Update to the study protocol: minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): a multicentre, stepped-wedge, cluster-randomised controlled trial.

This document reports a brief update to the previously published protocol of the MinDial study.Trial registration German Clinical Trials Register DRKS00029691. Registered on 12 Sept. 2022, https://drks.de/search/en/trial/DRKS00029691 .

Minimisation of dialysis risk in hospital patients with chronic kidney disease (MinDial): study protocol for a multicentre, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.

Classification of vertebral compression fractures in magnetic resonance images using spectral and fractal analysis.

Fractures with partial collapse of vertebral bodies are generically referred to as "vertebral compression fractures" or VCFs. VCFs can have different etiologies comprising trauma, bone failure related to osteoporosis, or metastatic cancer affecting bone. VCFs related to osteoporosis (benign fractures) and to cancer (malignant fractures) are commonly found in the elderly population. In the clinical setting, the differentiation between benign and malignant fractures is complex and difficult. This paper presents a study aimed at developing a system for computer-aided diagnosis to help in the differentiation between malignant and benign VCFs in magnetic resonance imaging (MRI). We used T1-weighted MRI of the lumbar spine in the sagittal plane. Images from 47 consecutive patients (31 women, 16 men, mean age 63 years) were studied, including 19 malignant fractures and 54 benign fractures. Spectral and fractal features were extracted from manually segmented images of 73 vertebral bodies with VCFs. The classification of malignant vs. benign VCFs was performed using the k-nearest neighbor classifier with the Euclidean distance. Results obtained show that combinations of features derived from Fourier and wavelet transforms, together with the fractal dimension, were able to obtain correct classification rate up to 94.7% with area under the receiver operating characteristic curve up to 0.95.

Measurement and modeling of bentazone in the river Main (Germany) originating from point and non-point sources.

A Water Framework Directive pilot project combines measured data and model approaches to calculate fluxes and mass balance of the pesticide bentazone in an 81 km section of the river Main (Germany). During the study period (six weeks in spring 2004) the observed bentazone inflow and outflow in the river section amounted to 52.8 and 53.1 kg, respectively; the maximum concentrations reached 220 and 290 ng l(-1). Based on sampling of seven sewage treatment plants a specific loss of 0.87 g bentazone per farm was calculated. Extrapolation to the entire sub-basin results in 2.6 kg bentazone in total as point source contribution from farms. Diffuse input into the surface water network occurred after an intensive rainfall event on May 7th. Total bentazone load was simulated with the pesticide emission model DRIPS to be 23.2 kg. One third of this load was estimated to be degraded by photolysis before reaching the main waterway, the river Main. The ATV water quality model was applied to predict the concentration profile of bentazone in river Main between Schweinfurt and Würzburg with reasonable results. The difference between total measured and modeled fluxes amounted to 1.5 kg corresponding to 2% of the overall input. The combined approach of monitoring and modeling appears to be a valuable strategy to quantify the relevance of point and non-point sources and to focus effective mitigation measures to the most relevant origins within a river basin.

[Urinary bladder perforation caused by a loosened acetabular reinforcement ring]. / Harnblasenperforation durch Migration eines Burch-Schneider-Stützrings.

Reinforcement cages are widely used for the treatment of large acetabular bone defects. We report the case of a loosened Burch-Schneider reinforcement ring causing a recurrent macrohaematuria due to a perforation of the urinary bladder. After performing several diagnostic procedures, the patient underwent interdisciplinary revision surgery. Due to the severe destruction of the acetabular bone stock and an infection of the total hip prosthesis as confirmed by fresh frozen section, the hip prosthesis was explanted. At the last follow-up the patient was free of infect-related symptoms and was able to walk with one crutch.

[Incidence of anterior intertrochanteric ossifications after total hip arthroplasty--a retrospective long-term follow-up study]. / Inzidenz von anterioren intertrochantären Ossifikationen bei Hüfttotalendoprothesen--eine retrospektive Langzeituntersuchung.

