The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.

Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.

[Sensitivity of parents with psychosocial stress]. / Elterliche Feinfühligkeit bei Müttern und Vätern mit psychosozialen Belastungen.

This explorative study examines differences and similarities in parental sensitivity by mothers and fathers in particularly strained families with infants in the prevention project"Nobody slips through the cracks" ("Keiner fällt durchs Netz"). By means of the CARE index, parental sensitivity of both parents is determined, as well as relations to the factors parental stress, postpartum depression, attachment style, and parents' sense of coherence. An association between maternal and paternal sensitivity is shown. In addition an association between maternal, but not paternal sensitivity and familial stress is reported. Furthermore, a clear difference between mothers' and fathers' sense of coherence is shown. Overall, the CARE index proves to be an adequate instrument for research in the context of early prevention and intervention projects as well as the inclusion of fathers in researching parental sensitivity. Finally, practical implications of these results for interventions in projects of early prevention are discussed.

Ductal anatomy: a determinant of successful stenting in hypoplastic left heart syndrome.

Interventional palliation for hypoplastic left heart syndrome (HLHS) could reduce the current morbidity and mortality. Stenting of the arterial duct is the critical interventional step for HLHS. We reviewed our experience with 40 consecutive patients with HLHS referred for stenting of the ductus arterious (DA). Thirty-nine of 40 (97%) infants had suitable anatomy and were successfully stented. The infants were grouped by orientation of the ductus in the frontal plane. Type 1 DA anatomy had a leftward loop at a mean orientation of 18 degrees from the vertical plane. Type 2 ductal anatomy was mesoverted, with a mean orientation of 7.1 degrees from the vertical plane. Type 3 ductal anatomy displayed a rightward axis, with a mean of -4 degrees rightward. Orientation of the DA was significantly related to length of the ductus, number of stents required for complete coverage, and technical and procedural complications. Type 1 DA occurred in 65% of patients, and there was 100% technical success, no mortality, and only an 8% incidence of complications. Type 2 anatomy occurred in 27% of patients and there was 100% success. However, the technical and procedural complications increased to approximately 50%. Type 3 ductal anatomy was seen in only 3 patients, 2 of whom were successfully stented. There was no procedural-related mortality, and all stented patients were weaned from prostaglandin. There were only two late complications (coarctation). We conclude that ductal stenting using self-expanding nitinol stents is successful in more than 95% of infants with HLHS. Patients with HLHS and favorable ductal anatomy should be considered for primary ductal stenting.

Reactivation of a Trypanosoma cruzi infection in a rhesus monkey (Macaca mulatta) experimentally infected with SIV.

Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected. Analysis of the small subunit rRNA gene of the trypanosome identified the protozoan as T. cruzi.

[Induction of arthritis in healthy knee joints after intra-articular injection of the proteolytic enzyme elastase - An experimental investigation in the rabbit]. / Arthroseinduktion im gesunden Kniegelenk durch intraartikuläre Injektion des proteolytischen Enzyms Elastase - eine tierexperimentelle Untersuchung.

AIM: Humoral aspects are being discussed in the initiation of arthritis. Therefore, the effects of the proteolytic enzyme elastase on the cartilage of knee joints in rabbits have been investigated. The enzyme was evaluated using activities comparable to those in post-traumatic knee joint hemarthrosis in humans. METHOD: Polymorphonuclear leukocyte elastase was injected into one of the knee joints of 10 rabbits. In 5 animals (first study group), joints were then immobilized with a cast for 6 weeks. In the other 5 (second study group), no immobilization was applied. In the first zero group (2 animals), 0.9 % NaCl was injected intra-articularly without immobilization, whereas in the second zero group (2 anmals) knees were immobilized for 6 weeks without prior injection. Thus, the effect of immobilization could be evaluated additionally. Joint specimens were then examined histologically and electron microscopically. RESULTS: There was clear evidence of elastase having severe destructive effects on cartilage regardless of additional joint-immobilization. In neither zero group was there prearthritic damage to the cartilage. CONCLUSION: To prevent the initiation of cartilage damage by humoral factors, early elimination of the pathological intra-articular effusion is necessary.

Study of lung cancer and residential radon in the Czech Republic.

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Risk from residential radon can be estimated from occupational studies. Nevertheless, as such extrapolations depend on a number of assumptions, direct estimation of the risk is needed. The present study of lung cancer mortality was designed as a follow-up of a population (N = 12,004) in a radon prone area of the Czech Republic covering the period 1960-1999. Information on vital status and causes of death were obtained mostly from local authorities and from the national population registry. Exposure estimates were based on one year measurements of radon progeny in most houses of the study area (74%). Exposures outside the area (16%) were based on country radon mapping. Mean concentration of 509 Bq/m3 is higher than the country estimate by a factor of 5. By 1999, a total of 210 lung cancers were observed, somewhat more than the nationally expected number (O/E = 1.10) in comparison to generally low numbers corresponding to cancers other than lung (O/E = 0.81). The excess relative risk per standard radon concentration (100 Bq/m3) was 0.087 (90% CI: 0.017-0.208). This value is consistent with risk coefficients derived in other indoor studies. The present follow-up demonstrated that increased incidence of lung cancer depends linearly on exposure in terms of average radon concentration in the course of previous 5-34 years. Adjustment for smoking did not substantially change this estimate, although the risk coefficient for non-smokers (0.130) was higher in comparison to that for ever smokers (0.069), but not statistically different.

