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Biomedical subjects

A Thomas

Publications and source records attributed to A Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1998

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

PURPOSE: Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS: Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION: Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

Adult↗
PubMed1998

Gabapentin in orthostatic tremor: results of a double-blind crossover with placebo in four patients.

We treated four patients affected by orthostatic tremor (OT) with gabapentin in increasing doses (300 to 2,400 mg/d). OT was evaluated with patients' self-monitoring scales, tremor rating scales, electromyography (EMG) showing the 14- to 18-Hz frequencies, and EMG frequency analysis. All patients had transitory responses to clonazepam. Gabapentin induced disappearance of OT in three patients and consistent reduction in one. Crossover to placebo induced reappearance of tremor.

Acetates↗
PubMed1998

Optic neuritis with residual tunnel vision in perchloroethylene toxicity.

CASE REPORT: In a 57-year-old female owner of a dry-cleaning shop, we describe the association of severe bilateral optic neuritis with unexpectedly high concentrations of perchloroethylene/metabolites in the blood and of chloroform in urine. Visual disturbances consisted of complete blindness for 9 days in the left eye, for 11 days in the right eye, with bright phosphenes and pain on eye rotation. Only central (2-3 degrees radius) vision recovered in the following months. CONCLUSION: Although environmental concentrations of perchloroethylene were within normal limits, we measured five-fold increases in vapors emitted when ironing freshly dry-cleaned fabrics, and suggest that inhalation of perchloroethylene vapors was the cause of this case of ocular nerve toxicity, recapitulating a previous report of major perchloroethylene toxicity.

Blindness↗
PubMed1998

[A study on abnormal chondrocyte differentiation and abnormal expression of collagen types in articular cartilage from patients with Kaschin-Beck disease].

OBJECTIVE: To study the abnormal characteristics of chondrocyte differentiation and abnormal expression of collagen types in articular cartilage from patients with Kaschin kaschin-Beck disease (KBD). METHODS: The abnormal differentiation and expression of collagen types I, II, III, IV and X in articular cartilage from five cases of KBD patients were examined using monoclonal immunohistochemical methods. RESULTS: (1) The expression of tyep II collagen was decreased in the upper zone in KBD articular cartilage. (2) The expression of types I, III and VI collagen were found throughout the articular cartilage, but type X collagen was located in the calcified cartilage zone and around chondrocyte clusters in the deep zone. (3) Chondrocyte clusters exhibited significant pericellular staining for types I, II, III and VI collagen, but did not stain with any collagen antibody in the chondronecrosis areas. CONCLUSION: The abnormal collagen pattern in the articular cartilage of KBD patients was similar to that seen in primary osteoarthritic cartilage, but having more pronounced type I collagen expression in the surface zone and no collagen expression in the chondronecrosis areas.

Adult↗
PubMed1997

BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing.

CONTEXT: A mutation in the BRCA1 gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between risk factors and mutations is incomplete. OBJECTIVES: To identify BRCA1 mutations and to determine factors that best predict presence of a deleterious BRCA1 mutation in patients with breast and/or ovarian cancer. DESIGN: A complete sequence analysis of the BRCA1 coding sequence and flanking intronic regions was performed in 798 women in a collaborative effort involving institutions from the United States, Italy, Germany, Finland, and Switzerland. PARTICIPANTS: Institutions selected 798 persons representing families (1 person for each family) thought to be at elevated a priori risk of BRCA1 mutation due to potential risk factors, such as multiple cases of breast cancer, early age of breast cancer diagnosis, and cases of ovarian cancer. No participant was from a family in which genetic markers showed linkage to the BRCA1 locus. MAJOR OUTCOME MEASURES: Sequence variants detected in this sample are presented along with analyses designed to determine predictive characteristics of those testing positive for BRCA1 mutations. RESULTS: In 102 women (12.8%), clearly deleterious mutations were detected. Fifty new genetic alterations were found including 24 deleterious mutations, 24 variants of unknown significance, and 2 rare polymorphisms. In a subset of 71 Ashkenazi Jewish women, only 2 distinct deleterious mutations were found: 185delAG in 17 cases and 5382insC in 7 cases. A bias in prior reports for mutations in exon 11 was revealed. Characteristics of a patient's specific diagnosis (unilateral or bilateral breast cancer, with or without ovarian cancer), early age at diagnosis, Ashkenazi Jewish ethnicity, and family history of cancer were positively associated with the probability of her carrying a deleterious BRCA1 mutation. CONCLUSIONS: Using logistic regression analysis, we provide a method for evaluating the probability of a woman's carrying a deleterious BRCA1 mutation for a wide range of cases, which can be an important tool for clinicians as they incorporate genetic susceptibility testing into their medical practice.

