[Using social network analysis to examine care for older drug users in three major cities in Germany : Results of a pilot study]. / Soziale Netzwerkanalyse der Versorgungsstrukturen für ältere Drogenabhängige in drei deutschen Großstädten : Ergebnisse einer Pilotstudie.

BACKGROUND: Compared with the general population, chronic drug addicts already start showing typical aging problems by the age of 40 years. The increasing number of older drug addicts leads to questions of what an adequate health and social care should look like. This discussion particularly takes place in the context of a sufficient integration of different care systems. A sufficient integration requires an improvement in the networking of substance treatment, nursing care and medical care services. OBJECTIVE: The purpose of this study was to investigate the care structure of older people who use drugs and the services involved in a social network analysis. This was a descriptive design of the pilot study. The study objective was to gain first-hand knowledge about the health and social care situation, the quality of care concerning this client group and to identify supply gaps. Therefore, the three regions Cologne, Dusseldorf and Frankfurt/Main were exemplarily examined. MATERIAL AND METHODS: The data for the social network analysis was gathered by a quantitative online questionnaire. Therefore, especially central network members were contacted and asked to participate. The survey was conducted in two waves. RESULTS: In total, 65 practitioners of all surveyed cities participated in the second wave. The centrality measures assessed indicated that in all regions institutions of the substance abuse service network hold central positions in terms of conveying information. The moderate density values of the networks suggest that there are sufficient cooperation structures. Care deficits were identified most frequently in the areas of housing and nursing care. CONCLUSION: The results provide the first systematic insights and a description of the cooperation practice in the care system. Because of the limitations, further research and practice issues are raised.

[Analysis and long-term observation after surgical treatment of patients with tumours of the iris]. / Analyse und Langzeitbeobachtung nach chirurgischer Therapie bei Patienten mit Iristumoren.

BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in adults. Iris melanomas are rare tumours: they account for 2-3 % of all uveal melanomas. The clinical differentiation between benign iris nevi and malignant iris melanomas can be difficult. PATIENTS AND METHODS: The aim of this study was the registration, analysis and observation of all patients with tumours of the anterior uvea who had been treated surgically between 1992 and 2011 at the ophthalmic department of the University Hospital of Jena. 40 patients were analysed and compared concerning their preoperative states, operating methods including complications, histological results, postoperative function, subjective complaints as well as the risk of metastasis and the associated dependence on mortality of the dignity of the tumours. In this time period 26 patients has been observed in a follow-up visit. Patients with a malignant tumour were offered an examination. RESULTS: The histological examination revealed for 24 patients a benign tumour and for 16 patients a malignant tumour. After an exact analysis of multiple parameters there was only a statistically significant difference in the preoperative visual acuity (p = 0.025) and in the tumour size (p = 0.011) between the two analysed groups of patients. The rate of serious postoperative complications was 11.4 %. One fourth of the patients complained of subjective problems after the surgical intervention. In the follow-up visit a visual acuity of 0.5 or better was achieved in 68 % of all interventions. CONCLUSIONS: A reliable diagnosis is only possible after histological examination. The analysed parameters can only give indications for the dignity of the tumour. The strategy of the ophthalmic department of the University Hospital of Jena to remove a tumour of uncertain dignity at an early state makes sense, because there are few postoperative complications, few patients complain about subjective problems and the chances for achieving good visual acuity are high.

Effect of microstructure on the mechanical properties of as-cast Ti-Nb-Al-Cu-Ni alloys for biomedical application.

The correlation between the microstructure and mechanical behavior during tensile loading of Ti68.8Nb13.6Al6.5Cu6Ni5.1 and Ti71.8Nb14.1Al6.7Cu4Ni3.4 alloys was investigated. The present alloys were prepared by the non-equilibrium processing applying relatively high cooling rates. The microstructure consists of a dendritic bcc ß-Ti solid solution and fine intermetallic precipitates in the interdendritic region. The volume fraction of the intermetallic phases decreases significantly with slightly decreasing the Cu and Ni content. Consequently, the fracture mechanism in tension changes from cleavage to shear. This in turn strongly enhances the ductility of the alloy and as a result Ti71.8Nb14.1Al6.7Cu4Ni3.4 demonstrates a significant tensile ductility of about 14% combined with the high yield strength of above 820 MPa already in the as-cast state. The results demonstrate that the control of precipitates can significantly enhance the ductility and yet maintaining the high strength and the low Young's modulus of these alloys. The achieved high bio performance (ratio of strength to Young's modulus) is comparable (or even superior) with that of the recently developed Ti-based biomedical alloys.

