Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 235 records · Page 13Linked to original sources

PubMed1999

Evaluation of cochlear implantation in post-meningitic adults.

Meningitis is an important cause of deafness and in some studies has been associated with poorer outcomes in adult patients following cochlear implantation. Of the first 100 adults implanted under the Midland Cochlear Implant Programme, 28 were deafened as a result of meningitis. We compare our experience with these patients with patients with a non-meningitic aetiology. A degree of cochlear ossification was a more common finding in the meningitic group. In six cases (four meningitis, two non-meningitis) ossification was encountered only during surgery, not being apparent on pre-operative radiology. The average scores achieved on auditory tests by the meningitic group were similar to those achieved by non-meningitic patients. At nine months, using only the implant, users were able to identify 54 per cent of common environmental sounds, achieved an average score of 30 words per minute on connected discourse tracking and identified an average of 42 per cent of words correctly in BKB sentences. Poorer outcomes were more commonly associated with cochlear ossification. In patients with cognitive and neurological sequelae, benefits with the implant were not always apparent in the early months, however, with intensive therapy these patients can obtain measurable sustained benefit from their implant.

Adult↗

PubMed1999

Rural-urban differences in food and nutrient intake of Pakistani children.

BACKGROUND: Global increase in urbanisation accompanied by increase in complexity of nutritional problems is a cause of concern for most nations. OBJECTIVE: The aim of this study was to assess the differences in frequency of food consumption and nutrient intake of urban and rural Pakistani children. SETTING: Forty rural, 59 middle income urban and 81 affluent urban children belonging to the province of Punjab. Children were recruited through schools in Lahore and Rayonpura, Kala-Shah-Kaku (Sheikhupura district). METHOD: Three-day estimated diet records were kept by a total of 180, 10-12 year old school-children. The nutrient intake was calculated by the nutritional analysis package COMP-EAT and analysed on SPSS. The results of the three groups were compared. RESULTS: Consumption of chapati, eggs, yoghurt and some of the traditional vegetarian snacks was very similar in all the three groups. Consumption of lentils, cooked vegetables, paratha (fried Asian bread) and tea decreased and that of milk, meat curry, chicken curry, chocolates, cakes, ice-cream, fruit and raw vegetables increased with urbanization. As compared with the rural children, the urban children had a higher mean daily intake of calories, sugar, protein, total fats, cholesterol, calcium, sodium, potassium, niacin, vitamin B12, folic acid, antioxidant vitamins A, C and E and lower intake of total carbohydrates, fibre and starch. CONCLUSION: It is concluded that although the macro-nutrient consumption pattern of rural children appears to be heart healthy lower consumption of protective micro-nutrients by them may put them at risk. In view of rapid urbanisation and its multidimensional impacts on the health of the populations living in the urban areas of the developing world, these dietary trends provide baseline information for health professionals.

Child↗

PubMed1998

Virus-induced immunoinflammatory lesions in the absence of viral antigen recognition.

Herpetic stromal keratitis (HSK) is a CD4+ T cell-controlled immunopathologic lesion in the eye that results from infection with herpes simplex virus (HSV). Target Ags involved in HSK remain undefined. In this study, we determined if HSK could be induced in animals genetically incapable of generating HSV Ag-specific CD4+ T cells. Mice bearing transgenic TCR specific to OVA peptide 323-339 (DO11.10) were crossed to SCID mice whose offspring (Tg-SCID) possessed CD4+ T cells, >98% of which expressed the OVA peptide-specific TCR. HSV infection of Tg-SCID mice was lethal, and mice failed to generate detectable T cell responses even after repeated immunization with a mutant avirulent virus (AN-1). Immunization with AN-1 virus followed by ocular challenge with HSV resulted in ocular inflammation before encephalitis, in contrast to the protection conferred in the control BALB/c and DO11.10 mice. These results indicate that clinical HSK may not require viral Ag recognition by CD4+ T cells and that T cells of irrelevant specificity can be recruited, activated, and driven into effector function in the HSV-infected cornea. This is suggested to represent a bystander activation effect resulting from the presence of proinflammatory mediators resulting from HSV replication.