AIM: This retrospective study investigates the incidence of anterior intertrochanteric ossifications (AIO), especially in comparison with heterotopic ossifications classified according to Brooker. A classification system of AIO regarding short-term results (< 1 year after surgery) was introduced in 2003: AIO occurred solely in 13 % of all cases (ossifications according to Brooker grade 0) and would have been "overlooked" without a lateral X-ray. The incidence of AIO combined with ossifications according to Brooker > 0 was 48.8 % of all cases. Our study reports long-term results, furthermore correlations between ossifications and clinical outcome, rated by the Harris hip score (HHS) and range of motion (ROM), are evaluated. MATERIAL AND METHODS: 149 cementless total hip arthroplasties (Hofer-Imhof threaded cup, straight stem), implanted into 140 patients from November 1991 to December 1994 underwent complete clinical and radiological follow-up from December 2005 to October 2006. The average age of the 81 female and 59 male patients at the time of implantation was 64 years. Without exception, a conventional, transgluteal approach (Bauer) was performed. All patients received indomethacin prophylaxis for 8 consecutive days after surgery. Current X-rays (a.-p. and lateral view) were evaluated in comparison with the former X-rays. RESULTS: AIO were found in 77 cases (51.7 %), heterotopic ossifications corresponding to Brooker in 93 cases (62.4 %), a combination of AIO and Brooker in 58 cases (38.9 %) and solitary AIO in 19 cases (12.8 %). HHS and ROM were not significantly altered by ossifications. CONCLUSION: Our long-term findings compare with the short-term results (indicating lack of new bone formation [heterotopic ossification] after more than one year after surgery, as previously described in the literature concerning ossifications according to Brooker) and verify the incidence rate of solitary AIO. Despite a minor correlation with clinical outcome, AIO could be considered as a possible indicator for predilection of heterotopic bone formation, especially if revision arthroplasty or THA of the contralateral side is needed.

[Long-term results of the cementless Hofer-Imhof threaded titanium cup]. / Langzeitergebnisse der zementfreien Hofer-Imhof-Titan-Schraubpfanne.

AIM: This retrospective monocentre study investigates long-term results of the cementless parabolic-shaped HI threaded cup. MATERIAL AND METHODS: 678 threaded cups made of titanium were implanted into 641 patients from November 1991 to May 1995. Mean age was 67 years, 65 % female, 35 % male. From December 2005 until October 2006, 165 patients (168 hips) underwent complete clinical and radiological follow-up, data of the remaining group were taken from the files. Using the Kaplan-Meier method, survival rates of the threaded cup were calculated. RESULTS: For all patients the average survival time of the cup was 14.2 years, the corresponding survival probability was 93 % (+/- 3.7 %) after 14.5 years. For the patients with complete follow-up, average survival time of the cup was 14.0 years, the corresponding survival probability was 93 % (+/- 5.2 %) after 14.5 years. CONCLUSION: Our results are comparable to those of threaded cups with a conical design (Zweymüller), the HI threaded cup can thus be recommended for primary implantation.

[(15)N(2)]arginine as a first potential inhaled diagnostic agent to characterize respiratory diseases.

Conventional diagnosis of the pulmonary tract uses physical methods such as spirometry and oscillometry. However, the inhalation of a chemical diagnostic agent ought to provide novel ways of more specific diagnosis, for instance of inflammatory states of the bronchial and lung mucosa. The stable isotope technique using a (15)N-labeled substrate appears to be a suitable tool for this application. In a pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a diagnostic agent by healthy volunteers and pulmonary patients suffering from asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO. The exhaled air was collected under defined conditions in 10-L breath bags and analyzed for NO using chemiluminescence. Under standardized test conditions, healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was expected comparing the (15)NO exhalation. The (15)N abundance of NO was determined using a Cryotrap gas chromatography - mass spectrometry set-up. Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with a plateau of the (15)NO abundance was found in the exhaled air. At this time, healthy and asthmatic subjects exhibited clear differences in their exhaled (15)NO amounts. Under standardized test conditions, the healthy persons (n = 6) exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n = 7) exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded after the inhalation of (15)N-labeled arginine could be a potential marker for demonstrating pathophysiological changes in the lung epithelium. This method could pave a new diagnostic principle of "inhalative breath test."

Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life results of the LARS-study. Leipzig Allergy High-Risk Children Study.

INTRODUCTION: The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. DESIGN AND METHODS: 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infant's bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of six weeks and 1 year. The parents answered a questionnaire. RESULTS: Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95% Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95% Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (> 2.0 micrograms/m3, indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95% Cl 1.1-4.2). Environmental benzene > 5.6 micrograms/m3 increased the risk of airway infections in six-week-old babies (OR = 2.4; 95% Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95% Cl 1.1-3.5) as well as restoration (OR = 1.9; 95% Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. CONCLUSIONS: The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.

Mycotoxins in house dust - an underestimated problem?

