PubMed Health⌕ Search

Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 19 recordsLinked to original sources
PubMed2007

Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections.

BACKGROUND: Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is co-synthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI. MATERIALS AND METHODS: Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum copeptin levels were measured with a new chemiluminescent sandwich immunoassay. RESULTS: Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0.001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0.001). In patients who died, copeptin levels on admission were significantly higher as compared to levels in survivors [70.0 (28.8-149.0) vs. 24.3 (10.8-43.8) pmol L(-1), P < 0.001]. The area under the receiver operating curve (AUC) for survival was 0.75 for copeptin, which was significantly higher as compared to C-reactive protein (AUC 0.61, P = 0.01), leukocyte count (AUC 0.59, P = 0.01) and similar to procalcitonin (AUC 0.68, P = 0.21). CONCLUSIONS: Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI.

Aged↗
PubMed2006

[Long-term follow up after antithyroid drug treatment in Graves' disease].

BACKGROUND AND OBJECTIVE: In Europe antithyroid drug (ATD) therapy is the preferred initial treatment for patients with a first episode of Graves' disease. Results of long-term recurrence rates following ATD therapy are conflicting. The main goal was to assess long-term recurrence rate after ATD treatment. Secondarily we tried to verify chemical and clinical findings (thyrotropin receptor antibodies (TRAb), duration of primary treatment, age and goitre size) as predictive factors. PATIENTS AND METHODS: Records of 94 patients with a first episode of Graves' disease (1990-1995) treated by ATD were retrospectively analyzed. 18 patients were lost for follow up investigations, the remaining 76 (65 women, 11 men, age 16-76 years) patients were followed for 99 (+/- 22) months (mean +/- SD). To verify the predictive factors a logistic regression analysis was done. RESULTS: Among the 76 patients 16 underwent near-total resection (n = 5) or radioiodine therapy (n = 11) after initial ATD treatment. Sixty patients were treated during 19 +/- 16 months (mean +/- SD) with ATDs and were euthyroid when treatment was stopped. Thirteen of the 60 patients (21.7%) remained in remission after discontinuation of ATD therapy, in 42 patients (70%) hyperthyroidism recurred, in four patients (6.7%) ATD could not be stopped, one patient (1.7%) had a persistent hypothyroidism after discontinuation of ATD. Relapse rate was inversely correlated with duration of primary ATD treatment (p < 0.05), but not with TRAb titer at the time of diagnosis nor at the time of ATD discontinuation. Also, no correlation could be noticed with goitre size at the time of diagnosis. An inverse correlation of the age at the time of diagnosis with relapse rate was of only borderline significance (p = 0.055). CONCLUSIONS: Initial successful treatment with ATD is followed by a high recurrence rate in our population. Two possible negative predictors of relapse are short duration of primary ATD treatment and young age at the time of diagnosis. TRAb titer at the time of diagnosis or at the time of ATD discontinuation and goitre size seem to have no influence on the outcome.

Adolescent↗
PubMed2006

Anomalous viscosity of an expanding quark-gluon plasma.

We argue that an expanding quark-gluon plasma has an anomalous viscosity, which arises from interactions with dynamically generated color fields. We derive an expression for the anomalous viscosity in the turbulent plasma domain and apply it to the hydrodynamic expansion phase, when the quark-gluon plasma is near equilibrium. The anomalous viscosity dominates over the collisional viscosity for weak coupling and not too late times. This effect may provide an explanation for the apparent "nearly perfect" liquidity of the matter produced in nuclear collisions at the Relativistic Heavy Ion Collider without the assumption that it is a strongly coupled state.

Journal Article↗
PubMed2006

Radiosensitivity in breast cancer assessed by the Comet and micronucleus assays.

Spontaneous and radiation-induced genetic instability of peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=50) was examined using the single-cell gel electrophoresis (Comet) assay and a modified G2 micronucleus (MN) test. Cells from apparently healthy donors (n=16) and from cancer patients (n=9) with an adverse early skin reaction to radiotherapy (RT) served as references. Nonirradiated cells from the three tested groups exhibited similar baseline levels of DNA fragmentation assessed by the Comet assay. Likewise, the Comet analysis of in vitro irradiated (5 Gy) cells did not reveal any significant differences among the three groups with respect to the initial and residual DNA fragmentation, as well as the DNA repair kinetics. The G2 MN test showed that cells from cancer patients with an adverse skin reaction to RT displayed increased frequencies of both spontaneous and radiation-induced MN compared to healthy control or the group of unselected BC patients. Two patients from the latter group developed an increased early skin reaction to RT, which was associated with an increased initial DNA fragmentation in vitro only in one of them. Cells from the other BC patient exhibited a striking slope in the dose-response curve detected by the G2 MN test. We also found that previous RT strongly increased both spontaneous and in vitro radiation-induced MN levels, and to a lesser extent, the radiation-induced DNA damage assessed by the Comet assay. These data suggest that clinical radiation may provoke genetic instability and/or induce persistent DNA damage in normal cells of cancer patients, thus leading to increased levels of MN induction and DNA fragmentation after irradiation in vitro. Therefore, care has to be taken when blood samples collected postradiotherapeutically are used to assess the radiosensitivity of cancer patients.