Animals↗

PubMed1998

Predictors of differential response to clozapine and haloperidol. Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: We sought to identify baseline predictors of response to clozapine. METHODS: Data were from a 15-site randomized clinical trial comparing clozapine and haloperidol in hospitalized patients with refractory schizophrenia (n = 423). Three-month outcomes were analyzed with the full sample (n = 368 due to attrition). Because of crossovers, analyses of 12-month outcomes were conducted with crossovers excluded (n = 291). Clinical predictors included age, race, diagnosis (current substance abuse, paranoid subtype of schizophrenia, or depressive syndrome), severity of symptoms, quality of life, age at onset of schizophrenia, extrapyramidal symptoms, and VA compensation payment. Multiple regression analysis was used to examine the interaction of treatment condition and each of these variables in predicting outcomes for symptoms, quality of life, side effects, and days hospitalized. RESULTS: Patients with higher quality of life at baseline (p = .04) and higher symptoms (p = .02) had relatively smaller declines in hospital days at 6 months. In the 12-month sample patients with higher levels of symptoms had greater symptom reductions at 12 months (p = .03) and greater improvement in quality of life (p = .004). CONCLUSIONS: Although high levels of symptoms were associated with greater improvement on clozapine, these findings are not robust enough to suggest that any specific, clinically defined subgroup of refractory patients should be preferentially targeted for clozapine treatment.

Adult↗

PubMed1998

Immunopathology of herpetic stromal keratitis: discordance in CD4+ T cell function between euthymic host and reconstituted SCID recipients.

Infection of the mouse cornea with herpes simplex virus (HSV) results in an immunopathologic disease of the eye termed herpetic stromal keratitis (HSK), in which the principal orchestrator is the CD4+ T cell. The mouse genotype largely determines susceptibility or resistance to HSK. BALB/c mice (H2dIgh-1a) are susceptible, while its congenic C.B-17 strain (H2dIgh-1b), which differs only in the Ig heavy chain locus, is resistant to HSK. As the magnitude and duration of viral replication as well as anti-HSV immune responses were similar in both strains, it was determined whether resistance was due to failure of CD4+ T cells to organize the immunopathologic reaction. Adoptive transfer of HSV-primed or naive CD4+ T cells from resistant C.B-17 strain into HSV-infected SCID mice resulted in HSK lesions indistinguishable from those caused by similar transfers of BALB/c CD4+ T cells. Similar results were obtained with transfers of whole T cell populations as well as with unfractionated splenocytes from the resistant mice. These results show that while intact C.B-17 mice exhibit resistance to HSK, they possess potentially pathogenic CD4+ T cells in their repertoire. The data suggest that the HSV-infected SCID mouse provides a proinflammatory microenvironment that overrides regulatory controls and/or cause activation of quiescent cells into aggressive effector T cells that orchestrate HSK.

Adoptive Transfer↗

PubMed1998

Tools, information sources, and methods used in deciding on drug availability in HMOs.

The use and importance of specific decision-making tools, information sources, and drug-use management methods in determining drug availability and use in HMOs were studied. A questionnaire was sent to 303 randomly selected HMOs. Respondents were asked to rate their use of each of four formal decision-making tools and its relative importance, as well as the use and importance of eight information sources and 11 methods for managing drug availability and use, on a 5-point scale. The survey response rate was 28%. Approximately half of the respondents reported that their HMOs used decision analysis or multiattribute analysis in deciding on drug availability. If used, these tools were rated as very important. There were significant differences in levels of use by HMO type, membership size, and age. Journal articles and reference books were reported most often as information sources. Retrospective drug-use review was used very often and perceived to be very important in managing drug use. Other management methods were used only occasionally, but the importance placed on these tools when used ranged from moderately to very important. Older organizations used most of the management methods more often than did other HMOs. Decision analysis and multiattribute analysis were the most commonly used tools for deciding on which drugs to make available to HMO members, and reference books and journal articles were the most commonly used information sources. Retrospective and prospective drug-use reviews were the most commonly applied methods for managing HMO members' access to drugs.