People in developed countries spend up to 90% of their time indoors. This led to an increased awareness for problems regarding indoor environment in recent years. It is known that especially spores, mycelia and organic compounds released by the microbial colony e.g. mycotoxins and microbial volatile organic compounds (MVOCs) can be harmful to human health. The aim of a pilot program is to investigate mould-dependent health complaints in a burdened population of the city of Leipzig, Germany. Phase 1 of the investigation includes inspection of dwellings, determination of exposure and clinical examination of exposed persons. In phase 2 it is planned to analyse the influence of burdens with mould spores and their metabolites like mycotoxins on health complaints. House dust seems to be a representative sample medium for sedimented spores and mycelia which may contain mycotoxins. The analysis will be performed by LC-MS-MS after extraction of the crude dust samples by accelerated solvent extraction. The qualitative proof of mycotoxins in house dust was successful in a case study with a high burden.

Biodegradation in laboratory activated sludge plants and aquatic toxicity of herbicides.

The biodegradation and the aquatic toxicity of four herbicides (isoproturon, terbuthylazine, mecoprop, metamitron) were investigated. Laboratory activated sludge plants were used for biodegradation experiments. The biodegradation of mecoprop reached nearly 100%, the other herbicides were not eliminated by biodegradation. The acute Daphnia magna 24-h assay, the algal 72-h inhibition test, and the recently developed lemna growth inhibition 7-d test were applied to evaluate the biological effects of herbicides as original substances. EC 50 and EC 10 values were determined. Algal and lemna test show that isoproturon and terbuthylazine are both much more toxic than mecoprop and metamitron. Daphnids are generally less sensitive against herbicides than plants. Biodegradation and toxicity test were coupled for mecoprop to assess biological long-term effects of possible biodegradation products of this herbicide. The effluents of the laboratory activated sludge units were used in toxicity tests (Daphnia magna 21-d reproduction test, lemna growth inhibition 7-d test). No inhibiting effect on the tested organisms was observed.

[Genotoxicity of stack gas condensates of Bavarian waste incineration plants. II. Suitability of fast bacterial tests of emission monitoring]. / Zur Genotoxizität von Rauchgaskondensaten bayerischer Abfallverbrennungsanlagen. II. Eignung bakterieller Kurzzeit-Tests zum Emissionsmonitoring.

The genotoxicity of stack gas condensates of 21 waste incineration plants (located in Bavaria) was examined in the years 1990-1995 using two bacterial short time tests. The SOS chromotest was carried out with the tester strains Escherichia coli PQ37, PQ243 and PQ300. In addition, for the purpose of comparison, the Ames-Test was performed for selected examples with the tester strains Salmonella typhimurium TA97, TA98, TA100 and TA1537. In a pilot study, carried out in the years 1990 to 1991, the stack gas condensates from five plants were examined. They showed clear genotoxic and mutagenic effects. On the other hand, in subsequent tests we generally discovered only weak inductions for 9 of 18 crude and 24 of 78 clean gas condensate extracts, mostly after metabolic activation. Four plants were tested continuously in the years 1992 to 1995. Three of them showed a clear reduction of the detectable genotoxic potential. The fourth one gave negligible SOS inducing emissions in the whole examining period. On the other hand, for 6 of the 21 tested plants we found chromotest positive results even at the last test point. Correlations between the SOS inducing potential of the stack gas condensates and the analytical parameters detected at the same time (6 summary parameters, 24 inorganic and 63 organic chemical parameters) were not evident. Only the two highest emissions of nitropyrenes were associated with SOS inductions. Organic substances which are not analytically detected or synergistic effects might be responsible for the SOS inducing potency of the other genotoxic stack gas condensates.

[Genotoxicity of stack gas condensates of Bavarian waste incineration plants. III. Emission monitoring with a simple UDS assay using the human lung cell lines NCI-H 322 and 358]. / Zur Genotoxizität von Rauchgaskondensaten bayerischer Abfallverbrennungsanlagen. III. Emissionsmonitoring mit einem einfachen UDS-Testverfahren unter Nutzung der humanen Lungenzell-Linien NCI-H 322 und 358.

