[47th Annual Meeting of the North-German Orthopedic Society. Leipzig, 20 June 1998].
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Germany↗
Biomedical subjects
M Thomas
Publications and source records attributed to M Thomas.
Measurements of radioactivity in environmental samples from the southern Urals.
A region between Chelyabinsk and Ekaterinburg in the Southern Urals has been heavily contaminated due to operational and accidental releases from the first Soviet plutonium production facility Mayak. In 1992 and 1993, the German Federal Office for Radiation Protection organized a measuring campaign involving two Russian institutes to assist with the validation of former Soviet measurement data. The results of this measuring campaign are reported here. Environmental samples were collected from areas affected by significant radioactive releases into the Techa river, which started in 1948, and by fallout from the explosion of a fission product storage tank in 1957. Soil, sediment, water, milk and food samples were independently analysed for 90Sr, 137Cs and plutonium by the three institutes involved. This paper presents data on the present levels of environmental radioactivity. The highest contamination of areas accessible to the local population was found in the vicinity of the Techa river around Muslumovo. Activity concentration of floodplain samples reached up to 37,000 Bq.kg-1 137Cs, 5,600 Bq.kg-1 90Sr and 9.9 Bq.kg-1 Pu. Milk and potatoes from private farms in Muslumovo showed low activity in the range from 0.7 Bq.kg-1 to 25 Bq.kg-1 90Sr. The results of the three independent measurement teams showed sufficient agreement. One Russian laboratory obtained plutonium activities that exceeded the results of the other laboratories by about 20%. Contrary to the International Chernobyl Project, there was no overestimation of 90Sr activities in the Russian analyses. Therefore, the validity of earlier data sets acquired with same methodology and quality control can be considered a valuable basis for further assessments and for dose reconstruction in epidemiological projects.
Animals↗
Lipoprotein and cholesterol metabolism in diet-induced coronary artery atherosclerosis in primates. Role of cholesterol and fatty acids.
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Animals↗
Effects of the common cold on mood and performance.
Previous research has shown that both experimentally-induced and naturally occurring upper respiratory tract illnesses (URTIs) influence mood and mental functioning. None of the previous studies of naturally occurring colds has conducted appropriate virological assays to determine the nature of the infecting agent. This is an essential methodological step in studies of malaise associated with URTIs. The aim of this research was to investigate the effects of naturally occurring colds on mood and objective measures of performance. This was done by first conducting a cross-sectional comparison of 37 healthy people and 158 volunteers with colds and then a longitudinal study in which 100 volunteers developed colds and 87 remained healthy. Virological techniques were used to identify infecting agents and comparisons made across the different groups. The results showed that having a cold was associated with reduced alertness and slowed reaction times. These effects were observed both for colds where the infecting virus was identified and those where it was not. Similar effects were obtained for both rhinovirus and coronavirus colds. One may conclude that upper respiratory tract illnesses lead to a reduction in subjective alertness and impaired psychomotor functioning. This was true for both illnesses where the infecting agent was identified and for those clinical illnesses where no virus was detected. It is now important to identify the mechanisms linking infection and illness with the behavioural changes. Similarly, the impact of these effects on real-life activities such as driving needs examining. Finally, methods of treatment need to be developed which not only treat the local symptoms of the illnesses but remove the negative mood and the performance impairments.
Adolescent↗
One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial.
The aim of this phase II study was to determine the activity and toxicity of paclitaxel (administered by 1-h infusion) and carboplatin in advanced non-small cell lung cancer when used in a multicentre, community-based treatment setting. 100 chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer were treated between March 1995 and February 1996. All patients had Karnofsky performance status 70-100, measurable disease and adequate bone marrow, kidney and liver function. All patients received intravenous (i.v.) paclitaxel 225 mg/m2 by 1-h infusion followed immediately by carboplatin at a targeted area under the concentration time curve (AUC) of 6.0 using the Calvert formula. Courses were repeated every 21 days. Colony stimulating factors were not used routinely. 38 of 94 evaluable patients (40%) had objective responses to treatment (3 complete responses, 35 partial responses). An additional 32 patients had stable disease at initial re-evaluation. Weight gain during treatment was experienced by 47% of patients with objective response or stable disease. The median survival in this group of 100 patients was 8 months, with an actuarial 1-year survival of 42%. Leucopenia was common, but hospitalisation for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy was common, but usually appeared after the third or fourth course and was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. There was one treatment-related death due to sepsis. This large multicentre community-based phase II trial demonstrated the efficacy of paclitaxel and carboplatin combination chemotherapy in advanced non-small cell lung cancer. When paclitaxel is given by 1-h infusion, this regimen is easily administered in the outpatient setting.