Origin of intermittent plastic flow and instability of shear band sliding in bulk metallic glasses.

Intermittent or serrated plastic flow is widely observed in the deformation of bulk metallic glasses (BMGs) or other disordered solids at low temperatures. However, the underlying physical process responsible for the phenomena is still poorly understood. Here, we give an interpretation of the serrated flow behavior in BMGs by relating the atomic-scale deformation with the macroscopic shear band behavior. Our theoretical analysis shows that serrated flow in fact arises from an intrinsic dynamic instability of the shear band sliding, which is determined by a critical stiffness parameter in stick-slip dynamics. Based on this, the transition from serrated to nonserrated flow with the strain rate or the temperature is well predicted and the effects of various extrinsic and intrinsic factors on shear band stability can be quantitatively analyzed in BMGs. Our results, which are verified by a series of compression tests on various BMGs, provide key ingredients to fundamentally understand serrated flow and may bridge the gap between the atomic-scale physics and the larger-scale shear band dynamics governing the deformation of BMGs.

Monozygotic twins discordant for trisomy 18.

We report on the pre- and postnatal cytogenetic, molecular genetic and clinical findings in monochorionic-diamniotic twins discordant for trisomy 18. Structural anomalies were identified in one of the twins on prenatal ultrasound examination at 20 weeks' gestation and sampling of amniotic fluid from both sacs was performed for karyotyping. This revealed trisomy 18 in the twin with abnormalities and a normal karyotype in the other twin. Elective Cesarean section was performed at 31 + 5 weeks and the aneuploid twin died shortly after delivery. The surviving twin showed low-grade mosaicism for trisomy 18 on postnatal analysis but has shown normal development. For prenatal diagnosis in monochorionic-diamniotic twin pregnancy the sampling of both amniotic sacs is recommended, especially if one twin has structural anomalies on ultrasound scan.

Transformation-mediated ductility in CuZr-based bulk metallic glasses.

Bulk metallic glasses (BMGs) generally fail in a brittle manner under uniaxial, quasistatic loading at room temperature. The lack of plastic strain is a consequence of shear softening, a phenomenon that originates from shear-induced dilation that causes plastic strain to be highly localized in shear bands. So far, significant tensile ductility has been reported only for microscopic samples of around 100 nm (ref. 4) as well as for high strain rates, and so far no mechanisms are known, which could lead to work hardening and ductility in quasistatic tension in macroscopic BMG samples. In the present work we developed CuZr-based BMGs, which polymorphically precipitate nanocrystals during tensile deformation and subsequently these nanocrystals undergo twinning. The formation of such structural heterogeneities hampers shear band generation and results in macroscopically detectable plastic strain and work hardening. The precipitation of nanocrystals and their subsequent twinning can be understood in terms of a deformation-induced softening of the instantaneous shear modulus. This unique deformation mechanism is believed to be not just limited to CuZr-based BMGs but also to promote ductility in other BMGs.

Phenotyping with sulfasalazine - time dependence and relation to NAT2 pharmacogenetics.

