Asthma und asthmatypische Beschwerden bei Schulkindern: Vergleich von Gebieten in Deutschland und Osterreich

Conclusion

Geographical differences in morbidity of asthma and asthmalike complaints were ascertained and remained stable after adjustment for potential confounders. However, the choice of the way of presentation (relative risk versus deviation from the weighted mean of the prevalences) can provoke different suggestive effects.     

The influence of gemcitabine on the CD4/CD8 ratio in patients with solid tumours

Gemcitabine (dFdC) is a novel pyrimidine antimetabolite with documented antineoplastic activity against metastatic non-small cell lung cancer (NSCL), pancreatic carcinoma, ovarian and breast cancer. The side effects of gemcitabine are generally mild; severe infections are reported in less than Ilo of patients. In contrast, other new nucleoside analogues such as the purine antimetabolite fludarabine lead to a significant alteration of the CD4/CD8 lymphocyte ratio associated with an increased risk for opportunistic infections. This study investigates the effect of gemcitabine on different lymphocyte subsets during consecutive applications. 16 patients with solid rumours (3 non-small cell lung cancer, 3 pancreas, 3 testicular, 2 breast, ovarian germ-cell, 1 ovarian, 1 small cell lung, 1 gastric cancer, 1 carcinoma of unknown primary); 15 patients were previously treated, received at least 3 applications of gemcitabine (1,000 mg/m(2) as a 30 min infusion, at days 1, 8, 15; q 4 weeks). Lymphocytes surface antigens were analysed by standard technique flow cytometry prior to every infusion. The median number of leukocytes before therapy was 7823/mu l, with lymphocytes 875/mu l, including 68% T-cells (CD3(+)), 9% B-cells (CD19(+); CD20(+)) and 15% NK-cells (CD56(+); CD16(+); CD3(-)), the CD4/CD8 ratio was 1.7. After gemcitabine therapy the median number of leukocytes was 5136/mu l, with lymphocytes 1012/mu l, including 77% T-cells, 8% B-cells and 10% NK-cells and a CD4/CD8 ratio of 2.2. Severe complications or opportunistic infections were not seen in these 16 patients. No significant change of CD4/CD8 ratios and NK-ccll numbers was seen in our patients with solid tumours during weekly treatment with gemcitabine. A severely increased risk for opportunistic infections following treatment with the new antimetabolite gemcitabine appears unlikely.     

Use of crayfish in biomonitoring studies of environmental pollution of the river Meuse

The river Meuse, located in western Europe, is contaminated by different pollutants, of both organic and inorganic nature. The predominant sources of Meuse contamination in The Netherlands are agricultural activities and pollution derived from urban areas. Crayfish, water, and sediment samples were collected at four different locations of the river Meuse, in order to cover a large part of the catchment area of this river in The Netherlands. Crayfish may be very useful in biomonitoring studies, since they can integrate body load by pollutants over time in an area-bound manner. In these crayfish, levels of aromatic DNA adducts, heavy metal residues, polychlorinated biphenyls (PCBs), and organochlorine pesticides were determined in hepatopancreatic tissue. Also analyzed were water and sediment samples derived from the same locations, for polycyclic aromatic hydrocarbons (PAHs), heavy metals, and organochlorine compounds. In sediments from the four different sampling sites, no clear differences were observed in PCB levels. Organochlorine pesticide concentrations were highest at location A, the most upstream sampling site, whereas a general decrease was observed following the river Meuse downstream. A similar pattern was observed for the metal compounds. For PAH sediment levels no consistent tendency could be observed. Highest values were detected at site B, followed by, respectively, locations A, D, and C. In water samples, a different pattern was observed. The highest metal concentration was observed at location D, whereas the total organochlorine level was higher at sites B and D, compared to the two other sampling sites. Differences in pollution levels in crayfish between sampling sites were evident. Site D, the most downstream-situated site examined, appeared to be the most polluted site with respect to PCBs, DDT, DDE, and Cu in crayfish. Moreover, DNA adduct levels, which may serve as a dosimeter for the internal dose of aromatic compounds such as PAHs and PCBs, were also significantly higher in hepatopancreatic tissue of crayfish captured at site D, compared to the three other sampling sites. Moreover, significant correlations were observed between DNA adduct levels and the lower chlorinated PCB congeners (PCB 28-PCB 101). By correlating the different pollutants in water and/or sediment with xenobiotic levels in crayfish, no consistency could be observed, indicating that monitoring aquatic species may provide specific information on the presence of surface water pollutants. These results indicate that crayfish can be used as biological indicators of exposure to both organic and inorganic pollution in aquatic systems.     

