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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 235 records · Page 13Linked to original sources
PubMed2000

The role of CD23 on allergen-induced IgE levels, pulmonary eosinophilia and bronchial hyperresponsiveness in mice.

BACKGROUND: The role of Immunoglobulin (Ig)E in inflammation is the subject of considerable study and a number of studies have shown conflicting evidence for its role in eosinophil recruitment and bronchial hyperresponsiveness in a number of murine models. The low affinity IgE receptor, CD23, is known to act as a negative regulator of IgE production and we have used knockout mice deficient in CD23 to investigate the role of IgE in eosinophil recruitment and bronchial hyperresponsiveness in a murine model of airway inflammation. OBJECTIVE: To study the role of the low affinity FcepsilonII receptor, CD23 in IgE production, lung inflammation and bronchial hyperresponsiveness. METHODS: Wild-type and CD23 knockout C57Bl/6 mice (CD23-/-) were immunized by intraperitoneal injection with ovalbumin on days 0 and 14 and challenged with aerosolized antigen on day 21 for a period of up to 1 week. Blood samples, bronchoalveolar lavage and lung tissue samples were obtained to determine serum IgE levels and inflammatory cell numbers, respectively. Furthermore, airway resistance was measured to increasing concentrations of aerosolized 5-hydroxytryptamine in order to evaluate the effect of CD23 deficiency on bronchial hyperresponsiveness to antigen challenge. RESULTS: Sensitization of wild-type C57Bl/6 mice to ovalbumin resulted in elevated levels of total serum IgE and ovalbumin-specific IgE, which was significantly augmented in CD23 knockout C57Bl/6 mice (CD23-/-). A significant increase in the percentage of eosinophils recovered in bronchoalveolar lavage fluid from wild-type and CD23-/- mice was observed 24 h following 3 or 7 days aerosol exposure with ovalbumin (10 mg/mL). At 3 days, the increase in the percentage of eosinophils was significantly greater in CD23-/- groups. Immunohistochemical analysis of lungs sections revealed the presence of CD3+, CD4+ and CD23+ cells in wild-type mice but a lack of immunofluorescence of CD23+ cells in CD23-/- mice. In wild-type ovalbumin-immunized mice, bronchial hyperresponsiveness to aerosolized 5-hydroxytryptamine was observed following a 3-day antigen challenge, which was significantly greater in CD23-/- ovalbumin-immunized mice. CONCLUSION: These studies demonstrate that CD23-/- mice have increased capacity to produce IgE consistent with the view of a negative feedback role for membrane-bound CD23 and under such conditions, may account for the greater numbers of eosinophils recruited to the airways and bronchial hyperresponsiveness observed following acute but not chronic antigen challenge.

Allergens↗
PubMed2000

Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity.

The negative effects of sleep deprivation on alertness and cognitive performance suggest decreases in brain activity and function, primarily in the thalamus, a subcortical structure involved in alertness and attention, and in the prefrontal cortex, a region subserving alertness, attention, and higher-order cognitive processes. To test this hypothesis, 17 normal subjects were scanned for quantifiable brain activity changes during 85 h of sleep deprivation using positron emission tomography (PET) and (18)Fluorine-2-deoxyglucose ((18)FDG), a marker for regional cerebral metabolic rate for glucose (CMRglu) and neuronal synaptic activity. Subjects were scanned prior to and at 24-h intervals during the sleep deprivation period, for a total of four scans per subject. During each 30 min (18)FDG uptake, subjects performed a sleep deprivation-sensitive Serial Addition/Subtraction task. Polysomnographic monitoring confirmed that subjects were awake. Twenty-four hours of sleep deprivation, reported here, resulted in a significant decrease in global CMRglu, and significant decreases in absolute regional CMRglu in several cortical and subcortical structures. No areas of the brain evidenced a significant increase in absolute regional CMRglu. Significant decreases in relative regional CMRglu, reflecting regional brain reductions greater than the global decrease, occurred predominantly in the thalamus and prefrontal and posterior parietal cortices. Alertness and cognitive performance declined in association with these brain deactivations. This study provides evidence that short-term sleep deprivation produces global decreases in brain activity, with larger reductions in activity in the distributed cortico-thalamic network mediating attention and higher-order cognitive processes, and is complementary to studies demonstrating deactivation of these cortical regions during NREM and REM sleep.