Data Collection↗

PubMed1998

Participation and influence of individuals and committees that decide on drug availability in HMOs.

The individuals and committees involved in each phase of the process for deciding which drugs to make available to HMO enrollees were identified, and level of participation and influence were studied. A questionnaire based on eight phases of the drug availability decision-making process that listed eight individuals and four committees was developed. The questionnaire was pretested and sent to 303 HMOs randomly selected from a 1993 national directory. Respondents were asked to rate on a 5-point scale the frequency of participation and the perceived influence of each person and committee at each phase. The survey response rate was 28%. Individuals and committees varied significantly within each phase of the process. Pharmacy directors, pharmacy and therapeutics (P&T) committees, formulary committees, and drug information specialists participated frequently to always in the first six phases; only pharmacy directors and P&T committees exerted a large influence to complete control during those phases. Pharmacy directors and drug information specialists participated most, compared with other individuals. Nursing directors and nurses participated least and exerted the least influence. Pharmacy directors and P&T committees participated the most and exerted the greatest influence in determining which drugs HMOs should include in their prescription benefits.

Health Maintenance Organizations↗

PubMed1998

Does participation in psychosocial treatment augment the benefit of clozapine? Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examines the role of participation in psychosocial treatment as a mediator of the clinical effectiveness of clozapine. METHODS: Subjects participated in a 12-month double-blind random-assignment trial comparing clozapine and haloperidol in patients hospitalized 30 to 364 days for refractory schizophrenia at 15 Department of Veterans Affairs medical centers. A broker-advocate case management intervention was used to facilitate participation in psychosocial treatments and to document such participation. RESULTS: Between those who continued receiving clozapine (n=122) or a conventional antipsychotic drug (n=169) for 12 months, those receiving clozapine were more likely to participate in psychosocial rehabilitation treatment. Although they were no more likely to receive clinical recommendations for such treatments, they were more likely to both verbally accept recommendations and to act on them. Structural equation modeling shows that participation in psychosocial treatment did not play a mediating role in clozapine's effect on outcomes at 6 months, but was associated with both reduced symptoms and improved quality of life at 12 months. CONCLUSIONS: Clozapine facilitates participation in psychosocial treatment, and such enhanced participation is associated with improved quality-of-life and symptom outcomes. Psychosocial rehabilitation should be offered concomitantly with clozapine.

Adult↗

PubMed1998

Epithelioid leiomyosarcoma of the larynx.

BACKGROUND: Tumors of smooth muscle origin are rare in the upper aerodigestive tract, due to the paucity of smooth muscle in the area. A review of the literature revealed 34 reported cases of leiomyoma, 9 cases of leiomyosarcoma, and only 2 cases of epithelioid leiomyoma arising in the larynx. METHODS: A case report of an epithelioid leiomyosarcoma arising in the right piriform fossa of a 38-year-old man is presented. RESULTS: The tumor was treated with conservative surgical resection and postoperative radiotherapy. There was no evidence of locoregional recurrence 2 years postsurgery, and laryngeal function was preserved. CONCLUSIONS: To our knowledge, this is the third case of a laryngeal epithelioid smooth muscle tumor to be reported in the world literature and the only documentation of an epithelioid leiomyosarcoma arising in the larynx.

Adult↗

PubMed1998

Combined modality treatment is the treatment of choice for stage I/IE intermediate and high grade non-Hodgkin's lymphomas.

BACKGROUND AND PURPOSE: In a retrospective study, the efficacy of radiotherapy alone was compared with combined modality treatment in patients with stage I/IE non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between 1980 and 1994, 296 patients with stage I/IE non-Hodgkin's lymphoma of intermediate or high grade malignancy (according to the Working Formulation) were treated in four different institutions. All patients were included except patients that presented with NHLs localized in the central nervous system, testis or skin. Two hundred two patients were treated with radiation therapy alone and 94 patients were treated with combined modality treatment. RESULTS: Increasing age and radiation as a single treatment (versus combined modality treatment) were highly significant adverse prognostic factors by multivariate analysis. The actuarial 10-year rates for progression-free and overall survival were 83 and 70%, respectively, for the patients treated with combined modality treatment and 47 and 43%, respectively, for the patients treated with radiation therapy alone. CONCLUSION: Combined modality treatment is the treatment of choice for patients with stage I/IE intermediate and high grade non-Hodgkin's lymphomas.