Occupational therapy in mental health: challenges and opportunities

The National Mental Health Policy and National Mental Health Plan published in 1992 provided directions for the reform of mental health services in Australia. They stated that mental health services should be part of the mainstream health system and that integrated mental health programmes should be developed to cover the full range of specialist mental health services, focusing on improved quality of service, the consumers, equity of access, continuity of care and redistribution of resources. The Queensland Mental Health Plan published in 1994 set out specific objectives and strategies for implementing mental health service reform in Queensland. In Queensland there has been a concentration on developing core mental health services involving the reorientation of service delivery from institutions to the community, based on the principles of integration, mainstreaming and regional self-sufficiency. Major restructuring of mental health services is taking place, which has meant changes in service development, organizational structures and work practices. There has been a significant impact on the roles and skills required by the mental health workforce in the context of today's mental health services climate. There is a focus on staff providing individualized assessment and continuing treatment using a case management approach, within a continuum of care. Implications for occupational therapists include developing a generic skill base in preparation for broad-spectrum mental health professional roles while maintaining their professional identity. It is recommended that research be conducted to examine the capacity of occupational therapists to adapt to the changing mental health environment. Copyright © 1999 Whurr Publishers Ltd.     

Long-term treatment with Pilogel/β-blocker in glaucoma patients

In a multicentre clinical trial thirteen patients with primary open angle glaucoma or ocular hypertension were followed during at least six months while selfinstilling Pilogel (once daily) and topical -blocker (twice daily). After six months of combination therapy there was an average decrease in intra-ocular pressure (IOP) of 33.6% 9.5 hours after Pilogel administration and an IOP decrease of 23.4% 22.5 hours after Pilogel administration. With topical -blocker alone, an average IOP decrease of 15% was measured. Throughout the study we observed in six patients (46.1%) a superficial punctate keratitis which mostly spontaneously cleared. We did not see any serious side-effects after six months of combination therapy.     

Lateral deviation of the eyes on forced lid closure in patients with cerebral lesions

We examined 35 patients with unilateral cerebral lesions to determine the incidence of lateral deviation of the eyes under forcefully closed lids and the reliability of this sign in predicting the side of the lesion. Only patients with radiologically confirmed unilateral lesions were studied. Over 70% of patients had contralateral ocular deviation (Cogan's "spasticity of conjugate gaze"), 20% had ipsilateral deviation, and less than 9% of the patients had no deviation. Lateral ocular deviation was as sensitive, but not as specific, as a unilateral Babinski plantar response in determining the side with the lesion. Contralateral deviation was more common with parietotemporal localization, suggesting that the phenomenon reflects an underlying disturbance of attentional mechanisms.     

Using personal digital assistants to document pharmacist cognitive services and estimate potential reimbursement.

The use of personal digital assistants (PDAs) to document pharmacist cognitive services and estimate potential reimbursement was studied. Between September 2001 and February 2002, four pharmacy residents and four clinical pharmacists used PDAs for documenting cognitive services. Interventions recorded on paper during the same six-month period one year earlier were reviewed for comparison. Potential reimbursement for these services was calculated by linking current procedural terminology codes and charges to the electronically documented services. Over the six-month study period, pharmacists recorded 7319 interventions with PDAs, compared with 5028 documented on paper during the earlier six-month period. Potential claims for pharmacists' cognitive services documented with PDAs amounted to more than $1 million in the six months, assuming a 100% reimbursement rate. PDAs provide a simple, efficient paperless system for documenting pharmacists' clinical services and generating reimbursement claims.     

Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-alpha?

PURPOSE: Imiquimod represents a synthetic local immune response modifier that has demonstrated efficacy in clearing basal cell carcinoma. Via interaction with Toll-like receptor 7 on immune cells, imiquimod induces local production of cytokines, such as interferon (IFN)-alpha. EXPERIMENTAL DESIGN: To more closely define and elucidate mechanisms leading to basal cell carcinoma clearance in vivo, we examined gene expression profiles of skin basal cell carcinoma before and after treatment with 5% imiquimod cream (Aldara) by using high-density oligonucleotide arrays. RESULTS: We show that imiquimod predominantly induces genes involved in different aspects of immune response. In addition to effects on immunity, imiquimod treatment modulates the expression of genes involved in the control of apoptosis and oncogenesis. Array data indicated that imiquimod treatment induces expression of opioid growth factor receptor, a molecule recently reported to be a target for antitumor antibody responses. Immunohistochemistry revealed in vivo up-regulation of opioid growth factor receptor protein on tumor and on infiltrating cells after treatment. By using basal cell carcinoma cell lines treated with IFN-alpha or imiquimod, we show that opioid growth factor receptor up-regulation is IFN-alpha-mediated, rather then directly imiquimod-mediated. By using tissue microarray containing 52 basal cell carcinomas, we demonstrate opioid growth factor receptor expression in almost half of the cases. Expression of opioid growth factor receptor correlated with a longer recurrence-free period in basal cell carcinoma that recurred after radiotherapy (Kaplan-Meier analysis, P = 0.041). CONCLUSIONS: In addition to its immunomodulatory and antiproliferative activity, opioid growth factor receptor seems to have a prognostic significance in basal cell carcinoma patients. Our data add to the growing list of basal cell carcinoma-associated tumor antigens.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.     

Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study.

PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.