Health-related quality of life in women and men with type 2 diabetes: a comparison across treatment groups.

AIM: This study compares health-related quality of life (HRQL) in patients with type 2 diabetes (T2DM) across treatment groups and explores gender differences. METHODS: Four regional surveys (KORA, CARLA, SHIP, DHS) and a national survey (GNHIES98) were pooled at individual level. HRQL was assessed with the SF-12/-36v1. Linear regression models were used to assess the effect of T2DM by treatment type (no medication; oral; oral/insulin combination; insulin) on the physical (PCS-12) and mental summary score (MCS-12) and the SF-6D, controlling for age, sex, study and covariates. We also performed an explanatory analysis of single items. RESULTS: PCS-12 scores and treatment type were associated (P-value 0.006), with lowest values for insulin treatment (-4.44 vs. oral; -4.41 vs. combination). MCS-12 scores were associated with treatment type and gender (P-value <0.012), with lower scores for women undergoing oral (-4.25 vs. men) and combination treatment (-6.99 vs. men). Similar results were observed for SF-6D utilities and single items, related to mental health, social functioning, vitality and role limitation (emotional). Comorbidities were predictors of lower PCS-12 and SF-6D scores. CONCLUSIONS: T2DM treatment impacts differently on physical and mental HRQL and on women and men. Further studies of gender-specific perceptions of T2DM treatment regimens are needed.

Long-term tooth loss in periodontally compromised but treated patients according to the type of prosthodontic treatment. A retrospective study.

If prosthodontic treatment is considered after periodontal therapy, the questions arise i) does prosthodontic treatment affect the treatment outcome of the dentition in general and ii) which type of prosthesis is related to best treatment outcome of abutment teeth? Our goal was to compare long-term tooth loss after comprehensive periodontal therapy in patients with or without prosthodontic treatment. Ninety patients' charts with a total of 1937 teeth who had received comprehensive periodontal treatment 5-17 years ago by the same periodontist were retrospectively evaluated. Sixty-five patients received fixed dental prostheses (FDP; n = 29) and/or removable partial dentures anchored with clips (RPDC; n = 25) or double crowns (RPDD; n = 25). Twenty-five patients were also periodontally compromised but treated without prosthodontic treatment and served as a control group. A total of 317 teeth and 70 abutment teeth were lost during 9.7 ± 4.1 years of observation. Thereof, 273 teeth and 48 abutment teeth were lost due to periodontal reasons. Mean tooth loss amounted to 1.2 ± 1.5 (controls) and 4.4 ± 3.4 (partial dentures). Abutment tooth loss was 0.4 ± 1.1 (FDP), 1.0 ± 1.2 (RPDC) and 1.3 ± 1.0 (RPDD). Poisson regressions identified prosthodontic treatment, age, socio-economic status, diabetes mellitus, mean initial bone loss and aggressive periodontitis as factors significantly contributing to tooth loss. Age, diabetes and non-compliance contributed to abutment tooth loss. Not considering biomechanical factors, patients with prosthodontic reconstructions under long-term supportive periodontal therapy were at higher risk for further tooth loss than patients without prostheses. Not only the type of partial denture but also the patient-related risk factors were associated with abutment tooth loss.

[Cost analysis of telemedical treatment of stroke]. / Kostenanalyse telemedizinischer Schlaganfallbehandlung.

BACKGROUND: Telemedicine-enabled stroke networks increase the probability of a good clinical outcome. There is a shortage of evidence about the effects of this new approach on costs for inpatient care and nursing care. METHODS: We analysed health insurance and nursing care fund data of a statutory health insurance company (AOK Bayern). Data from stroke patients initially treated in a TeleStroke network (TEMPiS - telemedical project for integrative stroke care) between community hospitals and academic stroke centres were compared to data of matched hospitals without specialised stroke care and telemedical support. Costs for nursing care were obtained over a 30-month period after the initial stroke. To rule out pre-existing differences between network and control hospitals, costs of stroke care were also analysed during a time period before network implementation. FINDINGS: 1 277 patients (767 in intervention, 510 in control hospitals) were analysed in the post-implementation period. An increased proportion of patients treated in intervention hospitals had a favourable outcome concerning the level of required nursing care. Patients in intervention hospitals had higher costs for acute inpatient care (5 309 € vs. 4 901 €, p=0.04), but lower nursing care fund costs (3 946 € vs. 5 132 €; p=0.04). There was no difference in relation to absolute total costs obtained in the post-implementation period. However, nursing care costs per survived year were significantly lower in intervention hospitals (1 953 € vs. 2 635 €; p=0.005). No significant differences were found in the pre-implementation period. CONCLUSIONS: Considering both health insurance and nursing care fund costs, the incremental costs for TeleStroke network care in hospitals are compensated by savings in outpatient care.