Adolescent↗
PubMed2006

Women with polycystic ovary syndrome are sensitive to the TNF-alpha-lowering effect of glucose-induced hyperinsulinaemia.

BACKGROUND: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation. MATERIALS AND METHODS: Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min. RESULTS: The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha. CONCLUSIONS: The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.

Adult↗
PubMed2006

Circulating levels of pro-atrial natriuretic peptide in lower respiratory tract infections.

OBJECTIVE: To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. DESIGN: Prospective observational study. Setting. Emergency department of a university hospital. SUBJECTS: A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. RESULTS: MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07). CONCLUSIONS: MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Acute Disease↗
PubMed2005

Presymptomatic thyroidectomy in multiple endocrine neoplasia 2a.

AIMS: To evaluate the value of prophylactic total thyroidectomy in multiple endocrine neoplasia 2a (MEN 2a), based on results of genetic testing, in a presymptomatic early stage of the disease. METHODS: Fourteen presymptomatic patients genetically diagnosed and surgically treated at our centre. We analysed age, gender, location of the RET mutation, calcitonin tests, surgery, histologic findings, TNM classification, and postoperative follow-up. RESULTS: The 14 patients belonged to two families with MTC (MEN 2a). Median age was 16 years. The RET mutation was located in codon 618 and 634. Basal calcitonin (CT) levels were normal in all patients. Twelve had pathologic peak CT measurements. Total thyroidectomy was performed in all and associated central neck dissection in 12 patients. Pathohistologic assessment showed C-cell hyperplasia in all specimens and 11 MTCs; the median size of the tumours was 0.2 cm; two patient had lymph-node metastases. According to TNM, three had stage 0, nine had stage I, one had stage II, and one had stage III disease. Postsurgery basal and peak CT values were normal in all but one patients, indicating a biochemical curative rate of 95%. Calcitonin determination did not distinguish between MTC and C-cell hyperplasia. CONCLUSION: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease. Pathologic peak CT values are markers for the presence of microscopic MTC and should be considered in selecting operative procedures for these patients.

Adolescent↗
PubMed2005

Pro-A-type and N-terminal pro-B-type natriuretic peptides in different thyroid function states.

QUESTIONS UNDER STUDY: Natriuretic peptides are produced predominantly in the heart and secreted in response to volume expansion and pressure overload. A wide spectrum of cardiac changes is observed in thyroid dysfunctions. This study investigates mid regional pro A-type (proANP) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels in different thyroid states and evaluates the effect of L-thyroxine treatment on natriuretic peptides in patients with subclinical hypothyroidism. METHODS: Case-control and double-blind, placebo-controlled trial. Sera from 161 female patients (35 with overt, 63 with subclinical hypothyroidism; 10 with overt, 14 with subclinical hyperthyroidism; 40 euthyroid controls) were analysed. ProANP and NT-proBNP were measured at baseline and 48 weeks after L-thyroxine treatment in subclinical hypothyroidism. RESULTS: Circulating proANP and NT-proBNP levels were higher in hyperthyroid patients than in hypothyroid and euthyroid patients (p <0.001). Plasma proANP levels tended to be lower in overt hypothyroidism than in subclinical hypothyroidism. ProANP and NT-proBNP levels correlated weakly to thyroid stimulating hormone (TSH) (r = -0.3 and -0.2, respectively). The natriuretic peptide levels of subclinical and overt hypothyroid subjects showed no difference with those of euthyroid subjects. L-thyroxine treatment had no effect on natriuretic peptide levels in subclinical hypothyroidism. CONCLUSION: Natriuretic peptide levels are altered in different thyroid states with a more pronounced effect in hyperthyroidism than in hypothyroidism. Hyperthyroidism should be considered in patients presenting with unclear symptoms and mildly elevated natriuretic peptide levels, as overt hyperthyroidism results in increased serum A- and B-type natriurectic peptide levels, typically seen in mild heart failure.

Atrial Natriuretic Factor↗
PubMed2005

Correlated emission of hadrons from recombination of correlated partons.

We discuss different sources of hadron correlations in relativistic heavy ion collisions. We show that correlations among partons in a quasithermal medium can lead to the correlated emission of hadrons by quark recombination and argue that this mechanism offers a plausible explanation for the dihadron correlations in the few GeV/c momentum range observed in Au+Au collisions at the BNL Relativistic Heavy Ion Collider.