Breast Neoplasms↗
PubMed1997

Cholelithiasis in early infancy

This report describes three children, age range 7 weeks to 5 months, who presented with obstructive jaundice secondary to gallstones. Previous Escherichia coli septicaemia and frusemide therapy were predisposing risk factors in two of the patients. All three were successfully treated with cholecystectomy and exploration of the common bile duct.

Journal Article↗
PubMed1997

Analysis of mutations within the cytoplasmic domain of the Moloney murine leukemia virus transmembrane protein.

The role of the cytoplasmic tail of the Moloney murine leukemia virus transmembrane protein in the regulation of syncytia was examined. Three mutations within the cytoplasmic tail were studied. Linker-insertion in7705-12a is within the viral-associated cytoplasmic tail, linker-insertion in7748-12a is within the R peptide, and a third mutation expresses TM lacking the R peptide (Env R-). The Env R- construct was nonviable in Rat1 cells, however, rapidly reverted to a form containing the R peptide when passaged in NIH/3T3 cells. in7705-12a was temperature-sensitive in Rat1 cells, as previously characterized, but was viable at either temperature in NIH/3T3 cells. in7748-12a was comparable with wild-type M-MuLV. The ability of the env constructs to form large multinucleated syncytia with NIH/3T3 and XC cells were examined using transient expression assays, eliminating reversion events due to viral passage and reverse transcription. The Env R- constructs formed syncytia with NIH/3T3 cells. in7705-12a displays enhanced proteolytic cleavage of the R peptide. Neither linker-insertion mutation in7705-12a or in7748-12a activated fusion with NIH/3T3, despite the abundance of processed TM with in7705-12a. All three mutants were fusion competent with Rat XC cells, even in the absence of any cleavage of the R peptide. These results provide insights regarding steric and the temporal affects of cleavage of the R peptide and the assembly of a fusion competent oligomer.

3T3 Cells↗
PubMed1997

Lipopeptide immunization without adjuvant induces potent and long-lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees.

We have employed a 26-amino-acid synthetic peptide based on Plasmodium falciparum liver stage antigen-3 to evaluate improvements in immunogenicity mediated by the inclusion of a simple lipid-conjugated amino acid during peptide synthesis. Comparative immunization by the peptide in Freund's adjuvant or by the lipopeptide in saline shows that the addition of a palmitoyl chain can dramatically increase T helper (Th) cell responses in a wide range of major histocompatibility complex (MHC) class II haplotypes, to the extent that responses were induced in mice otherwise unable to respond to the non-modified peptide injected with Freund's adjuvant, and that the increased immunogenicity of the lipopeptide led to high and longer lasting antibody production (studied up to 8 months). B and T cell responses induced by the lipopeptide were reactive with native parasite protein epitopes, and a lipopeptide longer than ten amino acids was endogenously processed to associate with MHC class I and elicit cytotoxic T lymphocyte (CTL) responses. Finally, the lipopeptide was safe and highly immunogenic in chimpanzees, whose immune system is very similar to that of humans. Our results suggest that relatively large synthetic peptides, carefully chosen from pertinent areas of proteins and incorporating a simple palmitoyl-lysine, can induce not only CTL, but also strong Th and antibody responses in genetically diverse populations. Lipopeptides engineered in this way are simple to produce and purify under GMP conditions, they are well tolerated by apes, and with the enhanced immunogenicity without the need for adjuvant that we report here, they offer a quick and relatively low-cost route to provide material for human malaria vaccination trials.