Health-related quality of life in subjects with and without Type 2 diabetes: pooled analysis of five population-based surveys in Germany.

AIMS: To estimate population values of health-related quality of life (HRQL) in subjects with and without Type 2 diabetes mellitus across several large population-based survey studies in Germany. Systematic differences in relation to age and sex were of particular interest. METHODS: Individual data from four population-based studies from different regions throughout Germany and the nationwide German National Health Interview and Examination Survey (GNHIES98) were included in a pooled analysis of primary data (N = 9579). HRQL was assessed using the generic index instrument SF-36 (36-item Short Form Health Survey) or its shorter version, the SF-12 (12 items). Regression analysis was carried out to examine the association between Type 2 diabetes and the two component scores derived from the SF-36/SF-12, the physical component summary score (PCS-12) and the mental component summary score (MCS-12), as well as interaction effects with age and sex. RESULTS: The PCS-12 differed significantly by -4.1 points in subjects with Type 2 diabetes in comparison with subjects without Type 2 diabetes. Type 2 diabetes was associated with significantly lower MCS-12 in women only. Higher age was associated with lower PCS-12, but with an increase in MCS-12, for subjects with and without Type 2 diabetes. CONCLUSIONS: Pooled analysis of population-based primary data offers HRQL values for subjects with Type 2 diabetes in Germany, stratified by age and sex. Type 2 diabetes has negative consequences for HRQL, particularly for women. This underlines the burden of disease and the importance of diabetes prevention. Factors that disadvantage women with Type 2 diabetes need to be researched more thoroughly.

[Improvements in type 2 diabetes care? Pooled analysis of survey data in southern Germany (KORA) from 1999-2008]. / Verbesserungen in der Versorgung von Patienten mit Typ-2-Diabetes? Gepoolte Analyse dreier bevölkerungsbasierter Studien (KORA) in der Region Augsburg zwischen 1999 und 2008.

To evaluate the quality of diabetes care, processes and outcomes of health care for type 2 diabetes were compared across three population-based surveys in Germany with cross-sectional and longitudinal perspectives. The surveys were conducted in the Augsburg region, southern Germany, in 1999-2001, 2003-2005, and 2006-2008 and included physical examinations, an interview, self-administered diabetes questionnaires, and laboratory tests. Quality indicators derived from guidelines for type 2 diabetes managed care programs in Germany served as the evaluation framework. Multiple regression models were used for analysis, adjusting for age, sex, education, diabetes duration, and cardiovascular comorbidity. Results show that medical examinations of eyes (61-71%) and feet (38-55%) and the use of antihypertensives, antiplatelet drugs, and lipid-lowering medications were reported more frequently over time. There was no increase in patient self-care behaviors or diabetes education. Blood pressure and cholesterol outcome targets were achieved more frequently over time. In conclusion, medical care and drug therapy of type 2 diabetes have improved; however clinical practice has failed to intensify patient participation and health behavior.

Time trends in type 2 diabetes patients' disease management and outcomes: evidence from two KORA surveys in Germany.

To explore time trends in diabetes management and intermediate health outcomes of people with type 2 diabetes, data from two population-based survey studies were compared. The surveys were conducted in the Augsburg region of Southern Germany in 1997/98 and in 2004/05, and included physical examinations, interviews, self-administered questionnaires and laboratory tests. Data from 334 participants aged 40-84 were analysed, including a longitudinal sub-sample of 50 persons. Results show significant time trends towards improvements over the seven year period. Controlling for age, sex, education and duration of diabetes, people felt better informed about diabetes (Odds Ratio (OR) 1.87; 95% CI: 1.12, 3.14) and stated greater adherence to the treatment plan (OR 4.42; CI: 2.62, 7.45) as well as higher participation in diabetes education programmes (OR 2.20; CI: 1.44, 3.38). Mean haemoglobin A1c levels decreased by -0.97% from 7.3% to 6.3% (CI:-0.66%, -1.28%). Physical activity (> or =1 h/week) was more frequent (OR 2.75; CI: 1.65, 4.59), although Body Mass Index increased by 1.43 kg/m (2) (CI: 0.86, 2.00). The positive changes in disease management and metabolic outcomes for type 2 diabetic patients between 1997/98 and 2004/05 indicate a shift towards greater patient involvement in diabetes care and possibly more efficient medical management practices.