Adolescent↗

PubMed1998

Bcl-X is the major pleiotropic anti-apoptotic gene activated by retroviral insertion mutagenesis in an IL-3 dependent bone marrow derived cell line.

In order to identify genes capable of inhibiting apoptosis induced by different pathways, without inducing proliferation we have performed retroviral insertion mutagenesis in the IL-3 dependent bone marrow derived Baf-3 cell line. Out of 200 mutants obtained in three separate mutagenesis experiments, four mutants were resistant to multiple apoptosis inducing pathways (including growth factor starvation, staurosporine, etoposide and cyclosporin A) and did not proliferate in the absence of IL-3. These four mutants overexpress the bcl-X gene following a retroviral insertion 5' of the translation initiation site. These results indicate that the bcl-X gene is a major pleiotropic anti-apoptotic gene in Baf-3 cells. They also suggest that the Bcl-2 family of genes might be the only one capable of inhibiting apoptosis induced by multiple pathways without inducing cell proliferation.

Alleles↗

PubMed1998

Squamous cell carcinoma associated with lupus vulgaris.

Squamous cell carcinomas are known to arise in certain chronic, scarring dermatoses and also to be associated with exposure to ultraviolet radiation. We now report a case arising in a plaque of lupus vulgaris, the patient having received radiation from a Finsen lamp as a child for a tuberculous abscess in that region.

Aged↗

PubMed1998

The changing incidence of lymphoproliferative disorders in Yorkshire.

Secular trends in the incidence of lymphoproliferative disorders on North and West Yorkshire and Humberside from 1985 to 94 were studied and changes in incidence by tumour subtype were analysed. Population-based data on the incidence of lymphoproliferative disorders were obtained from a specialist registry with a high level of ascertainment. Cases of chronic lymphocytic leukaemia and plasma cell myeloma were excluded and the remaining cases classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). NHL were subdivided by site of origin and immunophenotype. Nodal B-cell lymphomas were further classified as diffuse large B-cell lymphoma, follicle centre lymphoma, mantle cell lymphoma and miscellaneous. During the study period there was a significant increase in total lymphoproliferative disorders with an average change of 2.5% per annum equivalent to 0.84/10,0000. Most of this increase was due to an increasing incidence of extranodal B-cell lymphomas and peripheral T-cell lymphomas. A numerically small but significant increase in diffuse large B-cell lymphomas was seen. There was no significant increase in other subtypes. The increased incidence of lymphomas in the area studied is mainly due to changes in two specific subgroups. There are several reasons why changes in extranodal B-cell lymphoma and peripheral T-cell lymphoma may have been particularly affected by changing diagnostic practices. Epidemiological studies of particular subtypes of lymphoproliferative disorder facilitate the identification of environmental factors involved in the pathogenesis of these tumours.

Adolescent↗

PubMed1998

Docetaxel is a potent cytotoxic drug in the treatment of advanced breast cancer.

Docetaxel (Taxotere) belongs to a new class of anti-neoplastic agents, the taxanes. As the structurally related compound, paclitaxel, it enhances microtubule assembly and inhibits depolymerization of tubulin, thereby disrupting mitosis and cell replication. From august 1994 till december 1995, we treated thirty patients with advanced or metastatic breast cancer in a protocol aiming at evaluating the efficacy of docetaxel, administered in second, third or fourth line chemotherapy. The drug was given at a dosage of 100 mg/m2, delivered as a 1-hour infusion once every 3 weeks. Among the 30 patients, 9 (30%) showed an objective response (PR) and 15 (50%) had disease stabilization. For those 2 groups, the median time to progression was 20 weeks (range 13-61) and 13.5 weeks (range 10-37) respectively; the median survival for the whole group was 22.5 weeks (range 1-72). Myelosuppression (neutropenia) was the dose-limiting toxicity. We conclude that docetaxel is a potent single agent in heavily pretreated locally advanced or metastatic breast cancer, even in those who are resistant to an anthracycline or an anthracenedione.