OBJECTIVE: N-acetyltransferase 2 (NAT2) genotype-phenotype relation with sulfasalazine as probe drug by means of detailed genotype analysis and kinetic data evaluation. BACKGROUND: Though phenotype analysis of sulfasalazine metabolism has been described before, genotype investigations in this regard are scarce. The influence of different single point mutations on the metabolism of the sulfasalazine metabolite sulfapyridine (SP) should give more insight into the functionality of different alleles especially with those still under discussion. METHODS: In two bioavailability studies performed under comparable conditions with 24 healthy subjects of both genders equally distributed, plasma levels of SP and acetylsulfapyridine (Ac-SP) were determined after oral intake of enteric coated formulations of sulfasalazine (500 mg and 1,000 mg, respectively). The resulting metabolic ratios were calculated. NAT2 genotype was analyzed in parallel for all subjects deducing haplotype set as well as putative functional phenotype as (homozygous or heterozygous) rapid acetylator (RA) or slow acetylator (SA) and correlated with the PK results. RESULTS AND DISCUSSION: RA genotype in the overall study population was seen with 45.5% (including 6.8% homozygous wildtype *4/*4) and SA genotype with 54.5%. Compared to RA genotype, apparent terminal elimination half-life of SP as well as of Ac-SP was prolonged in the SA genotype population, C(max) and AUC values of SP were higher whereas average C(max) value of Ac-SP was lower (with AUC only some tendency to lower values). In general, phenotype-genotype correlation was good with only few exceptions. Strongest functional effect on enzyme activity was noticed in slow acetylators carrying the 341T > C mutation, followed by 590G > A mutation whereas the influence of 857G > A was considerably less pronounced. Homozygous 803A > G mutation (lysine > arginine shift) did not reveal enzyme activity reduction.

[External cephalic version in cases of breech presentation: renaissance of a well-known procedure?]. / Die äussere Wendung bei Beckenendlage: Renaissance eines altbekannten Verfahrens?

OBJECTIVE: About 3-4% of all pregnant women will have a fetus presenting by the breech at term. External cephalic version offers the opportunity to reduce the rate of caesarean sections caused by breech presentation. We analysed retrospectively 51 cases of external cephalic version at our clinic. METHODS: External cephalic version was performed 51 times between 37 and 41 weeks of pregnancy. RESULTS: External cephalic version was successful in 32/51 cases (62,7%) with a consecutive rate of vaginal delivery of 71,9%. The best results were seen at 37 weeks of pregnancy with 81,25% of successful versions followed by 76,9% of vaginal deliveries. Complications were rare. There was just 1 case of emergency caesarean section due to persisting fetal bradycardia. CONCLUSION: External cephalic version is an effective and safe treatment to enable vaginal delivery of cephalic presentation. For this operation, 37 weeks of pregnancy can be considered the best time.

Methanol emissions from deciduous tree species: dependence on temperature and light intensity.

Methanol emissions from several deciduous tree species with predominantly mature leaves were measured under laboratory and field conditions. The emissions were modulated by temperature and light. Under constant light conditions in the laboratory, methanol emissions increased with leaf temperature, by up to 12% per degree. At constant temperatures, emissions doubled when light intensity (PAR) increased from darkness to 800 micromol x m(-2) x s(-1). A phenomenological description of light and temperature dependencies was derived from the laboratory measurements. This description was successfully applied to reproduce the diel cycle of methanol emissions from an English oak measured in the field. Labelling experiments with (13)CO(2) provided evidence that less than 10% of the emitted methanol was produced de novo by photosynthesis directly prior to emission. Hence, the light dependence of the emissions cannot be explained by instantaneous production from CO(2) fixation. Additional experiments with selective cooling of plant roots indicated that a substantial fraction of the emitted methanol may be produced in the roots or stem and transported to stomata by the transpiration stream. However, the transpiration stream cannot be considered as the main factor that determines methanol emissions by the investigated plants.

Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer.

BACKGROUND AND AIM: Although more than 80% of undifferentiated early gastric cancers (EGC) are not associated with lymph node metastasis, endoscopic mucosal resection is not generally accepted as a means of curative treatment because of an abundance of conflicting data concerning clinicopathological characteristics and prognoses. The aim of this study was to define a subgroup of undifferentiated EGC that could be cured by endoscopic treatment without the risk of lymph node metastasis. METHOD: A total of 591 patients surgically resected for undifferentiated EGC between January 1999 and March 2005 were reviewed. Associations between various clinicopathological factors and the presence of lymph node metastasis were analyzed to identify the risk factors of lymph node metastasis. RESULTS: Lymph node metastasis was found in 79 patients (13.4%). By multivariate logistic regression analysis, a tumor diameter 2.5 cm or larger, invasion into the middle third of the submucosal layer or deeper, and lymphatic involvement were identified as independent risk factors of lymph node metastasis (P < 0.001, respectively). Lymph node metastasis was not found in any patient with undifferentiated EGC smaller than 2.5 cm confined to the mucosa or upper third of the submucosal layer without lymphatic involvement. CONCLUSIONS: Undifferentiated intramucosal EGC smaller than 2.5 cm without lymphatic involvement was not associated with lymph node metastasis. Thus, we propose in this circumstance that endoscopic mucosal resection could be considered a definitive treatment without compromising the possibility of cure.