[Regional differences in health behaviour in bavaria - a multilevel analysis of a representative population questionnaire in combination with socioeconomic structural data]. / Regionale Unterschiede des Gesundheitsverhaltens in Bayern - Mehrebenenanalyse einer bevölkerungsrepräsentativen Befragung in Verbindung mit sozioökonomischen Strukturdaten.

OBJECTIVES: There are regional differences in mortality in Bavaria. Although these regional dif-ferences in mortality were associated with behavioural risk factors and socioeconomic factors in a study conducted for this reason, the quantitative effect of behavioural risk factors and socio-economic factors as well as the regional structure on the individual health as a predictor of mortality were not known. METHODS: Persons between the age of 18 and 80 were interviewed with the Behavioral Risk Factor Surveillance System (BRFSS) in two Bavarian regions with high mortality, two Bavarian regions with low mortality and in the capital of Bavaria, Munich. For regional structural data, the INKAR database was used. Data were analysed descriptively, with a multivariable-adjusted logistic regression and with a multilevel analysis. RESULTS: There were lower proportions of persons with a good or very good state of health as well as adverse results for overweight/adipositas, the behavioural risk factors for doing sports, smoking and consuming fruits and vegetables and the socioeconomic factors education and unemployment in the two regions with high mortality "Ostbayerische Grenzregion" and "Oberfranken". In a multivariable adjusted logistic regression, the body mass index, smoking, doing sports, climbing stairs, consuming alcohol, being satisfied with the job and the interaction between education and marital status were found to have an influence on the individual health. The small remaining regional component could be explained in the multilevel analysis by different variables which describe the economical situation of the regions. CONCLUSIONS: In accordance with the study hypotheses, a consistency between behavioural risk factors and regional differences in mortality could be observed. Socioeconomic influences and a small regional component are involved. In addition to specific prevention programmes for the target groups, structural support is also meaningful with regard to its potential health impact.

Knowledge about diabetes and participation in diabetes training courses: the need for improving health care for diabetes patients with low SES.

The association between socioeconomic status (SES) and health is well known, and many determinants of these health inequalities have been studied. Concerning the role of health care, the results are conflicting, though. The study adds to this discussion by focussing on health care differences for people with type 2 diabetes. The analyses are based on a study conducted in Southern Germany (WHO MONICA study, Augsburg myocardial infarction registry). The sample consists of 378 type 2 diabetic patients, divided into two clearly distinct groups: one group (n = 210) from a MI registry with clinically confirmed myocardial infarction (MI), the other (n = 168) from a population based survey, characterised by the absence of a previous MI. Ten topics are differentiated in the assessment of diabetes knowledge (diet, weight control, etc.). The analyses show that knowledge about diabetes increases with increasing educational level. Concerning "very well informed about diet", for example, the odds ratio for the high educational group is 3.45 (95 % CI: 1.34 - 8.86) as compared with the low educational group. This association is restricted to those diabetic persons with previous MI. For diet, the odds ratio for this subsample increases to 7.35 (p < 0.05). Similar results are seen for the other topics of diabetes knowledge. Also, diabetic persons with a low educational level participated in diabetes training courses least often, especially in the subsample with previous MI. Thus, taking the example of type 2 diabetes, the study adds to the evidence that the inverse care law is still present today in Germany.

[Direct medical costs of (severe) obesity: a bottom-up assessment of over- vs. normal-weight adults in the KORA-study region (Augsburg, Germany)]. / Direkte medizinische Kosten der (starken) Adipositas: ein Bottom-up-Vergleich über- vs. normalgewichtiger Erwachsener in der KORA-Studienregion.