Adult↗

PubMed1998

Herpes simplex virus replication-induced expression of chemokines and proinflammatory cytokines in the eye: implications in herpetic stromal keratitis.

On infection of the cornea with herpes simplex virus (HSV), an immunopathologic response termed herpetic stromal keratitis (HSK) ensues. This response is mediated primarily by CD4+ T cells and only occurs if mice are infected with replication-competent virus, although replication-defective mutants induce cellular immune responses following infection. To determine the consequences of HSV replication in the cornea, which is crucial for HSK manifestation, corneas infected with productive virus and replication-defective mutants were analyzed for chemokines and proinflammatory cytokine mRNA expression by RT-PCR at various times. While productive infection resulted in rapid upregulation and sustained expression of such chemokines as N51/KC, macrophage inflammatory protein-1beta (MIP-1beta), MIP-2, and monocyte chemotactic protein-1 (MCP-1) and such cytokines as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha), expression of such inflammatory mediators was minimal and transient after unproductive infection. Expression of MIP-1alpha and lymphotactin along with a biphasic expression of IL-6 and MIP-2 were seen only with productive infection. Initial PMN recruitment into the cornea was approximately 50-fold greater with productive infection than with unproductive infection. These data suggest that a replication-induced proinflammatory milieu in the cornea is crucial for the subsequent progression of HSK possibly because of enhancement of the expression of corneal agonists that drive HSK manifestation.

Animals↗

PubMed1998

Women and abortion in 1930s Britain: a survey and its data.

This paper examines over 3,000 questionnaires on abortion that were distributed through the National Birthday Trust Fund, a non-governmental orrganization, to working-class women in municipal hospitals in 1930s Britain. The aim of the survey was to "discover the proportion of induced to spontaneous abortions". Although the study was abandoned due to weaknesses in its design, the collected data contain a mass of detailed information about the lives and reproductive history of working-class women in this period. The background to the survey is discussed, setting it within the development of research on poverty and women's health, as well as contemporary debate on the issue of abortion. The survey data, which are both qualitative and quantitative, are analysed and presented in figures with accompanying commentary. Issues covered include the impact of poverty, overcrowding, reasons for avoiding pregnancy, and contraception.

Abortion, Spontaneous↗

PubMed1998

Acetaminophen as an adjunct to morphine by patient-controlled analgesia in the management of acute postoperative pain.

UNLABELLED: Opioids play a fundamental role in the management of postoperative pain, but their use is associated with a number of side effects, including nausea and vomiting, sedation, and respiratory depression. Co-administration of a nonopioid has been proposed as a method of reducing opioid intake and minimizing side effects. Sixty-one ASA physical status I and II patients were enrolled in a double-blind, randomized, placebo-controlled, parallel study to investigate the effect of a combination of acetaminophen and morphine after open reduction and internal fixation of acute limb fractures. Patients were randomized to receive either oral acetaminophen (1 g every 4 h) or placebo as an adjuvant to morphine by patient-controlled analgesia (PCA) postoperatively. They were assessed daily for 72 h or until the PCA was discontinued according to standardized guidelines. The outcome variables collected were pain scores (11-point scale), amount of morphine self-administered, duration of PCA use, compliance with study design, incidence of nausea and sedation, and overall patient satisfaction. The acetaminophen group had lower pain scores on Day 1 (2.1 vs 3.3; P = 0.03) and a shorter average duration of PCA use (35.8 vs 45.5 h; P = 0.03). Overall patient satisfaction was also significantly greater in the acetaminophen group (8.7 vs 7.9; P = 0.04). These data suggest that acetaminophen is a useful adjunct to morphine PCA. IMPLICATIONS: This study assesses the benefit of combining two analgesics for the treatment of postoperative pain. Such a combination improves the quality of pain relief and patient satisfaction.

Acetaminophen↗

PubMed1998

Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study.

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.

Adult↗