Journal Article↗
PubMed2005

Depression, anxiety, and obsessionality in long-term recovered patients with adolescent-onset anorexia nervosa.

Anorexia nervosa (AN) is frequently associated with symptoms of depression, anxiety, and obsessive-compulsive behavior which also develop secondary to semistarvation. It is less certain if these symptoms persist after recovery. A few studies have already reported on high prevalence rates of anxious, depressive, and obsessive features in long-term recovered patients with AN, but several of these so called "long-term" recovered patients had only maintained weight restoration for six to twelve months. The aim of this study was to determine whether depressive, anxious, and obsessive-compulsive symptoms persist in truly long-term recovered patients (BMI 20.3+/-2.5 kg/m(2)) who no longer had any eating disorder symptoms (including weight phobia) for at least 3 years. Seventeen subjects of an AN sample (n=39) previously described in a 10-year follow-up met our strict criteria of at least 3 years of complete recovery of AN. In comparison to 39 age-, sex-, and occupation-matched healthy subjects without a history of psychiatric or eating disorder, long-term recovered patients had higher levels of depressive (p=0.002), anxious (p=0.006), and obsessive-compulsive (p=0.015) features but did not differ with regard to psychiatric morbidity and psychosocial adaptation. In conclusion, depressive, anxious, and obsessive-compulsive symptoms may be personality traits in subjects with former adolescent anorexia nervosa.

Adolescent↗
PubMed2005

The expression pattern of four odorant-binding proteins in male and female silk moths, Bombyx mori.

Four recombinant odorant-binding proteins of Bombyx mori, pheromone-binding protein (PBP), general odorant-binding protein 1 (GOBP1), general odorant-binding protein 2 (GOBP2) and antennal binding protein X (ABPX), were expressed in E. coli and used to raise polyclonal antisera. Immunoblots of antennal homogenates showed that these antisera were specific. In Western blot analysis and immunocytochemical labelling experiments, the sera against recombinant PBP and GOBP2 of B. mori gave identical results as sera against native PBP and GOBP2 of Antheraea polyphemus, respectively, thus confirming earlier results obtained with the latter. Labelling consecutive cross sections of various sensillum types with all four antisera revealed different labelling patterns in male and female sensilla (s.) trichodea and s. basiconica. Long s. trichodea in males and females represented uniform labelling types, whereas for short s. trichodea, s. intermedia, and s. basiconica a great variety of labelling patterns was observed, some being more common than others. Long s. trichodea, which in males are uniformly tuned to the pheromone components bombykol and bombykal, all strongly expressed PBP; labelling with antisera against the other three odorant-binding proteins hardly was above background, only in some hairs GOBP1 was expressed somewhat more strongly. Long s. trichodea of females, which respond specifically to linalool and benzoic acid, showed a different labelling pattern. Here, we observed strong labelling with antibodies against GOBP2 and medium labelling with anti-GOBP1, sometimes with anti-ABPX. S. basiconica in both sexes most commonly co-expressed GOBP1 and GOBP2, but other patterns were occasionally found, with some of them showing PBP expression, also in females. The great variety of labelling types in short s. trichodea, s. intermedia, and s. basiconica suggests a similar variety of functional subtypes as observed in plant odour-sensitive sensilla of other moth species.

Animals↗
PubMed2005

European union system for the evaluation of substances: the second version.

This publication presents major changes in the assessment of the risks of chemicals to human health and the environment as implemented in the second version of the European Union System for the Evaluation of Substances, EUSES 2.0. EUSES is a harmonised quantitative risk assessment tool for chemicals. It is the PC-implementation of the technical guidelines developed within the framework of EU chemical legislation for industrial chemicals and biocides. As such, it is designed to support decision making by risk managers in government and industry and to assist scientific institutions in the risk assessment for these substances. The development of EUSES 2.0 is a co-ordinated project of the European Chemicals Bureau, EU Member States and the European chemical industry. Several model concepts, the technical background and the user interface of EUSES have been improved considerably. Major changes in the environmental assessment such as the implementation of emission scenario documents for industrial chemicals and biocides, the addition of the marine risk assessment, the enhancement of the regional model to include global scales, and improvements in the secondary poisoning and environmental effects modelling will be discussed. The update of the human risk assessment module in EUSES focuses on the risk characterisation for both threshold and non-threshold substances with, among others, the introduction of assessment factors. The performance of EUSES is illustrated in an example showing the human and environmental risk assessment of a sanitation disinfectant for private use.

Animals↗
PubMed2005

TNF-alpha-, TNF-beta-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case-control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-alpha)-308, TNF-beta-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I degrees -III degrees ), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group, P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases [odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01-2.75; P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47-4.41; P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease.

Genetic Predisposition to Disease↗
PubMed2005

Radioiodine uptake and thyroid hormone levels on or off simultaneous carbimazole medication: a prospective paired comparison.