Adjuvants, Immunologic↗
PubMed1997

Comparative evaluation of body composition in medically stable elderly.

OBJECTIVE: Accurate assessment is needed to identify the nutritional status of elderly persons. Anthropometric data were collected to describe body composition of the sample, including blacks and whites aged 55 to 89 years, and to explore the usefulness of several methods of body composition measurement. DESIGN: Baseline measurements were made as part of a longitudinal study. Body composition variables, particularly lean and lean-to-height measures, were used. SUBJECTS/SETTING: One hundred twenty-nine free-living medically stable elderly at senior community centers were self-selected into the study. STATISTICAL ANALYSIS: Descriptive statistics were generated for all variable by gender, race, and age (< 65, 65 to 74, and > or = 75 years). Actual height was correlated with estimated height using published equations. Analysis of variance revealed the effect of gender, race, or age on outcome variables. RESULTS: White women, black women, and white men made up 54%, 23%, and 23% of the sample, respectively. Most gender differences were expected. Black women had greater weight, body mass index, arm muscle circumference, and ratio of lean to height but lower percent lean body mass than white women. Subjects over 75 years old were shorter, lighter, and had lower ratio of lean to height. Gender and age had the greatest effect on ratio of lean to height. CONCLUSIONS/APPLICATIONS: A lean-to-height index appears to be a useful tool for tracking the status of lean mass in the elderly. Knee height may be especially useful because it, unlike stature, does not decrease with age. Furthermore, some published equations for estimating stature from knee height need adjustment, specifically for elderly black women.

Age Factors↗
PubMed1997

Hyaluronic acid induces tumour necrosis factor-alpha production by human macrophages in vitro.

Foetal wounds heal with minimal or no scar formation. High levels of hyaluronic acid (HA) have been implicated as a contributory factor. Macrophages are essential for normal wound healing, a role facilitated by secretion of an array of cytokines. Of these, tumour necrosis factor alpha (TNF-alpha) has been shown to reduce wound collagen levels and thus scarring. This study examines the ability of HA to stimulate TNF-alpha production by human macrophages. The human U937 myelomonocytic cell line was differentiated into DU937 adherent macrophages. DU937 monolayers were exposed to HA at concentrations of 0.1, 1, 10 and 100 micrograms/ml. Conditioned media from HA-exposed monolayers were assayed for TNF-alpha activity using a standard L929 fibroblast bioassay. TNF-alpha activities of HA-exposed DU937 culture supernatants were compared to those of controls and expressed as % cytotoxicity. Exposure of macrophages to HA at concentrations of 10 micrograms/ml and 100 micrograms/ml significantly stimulated TNF-alpha production, as demonstrated by % cytotoxicities expressed as median (interquartile range) of 33.5 (29-34.5)% (P = 0.03) and 77.5 (67-85)% (P = 0.029) respectively (Mann-Whitney U test). This effect was specifically associated with TNF-alpha generated during HA exposure, as these cytotoxic effects could be abolished by addition of anti-TNF-alpha antibody, reducing cytotoxicity to 9 (6.5-13.5)% and 8.5 (6-12)% respectively. These observations indicate that HA stimulates TNF-alpha production by human macrophages. TNF-alpha is known to downregulate fibroblastic collagen synthesis within experimental wounds. We suggest that the high levels of HA within foetal wounds may play a part in limiting fibroplasia, and thereby limit scarring, via an upregulation of TNF-alpha production from wound macrophages.

Animals↗
PubMed1997

Iodine released from the wound dressing Iodosorb modulates the secretion of cytokines by human macrophages responding to bacterial lipopolysaccharide.