Adult↗
PubMed2000

A painful limp.

We describe a healthy 18-month-old child who developed a painful limp, without a history of trauma or fever. The initial laboratory investigations showed normal results but the radiological findings were suggestive of scurvy. Diagnosis was confirmed by blood tests and by a rapid recovery following replacement therapy.

Ascorbic Acid↗
PubMed2000

Diagnosis, treatment and outcome of patients with Askin-tumors.

Askin tumors are highly malignant small-round-cell tumors of the thoracopulmonary region, which occur rarely. Therefore, we report on our experiences with eight patients (5 male, 3 females), who were treated in our department between 11'94 and 10'97 (age: 9-40 years, mean age: 20.5 years). All Askin tumors were diagnosed by histological and immunohistochemical examinations as well as molecular genetic proof of characteristic translocations. In all patients, the tumor arose from the chest wall, infiltrating adjacent ribs and parts of the lung. At the time of first diagnosis, five patients did not reveal any metastases. One patient suffered from intrapulmonary metastases and two patients from an infiltration of the diaphragm and of adjacent vertebral bodies. Treatment consisted of a pre- and postoperative (radio-) chemotherapy according to the EVAIA protocol and a radical tumor resection in all patients. The postoperative course was uneventful in seven patients, one patient suffered from pneumonia after multiple wedge resections for intrapulmonary metastases. Four patients, in whom primary tumor resection was complete, are alive 14, 20, 35 and 84 months after first diagnosis - only one patient had to undergo a second operation for a local relapse 17 months after first diagnosis. The other 4 patients, who suffered from a very extensive primary tumor, expired 13, 17, 18 and 39 months after the diagnosis was made. Our data demonstrate that Askin tumors require an aggressive multimodality treatment consisting of pre- and postoperative chemotherapy, radical surgical resection and postoperative irradiation, which may be performed preoperatively in selected cases, too.

Adolescent↗
PubMed2000

Effects of upper respiratory tract illnesses on mood and performance over the working day.

The present study examined whether volunteers with common colds showed impairments in objective and subjective indicators of alertness over the course of the working day. All the volunteers (n = 21) were tested when healthy to provide baseline data for simple and choice reaction time tasks, visual search tasks and ratings of mood. These measures were taken before work (08.30 hours), at lunchtime (13.00) and after work (17.30). When participants developed a cold (n = 6) they repeated the procedure. Volunteers (n = 15) who remained healthy were recalled as controls and also repeated the procedures. The results showed that those with colds had significantly slower simple and choice reaction times, and felt less alert, more tense and less sociable. The effects of having a cold on simple reaction time, alertness and anxiety increased over the day. This extends earlier research and shows that some of the effects of upper respiratory tract illnesses on mood and performance will depend on when assessments are made. These results also imply that performance and well-being at work will be impaired by upper respiratory tract illnesses.

Adult↗
PubMed2000

After-effects of the common cold on mood and performance.

The present study examined whether volunteers who had recently had common colds showed impairments in mood and performance in the weeks following the illness. All volunteers (n = 24) were tested when healthy to provide baseline data for simple and choice reaction time tasks, attention and memory tasks and ratings of mood. When participants developed a cold (n = 13) they returned to the laboratory so that the illness could be verified. When they were symptom free they returned to the laboratory and repeated the procedure. They then completed the study with a final session 1 week later. Volunteers (n = 11) who remained healthy over 10 weeks were recalled as controls and also repeated the procedures. The results showed that those who had recently had colds showed few impairments in mental performance and mood. Taken together with the results of previous studies, this suggests that after-effects of viral infection are largely restricted to severe illnesses such as infectious mononucleosis and influenza. After-effects of colds may occur but these probably reflect poor learning at the time of the illness.

Adolescent↗
PubMed2000

Assessment of the myotoxicity of pharmaceutical buffers using an in vitro muscle model: effect of pH, capacity, tonicity, and buffer type.

