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Biomedical subjects

D J Thomas

Publications and source records attributed to D J Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1999

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up.

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.

Adult↗
PubMed1999

Excretion of arsenic in urine as a function of exposure to arsenic in drinking water.

Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first morning urine voids for up to 5 consecutive days. The study population was 56% male, and 44% was younger than 18 years of age. On one day of the study period, all voided urines were collected over a 24-hr period. Arsenic intake from drinking water was estimated from daily food diaries. Comparison between the concentration of As in individual urine voids with that in the 24-hr urine collection indicated that the concentration of As in urine was stable throughout the day. Comparison of the concentration of As in each first morning urine void over the 5-day study period indicated that there was little day-to-day variation in the concentration of As in urine. The concentration of As in drinking water was a better predictor of the concentration of As in urine than was the estimated intake of As from drinking water. The concentration of As in urine did not vary by gender. An age-dependent difference in the concentration of As in urine may be attributed to the higher As dosage rate per unit body weight in children than in adults. These findings suggest that the analysis of a small number of urine samples may be adequate to estimate an individual's exposure to InAs from drinking water and that the determination of the concentration of InAs in a drinking water supply may be a useful surrogate for estimating exposure to this metalloid.

Adolescent↗
PubMed1999

The challenge of diagnosing the cause of jaundice.

The patient presenting with jaundice may have a variety of hepatobiliary or hematologic conditions. Understanding the causes of jaundice and the history and physical examination hallmarks provide the basis for choosing the most efficacious laboratory and diagnostic studies. A case report illustrating the reasoning involved in distinguishing between the different causes of jaundice is presented.

Bilirubin↗
PubMed1999

Vitamins: common supplements and therapy.

Vitamin supplements and therapies have recently gained popularity because of current scientific studies supporting their benefits. Although many consumers are taking vitamins and other supplements, they may not be aware of the numerous benefits and hazards associated with many of these over-the-counter substances. Clinicians should be familiar with common vitamin products so that they may prescribe and monitor their use. This article provides an overview of fat- and water-soluble vitamins, and addresses functions, deficiency effects, recommended dietary allowances, therapy uses, toxicity concerns, and food sources.

Adolescent↗
PubMed1997

A survey in the West Midlands on the use of the courtesy title 'Dr' by UK dental practitioners.

OBJECTIVE: To assess the 1995 General Dental Council's decision to remove restrictions on GDPs using the courtesy title 'Dr'. METHODS: In 1996 this survey undertook a qualitative analysis of the views of four groups involved in primary dental care: 72 GDPs, 25 medical practitioners, 46 vocational dental practitioners, 89 patients. RESULTS: These indicated that some respondents thought that there would possibly be better quality of patient care due to improved medical history taking, that the public's image of the dental profession might be enhanced and that 87% of newly qualified dentists were in favour of the use of the title 'Dr'. CONCLUSIONS: Use of the title appears to be on the increase and if use of the title does become widespread, then all practitioners will need to re-evaluate their choice of personal titles. GDPs need to consider if using the title 'Dr' will encourage patients to give more detailed medical histories.

Attitude of Health Personnel↗
PubMed1997

Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study.

BACKGROUND: Patients with gout are encountered frequently in clinical practice. Previous studies have suggested that hyperuricemia and gout may represent risk factors for coronary heart disease (CHD), the most common cause of death in American men. METHODS: Prospectively collected data from 2 longitudinal cohort studies of former medical students--371 black men in the Meharry Cohort Study and 1181 white men in the Johns Hopkins Precursors Study--were analyzed. The development of gout and of CHD was determined by physician self-report, and validated by using published criteria. The risk for CHD associated with gout was evaluated using Cox proportional hazards analysis. RESULTS: During a median follow-up of 30 years, there were 38 gout cases and 44 CHD events among the Meharry men, and 68 gout cases and 138 CHD events among the Hopkins men. Prior gout was not associated with an increased risk for incident CHD (relative risk = 1.20; 95% confidence interval, 0.37-3.92) among the Meharry men or among the Hopkins men (relative risk = 0.66; 95% confidence interval, 0.24-1.79). Multivariate analysis adjusted for known CHD risk factors did not alter these findings. CONCLUSION: These results, in black and white male physicians, do not suggest a role in men for targeting gout identification in the primary prevention of CHD.

Adult↗
PubMed1997

Binding of arsenicals to proteins in an in vitro methylation system.

