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Biomedical subjects

A Thomas

Publications and source records attributed to A Thomas.

At least 127 records · Page 7Linked to original sources
PubMed2001

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗
PubMed2001

Avulsed permanent incisors: knowledge and attitudes of primary school teachers with regard to emergency management.

OBJECTIVES: This study was designed to examine the knowledge and attitudes of primary school teachers with regard to the emergency management of avulsed permanent incisors. DESIGN: Data were collected by self-administered questionnaire. SETTING: The study was conducted in primary schools lying within a 2-mile radius of the University Dental Hospital, Cardiff. Sample and methods. A total of 388 teachers in 31 participating schools were asked to complete a questionnaire, which was subsequently collected by two of the authors (CS and AT). RESULTS: Two hundred and seventy-four teachers returned completed questionnaires, a response rate of 70.6%. One hundred and eighty-one respondents (60.1%) had received no advice about the emergency management of dental avulsion. Of the 133 teachers (48.5%) who possessed a first aid certificate, 39 (29.3%) had been given relevant advice as part of this training. Less than one-third of respondents (85 (31%)) cited an optimum extra-oral time of 30 min or less, with only 43 (15.7%) considering that this should be 10 min or less. However, 125 (45.6%) knew milk to be the best transport medium. Two hundred and four teachers (74.5%) stated that they would not be prepared to replant an avulsed tooth themselves, 133 (80%) basing this decision on lack of expertise and training. Two hundred and sixty-two teachers (95.6%) expressed a desire for further information. CONCLUSIONS: The majority of respondents possessed, at best, rudimentary knowledge of the emergency management of dental avulsion. Teachers, and other individuals who supervise children in schools, should receive simple instruction in dental first aid.

Animals↗
PubMed2001

Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASp) give rise to Wiskott-Aldrich syndrome (WAS), a condition that exhibits a wide spectrum of clinical severity. Patients may develop mild thrombocytopenia or suffer from a wide range of associated disorders including eczema, immune dysfunction, autoimmune disease and malignancy. The clinical diagnosis of Wiskott-Aldrich syndrome (WAS) can be difficult and is usually supported by the detection of WASp gene mutations using genetic analysis. Recently, protein-based assays have been used to demonstrate the absence of WASp in patients known to have WASp gene mutations. We have now reversed this approach and report on the use of immunoblot assays to rapidly diagnose WAS in 13 patients. There was a complete absence of WASp in 10 out of 13 patients and an abnormal protein form was detected in the remaining three patients. In all cases, subsequent genetic analysis confirmed the presence of a WASp gene mutation. We believe that protein-based assays should be employed as the first line of investigation in the diagnosis of WAS spectrum disorders.

Aged↗
PubMed2001

Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia.

Flavopiridol, a synthetic flavone, is currently under clinical investigation for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL). In this study, we examined the in vitro effects of flavopiridol and fludarabine on B-CLL cells from 64 patients (36 treated and 28 untreated) in terms of apoptosis induction and Bcl-2 family expression. Both flavopiridol and fludarabine induced apoptosis in all the samples tested with mean LD(50) values (+/- SD) of 59.7 nmol/l (+/- 36.5) and 6.2 micromol/l (+/- 7.5) respectively. Mean flavopiridol LD(50) values were not significantly different between the treated and untreated patient groups (P = 0.35), whereas the fludarabine LD(50) values were significantly higher in the previously treated patient group (P = 0.01). Bcl-2 and Mcl-1 expression were downregulated in both flavopiridol and fludarabine-induced apoptotic cells, but the increase in Bax expression that accompanied fludarabine-induced apoptosis was not evident in flavopiridol-treated cells. In addition, Bcl-2:Bax ratios were not predictive of flavopiridol cytotoxicity (P = 0.82), whereas they were highly predictive of in vitro responsiveness to fludarabine (P = 0.001). Overall, these findings suggest that flavopiridol exerts its cytotoxic effect through a novel cell-death pathway that is not subject to the Bcl-2 family mediated resistance mechanisms that reduce the efficacy of many conventional chemotherapeutic drugs.

Antineoplastic Agents↗
PubMed2001

Pseudotumour in von Willebrand disease.

Pseudotumour is a rare complication of haemophilia; it has previously been reported in patients with moderate or severe haemophilia and rarely in mild disease. We report a case of a proximal pseudotumour occurring in a 36-year-old patient with mild von Willebrand disease (vWD) who made a good recovery with conservative management. Surgery has been advocated as the optimal treatment for proximal pseudotumours due to the risk of continued bleeding and progression. However, in mild haemophilia or vWD, where the risk of spontaneous bleeds is low, conservative management may be an appropriate alternative.

Adult↗
PubMed2001

Rapid diagnostic evaluation of bronchial washings in patients with suspected coccidioidomycosis.