Clinical data suggests that iodine released into the wound environment by Iodosorb may enhance the healing of chronic leg ulcers by a mechanism additional to its anti-bacterial activity. The macrophage is considered to play a central role in controlling wound healing and this study was designed to determine whether interaction with iodine could modulate macrophage cytokine output. The human macrophage cell line U937 was co-cultured with Iodosorb, Iodosorb conditioned medium or elemental iodine in the presence of optimal and sub-optimal stimulatory concentrations of bacterial lipopolysaccharide (LPS). The concentration of tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) were assayed in the culture medium after 24 hr culture. Co-culture with 0.25% Iodosorb, Iodosorb conditioned medium or 20 micrograms/ml iodine enhanced TNF alpha secretion (48 +/- 3% cytotoxicity in L929 bioassay to 78 +/- 2% cytotoxicity, +/-SD) by U937 cells stimulated with sub-optimal concentrations of LPS (0.25 ng/ml) and inhibited secretion of IL-6 from cells stimulated with 10 ng/ml LPS (> 750 pg/ml to 267 +/- 52 pg/ml, +/-SD, n = 4). Immunohistological staining of sections prepared from biopsies of chronic leg ulcers indicated that the majority of macrophages present were negative for TNF alpha. Thus one potential mechanism of action of iodine released from Iodosorb used as a wound dressing is to provide a pro-inflammatory stimulus in the wound tissue by activation of the resident macrophage population. This would result in a localized production of pro-inflammatory cytokines and generate an influx of monocytes and T-lymphocytes into the wound that may trigger the wound into a healing phase.

Animals↗
PubMed1997

Impairment, disability and handicap as risk factors for depression in old age. The Gospel Oak Project V.

BACKGROUND: An association between disablement and late-life depression is often reported in cross-sectional studies. However, many lack effect sizes, and do not control for confounding. Therefore, it is difficult both to quantify the overall impact of poor health on depression and to understand which aspects are most salient. METHODS: A catchment area survey of all over 65-year-old residents of an electoral district in London, UK, using a population register derived from a door-to-door census was undertaken. Depression was measured using SHORT-CARE, and the consequences of disease classified according to the WHO International Classification of Impairments, Disabilities and Handicaps. RESULTS: Six hundred and fifty-four subjects were interviewed out of an older population of 889. The prevalence of SHORT-CARE pervasive depression was 17%. Impairment, disability and, particularly, handicap were strongly associated with depression. The adjusted odds ratio for depression in the most handicapped quartile compared with the least was 24.2 (8.8-66.6). The population attributable fraction (PAF) for depression attributable to handicap was 0.78. The PAFs for recent life events and female gender were much lower. Handicap explained most of the depression associated with individual impairments and disabilities. Adjusting for handicap abolished or weakened the associations between depression and social support, income, older age, female gender and living alone. CONCLUSIONS: Even given some uncertainty in distinguishing handicap and depression as constructs, and the impossibility of deciding direction of causality, it seems likely that handicap is of central significance to late-life depression. Handicap may be more amenable to intervention than either impairment or disability.

Activities of Daily Living↗
PubMed1997

Social support deficits, loneliness and life events as risk factors for depression in old age. The Gospel Oak Project VI.

BACKGROUND: A companion paper reported a very strong cross-sectional association between handicap and late-life depression. Adjusting for handicap weakened associations between sociodemographic variables and depression. It was unclear whether handicap was a confounder, or a useful summary variable, mediating the effect of a range of sociodemographic disadvantages. This paper focuses on the cross-sectional relationship between depression and demographic variables, social support, and life events. METHOD: A community survey of all residents over the age of 65 years of an electoral district in London, UK. RESULTS: There was a moderate association between SHORT-CARE pervasive depression and the number of life events experienced over the previous year. Personal illness, bereavement and theft were the most salient events. There was a stronger, graded, relationship between the number of social support deficits (SSDs) and depression. Number of SSDs also related to age, handicap, loneliness and use of homecare services. Loneliness was itself strongly associated with depression; odds ratio 12.4 (7.6-20.0). CONCLUSIONS: Problems of collinearity, and the cross-sectional design of the study limited interpretation of the exact nature of the relationship between social support, loneliness, handicap and depression. However, the clustering of these four factors can be used to define a large part of the elderly population with a poor quality of life. An important avenue for future research will be the development and implementation of population intervention strategies designed to address some or all of these problems among older people in general.

Aged↗
PubMed1997

After-effects of a high altitude expedition on blood.