The purpose of the present study was to investigate the myotoxicity of three buffers containing carboxylic acid groups (i.e., acetate, succinate, and citrate) as a function of their pH, capacity, and tonicity. The myotoxicity of these buffers in the range of pH 2-6 and 0.001-0.1 M buffer capacity was assessed using cumulative creatine kinase (CK) release from an isolated rodent muscle model following injection. Phenytoin and 0.9% NaCl injection were used as positive and negative controls, respectively. Buffer solutions were prepared. A lower pH and higher buffer capacity was linked to increased myotoxicity for the acetate buffers. However, for succinate and citrate buffers, pH appeared to influence the extent of myotoxicity, whereas buffer capacity did not seem to have an effect. When either NaCl or trehalose was used as a tonicity-adjusting agent at pH 6, isotonic 0.01 M buffer solutions dramatically lowered the cumulative CK release compared to those that were not isotonic. Isotonic succinate buffers displayed the lowest myotoxicity, whereas citrate buffers displayed the highest values. Citrate buffers containing three carboxylic acid groups showed higher myotoxicity than succinate buffers and acetate buffers at 0.001 and 0.01 M buffer capacities, whereas acetate buffer produced higher cumulative CK release than citrate and succinate buffers at 0.1 M buffer capacity. The myotoxicity of pharmaceutical buffers containing carboxylic acid groups appears to be directly affected by lowering the pH of the solution.

Acetates↗
PubMed2000

Prospective study of the impact of fear of falling on activities of daily living, SF-36 scores, and nursing home admission.

BACKGROUND: The aim of this study was to assess the impact of fear of falling on the health of older people. METHODS: A total of 528 subjects (mean age 77 years) were recruited from two hospitals in Sydney, Australia, and followed for approximately 12 months. Eighty-five subjects died during follow-up, and 31 were admitted to an aged care institution. Tinetti's Falls Efficacy Scale (FES) was successfully administered to 418 subjects as part of the baseline assessment. Among those with baseline FES scores, ability to perform 10 activities of daily living (ADLs) was assessed at baseline and follow-up in 307 subjects, and SF-36 scores were assessed at baseline and follow-up in 90 subjects recruited during the latter part of the study. Falls during follow-up were identified using a monthly falls calendar. RESULTS: Compared with those with a high fall-related self-efficacy (FES score = 100), those with a low fall-related self-efficacy (FES score < or = 75) had an increased risk of falling (adjusted relative risk 2.09, 95% confidence interval [CI] 1.31-3.33). Those with poorer fall-related self-efficacy had greater declines in ability to perform ADLs (p < .001): the total ADL score decreased by 0.69 activities among persons with low FES scores (< or =75) but decreased by only 0.04 activities among persons with FES scores of 100. Decline in ADLs was not explained by the higher frequency of falls among persons with low FES scores. SF-36 scores (particularly scores on the Physical Function and Bodily Pain subscales) tended to decline more among persons with poor fall-related self-efficacy. Nonfallers who said they were afraid of falling had an increased risk of admission to an aged care institution. CONCLUSIONS: Fear of falling has serious consequences for older people. Interventions that successfully reduce fear of falling and improve fall-related self-efficacy are likely to have major health benefits.

Accidental Falls↗
PubMed2000

Ethyl 2-[N-(tert-butyloxycarbonyl)-L-alanylamino]-4-methyl-1, 3-thiazole-5-carboxylate reveals a trans orientation of the preceding amide N--H with respect to the thiazole-ring sulfur.

The title molecule, C(15)H(23)N(3)O(5)S, was prepared as a synthetic precursor to 4-methylthiazole-based DNA minor groove binders which would bear chiral amino acids in the sequence. The crystallographic evidence presented herein shows that the aromatic amide NH group preceding the thiazole ring points away from the direction of sulfur. The molecule is biplanar, with the dihedral angle between the N-terminus peptide moiety and the thiazole-containing plane being 49.7 (5) degrees, with a bend at the Calpha carbon.

Alanine↗
PubMed2000

The cost effectiveness of a home hazard reduction program to reduce falls among older persons.