Safety of modified extended right hepatectomy in living liver donors.

In living donor liver transplantation (LDLT), the standard right graft has been adopted by many centers to meet the metabolic demands of large recipients. In conventional right liver graft, congestion at anterior section may be problematic especially when graft volume is insufficient. We previously introduced a technical aspect of modified extended right hepatectomy (MERH), in which the middle hepatic vein was excavated by preserving the entire segment 4 (Sg4) to the donor. In this report, we investigated the safety of donors who received MERH. Between August 2002 and July 2005, 97 donors underwent right liver donation. MERH was considered when remnant-left liver volume exceeded 35% of whole liver. Eighteen donors underwent MERH (MERH group, n=18). We compared the clinical outcomes of MERH group with those of donors who underwent conventional right hepatectomy (RH) with remnant liver volume exceeding 35% (RH group, n=37). No donor mortality occurred. No intra-operative transfusion and no re-operation were performed. There were no differences in operative time (290.8 min in MERH group vs. 297.0 min in RH group, respectively), blood loss (453.3 ml vs. 426.5 ml), and postoperative hospital stay (12.5 days vs. 12.8 days) between the two groups (P>0.05). Period of drain removal was longer in MERH group (12.5 days vs. 9.4 days, P<0.05). But, there was no difference in complication rate between the two groups (11/18 vs. 23/37, P>0.05). Computed tomography scan showed that congestion of Sg4 was occurred in 13 out of 18 MERH donors in early postoperative period, but all recovered at 4 months. The regeneration of the remnant liver after MERH and RH were similar (209.8% vs. 200.0% at 4 months, P>0.05). Our results show that MERH did not impair recovery or liver regeneration in donors, and indicate that MERH can be safely done in adult LDLT when the remnant liver exceeds 35%.

Reboxetine and cytochrome P450--comparison with paroxetine treatment in humans.

OBJECTIVES: The noradrenaline-selective antidepressant reboxetine in vitro is a weak inhibitor of both cytochrome P450 (CYP) 2D6 and CYP3A4. Thus, in this study the pharmacokinetics of reboxetine in relation to pharmacogenetics and the effects of reboxetine compared to paroxetine treatment on the CYP2D6 and CYP3A4 phenotype were analyzed in healthy control subjects. METHODS: Healthy male volunteers were treated with either 6 mg reboxetine (n = 26) or 30 mg paroxetine (n = 25). On Days 10/11 of treatment, serum concentrations of the antidepressants were measured and pharmacokinetic parameters calculated. Volunteers were phenotyped at the end of treatment and after at least 3 weeks washout (true phenotype) using 30 mg dextromethorphan (DM) hydrobromide given orally and measuring DM and metabolites in serum 2 h after intake. CYP2D6 and CYP2C19 genotypes were determined in parallel. RESULTS AND CONCLUSION: Reboxetine serum concentrations showed no correlation with the CYP2D6 genotype and the CYP2D6 phenotype, whereas paroxetine concentrations showed some dependence on CYP2D6. In contrast to in vitro investigations, indicating a major role of CYP3A4 in reboxetine metabolism, reboxetine concentrations in serum showed no correlation with the respective DM metabolic ratios. There was also no correlation between paroxetine concentrations and the CYP3A4 phenotype data. The CYP2C19 genotype (only heterozygosity) had no influence on reboxetine and paroxetine pharmacokinetics. There were only minor changes in the DM metabolite pattern on treatment with reboxetine and no evidence of enzyme inhibition was obtained. In contrast and as expected, paroxetine strongly inhibited CYP2D6. Thus, reboxetine treatment has no effect on the CYP2D6 genotype and no clinically relevant drug interactions involving CYP2D6 are anticipated.