For the validation of the genotoxicity testing on stack gas condensates from waste incineration plants using bacterial short time tests (15), a modified UDS assay with the lung cell lines NCI-H 322 and 358 was developed. The UDS assay is more sensitive than the SOS chromotest and discriminates better between the negative or weakly positive and the clearly positive samples. It has a high sensitive and specificity and also accuracy, is practicable in a comparatively simple, speedy and reasonably priced manner and is therefore appropriate for an emission monitoring similar to simple bacterial short time tests. Especially in strongly concentrated crude and clean gas condensates, maximal induction factors were seen in the range of strong UDS inducers. From 55 samples on 16 incineration plants tested in the years 1992 to 1995, in 48 we found weak to strong UDS inductions in at least one of the two test cell lines. From three plants examined continuously in this period only two emitted stack gases with constantly low genotoxicity at the end of sampling. 5 clean gas condensates, that were taken in random samples from 3 other plants in the period 1994 to 1995, proved to be non-genotoxic in the UDS assay. However, one of these plants emitted stack gases with high cytotoxicity, which might have masked UDS-inducing single substances. It is not possible to make a statement on the human toxicological relevance. However, a clearly positive development towards more harmless stack gas condensates was established. A definite correlation could not be shown between the chemical analysis of the detected cancerogenic organic single substances of the samples and the detected UDS inductions. Further investigations for finding strong UDS inducers from the substance spectrum of municipal stack gas emissions are necessary.

[Genotoxicity of stack gas condensates of Bavarian waste incineration plants. IV. Overview and short comments on the results]. / Zur Genotoxizität von Rauchgaskondensaten bayerischer Abfallverbrennungsanlagen. IV. Uberblick und kurze Kommentare zu den Ergebnissen.

Emissions from waste incineration plants can be monitored relatively simply and cost-effectively via stack gas condensates. We compared quantitative chemical-analytic data of stack gases with two genotoxicity tests. The tests employed, i.e. a new, simple UDS assay variant with the human lung cell lines NCI-H 322 and 358, developed for this purpose, and an automated version of the SOS chromotest, were validated with respect to the contents of stack gases analytically detected. As judged by Bavarian waste incineration plants, sampled in the years 1990 to 1995, we obtained the following principle results: A drastic reduction of the genotoxicity from stack gases in the sampling period was observed with both tests. There were found genotoxic stack gases with the more sensitive UDS assay also in modern plants at the end of sampling period. Up to 99% of the organic components were not detected by chemical analysis despite an extensive program of analytics. The concentration of the quantified cancerogenic organic single substances from the samples did not suffice to explain genotoxic effects in the stack gases. Unknown, not identified stack gas contents are mainly responsible for the genotoxic potential of the stack gases. According to our results, emissions of modern waste incineration plants are likely to increase the genotoxic hazardous potential of the air only insignificantly even in pollution-free zones.

Papillomavirus-induced genital warts in a girl--management by surgery and immunomodulating therapy.

A 4-year-old girl with condylomata acuminata of the vulva and papular warts of the surrounding skin is presented. The lesions were removed by surgery. Histologic investigation showed koilocytosis of the squamous epithelium and in-situ hybridization revealed human papilloma virus type 6 infection. There were no signs of sexual abuse or sexual transmission of the virus. After ablation, an interferon-containing ointment was applied. In order to prevent recurrence, a low-molecular-weight immunomodulating leucocyte fraction was given for more than 1 year, during which time no relapse was observed.

Biodegradation and aquatic toxicity of beta-alaninediacetic acid (beta-ADA).

The aquatic toxicity and biodegradability of the new chelating agent beta-alaninediacetic acid (beta-ADA) were investigated. There is no inhibition effect of beta-ADA in the daphnia magna 24 h test up to a concentration of 1000 mg/L. The algal growth inhibition test resulted in an EC 50 of 19.7 mg/L. An EC 20 of 740 mg/L was determined in the luminescent bacteria test. An EC 50 was not obtained in this test up to a concentration of 2000 mg/L beta-ADA. The degree of biodegradation of beta-ADA was determined in a static and a continuous test. The beta-ADA removal reached 98% at the end of the test after eight weeks in the continuous test which was carried out with laboratory activated sludge units simulating a waste water treatment plant. Further, biodegradation and toxicity tests were coupled, i.e. the effluents of the laboratory activated sludge units were applied in the toxicity tests. A higher toxicity of the effluents of the test units in comparison with the control unit was not observed.

[Child abuse caused by thermal violence--determination and reconstruction]. / Kindesmisshandlung durch thermische Gewalt--Abgrenzung und Rekonstruktion.