BACKGROUND: The effectiveness of individual components (other than exercise) of multifactorial intervention packages aimed to reduce the incidence of falls in older people is uncertain. There have been no randomised trials of home modifications alone for the prevention of falls. OBJECTIVES: To estimate the cost-effectiveness of just one component of a multifactorial approach to falls prevention, that is, a home hazard reduction program. The study estimates the size and direction of change in resource use within and between the hospital, home and community sectors. METHODS: A randomised trial was conducted to evaluate the effectiveness of home modifications for prevention of falls among older people. An occupational therapist (O/T) with experience in aged care assessed homes for environmental hazards and supervised the necessary home modifications. SUBJECTS: The subjects in this study were people aged 65 years and older and most were recruited during a hospital stay. The cost-effectiveness analysis was based on a randomised trial with a total of 530 subjects. RESULTS: The incremental cost per fall prevented was $4,986. A sensitivity analysis was conducted by removing 12 outlier subjects (6 control and 6 intervention). The incremental cost per fall prevented was $1,921 for all subjects and was cost saving for subjects who had fallen in the 12 months prior to randomisation. CONCLUSIONS & IMPLICATIONS: A single factor home hazard reduction program is more likely to be most cost-effective amongst older people who have a history of falls.

Accidental Falls↗
PubMed2000

Hospitalisation for RSV infection in ex-preterm infants-implications for use of RSV immune globulin.

BACKGROUND: Respiratory syncytial virus (RSV) specific immune globulin is now being marketed for prevention of RSV infection in ex-preterm infants. However, there are no published UK data on the morbidity or mortality from RSV in these infants. AIMS: To determine the morbidity and mortality from RSV infection in a cohort of infants previously treated at a regional neonatal unit, and compare the cost of hospitalisation for RSV with the potential cost of administering RSV immune globulin (RSV-IG) prophylaxis. METHODS: Infants born at a gestation of less than 32 weeks were studied. Details of admissions for respiratory illness in the first two years of life were collected from hospital records, referring hospitals, and general practitioners. RESULTS: Data on 82 infants were collected. Up to three RSV seasons were encountered. The hospitalisation rate for confirmed RSV infection for the first season encountered was 4%. Rates of ward and paediatric intensive care unit admission were higher for infants with chronic lung disease. There were no deaths from RSV. RSV-IG would not have been cost effective for most infants. CONCLUSION: The morbidity and mortality rates from RSV observed in this group do not support the widespread introduction of RSV-IG prophylaxis for ex-preterm infants.

Antibodies, Monoclonal↗
PubMed2000

Expression of a homeobox gene (SIX5) in borderline ovarian tumours.

AIMS: To assess the expression of SIX5 (a homeobox gene) mRNA in surface coelomic epithelium, endocervical epithelium, Fallopian tube epithelium, and benign, borderline, and malignant epithelial ovarian tumours. METHODS: 10 normal premenopausal ovaries, 10 normal Fallopian tubes, 10 normal cervices, 10 normal postmenopausal ovaries, 10 benign epithelial ovarian tumours, 10 malignant epithelial ovarian tumours, and 40 borderline epithelial ovarian tumours were studied retrospectively. The tissues had been fixed in formalin and embedded in paraffin wax. The tumours had previously been typed into mucinous, serous, or mixed tumours and assigned to the borderline category according to the FIGO/WHO criteria. Expression was assessed by in situ binding of SIX5 specific sense and antisense riboprobes. Hybridization of the riboprobes was detected using a standard immunohistochemical technique and the results correlated with expression in the normal epithelium of the endocervix, Fallopian tube, surface coelomic epithelium, and ovarian tumours. RESULTS: Expression of SIX5 mRNA was demonstrated in normal Fallopian tube epithelium and normal endocervical epithelium. SIX5 mRNA was not detected in normal ovarian epithelial tissue at any of the times studied during the menstrual cycle. Expression of SIX5 was not shown in benign epithelial ovarian tumours or in any of the malignant epithelial ovarian tumours. In 31 of 37 borderline epithelial ovarian tumours (84%), SIX5 expression was found in the epithelial cells. CONCLUSIONS: SIX5 expression is present in the normal epithelium throughout most of the female reproductive tract, suggesting it may have a role in maintaining epithelial differentiation in these tissues. SIX5 expression appears to be restricted to borderline epithelial ovarian tumours and may be a marker of epithelial differentiation in these tumours; thus borderline ovarian tumours may not be part of a continuum of disease between benign and malignant epithelial ovarian tumours. Further investigation of expression of SIX5 may clarify the molecular processes that promote differentiation of the ovarian surface epithelium.

Cystadenoma, Mucinous↗
PubMed2000

Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer.

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.

Adenocarcinoma↗