Experimental Helicobacter pylori infection of rhesus macaques (Macaca mulatta).

The aim of the present study was to establish an animal model for Helicobacter pylori (H. pylori) infection at the German Primate Centre in rhesus monkeys (Macaca mulatta). During the experiments the susceptibility of three animals to different H. pylori strains of human origin was tested. In a follow-up study gastric biopsies from three different sites were investigated in regular intervals using microbiological, histological, electron microscopical and molecular biological methods to evaluate the presence of bacterial colonization and the occurrence of gastritis. It was possible to establish a persistent experimental infection. The rather long follow-up period of 18 months offered the possibility to demonstrate a permanent H. pylori infection in the gastric mucosa of the test animals. The three animals have now been successfully colonized with H. pylori for 18 months and presented a chronic active gastritis confirmed by microbiological and histological methods. By molecular typing, the identity of the isolates recovered from the animals was shown. It was possible to demonstrate that one infection strain outcompeted the second one. Taken together, prerequisites exist for making use of an attractive and useful animal model in rhesus monkeys especially for long term observations.

Radon exposure and lung cancer risk--Czech cohort study on residential radon.

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Nevertheless, direct evidence of risk from residential radon is desirable. In 1990, a study was started comprising 12,000 inhabitants of an area with elevated radon concentrations. The mean level in the houses was higher than general mean of the country by a factor of five. In the period 1961-1995, a total of 173 lung cancers were observed. Comparing to nationally expected numbers (E), the observed number (O) of cases is elevated (O/E = 1.11), in contrast to generally low figures for cancers other than lung (O/E = 0.85). Lung cancer risk related to cumulative exposures experienced in the past 5-24 or 5-35 years were both significant. In relation to standard radon progeny concentration 100 Bq/m3, the excess relative risk coefficient was 0.103 (95% CI, 0.039-0.168), the value somewhat lower than findings in other indoor studies.

The German Food Code and Nutrient Data Base (BLS II.2).

This article describes the conception and structure of the German Food Code and Nutrient Data Base (BLS). The data bank contains approx. 12,000 coded foods, menus and menu components in different stages of processing with up to 158 nutritional data for each product. Since comparatively few analytical data on the composition of foods are available, the majority of the data in the BLS are based on nutritional data calculated from recipes. Thus, a standard instrument for an uninterrupted (no missing values) evaluation of consumption surveys is made available.

Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study.

OBJECTIVE: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. DESIGN AND SUBJECTS: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. RESULTS: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5-0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C18:1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%. CONCLUSION: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included.

[Prevalence of hay fever in Germany--East-West comparison and temporal trends]. / Heuschnupfenprävalenz in Deutschland--Ost-West-Vergleich und zeitlicher Trend.

In recent years several studies in children and adults have shown an increase in prevalence of atopic diseases in East and West Germany. The observed frequency of allergic diseases, however, was significantly lower in the East compared to the West. Using data of the German National Health Interview and Examination Survey 1998 and of National Surveys from 1990/92 it was examined, whether the reported increase in prevalence could be confirmed for the total population and whether the differences between East and West are still present. In a self-administered questionnaire, study participants were asked whether they have ever had hay fever. Additionally, in a physician's interview, subjects were asked whether a physician had ever diagnosed hay fever. The questionnaire data were used in comparison with the previous national surveys for the calculation of time trends. A total of 6974 persons filled in the questionnaire and 7099 persons took part in the interview. Physician-diagnosed hay fever was reported by 15% of the total study population. Clear differences in the prevalence rates between East and West Germany are still existing; 11% in the East and 17% in the West suffer from hay fever. In both parts of the country prevalence decreases with increasing age. The highest rates were found among those aged 20-29 and 30-39 years. Based on the questionnaire data the morbidity rose from about 10% in 1990/92 to 17% in 1998. The overall relative increase is quite comparable in East and West Germany. Stratification by age and gender shows considerable differences. In young women from East Germany the increase in prevalence is substantially higher and in women aged 40 years or older much lower than in West German women. In men this pattern has not been observed.

[Incidence of allergic diseases in East and West Germany]. / Häufigkeit allergischer Krankheiten in Ost- und Westdeutschland.

Using data of the German National Health Interview and Examination Survey 1998, a remarkable difference in the prevalence of hay fever between East and West Germany has been observed. Several studies in children and adults have also shown a considerable East-West divergence in other allergic diseases and in sensitisation rates. The aim of this investigation was to examine whether in a representative sample of the adult German population East-West differences in the frequency of asthma, atopic dermatitis, food allergy, urticaria, contact dermatitis and "other allergies" can be found. The calculations base on data of a physician's interview in which study participants were asked whether a physician had ever diagnosed one of the above mentioned diseases. A higher prevalence of all allergic diseases has been observed in West compared to East Germany and women from both parts of the country have higher morbidity rates than men. At least one physician-diagnosed allergy was reported by 40% of the study participants, whereas in East Germany about 30% and in the West 43% suffer from an allergic disease. The prevalence in women is 47% and in men 33%. Extremely high allergy rates were found among West German women at the age of 30-39 years (62%). Although the frequency of allergies decreases with increasing age, considerably high morbidity rates were ascertained even in the oldest age groups. The prevalence in participants aged 70-79 years amounts to 25%. Clear differences between East and West could be demonstrated in this age group, too (West 27% and East 14%).