AIM OF THE STUDY: To estimate and compare direct medical costs of illness of German adults in different BMI-groups and different degrees of obesity. METHODS: In a sub-sample (n = 947) of the KORA-Survey S4 1999/2001, a cross-sectional health survey of the adult population in the Augsburg region (Germany; age: 25-74), visits to physicians, receipt and purchase of drugs, and inpatient days in hospital were assessed over half a year. Body mass index (BMI in kg/m(2)) was assessed anthropometrically. Respondents in normal weight (18.5 < or = BMI < 25), pre-obese (25 < or = BMI < 30), moderately obese (class 1: 30 < or = BMI < 35), and severely obese (classes 2-3: BMI > or = 35) range were compared in their costs of illness via analyses of covariance and regression analyses based on generalized linear models. Physician visits and inpatient days were evaluated as recommended by the Working Group "Methods in Health Economic Evaluation", and drugs by actual costs. Sex, age, socio-economic status (Helmert-Index), sickness fund (statutory vs. private), and place of residence (Augsburg City vs. District of Augsburg or Aichach-Friedberg) were adjusted for. RESULTS: While respondents with moderate obesity statistically did not differ significantly in their direct medical costs from those in normal weight or pre-obese range (1,080.14 euro vs. 847.60 euro and 830.59 euro; for users of care: 1,215.55 euro vs. 993.18 euro and 1,003.23 euro [all estimates adjusted and per annum]), those with severe obesity had significantly higher costs (2,572.19 euro; for users of care: 2,964.87 euro). Sub-analyses for individual parameters of health care use revealed that this pattern is largely due to inpatient days in hospital and receipt/purchase of drugs only available on prescription. CONCLUSIONS: On average, results indicate excess direct medical costs primarily in people with severe, and less with moderate obesity. In particular, they underline the need to distinguish moderate vs. severe obesity (classes 1 vs. 2-3) in health economics and health services research.

Utilization of out- and inpatient health services by obese adults: a population-based study in the Augsburg region, Germany.

The aim of this study is to compare out- and inpatient health services utilization by obese and normal weight adults. In a subsample of the KORA-Survey S4 1999/2001 in the Augsburg region, Germany (n = 947, age: 25-74 years), number of visits to general practitioners (GP) and inpatient hospital days were self-reported in three computer-aided telephone interviews (CATI) over half a year. Body mass index, based on measured body height and weight, was used to define obesity according to WHO classification. Participants, stratified in normal weight (18.5 < or = BMI < 25), preobese (25 < r = BMI < 30), obese class 1 (30 < or = BMI < 35) and obese classes 2-3 (BMI > or = 35), were compared via logistic, zero-truncated negative binomial, and multinomial models to elucidate obesity's associations with utilization at all, its frequency, and high utilization. Sex, age, social class, health insurance, and place of residence were adjusted for in all models. Respondents in obesity class 1 were more prone to report at least one visit to a GP than those normal weight (OR = 1.84, p < 0.01), while obesity classes 2-3 were associated with frequent (IRR = 1.63, p < 0.05) and high utilization (OR = 3.57, p < 0.05). Regarding days in hospital, only the extremely obese (i. e. classes 2-3) reported significantly more utilization than those normal weight (days if hospitalized at all: IRR = 3.24, p < 0.05; high utilization: OR = 5.4, p < 0.01). Sex did not play a significant role in any model. Older respondents reported more utilization in terms of GP-visits, while only tending to do so regarding inpatient utilization. Both those with statutory (vs. private) health insurance and rural (vs. urban) place of residence had higher odds to visit a GP at all. Results point to an excess utilization of out- and inpatient health services by especially extremely obese adults, and underline the need to contrast obesity classes 2-3 vs. 1 in health services utilization research.

[Switching sickness funds and risk compensation mechanisms in the statutory health insurance system in Germany--empirical results from the cooperative health research in the region of Augsburg (KORA)]. / Kassenwechsel und Risikostrukturausgleich in der gesetzlichen Krankenversicherung -- empirische Befunde der Kooperativen Gesundheitsforschung in der Region Augsburg (KORA).