In vitro investigations on the differential pro-oxidant and/or antioxidant properties of cyclosporin A and tacrolimus in human and rat liver microsomes.

OBJECTIVE: The use of cyclosporin A (CSA) and tacrolimus (TAC) in organ transplantation and in the therapy of immune disorders is often hampered by adverse effects, mainly nephro-, hepato- and neurotoxicity. For the development of these side effects, among others, an increased formation of reactive oxygen species, probably generated by the cytochrome P450 (CYP) system, has been accused. Since in this respect literature data are inconsistent, in the present study possible pro- and/or antioxidant effects of CSA and TAC and the involvement of the CYP system were re-evaluated in vitro. METHODS: Effects of CSA and TAC were examined on CYP mediated oxidase functions by stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) or luminol (LM) amplified chemiluminescence (CL) in liver microsomes of either untreated rats or of rats treated with beta-naphthoflavone (BNF), phenobarbital (PB) or dexamethasone (DEX) and in human liver microsomes. RESULTS: In rat liver microsomes, CSA displayed pro-oxidant properties (though only very slightly), whereas in human liver microsomes small antioxidant effects were seen. With TAC in both species the antioxidant capacity prevailed. Treatment of rats with BNF or DEX caused an increase in the pro-oxidant effects of CSA with respect to LPO or LM-CL, whereas in liver microsomes of DEX-treated rats H2O2 production and LC-CL were diminished. CONCLUSIONS: CSA seems to have both pro-oxidant and antioxidant properties, whereas with TAC mainly an antioxidant capacity was seen. The CYP system seems to be involved in the pro-oxidant influence of CSA. Whether pro-oxidant or antioxidant effects predominate may depend on the antioxidant capacity of a tissue and on the CYP isoforms mainly present.

Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth.

The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. It is believed that this tissue contains stem cells and lineage committed progenitor cells or precursor cells (PCs) for cementoblasts, periodontal ligament cells, and osteoblasts. In this study, we report the isolation of PCs derived from dental follicle of human third molar teeth. These fibroblast-like, colony forming and plastic adherent cells expressed putative stem cell markers Notch-1 and Nestin. We compared gene expressions of PCs, human mesenchymal stem cells (hMSCs), periodontal ligament cells (PDL-cells) and osteoblasts (MG63) for delimitation of PCs. Interestingly, PCs expressed higher amounts of insulin-like growth factor-2 (IGF-2) transcripts than hMSCs. Differentiation capacity was demonstrated under in vitro conditions for PCs. Long-term cultures with dexamethasone produced compact calcified nodules or appeared as plain membrane structures of different dimensions consisting of a connective tissue like matrix encapsulated by a mesothelium-like cellular structure. PCs differentially express osteocalcin (OCN) and bone sialoprotein (BS) after transplantation in immunocompromised mice but without any sign of cementum or bone formation. Therefore, our results demonstrate that cultured PCs are unique undifferentiated lineage committed cells residing in the periodontium prior or during tooth eruption.

Novel mutations in the CHST6 gene causing macular corneal dystrophy.

Macular corneal dystrophy (MCD) is an autosomal recessive disease characterized by corneal opacities and caused by mutations in a carbohydrate sulfotransferase gene, known as CHST6. MCD type I patients show missense mutations in the CHST6-coding region, and MCD type II patients show a large deletion and replacement in the upstream region of CHST6. The objective of this study was to identify the genetic defect in CHST6 gene causing MCD in Italian families. We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing, and results were confirmed by restriction analysis. An enzyme-linked immunosorbent assay was performed to assess the presence of sulfated keratan sulfate in the serum of MCD patients. Biochemical analysis revealed a MCD type I phenotype in two families and a type II phenotype in another family. Two novel missense mutations and a polymorphism in the coding region of CHST6 gene were identified in patients with MCD type I. In one MCD II family, a homozygous deletion in the upstream region of CHST6 gene was found.