Adult↗
Sezary syndrome - unmasked by cyclosporine.
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Adult↗
Comparison of outbred lines of chickens for resistance to experimental infection with coccidiosis (Eimeria tenella).
Coccidiosis causes dramatic economic losses in the poultry industry. Next to the extensive use of anticoccidial drugs, improving genetic resistance of birds to this parasitic disease represents an attractive alternative. An experiment was run in order to identify lines of chickens resistant and susceptible to coccidiosis as a tool to search for genetic markers of resistance. Five outbred lines were used: two Egyptian lines (Mandarah and Fayoumi), a Rhode Island Red line, and two White Leghorn lines (WLB21 and WLDW). The WLDW line segregated for three MHC haplotypes, B15, B19, and B21, and for the sex-linked dwarf gene, DW. Chicks were challenged at 4 wk of age with a high dose of Eimeria tenella (150,000 oocysts) and slaughtered 8 d postinoculation. Innate resistance was assessed individually by measures of lesion score, mortality, and body weight gain at slaughter, and plasma coloration 4 d postinoculation. Large differences in resistance to E. tenella were observed between lines. The Fayoumi line appeared clearly as the most resistant line, showing no mortality, less severe lesions than other lines, and a 30% reduction of growth as compared to control birds. The WLDW line was the most susceptible, with 27% mortality and a 85% reduction in growth. No major effect of MHC or dwarfism on resistance to E. tenella was found.
Animals↗
Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome.
OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a frequent complication of severe sepsis and a major cause of death in patients with hematologic malignancy during chemotherapy-induced leukocytopenia. Inflammatory mediators are important modulators of host response to injury and have been found to be increased in the bronchoalveolar lavage (BAL) fluid of nonleukocytopenic patients with ARDS. Since inflammatory cytokines in plasma of nonleukocytopenic patients seem to be efficient predictors of the course of ARDS, we examined this hypothesis in leukocytopenic patients with septic shock-induced ARDS. DESIGN: Prospective, observational study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Nineteen patients with leukocytopenia (white blood cell count of <1/nL) following cytoreductive chemotherapy for malignant disorders and severe sepsis with shock-induced ARDS (Murray score of >2.5). INTERVENTIONS: BAL and plasma sampling and ICU management. MEASUREMENTS AND MAIN RESULTS: The proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the BAL aspirates and in plasma samples, both obtained within 18 hrs after onset of ARDS. Hemodynamic and oxygen metabolism data were measured immediately before plasma samples were taken and BAL was performed. Of the 19 patients studied, nine patients responded to ICU treatment (e.g., mechanical ventilation as indicated by PaO2/FIO2, FIO2, shunt volume, and course of pulmonary infiltrates), whereas ten patients did not respond. BAL cytokine concentrations were significantly increased in nonresponders in comparison with responding patients (TNF-alpha, p = .021; IL-6, p = .008; IL-8, p = .019). In contrast, we did not observe any differences between the groups in terms of plasma cytokine concentrations. CONCLUSION: Determination of cytokine concentrations in BAL samples may be useful for evaluation of severity and course of ARDS in leukocytopenic patients, whereas measurement of plasma cytokines is not helpful.
Adult↗
Molecular, serological and population studies on a novel HLA-B allele--HLA-B*5002.