The dynamics of interactions between rat liver cytosolic proteins and arsenicals were examined in an in vitro methylation system that contained cytosol, glutathione, S-adenosylmethionine, and 1 microM -73As-arsenite. After incubation at 37 degrees C for up to 90 min, low-molecular-weight components of the assay system (<10 kDa) were removed by ultrafiltration and cytosolic proteins were separated by size-exclusion chromatography on Sephacryl S-300 gel. Five 73As-labeled protein peaks were found in chromatographic profiles. The estimated molecular masses of 73As-labeled proteins eluting in the three earliest peaks were as follows: Vo, >/=1000 kDa; A, 135 kDa; and B, 38 kDa. Peak C eluted immediately before the total volume (VT) of the chromatographic column; peak D eluted after the VT. 73As bound to proteins was released by CuCl treatment and speciated by thin-layer chromatography. Amounts and ratios of inorganic As, methyl As, and dimethyl As associated with cytosolic proteins depended upon the incubation interval. Inorganic As was present in all protein peaks. Methyl As was primarily associated with peaks A and C; dimethyl As was associated with peaks B and C. To examine the effect of valence on the binding of methylarsenicals to cytosolic proteins, trivalent or pentavalent 14C-labeled methyl As or dimethyl As was incubated in an in vitro system designed to minimize the enzymatically catalyzed production of methylated arsenicals. Proteins in peaks A, B, and C bound preferentially trivalent methyl and dimethyl As. Peak D bound either trivalent or pentavalent methyl and dimethyl As. Protein-bound inorganic and methyl As were substrates for the production of dimethyl As in an in vitro methylation system, suggesting a role for protein-bound arsenicals in the biomethylation of this metalloid.

Animals↗
PubMed1997

In vitro methylation of inorganic arsenic in mouse intestinal cecum.

The capacity of mouse intestinal cecal microflora to methylate inorganic arsenicals (iAs) was examined in vitro under conditions of restricted bacterial growth. Cecal contents incubated under anaerobic conditions at 37 degrees C for 21 hr methylated up to 40% of either 0.1 microM arsenite (iAsIII) or 0.1 microM arsenate (iAsV). Methylarsenic (MAs) was the predominant metabolite; however, about 3% of either substrate was converted to dimethylarsenic (DMAs). Over the first 6 hr, the rate of methylation was several times greater for iAsIII than for iAsV. There was a 3-hr delay in the production of methylated metabolites from iAsV, suggesting that reduction of iAsV to iAsIII before methylation could be rate limiting. Over the concentration range of 0.1 to 10 microM of iAsIII or iAsV, there was an approximately linear increase in the production of MAs and DMAs. There was evidence of saturation or inhibition of methylation at 100 microM of either substrate. Substrate concentration had little effect on MAs/DMAs ratio. Incubation of cecal contents at 0 degrees C abolished methylation of either arsenical. Under aerobic or anaerobic conditions, cecal tissue homogenates produced little MAs or DMAs from either arsenical. Addition of potential methyl group donors, L-methionine and methylcobalamin, into cecal contents significantly increased the rate of methylation, especially for iAsV. Addition of glutathione, but not L-cysteine, had a similar effect. Selenite, a recognized inhibitor of iAs methylation in mammalian tissues, inhibited methylation of either substrate by cecal contents. These data suggest that cecal microflora are a high capacity methylation system that might contribute significantly to methylation of iAs in intact animals.

Animals↗
PubMed1997

Damage to bicycle helmets involved with crashes.

The objective was to evaluate the relationship between helmet damage and head injuries in helmeted bicyclists in a sub-study of a large case-control study of bicycle injuries and helmet effectiveness. The setting consisted of seven hospital emergency departments in Seattle, WA. Hospitalized patients and medical examiners cases were included. The participants in the study were helmeted bicyclists who suffered a head injury or who damaged or hit their helmet in a crash. The Snell Memorial Foundation laboratory evaluated the helmets, blinded to crash circumstance and injury diagnosis. Damage was scored on a five-point scale (0 = none to 4 = destroyed). The damage location for each helmet was coded into regions (six longitudinal and three latitudinal) and mapped onto a three-dimensional CAD (computer-aided design) model of a helmet. The same procedure was also followed for injury location, which was mapped onto a three-dimensional ISO (International Organization for Standardization) headform for visualization of head-injury distribution. 785 helmeted subjects met the criteria for inclusion in the sub-study, and 527 helmets were purchased and evaluated (67%). 316 (60%) of the helmets had no or minimal damage, and 209 (39.7%) had significant damage (score 2, 3 or 4). Helmet types were 49.7% hard shell, 34.2% thin shell and 16.1% no shell. The risk of head and brain injury increased if the helmet was destroyed: OR = 5.3 (95% CI 2.9, 9.9) and OR = 11.2 (95% CI 3.5, 37.9), respectively. A high proportion of helmet impacts were along the front edge of the helmet, with a preponderance of head injuries in the same region. The large number of impacts to the front rim of the helmet, combined with the substantial number of riders with injuries to the forehead, indicate that some helmets, because of poor fit or wearing style, expose the forehead to injury. In addition, the data indicate that for a small proportion of injuries, the energy to the helmet may exceed design limits.

