative stress.

Animals↗
PubMed1999

Primary in situ extracorporeal shock wave lithotripsy in the management of ureteric calculi: results with a third-generation lithotripter.

OBJECTIVE: To review the results of primary in situ extracorporeal shock wave lithotripsy (ESWL) for the treatment of ureteric stones using a third-generation lithotripter, the Dornier MFL 5000 (Dornier Medizentechnic, Germany). PATIENTS AND METHODS: The study comprised a retrospective review of treatment outcome in 180 patients with 196 stones who were treated with primary in situ ESWL, assessing the success of this approach and establishing reasons for failure. RESULTS: At the 3-month follow-up, 88% of patients were stone-free; 21 patients failed ESWL and were treated by ureteroscopic stone extraction with no complications. Stone-free rates were 90% for upper ureteric, 89% for middle-third and 86% for lower-third calculi. Twenty-one patients required auxiliary procedures in the form of JJ stenting or nephrostomy. Failure of ESWL was associated with stone size (>1.3 cm) but not location or inadequate treatment. CONCLUSION: Where prompt access to ESWL is available, primary in situ ESWL remains an effective form of treatment for all ureteric calculi, although stone-free rates are lower for larger stones.

Female↗