Coccidioidomycosis is a regionally common fungal infection, primarily affecting the lung. While in the majority of cases the tempo of the disease allows for a more leisurely diagnostic plan, including multiple serologic tests and culture of respiratory secretions, occasionally, patients will present with rapidly progressive, life-threatening pulmonary illness, in whom there is an urgent need for rapid diagnosis. Evaluation of respiratory secretions including expectorated sputum as well as bronchial washings are frequently available or obtained for diagnosing pulmonary infiltrates. We compared the sensitivity of the Papanicolaou stain with 10% potassium hydroxide digestion (10% KOH) and with calcofluor white (cw). The Papanicolaou test performed the best and should be used in the evaluation of suspected patients with coccidioidomycosis.

Benzenesulfonates↗
PubMed2001

Home enteral tube feeding following cerebrovascular accident.

BACKGROUND AND AIMS: In the UK, cerebrovascular accident (CVA) is the third commonest cause of death and the commonest diagnosis in patients receiving home enteral feeding (HETF). This study aimed to use data from the British Artificial Nutrition Survey (BANS) collected between 1996 and 1999 to assess the outcome of patients on HETF, including mortality, return to oral feeding, level of physical activity, and level of dependency, which has resource implications. RESULTS: it is estimated that about 1.7% of all patients suffering a CVA in the UK between 1996 and 1999 received HETF. At one year, 29.6% died while receiving HETF and another 13% returned to oral feeding. Mortality increased with age and was twice as high in those managed in nursing homes compared to those in their own homes. The patients receiving tube feeding spent only 0.6% of their time in hospital. A total of 43.9% of patients were bed-bound at home (1.9% unconscious) and an additional 30.3% were house-bound. Only 21.2% were independent, and the majority were totally dependent on their carers. In CVA patients on HETF the level of dependency was greater than for those with all types of diagnoses (n=12,997). CONCLUSION: This study has described the outcome of a large number of patients receiving HETF in the UK. Since patients spent less than 1% of their time in hospital, HETF relieves pressure on the expensive hospital environment, but places more demands on the carers, who have to deal with severely disabled patients. Recovery of swallowing function should be assessed intermittently to prevent unnecessary HETF.

Adolescent↗
PubMed2001

Psychological reactance: factor structure and internal consistency of the Questionnaire for the Measurement of Psychological Reactance.

Psychological reactance, the theory that people resist attempts to constrain either their thoughts or their behaviors (J. W. Brehm, 1966), has been an influential concept in social psychology. In an attempt to measure reactance, J. Merz (1983) developed the Questionnaire for the Measurement of Psychological Reactance (QMPR). Subsequent researchers (S.-M. Hong & R. Ostini, 1989; R. K. Tucker & P. Y. Byers, 1987) have debated both the exact factor structure and the psychometric stability of the QMPR. In the present study, 898 undergraduates completed the QMPR. Factor analysis suggested that psychological reactance is multidimensional. The authors found 3 factors underlying the QMPR, but the QMPR provided unreliable estimates for each of those factors. According to the results, the QMPR as currently written is psychometrically unsatisfactory.

Adolescent↗
PubMed2001

The effect of telepharmacy counseling on metered-dose inhaler technique among adolescents with asthma in rural Arkansas.

The increased prevalence, morbidity, mortality, and health costs associated with asthma among children suggest the need for accessible asthma education. This study examined the effect of telepharmacy counseling, using interactive compressed video, on metered-dose inhaler (MDI) technique and patient satisfaction among adolescents with asthma in rural Arkansas. The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study. Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI. The study used an experimental design with random assignment of participants to a telepharmacy counseling group (n = 15) or a control group (n = 21). Both groups participated in pre-test, post-test, and 2- to 4-week follow-up assessments for MDI technique and patients satisfaction (follow-up assessment only) via interactive compressed video. Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group (p < 0.001). There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions (p = 0.132). Both groups had high levels of satisfaction with the telepharmacy sessions. The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert. Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural, adolescent, predominantly African-American population.

Administration, Inhalation↗
PubMed2001

Maternal mortality in rural India: a hospital based, 10 year retrospective analysis.

OBJECTIVES: To estimate the maternal mortality ratio (MMR) in Ludhiana, a city of Northern India in order to determine the causes associated with MMR and to suggest ways to reduce it. METHODS: Retrospective analysis of the mortality records of obstetrics cases in Christian Medical College, Ludhiana, India. RESULTS: The mean MMR for the 10 year period was 785 per 100,000 live births. Of the total 116 reported maternal deaths, 44 (41.9%) were due to induced septic abortion. The reasons were unwanted pregnancy in 22 (50%) and 11 (25%) were female feticide. CONCLUSIONS: In our hospital based analysis, MMR was very high. Most maternal deaths are preventable by intervention at the appropriate time and it is important for health professionals, policy makers and politicians to implement the introduction of programs for reducing maternal mortality. Special emphasis should be placed on antenatal care, the establishment of a registration system and measures to abolish illegal abortion.

Abortion, Induced↗
PubMed2001

A randomised controlled trial comparing a dilating vaginal speculum with a conventional bivalve speculum.