Accidents, Traffic↗
PubMed1997

Comparative inhibition of yeast glutathione reductase by arsenicals and arsenothiols.

Tri(gamma-glutamylcysteinylglycinyl)trithioarsenite (AsIII(GS)3) is formed in cells and is a more potent mixed-type inhibitor of the reduction of glutathione disulfide (GSSG) by yeast glutathione (GSH) reductase than either arsenite (AsIII) or GSH. The present work examines the effects of valence and complexation of arsenicals with GSH or L-cysteine (Cys) upon potency as competitive inhibitors of the reduction of GSH disulfide (GSSG) by yeast GSH reductase. Trivalent arsenicals were more potent inhibitors than their pentavalent analogs, and methylated trivalent arsenicals were more potent inhibitors than was inorganic trivalent As. Complexation of either inorganic trivalent As or methylarsonous diiodide (CH3As(III)I2) with Cys or GSH produced inhibitors of GSH reductase that were severalfold more potent than the parent arsenicals. In contrast, dimethylarsinous iodide ((CH3)2As(III)I) was a more potent inhibitor than its complexes with either GSH or Cys. Complexes of CH3AsIII with GSH (CH3-AsIII(GS)2) or with Cys (CH3AsIII(Cys)2) were the most potent inhibitors, with Ki's of 0.009 and 0.018 mM, respectively. Inhibition of GSH reductase by arsenicals or arsenothiols was prevented by addition of meso-2,3-dimercaptosuccinic acid (DMSA) to a mixture of enzyme, GSSG, and inhibitor before addition of NADPH. DMSA added to the reaction mixture after NADPH reversed inhibition by (CH3)2As(III)I but had little effect on inhibition by CH3As(III)I2, Ch3AsIII(GS)2, CH3AsIII(Cys)2, or AsIII(GS)3. Partial redox inactivation of the enzyme with NADPH increased the inhibitory potency of CH3As(III)I2 and (CH3)2As(III)I and changed the mode of inhibition for CH3As(III)I2 from competitive to noncompetitive. The greater potency of methylated trivalent arsenicals and arsenothiols than of inorganic trivalent As suggests that biomethylation of As could yield species that inhibit reduction of GSSG and alter the redox status of cells.

Arsenicals↗
PubMed1997

Cardiovascular disease in African American and white physicians: the Meharry Cohort and Meharry-Hopkins Cohort Studies.

Differences in cardiovascular disease (CVD) were studied in a cohort of medical students from the classes of 1958-65 of Meharry Medical College (n = 435), all African Americans, and the classes of 1957-64 of Johns Hopkins University (n = 580), all white. At baseline, African Americans were older (27 vs. 24 years, p = 0.001), more likely to smoke (71 vs. 47 percent), had greater body mass index (24 vs. 23 kg/m), and had higher systolic blood pressure (120 vs. 116 mmHg). At follow-up (23-35 years later), African American physicians had higher CVD risk (RR = 1.65, 95% CI = 1.3-2.41), higher incidence of coronary artery disease (1.4 times), and much higher case fatality (51.5 vs. 9.4 percent). Risk factor levels in youth can predict CVD events several years later; predictors may differ between racial groups. Best predictors were cigarette smoking, cholesterol, and paternal history in white physicians, and blood pressure in African American physicians.

Adult↗
PubMed1996

Liberation and analysis of protein-bound arsenicals.

Protein-bound arsenicals were liberated from binding sites on liver cytosolic proteins by exposure to 0.1 M CuCl at pH 1. This method released greater than 90% of the arsenicals associated with biological matrices. Ultrafiltrates of CuCl-treated cytosols were subjected to thin-layer chromatography to speciate and quantify inorganic and methylated arsenicals. For rat liver cytosol in an in vitro methylation assay and for liver and kidney cytosols from arsenite-treated mice, most inorganic arsenic was protein bound. Appreciable fractions of the organoarsenical metabolites present in these cytosols were also protein bound. Therefore, CuCl treatment of cytosols releases protein-bound arsenicals, permitting more accurate estimates of the pattern and extent of arsenic methylation in vitro and in vivo.