AIM: To allow radioiodine (RAI) treatment in patients with need for anti-thyroid drug medication and low RAI uptakes we investigated the feasibility of discontinuing carbimazole for 3 days to enhance the RAI uptake without concurrent exacerbation of hyperthyroidism. METHODS: We prospectively investigated RAI dynamics and thyroid hormone concentration in 12 patients with low RAI uptake (<30%) under simultaneous carbimazole medication and 3 days after discontinuation. At both time points fT(4), T(3) and TSH were monitored. RESULTS: Discontinuation of carbimazole for 3 days led to a significant increase of RAI uptake in all patients. We found an enhancement up to 4.9-fold compared to the measurement on carbimazole. The mean RAI uptake increased from 15.2 +/- 4.4% to 50.1 +/- 15.5% (p<0.001). The intrapersonal radioiodine half-life increased from 4.2 +/- 1.6 days to 5.4 +/- 0.7 days (p = 0.13). Mean thyroid hormone concentration was not affected by the three day withdrawal of anti-thyroid drugs and no patient suffered from an aggravation of biochemical hyperthyroidism. CONCLUSION: A withdrawal of carbimazole for 3 days is long enough to provide sufficiently high RAI uptakes for RAI treatment in patients with low RAI uptakes and short enough to avoid the risk of exacerbation of hyperthyroidism.

Adult↗
PubMed2005

Bruton's Tyrosine Kinase is involved in innate and adaptive immunity.

Btk is a cytoplasmic tyrosine kinase, which is mainly involved in B cell receptor signalling. Gene targeting experiments revealed that Btk is important for B cell development and function. However, Btk is not only expressed in B cells, but also in most other haematopoietic lineages except for T cells and plasma cells. Recently we found that Btk is involved in Toll-like receptor signalling. Toll-like receptors play an important role in innate immunity. They are highly expressed on mast cells, macrophages and dendritic cells, which are essential for the recognition and consequently for the elimination of microbial pathogens. Therefore Btk might play an important role for the function of immunocompetent cells of innate as well as adaptive immunity.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2004

Comparison of microfocus- and synchrotron X-ray tomography for the analysis of osteointegration around Ti6Al4V implants.

Micro-computed tomography (microCT) provides quantitative three-dimensional information of bone around titanium implants similar to classical histology. The study, based on an animal model, containing cuboid-shaped biofunctionalised Ti6Al4V implants with surrounding bone after 4 weeks, is performed using 3 microCT-systems with X-ray tubes, one synchrotron-radiation-based microCT-system (SRmicroCT), and classical histology. Although the spatial resolution of the microCT-systems is comparable, only the results of SRmicroCT agree with results of classical histology. The X-ray tube sources give rise to huge artefacts in the tomograms (interface scattering, beam hardening), which impaired the quantitative analysis of bone up to about 200microm from the implant surface. Due to the non-destructive character of microCT the specimens can be subsequently examined by classical histology without restriction. The quantitative comparison of bone formation uncovers the strong dependence of the newly formed bone from the selected slice. This implies the necessity of 3D analysis. SRmicroCT and classical histology prove that surface modifications of the titanium implant significantly influence the bone formation. Using SRmicroCT, the preparation artefacts due to cutting and polishing are excluded.

Animals↗
PubMed2004

[Diabetes in childhood: everyday burden and professional consequences for parents].

BACKGROUND AND OBJECTIVE: To investigate the burden and the financial and professional consequences for mothers and fathers after the onset of diabetes in their child in relationship to age at onset and family structure. PATIENTS AND METHODS: All families of children with an age at onset < 14 years and a diabetes duration < 10 years treated at four large pediatric diabetes centers received a structured questionnaire (burden of diabetes, professional position and career development, financial consequences for both parents, demographic data). RESULTS: 580 families with 583 children with type 1 diabetes (46 % girls, diabetes duration 5.0 +/- 3.2 years, age at onset 6.9 +/- 3.9 years) participated. 42 % of the children had an age at onset below 6 years. 11 % had single parents. Before the onset of diabetes in their children 93 % of the fathers worked full-time, thereafter 4 % changed their employment. Mothers worked at onset full-time in 22 % and part-time in 38 %; thereafter 31 % reduced their working time or stopped working. 33 % of the mothers reported handicaps in their professional career development, especially those with a child with age at onset below 6 years (44 %). Negative financial consequences were present in 44 % of the families. The day to day burden on a scale from 1 to 5 decreased both in mothers and in fathers with increasing age at onset. The individual burden was higher in mothers (3.6 +/-1.1) than in fathers (2.8 +/- 1.1) (p = 0.000). CONCLUSIONS: Initiatives to reduce the burden on families with a child with diabetes are urgently needed. Particularly the social and professional integration of mothers with younger children at diabetes onset need to be improved through support measures outside the family.

Adolescent↗