Since 1996, all citizens of the Federal Republic of Germany who are insured in the statutory health insurance system are entitled to switch their sickness fund. The rationale of this regulation was to strengthen elements of competition in this system in order to stimulate the sickness funds to improve the efficiency of health care and to respond to consumers' preferences. Simultaneously, to avoid the implicit incentives for sickness funds to engage in risk selection, a risk compensation mechanism was introduced, including as morbidity-related risk adjusters age, sex and incapacity to work. Based on the KORA survey S4 (1999/2001) we take the case of switching behaviour in the region of Augsburg, and analyse whether this risk adjustment scheme was working effectively. The results show that persons changing their sickness fund were characterised by a comparatively smaller burden of chronic diseases and by a less frequent utilization of inpatient health care. Under these conditions, differences in the contribution rates do not accurately reflect differences in the performance and efficiency of sickness funds. Moreover, the migration of good risk to sickness funds with favourable contribution rates threatens the principle of financial solidarity. Therefore, the system of risk equalisation has to be developed towards measuring the risk volume borne by the sickness funds more precisely than hitherto.

Can inaccuracy of reported parental history of diabetes explain the maternal transmission hypothesis for diabetes?

BACKGROUND: The mode of inheritance of type 2 diabetes mellitus is still under discussion. Several studies have suggested an excess maternal transmission, however, more recent studies could not always confirm these findings. METHODS: We investigated the frequency of a maternal and paternal history of diabetes among diabetic and non-diabetic subjects and assessed the association between diabetes and a parental history of diabetes among participants of the MONICA Augsburg study. As an extension to previous studies, unknown parental status was taken into account. RESULTS: Of the 542 diabetic probands, 25.3% reported a positive maternal history of diabetes and 10.9% reported a positive paternal history of diabetes. Among the 12,209 non-diabetic participants a positive maternal history was also more common than a positive paternal history (12.5% versus 7.1%). Conversely, an unknown paternal status was more common than an unknown maternal status in both groups (diabetic subjects: 27.9% versus 16.8%, non-diabetic subjects: 16.8% versus 8.4%). Adjusted odds ratios (OR) for the association between a parental history of diabetes and diabetes status were similar for a positive maternal (OR = 2.9, 95% CI : 2.3-3.6) and paternal history (OR = 2.8, 95% CI : 2.1-3.8) and for an unknown maternal (OR = 1.3, 95% CI : 1.0-1.8) and paternal history (OR = 1.5, 95% CI : 1.2-1.9). CONCLUSION: Our findings do not support a strong excess maternal transmission of diabetes. Epidemiological biases and failure to account for 'don't know' responses may in part explain the previously observed predominance of a maternal history of diabetes.

Radiographic defect depth and width for prognosis and description of periodontal healing of infrabony defects.

BACKGROUND: The aims of the present study were to evaluate 1) defect depth and width as a prognostic factor and 2) change in defect width as a describing parameter of periodontal healing in infrabony defects treated by regenerative therapy after 6 and 24 months. METHODS: In 24 patients with advanced periodontitis, 39 infrabony defects were treated by guided tissue regeneration (GTR) using expanded polytetrafluoroethylene (ePTFE) (n = 7) or bioabsorbable barriers (n = 32). Clinical parameters were assessed and 39 standardized radiographs (in triplicate) were taken before and 6 and 24 months after surgery. Using a computer-assisted analysis, the depth, width, and angle of the bony defects were measured. RESULTS: Statistically significant vertical clinical attachment gains (CAL-V: 3.15 +/- 1.63 mm to 3.31 +/- 1.65 mm; P<0.001) and bony fill (1.30 +/- 2.53 mm; P<0.01 to 1.54 +/- 2.70 mm; P<0.005) were observed 6 and 24 months postsurgically. In a multilevel regression analysis CAL-V gain was predicted by baseline CAL-V (P <0.0001), actual smoking (P <0.05), and age (P <0.1). Bony fill could be predicted by baseline height of the infrabony component (P<0.0001), gingival index at baseline (P<0.05), and actual smoking (P <0.01). In narrow (<26 degrees) and deep (> or = 3 mm) infrabony defects bony fill was more pronounced than in wide and shallow defects (P <0.05). CONCLUSIONS: Improvement achieved by guided tissue regeneration in infrabony defects can be maintained up to 24 months after surgery. Narrow and deep infrabony defects respond radiographically and to some extent clinically more favorably to GTR therapy than wide and shallow defects. However, depth of the infrabony component was a stronger prognostic parameter than defect angle. Actual smoking impairs the results of GTR therapy in infrabony defects.