Animals↗
PubMed1996

Mono- and dimethylation of arsenic in rat liver cytosol in vitro.

Production of methylarsonate and dimethylarsinate from radiolabelled [73 As]arsenite and [73 As]arsenate was examined in an assay system that contained cytosol prepared from a 20% homogenate (w/v) of livers from 8- 10-week-old male Fischer 344 rats. After a 60-min incubation at 37 degrees C with added S-adenosylmethionine and glutathione, up to 50% of carrier-free [73As]arsenite and about 15% of carrier-free [73As]arsenate were methylated. Incubation of cytosol at 100% degrees C for 1 min before addition to the assay system completely abolished methylation of arsenite. Production of methylarsonate increased in proportion to the arsenite concentration in the assay system; however, 50 microM arsenite inhibited production of dimethylarsinate. Methylarsonate production from carrier-free [73-As]arsenite was not dependent on addition of exogenous S-adenosylmethionine to the assay system. Addition of 0.1 mM S-adenosylmethionine maximized dimethylarsinate production. Addition of 0.1 or 1.0 mM S-adenosylhomocysteine decreased methylation of arsenite, especially dimethylarsinate production. Omission of glutathione from the assay system nearly abolished the methylation of arsenite. Addition of exogenous glutathione to the assay system (up to 20 mM) decreased protein binding of arsenic and increased the production of methylarsonate and dimethylarsinate. The effects of sodium selenite, mercuric chloride, EDTA, p-anisic acid and 2,3-dichloro-alpha-methylbenzylamine on the methylation of arsenite were determined. Addition of 10 microM selenite to the assay system nearly abolished the formation of either methylated species. Addition of 1 or 10 microM mercuric chloride inhibited dimethylarsinate production in a concentration-dependent manner but had little effect on methylarsonate yield. Addition of 10 mM EDTA to the assay system inhibited formation of both methylated metabolites, suggesting that an endogenous divalent cation might be involved in enzymatic methylation of arsenic. Neither p-anisic acid, an inhibitor of cytosolic methyltransferases, nor 2,3-dichloro-alpha-methylbenzylamine, an inhibitor of microsomal methyltransferases, inhibited the conversion of inorganic arsenic to mono- or dimethylated metabolites.

Animals↗
PubMed1996

The prediction of protein contacts from multiple sequence alignments.

We have studied the question of how much extra predictive power the correlated mutational behaviour of pairs of amino acid residues separated along a sequence has concerning the likelihood of those residues being in contact in the folded protein. The mutational behaviour is deduced from multiple sequence alignments. Our findings are that there is, indeed, some valuable information available from this source and that it is sufficient to make a significant improvement in our ability to predict contacts, when compared with earlier methods that do not take into account the correlations between the mutations. This improvement is approximately twice as large as can be obtained by the more economical method of simply averaging pair preferences over the same sequence alignment. Even when using a method based on pair preferences, a further significant improvement can be made by penalizing more variable regions (on the reasonable assumption that invariant residues are relatively more likely to be in contact), though we have found no way of improving the pair preference method to the extent that it matches the method based on correlated behaviour. Our new method is thought to be the best data-based method of contact prediction developed so far, achieving, on average, an improvement over a random (i.e. information-free) prediction of a factor of five when the number of contacts predicted is chosen to match the number that actually occur.

Algorithms↗
PubMed1996

Myasthenia gravis presenting with stridor.

The case is described of a 72 year old woman who presented with a two year history of exertional stridor in whom the diagnosis of myasthenia gravis was delayed. Although an uncommon cause, myasthenia gravis should be included in the differential diagnosis of stridor.

Aged↗
PubMed1996

Returning to work after liver transplant: experiencing the roadblocks.

Liver transplant has been the treatment of choice for people with end-stage liver disease since the mid-1980s. The theme of returning to work after liver transplantation emerged from the data of a phenomenological study examining the lived experience of people with liver transplants. Thirteen liver recipients were interviewed using a semistructured approach. Only one of the first nine participants was able to return to work after the transplant; therefore, the last four participants were purposely chosen because they had been able to return to work. The possibility of losing health insurance benefits and disability benefits prevented many participants from working. Those able to return to work had professional careers that afforded them flexibility in their work schedule. Some implications for health professionals lie in the area of healthcare and health insurance policy change. Avenues for health insurance reform could be explored in an effort to empower the transplant recipient.

Adaptation, Psychological↗