A novel HLA-B allele (B*5002), detected as a discrepancy between serological and PCR-SSP HLA-A and B phenotyping of bone marrow panel donors, was identified by nucleotide sequencing of exons 2 and 3. Titration studies on 39 HLA-B12/B21 cross-reactive antisera showed that the serological specificity of HLA-B*5002 was HLA-B45. PCR-SSP testing of 287 serologically defined HLA-B45-positive subjects from a panel of 12,411 donors, together with HLA-B*45 and B*5002 frequency data on 4,342 PCR-SSP typed subjects, indicated that 4.53% of serologically defined HLA-B45-positive subjects possess HLA-B*5002 and not HLA-B*4501. The phenotype frequency of HLA-B*5002 was 0.08954%; gene frequency was 0.00045 (n=16,753). In 73.3% of instances B*5002 appeared to be present on a haplotype with DRB1*0406 and DQB1*0402, 54.6% of which possessed A*2301. The B*5002, DRB1*0406, DQB1*0402 haplotype represents 52.4% of all haplotypes with DRB1*04 and DQB1*04 and 78.6% of haplotypes possessing DRB1*0406 and DQB1*0402.
Alleles↗
Iron status of Asian children aged 2 years living in England.
Haemoglobin and ferritin values were analysed in blood from 1057 children, aged 2 years, of Asian parents living in England. Children who had thalassaemia trait or a current/recent infection were excluded. Twenty nine per cent of Pakistani, 25% of Bangladeshi, and 20% of Indian children had haemoglobin < 110.0 g/l. The recent national diet and nutrition survey of preschool children found a prevalence of 12% of 2 year olds with haemoglobin < 110.0 g/l. No single factor accounted for more than a small proportion of the variance in haemoglobin and ferritin values, but the most significant factors that had a negative effect on iron status included the amount of cows' milk consumed, the use of a baby bottle, and mother's place of birth being outside of the UK. Taking vitamin or iron supplements was positively associated with iron status in one or more of the three groups.
Asia↗
Acute barium intoxication following ingestion of ceramic glaze.
A case of deliberate overdose of barium sulphide in a psychiatric setting is presented, with resulting flaccid paralysis, malignant arrhythmia, respiratory arrest and severe hypokalaemia, but ultimately with complete recovery. The degree of paralysis appears to be related directly to serum barium levels. The value of early haemodialysis, particularly with respiratory paralysis and hypokalaemia, is emphasised.
Adult↗
HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales.
Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele - A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05), for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/DQ and HLA-A/B/DR and B/DR/DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and A1, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient's extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.
Adolescent↗
Phase I trial of docetaxel administered by weekly infusion in patients with advanced refractory cancer.
PURPOSE: Docetaxel is a highly active antineoplastic agent; however, grade IV leukopenia occurs in the large majority of patients treated with a dose of 100 mg/m2 every 3 weeks. Recent experience with weekly paclitaxel has demonstrated a bone marrow-sparing effect when a weekly administration schedule is used. We investigated a weekly schedule of docetaxel in an attempt to alter the toxicity profile and improve the therapeutic index. PATIENTS AND METHODS: Thirty-eight patients with advanced, refractory malignancy entered this phase I trial between October 1996 and June 1997. Docetaxel was administered weekly for 6 consecutive weeks, followed by 2 weeks without treatment. Sequential cohorts of patients were treated at the following dose levels: 20, 25, 30, 36, 43, and 52 mg/m2. Patients were reevaluated after one course (8 weeks); patients with objective response or stable disease continued treatment for a maximum of four courses or until disease progression. RESULTS: Thirty-five patients completed at least one course of therapy. Myelosuppression was not a dose-limiting toxicity (DLT) at any of the doses tested. Only five episodes of grade III leukopenia occurred (14% of patients, 2% of doses), and no grade IV leukopenia was produced. No grade III or IV thrombocytopenia or anemia was observed. Grade III fatigue and asthenia were observed in all three patients treated at 52 mg/m2/wk and in two of 10 at 43 mg/m2/wk. Other grade III toxicity included acral erythema (n = 1), neuropathy (n = 1), peripheral edema (n = 1), and diarrhea (n = 1). The DLTs of this docetaxel schedule are fatigue and asthenia. Although the maximum-tolerated dose by definition of this study was 43 mg/m2/wk, we selected 36 mg/m2/wk for ongoing phase II studies. CONCLUSION: The toxicity profile of docetaxel is markedly altered when the drug is administered by a weekly schedule. Myelosuppression is mild and uncommon. Fatigue and asthenia are the DLTs; other nonhematologic toxicities, which included peripheral edema and neuropathy, are uncommon, and the arthralgia/myalgia syndrome was not observed. Weekly administration of docetaxel may provide a better tolerated, efficacious use of this drug; further investigation of weekly docetaxel as a single agent and in combination regimens is warranted.