Resampling-based methods for the analysis of multiple endpoints in clinical trials.

We consider multivariate tests for comparing two treatments with multiple endpoints. The test decision is drawn from the simultaneous consideration of the univariate tests for the single endpoints. A general class of these tests, called cut-off tests, can be given, which, however, can lead to highly conservative procedures because the dependencies among the endpoints are not taken into account. In applying resampling-based methods considerable improvements for these tests can be achieved. Resampling-based cut-off tests are proposed which are sensitive against a treatment difference in a single endpoint, in a subgroup of endpoints, or in all endpoints. The results of Monte Carlo simulations demonstrate that a remarkable gain in statistical power as compared to the crude simultaneous consideration can be reached. In particular, for the multivariate one-sided test situation the proposed tests can be recommended. As an example the application of the tests is demonstrated by data from a clinical trial.

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Correlation of developmental neurological findings with spectral analytical EEG evaluations in pre-school age children.

For the differentiation of developmental neurological disorders in pre-school age children, the relationship between automatically derived EEG parameters and developmental neurological findings was investigated. Within the scope of the Munich Pediatric Longitudinal Study, the sample sets of 4- and 5-year-old children (according to the frontal and parieto-occipital EEG derivations) with selected abnormal findings categorized by special items were compared with the corresponding control groups. This was carried out by means of one-sided t tests and relative frequency band-related as well as single-step spectral power parameters in the alpha range of the EEG. Automatic analysis using single-step power values was superior to that using band-related parameters. This led to the conclusion that use of age-specific single-step parameters for a quantitative EEG analysis and ignoring the classical frequency bands will yield statistically greatly improved results. For 4- and 5-year-old children, the best separation of the neurologically abnormal groups from the normal control groups was obtained using relative spectral values in the frequency range of 9.0-9.8 Hz with a maximum at 9.4 Hz. At the same time, the topographical conditions of brain immaturation should be taken into account. The results for the children examined in this study differ in a stronger distinction over the frontocentral brain region of 4- and 5-year-olds (P < 0.01) and through an additional distinction over the parietooccipital region of the 5-year-olds (P < 0.001). It still must be tested whether the spectral parameter at 9.4 Hz is age-specific for 4- and 5-year-old children or whether in other age groups different spectral parameters are of use. As an examiner-independent method, the automatic EEG analysis should become an integral component of developmental neurological diagnostics.

The association between baseline lung function and bronchial responsiveness to methacholine.

It has been reported that females show an increased frequency of bronchial hyperresponsiveness (BHR) compared to males and that this difference is abolished after taking into account differences in baseline FEV1. The aim of our study was to analyse how the distribution of BHR in males and females depends on the definition of BHR. Special emphasis was paid to the question whether the prevalence rates of BHR according to different definitions were related to baseline characteristics of the subjects and baseline lung function in the same manner. We analysed the data obtained within the European Community Respiratory Health Survey (ECRHS) in the Eastern German population sample of Erfurt aged 20-65 years (n = 931). In logistic regression analyses of different definitions of BHR, we used as parameters age, height, gender, smoking habits, baseline forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1 as a percent of FVC (FEV1% FVC). Symptoms and reported diagnosis of asthma did not significantly depend on gender or age. When BHR was defined as the provocative dose causing a 20% fall in FEV1, BHR was more prevalent in females than in males (27.6% vs. 13.2%). Similar gender differences were found when defining BHR via a 10% fall in FEV1 or by using corresponding cut-off values of the linear dose-response slopes of the percent decline in FEV1 (DRS). Multiple linear regression analyses of various transformations of the DRS also indicated a higher degree of BHR in females. Independently of the definition chosen, however, the gender difference in the prevalence of BHR disappeared when height and FEV1 or FEV1% FVC or appropriate combinations were included in the model. The reciprocally transformed DRS showed the best resolution of the spectrum of bronchial responsiveness. These data are compatible with the hypotheses that (1) estimates of the distribution of BHR are distorted by differences in the methacholine dosage per lung size and that (2) airway geometry affects the measurement of BHR. It appears that these factors and not intrinsic differences in BHR between males and females contribute to the gender differences in the prevalence of BHR. Furthermore, our data support the superiority of the dose response slope for the analysis of bronchial responsiveness in epidemiologic surveys.