Cervical smears are traditionally taken with the aid of a metal or disposable plastic bivalve speculum. Many women complain of discomfort with these specula. This study compares the efficacy and women's experiences of a new 'dilating speculum' called the Veda-scope, with a conventional metal bivalve speculum (Pederson). The aims of this study were: to determine whether the Veda-scope provides adequate visualisation of the cervix and vaginal walls and an adequate cervical cytology specimen; and to compare user acceptability and women's levels of comfort between the Veda-scope and the bivalve speculum. Sixty-four women were randomised to be examined with the Veda-scope and 60 with the bivalve speculum, by one of two operators. Each woman completed a questionnaire that included subjective views of their previous cervical smear experiences, and acceptability of the examination at the study consultation. Cytologists were blinded as to which speculum was used for cervical sampling. Of women examined, 7-83% of women found Veda-scope examinations comfortable, compared to 38-62% of women who found examinations with the bivalve comfortable; 94% of the women preferred the 'comfort' of the Veda-scope. The Veda-scope was as good as the bivalve speculum in providing samples for cytological analysis following the initial learning curve, and also provided markedly superior magnified views of the cervix and vaginal fornices.

Adult↗
PubMed2001

Current concepts in the polycystic ovary syndrome.

Over the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in approximately 50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.

Androgens↗
PubMed2001

Somatostatin, its receptors and analogs, in lung cancer.

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [(111)In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

Switch-over from tolcapone to entacapone in severe Parkinson's disease patients.

Forty patients affected by severe Parkinson's disease (PD) were treated with tolcapone as an adjunctive therapy to L-DOPA, for 3-7 months, until this drug was discontinued because of side-effects (2 diarrhoea, one of them with orthostatic hypotension, 2 increments of liver enzymes) or because of mandatory indications of the European drugs authority. All patients, after 3-6 months of L-DOPA therapy adjustments, received entacapone for 3 months again followed by withdrawal. L-DOPA daily dosage was significantly reduced by tolcapone and entacapone (p = 0.01 and 0.05). "On" time was increased by 15% during tolcapone treatment (p < 0.05), and by 8% during entacapone treatment. "Off" time was decreased by 16% during tolcapone and by 7% during entacapone treatment. Entacapone was withdrawn in the same patient who experienced diarrhoea and orthostatic hypotension during tolcapone because of recurrence of side-effects, in 6 patients because of increment of dyskinesias (with hallucinations) and in 1 patients because of rhythmic, jerking myoclonus.

Aged↗
PubMed2001

Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors.

We found that ROP Os/+ (Os/+) mice had diffuse glomerulosclerosis and glomerular hypertrophy and that their mesangial cells (the vascular smooth muscle cells of the glomerulus) displayed an apparent sclerosing phenotype. Since mesangial cells are the major source of scar tissue in glomerulosclerosis, we postulated that the sclerosis phenotype was carried by mesangial cell progenitors and that this phenotype could be derived from the bone marrow (BM). Therefore, we transplanted BM from Os/+ mice into congenic ROP +/+ mice (+/+ mice), which have normal glomeruli. We found that glomeruli of +/+ recipients of Os/+ marrow contained the Os/+ genotype, were hypertrophied, and contained increased extracellular matrix. Clones of recipient glomerular mesangial cells with the donor genotype were found in all +/+ recipients that developed mesangial sclerosis and glomerular hypertrophy, whereas +/+ recipients of +/+ BM had normal glomeruli. Thus, the sclerotic (Os/+) or normal (+/+) genotype and phenotype were present in, and transmitted by, BM-derived progenitors. These data show that glomerular mesangial cell progenitors are derived from the BM and can deliver a disease phenotype to normal glomeruli. Glomerular lesions may therefore be perpetuated or aggravated, rather than resolved, by newly arriving progenitor cells exhibiting a disease phenotype.

Animals↗
PubMed2001

Bcl-2 antisense oligonucleotides enhance the cytotoxicity of chlorambucil in B-cell chronic lymphocytic leukaemia cells.

We have previously shown that the Bcl-2 antisense oligonucleotide ODN 2009 can induce apoptosis in B-cell chronic lymphocytic leukaemia (B-CLL) cells. In this study we evaluated whether ODN 2009 could increase the sensitivity of B-CLL cells to Chlorambucil-induced cell death in vitro in order to establish whether the notion of antisense-mediated chemosensitisation could be applied to B-CLL. Bcl-2 antisense in combination with Chlorambucil resulted in a more marked reduction in Bcl-2 protein expression (p = 0.003), enhanced Bax expression (p < 0.0001) and increased apoptosis when compared to cells incubated with Chlorambucil alone (p = 0.03). This increased in vitro cytotoxicity demonstrates a proof of the concept that a combination of Bcl-2 antisense oligonucleotides with conventional chemotherapeutic drugs may elicit an enhanced therapeutic effect in B-CLL and should therefore be considered for further investigation in the form of a clinical trial.

Aged↗