[Rare tumors of the parotid gland. Lymphadenoma of a sebaceous gland and extracranial metastasis from glioblastoma]. / Seltene Parotistumoren. Talgdrüsenlymphadenom und extrakranielle Glioblastommetastase.

Tumors of the parotid gland can be benign or malignant lesions.The pathophysiology of rare tumors of the parotid gland is often not sufficiently explored in this paper two rare histological entities are described. In one patient a benign sebaceous lymph-adenoma was histologically diagnosed. This type of tumor accounts for only 0.196 of all adenomas. The international literature is not conclusive about whether the tumor originates in the parotid gland itself or in the parotid lymph nodes. The second patient presented with a metastasis from a glioblastoma in the parotid gland. Again, the mechanism for metastasis of an intra-cerebral tumor to the parotid gland remains unknown. Iatrogenic seeding during a neurosurgical intervention is a probable explanation. The actual clinical course of his patient and the cases described in literature render surgical removal of such a metastasis questionable.

Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients.

OBJECTIVE: An 8-week randomized, reference-controlled, double-blind, multi-centre clinical trial investigated Kava-Kava LI 150 in Generalized Anxiety Disorder (GAD; ICD-10: F41.1). METHOD: 129 out-patients received either 400 mg Kava LI 150, 10 mg Buspirone or 100 mg Opipramol daily for 8 weeks. At week 9, subjects were seen to check for symptoms of withdrawal or relapse. Primary outcome measures comprised the HAMA scale and the proportion of responders at week 8. Secondary measures were the Boerner Anxiety Scale (BOEAS), SAS, CGI, a self-rating scale for well-being (Bf-S), a sleep questionnaire (SF-B), a quality-of-life questionnaire (AL) and global judgements by investigator and patients. RESULTS: In 127 patients (ITT) no significant differences could be observed regarding all efficacy and safety measures. About 75% of patients were classified as responders (50% reduction of HAMA score) in each treatment group, about 60% achieved full remission. CONCLUSION: Kava-Kava LI150 is well tolerated and as effective as Buspirone and Opipramol in the acute treatment of out-patients suffering from GAD.

Indoleamine 2,3-dioxygenase expression in patients with acute graft-versus-host disease after allogeneic stem cell transplantation and in pregnant women: association with the induction of allogeneic immune tolerance?

Indoleamine 2,3-dioxygenase (IDO) is an interferon-gamma (IFN-gamma)-induced enzyme, which is suggested to play an important role in the prevention of allogeneic fetal rejection. IDO effects the suppression of T-cell activity by catabolizing the essential amino acid l-tryptophan. We studied IDO expression by reverse transcription polymerase chain reaction (RT-PCR) in dendritic cells and by real-time RT-PCR in monocytes of patients undergoing allogeneic transplantation for leukaemia, who developed acute graft-versus-host disease (aGvHD), and compared the IDO expression with that of pregnant women and healthy volunteers. A spontaneous IDO expression was detected in the monocytes of 20 pregnant women with an IDO/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio at a median of 1.0%, whereas none of 15 healthy volunteers or patients after allogeneic transplant had any detectable spontaneous IDO expression. The IDO expression increased by in vitro IFN-gamma stimulation in pregnant women (median 116%), healthy volunteers (median 11.7%) and patients with a low-grade aGvHD (grades 0-II) 28 days after transplant (median 433%) but not in patients with a severe aGvHD (grades III-IV) (median 0%), which was highly significant (P < 0.01). IDO expression was also measured in dendritic cells by qualitative RT-PCR, where a spontaneous IDO expression was detected in 16 of 31 (52%) pregnant women versus none of 17 healthy volunteers and none of 62 studied patients after transplant. IFN-gamma-induced IDO expression was detected in all pregnant women, all volunteers and 47 of 49 (96%) patients with a low-grade aGvHD (grades 0-II) after transplant, whereas only in two of 13 (16%) patients with aGvHD grade III-IV was IFN-gamma-induced IDO expression observed. These data suggest that IDO expression might be involved in the development of allogeneic immune tolerance.