Dietary recommendations and prevailing food and nutrient intakes in Germany.

Dietary recommendations on nutrient intakes as published by the German Society of Nutrition are only met by a very small proportion of the adult population in East and in West Germany. Dietary data from the Nutrition Survey and Risk Factor Analysis Study in West Germany and from the National Health Survey in East Germany were used to identify differences in nutrient intakes and in food consumption patterns between subgroups of the study participants that were close to, or failed to meet the dietary guidelines. The subgroups were created by dividing subjects into quartiles on the basis of their daily intakes of total fat (%energy), saturated fatty acids (%energy), fibre (g/d) and the food group fruit and vegetables (g/d). Comparisons of the consumption patterns between subjects in the first and in the fourth quartile of intake of the nutrients under study were performed. Differences in food and nutrient intakes were seen among those more compliant and less compliant with the recommendations. The presented analysis provides first indications for future improvements of the existing food-based dietary guidelines in Germany.

[Swiss 1992/1993 publications in the area of cardiovascular diseases with reference to "good clinical practice"]. / Schweizer Publikationen aus dem Gebiet der Herz- und Kreislauf-Erkrankungen 1992/1993 im Lichte von "Good clinical practice".

BACKGROUND: For most readers, the publication is the only source of information about a study, and therefore the quality of a publication is particularly important. On January 1, 1995, new guidelines on "Good clinical practice" were implemented in Switzerland. GOAL: Quality assessments of Swiss publications in the field of clinical cardiovascular research in the light of these new guidelines. METHODS: A catalogue of 119 questions was applied to 65 cardiovascular publications that appeared during the years 1992/93. The answers were quantified with the use of a point scale. RESULTS: Publication practice as represented by the years 1992/93 can be improved on most notably in the "methods" and "results" sections of the publications, as well as with regard to medical-ethical and statistical issues. The biggest improvements in quality seem to be achievable by more precise documentation of statistical and other methodology, precise definition of the variables examined, and adaptation of the number of cases to the number of variables. In addition, description of treatment modalities and of allowed and forbidden concurrent treatments should be more precise.

Estimating lung cancer mortality from residential radon using data for low exposures of miners.

Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

[Injury sequelae and late damage of dislocation fracture of the head of the tibia]. / Verletzungsfolgen und Spätschäden der Luxationsfraktur des Tibiakopfes.

Consequences of injury as well as succeeding joint-impairment after fracture dislocation of the tibial head are analysed. Of 38 patients who had undergone operative therapy for fracture dislocation of the tibial head between 1982 and 1991, 30 were followed up after a mean of 6.3 years. With an average age of 46.8 years and a distribution between sexes of 26 men vs. 12 women, types II (17) and V (14) (classification acc. to Moore) clearly outweighed types III (3) and IV (3) as well as type I (1). Causes of injury were dominated by traffic accidents (22/38), 9 patients suffered from accompanying ipsi-, another 9 from contralateral injuries of their lower extremities. For evaluating follow-up results, both Lysholmscore and IKDC-knee-evaluation-form were employed. The latter qualifies the overall result as "normal", "nearly normal", "abnormal" or "severely abnormal". None of the knee-joints assessed was evaluated normal. There were only 2 patients to be qualified nearly normal, whereas 5 had to be assessed abnormal and 23 severely abnormal. These poor results were mainly due to persistent symptoms (pain, swelling, giving-way) (30/30), limited range of motion (27/30) as well as impairment of joint-stability (25/30). Our results stress the need for sophisticated operative and p.op. therapy of these complex injuries.

[Problematic aspects of the Structural Health Regulation and minimal invasive surgery]. / Zur Problematik des Gesundheitsstrukturgesetzes und der minimal-invasiven Chirurgie.

Decisions in surgery will have to consider economic obligations more than ever before. Consequences are evident: the assessment of surgical efficiency will be insufficient when only considering the accuracy and results of a clinical study. We actually will have to document, moreover, the economic impact of therapeutic procedures, particularly with respect to minimally invasive surgery.

[Proteases and their inhibitors in posttraumatic knee joint effusion]. / Proteasen und deren Inhibitoren im posttraumatischen Kniegelenkserguss.

Humoral aspects are being discussed in development of arthrosis. Punctuate of 144 traumatized knee joints has been investigated. Proteolytic enzymes elastase and cathepsin D were assessed. Furthermore, protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin were determined. Activity of chondrolytic enzymes elastase and cathepsin D clearly correlates with the clinical severity of injuries. At the same time, primary inhibitory mechanisms for compensation seem to be non-sufficient, however.