Adult↗
Systemic yeast infection in owl monkeys (Aotus vociferans): ante-mortem screening and diagnosis by examination of bone marrow aspirates.
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Animals↗
Delivery of physiotherapy services to some First Nations communities in Manitoba.
PURPOSE: This program was instituted to extend physiotherapy services to communities without road access to traditional rehabilitation services. METHODS: Physiotherapy consulting services are provided on a monthly basis to communities involved in the program. Service is based in the communities' nursing stations and includes four components: direct care to clients, preventive care, professional resources, and education. RESULTS: Physiotherapy services can be effectively provided in isolated settings by an outreach program using experienced therapists based in a central location.
Adult↗
Treatment of allergic rhinitis: an evidence-based evaluation of nasal corticosteroids versus nonsedating antihistamines.
Allergic rhinitis is a high-cost, high-prevalence disease. In the 12 months ending March 31, 1997 $3.1 billion was spent in the United States for medications to manage this illness. Allergic rhinitis affects quality of life and interferes with work productivity. Nonsedating antihistamines are the most common and most expensive therapy for this condition. This study reviewed 13 randomized studies in which blinded investigators compared management of allergic rhinitis by means of intranasal steroids to management by means of nonsedating antihistamine. Evidence tables demonstrated that in all studies in which total nasal symptoms and nasal obstruction were recorded, the nasal steroid was statistically superior to the nonsedating antihistamine. For nasal blockage the nonsedating antihistamines did not perform better than placebo. For all other nasal symptoms the intranasal steroid was statistically superior in most reports and equal or numerically better in the remaining papers. When these data are linked to those from cost analysis and quality-of-life studies, the evidence strongly suggests that nasal steroids should be first-line therapy for allergic rhinitis. In four reports on the combination of a nonsedating antihistamine compared to a nasal steroid alone, there was no significant difference between these two treatments. Like asthma, allergic rhinitis is an inflammatory disease and should be managed with anti-inflammatory medication. Making such a change in the management of allergic rhinitis should increase efficacy and decrease costs.
Administration, Intranasal↗
Initial Clinical Experience of a Novel Device (the ÒFriend CatheterÓ) for Local Anesthetic Delivery Around Indwelling Arterial Sheaths.
The removal of femoral arterial sheaths, particularly after they have been in place for some hours, is a source of pain for patients undergoing invasiveive cardiac procedures. Methods of reducing this pain include systemic sedatives, analgesics and local anesthetic. We tested a new disposable plastic device, called the ÒFriend,Ó designed to reduce pain associated with sheath removal. The Friend wraps around a standard 8 Fr sheath allowing local anesthetic infiltration through side holes into local tissue. METHODS: Seventy-two patients undergoing interventional procedures were randomized to 3 groups for anesthetic administration just prior to sheath removal. Group 1 (control) received no local anesthetic. Group 2 (local) received 10 ml of lignocaine directly infiltrated with syringe and needle around the sheath. Group 3 (Friend) had the Friend inserted with the sheath and 10 ml of lignocaine was delivered via the device. Pain around the sheath was assessed prior to, during and just after, sheath removal using a 5 point verbal scale. RESULTS: Sixty-two patients completed the study. There were no serious complications related to the Friend device. The Friend group patients had significantly less pain associated with sheath removal than the control group. (Mean pain difference 1.28 vs. 0.34, p = 0.04). Pain scores in group 2 (local) did not differ significantly from the control group. The additional estimated cost involved in using the Friend was $16.93 per patient. CONCLUSIONS: The Friend device is a new, inexpensive and safe method of reducing pain associated with removal of arterial sheaths after cardiac interventional procedures.
Journal Article↗