UNLABELLED: Problems in the judgement of child abuse due to thermal violence are discussed by means of two examined cases. In a baby dermal lesions in the course of a bacterial infectious disease (bullous impetigo) were first misinterpreted as heat effects (cigarette, hot instrument). In the case of an infant presenting with marked imprints of a hot iron abuse was to be differentiated versus an accidental causation. CONCLUSIONS: In the interpretation of possible thermal injuries in children natural preexisting disorders of the skin should be taken into consideration. In cases of doubt an appropriate clinical diagnosis or a subsequent follow-up examination, respectively, is recommended. Thus, the course of events can be observed and an unjustified incrimination of persons having custody is avoided.

[Secretion of hCG by mononuclear cells--a specific and essential reaction in pregnancy?]. / Sekretion von hCG durch mononukleäre Zellen--eine spezifische und essentielle Reaktion während der Schwangerschaft?

Mononuclear cells in peripheral blood secrete immunoreactive hCG (ir-hCG) when they are stimulated in in-vitro culture with the proteinkinase C - activator phorbol-myristat-acetate (TPA). We examined the ir-hCG secretion in 61 fertile and 191 pregnant women and 38 men. Mononuclear cells of pregnant women secrete after TPA stimulation significantly more ir-hCG than mononuclear cells on non-pregnant but fertile women. This effect can be detected as early as 23rd days of a menstrual cycle which is accompanied by conception and persisted over the entire duration of a pregnancy. Maximal effects were observed in the 7th to 19th and 30th to 34th weeks of pregnancy. An artefact caused by adhesive serum-hCG could be excluded. The elevated potential of the mononuclear cells to be stimulated remained intact for about 14 days after termination of a normal pregnancy in the first trimester. An ir-hCG secretion similar to that seen in nonpregnant women was found in patients with early abortion. The possible physiological importance of the in-vivo secretion of beta-HCG during pregnancy is discussed.

Mitigating effects of dialysable leukocyte extract (DLE) on the experimental allergic uveitis (EAU) of the rabbit.

Experimental allergic uveitis (EAU) is an induced autoimmune disease by administering soluble retinal S antigen and complete Freund's adjuvant (CFA). In rabbits, the result is the occurrence of chorioretinitis in 90% of the cases. The first inflammation is followed by spontaneous relapses. The EAU of the rabbit was utilized to study the effects of the dialyzable leucocyte extract (DLE) on the course and the intensity of the disease in this autoimmune model. The DLE preparations examined differed with regard to their origin or the immunological stimulation of the initial material (DLE from humans (DLE Hu) and DLE from the normal rabbit (DLE RaO) or rabbits which had EAU (DLE RaEAU) and rabbits which had received CFA (DLE Ra (CFA). One unit of DLE corresponds to the extract from 10(9) cells. The administration of DLE starts with the onset of inflammation. 4 x 0.5 units were administered during the first week, 1 x 0.5 units per week from the 2nd to the 12th week. All preparations decrease the cumulative frequency of the days of illness significantly. The duration of the initial inflammation is reduced in all animals treated, but only in part significantly. There appears a graduation of efficacy: DLE RaEAU greater than DLE Ra CFA greater than DLE Hu greater than DLE RaO. Overall, it can be seen that, on the one hand, there is no specificity or restriction of the species for the efficacy and, on the other hand, the extent of the effects depends on the degree of the immunological stimulation. The maximum efficacy of DLE RaEAU is not exclusively due to the transmission of an antigen-specific sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, biochemical and immunological effectiveness of diacetyl-splenopentin (BCH 069) in hay fever.

Diacetyl-splenopentin (BCH 069) is a new pentapeptide of splenin modified by twofold acetylation. BCH 069 has thymopentin-like activity demonstrated by in vivo animal and in vitro human studies. Two groups of patients received 50 mg BCH 069 and placebo, respectively, by subcutaneous injection 3 times weekly for 4 weeks. The third group of patients received 50 mg BCH 069 by intravenous injection 3 times weekly for 6 weeks. The therapy was carried out during the peak of the pollen season. BCH 069 intravenous treatment was found to be significantly superior to placebo treatment in reducing clinical symptoms. Biochemical inflammatory signs were not observed. No increase of bronchomotoric reactivity was established in comparison to the placebo group. There was a significantly lower increase in gras-spollen specific IgE and IgG4 in the intravenous group of BCH 069. Subcutaneous therapy with BCH 069 was not effective. The study demonstrated that BCH 069 used intravenously induces clinical improvement in patients suffering from hay fever. Thus the possibility to influence hyperreactive conditions of the immune system has been confirmed. The study indicates that various application routes of BCH 069 have different effects on the immune system.