The aim of the study was to investigate blood alterations caused by altitude acclimatization which last more than few days after return and might play a role for exercise performance at sea level. Measurements were performed in 12 mountaineers before, during and either 7/8 or 11/12 days after a Himalaya expedition (26-29 days at 4900 to 7600 m altitude). [Erythropoietin] rose only temporarily at altitude (max. +11 +/- 1 [SE] mu/ml serum). After return hemoglobin mass (initially 881 +/- 44 g, CO-Hb method) was increased by 14% (p < 0.01); aspartate aminotransferase activity in erythrocytes (initially 682 +/- 25 U/l) was augmented (day 7: +964 +/- 152 U/l, day 11: +533 +/- 107 U/l) indicating reduced mean cell age. Calculated blood volume (+14%) was influenced by red cell formation at altitude but also by plasma expansion at sea level. The half saturation pressure for Hb-O2 (pH 7.4, 37 degrees C) as well as the 2.3-diphosphoglycerate concentration were already initially high (32.1 +/- 0.5 mmHg, 20.5 +/- 0.7 mumol/g Hb) and showed only a nonsignificant tendency to increase after return. Also Hill's n was consistently high in the mountaineers, whereas the Bohr coefficients were slightly increased only after descent. Probably the preparatory physical training, partly in the Alps, and the stay in the Himalaya influenced O2-affinity for a prolonged time. The adaptations might reduce the loss of physical performance capacity at altitude and be part of altitude training effects.

Acid-Base Equilibrium↗
PubMed1997

[Pharmacologic intolerance reaction after intravenous injection of pethidine].

We report on anaphylactoid reactions (urticae at the injection site and along the injection vein) after intravenous injections of pethidine in two patients. Skin tests with pethidine were negative, but intravenous challenge showed urticae. These results indicate that the reactions were due to a non-immunological mechanism resembling pharmacological intolerance. Retrospective analysis revealed a 5.6% incidence of pharmacological intolerance reactions to intravenous pethidine in 519 patients.

Adjuvants, Anesthesia↗
PubMed1997

Oocyte donation in Turner's syndrome: an analysis of the factors affecting the outcome.

A total of 29 women with Turner's syndrome (19 monosomy and 10 mosaic) had 68 cycles of oocyte donation that included 29 cycles of initial attempt and 39 cycles of subsequent attempts. Oral oestradiol valerate was used either in a variable dose (42 cycles) or in a constant dose (26 cycles) regimen for the endometrial preparation which was monitored by pelvic ultrasonography. The embryos/zygotes were transferred either fresh (50 cycles) or after cryopreservation (18 cycles) into the Fallopian tube (41 cycles) and uterine cavity (27 cycles) as appropriate. There were 28 clinical pregnancies including two sets of triplets resulting in a pregnancy rate of 41.2% per treatment cycle and an implantation rate of 17.1% per embryo transferred. The recipient's age, chromosomal constitution or associated uterine or tubal anomaly had no influence on the treatment outcome. The implantation and pregnancy rates were higher in the subsequent than initial cycles (22.6 versus 9.99%, P < 0.05; 51.3 versus 27.6%, P < 0.05). An endometrial thickness of > or = 6.5 mm was an important predictor of pregnancy but the endometrial echo pattern failed to predict the outcome. Although the total dose of oestradiol before embryo transfer was higher in the pregnant cycles than the non-pregnant ones and its gradation (< 50 mg, 50-100 mg, < 100 mg) influenced the implantation (3.4, 17.5, 26.3% respectively, P < 0.05) and pregnancy rates (10, 42.2, 61.5% respectively, P < 0.05), the effect was indirect by altering the endometrial thickness. The number of oocytes fertilized affected the pregnancy rate irrespective of the number of embryos transferred. The implantation and pregnancy rates were higher when fresh rather than frozen-thawed embryos were transferred (20.3 versus 8.2%, P < 0.05; 48 versus 22.2%, P < 0.05) but the route of transfer was of no statistical importance. The overall miscarriage rate was higher (50%), and was related to the presence of hypoplastic or bicornuate uterus and to a low oocyte fertilization rate.

Female↗