[35-year old patient with severe thromboembolism]. / 35-jähriger Patient mit ausgeprägter Thromboembolie.

We report a case of a 35 year old male with severe deep vein thrombosis of the lower limb on both sides and pulmonary embolism. A Klinefelter's mosaic (47,XXY [81%]/48,XXXY [19%]) was diagnosed. Because no other cause for this thromboembolism was found, we assume that in part, it was caused by the Klinefelter's mosaic. In all male patients presenting with thromboembolism, especially those with an unusual habitus, a Klinefelter's syndrome should be considered as differential diagnosis. Testosterone substitution therapy should be started in all patients with Klinefelter's syndrome to prevent further disease.

[Treatment of vesicoureteral reflux in childhood]. / Die Behandlung des vesikoureteralen Refluxes im Kindesalter.

The pathophysiology, evaluation and therapy of vesicoureteral reflux (VUR) were newly illuminated over the past years through different clinical studies and basic research. Our understanding of vesicoureteral reflux and the therapeutic spectrum of its treatment should therefore consistently undergo critical revision. The Swedish Reflux Study set up three different therapy options for small children with dilated VUR: antibiotic prophylaxis, endoscopic reflux correction and surveillance were prospectively analysed in a randomized fashion. The results are discussed in this work and completed with a statement about open operative reflux therapy.

[Undescended testis: aspects of treatment]. / Hodenhochstand : Aspekte der Behandlung.

Undescended testis (UDT) is the most frequent congenital malformation affecting 1% of 1-year-old mature birth boys. If untreated UDT leads to progressive histological changes with impaired spermatogenesis and an increasing risk of testicular cancer. For clinical reasons palpable testes should be differentiated from impalpable testes. Spontaneous testicular descent can be expected only before 6 months of age. Subsequently, treatment should start without delay and be finished before the child has reached the age of 1 year. Surgery is the cornerstone of treatment. Inguinal approaches are standard practice for palpable testes, whereas laparoscopy is used in non-palpable testes. Hormonal treatment is ineffective for inducing testicular descent but facilitates germ cell maturation and an improvement in fertility potential. Only early treatment of UDT reduces germ cell loss, improves fertility and reduces the risk of testicular cancer.

[Imaging studies in infants and children with dilatation of the upper urinary tract]. / Bildgebung bei Hohlsystemdilationen des oberen Harntraktes im Neugeborenen- und Kindesalter.

Prenatally or postnatally diagnosed dilatation of the upper urinary tract initiates postnatal investigations, including sonography, dynamic renography (MAG 3) and optional voiding cystourethrography. The first ultrasound examination should be performed 3-5 days after birth and in urgent cases 10-12 h after delivery of the baby. Dynamic renography (MAG 3) is the standard diagnostic investigation and permits simultaneous assessment of renal perfusion and drainage. MRI combines excellent anatomical detail with functional information, without exposure to radiation but needs general anaesthesia in infants and younger children. Intravenous urography is no longer performed routinely in children with a dilated upper urinary tract. The combination of ultrasound and MAG 3 produces the necessary anatomical and functional information to follow the degree of obstruction and to decide between surgical intervention or a conservative follow-up.

[Late diagnosis of cryptorchidism]. / Der spät diagnostizierte Hodenhochstand

Cryptorchidism is a risk factor for testicular cancer and reduced fertility. Failure of critical maturation steps, with the persistence of gonocytes beyond 6 months, results in a decreased number of adult dark (A-dark) spermatogonia, which causes a deficiency of primary spermatocytes at 3 years of age. We evaluated the histological findings in boys older than 4 years who were diagnosed with a testis located in the inguinal channel. From September 2007 to September 2008, 15 boys (mean age 8 years) underwent orchidopexy with a biopsy taken from the undescended testis of one side. Sonograms were performed in all 15 boys. The incidences of spermatogonia, primary spermatocytes, and Leydig cells (semiquantitative) were estimated as well as the exclusion of intratubular carcinoma in situ cells (Department of Pathology, Central EM Lab, University Medical Center Regensburg, Germany). Orchidopexy was performed on the right side in eight boys, the left side in one, and both sides in six. Sonographically, no parenchymal echotexture abnormalities were found. A-dark spermatogonia could be detected in nine biopsies. The Leydig cell score was reduced in 11 boys. No carcinoma in situ cells were detected. Late diagnosis of undescended testis will have a poor prognosis for future fertility.

Proposal for the integration of decentralised composting of the organic fraction of municipal solid waste into the waste management system of Cuba.

Municipal solid waste (MSW) generation and management in Cuba was studied with a view to integrating composting of the organic fractions of MSW into the system. Composting is already included as part of the environmental strategy of the country as an appropriate waste management solution. However, no programme for area-wide implementation yet exists. The evaluation of studies carried out by some Cuban and international organisations showed that organic matter comprises approximately 60-70% of the MSW, with households being the main source. If all organic waste fractions were considered, the theoretical amount of organic waste produced would be approximately 1 Mio. Mg/a, leading to the production of approximately 0.5 Mio. Mg/a of compost. Composting could, therefore, be a suitable solution for treating the organic waste fractions of the MSW. Composting would best be carried out in decentralised systems, since transportation is a problem in Cuba. Furthermore, low technology and low budget composting options should be considered due to the problematic local economic situation. The location for such decentralised composting units would optimally be located at urban agricultural farms, which can be found all over Cuba. These farms are a unique model for sustainable farming in the world, and have a high demand for organic fertiliser. In this paper, options for the collection and impurity-separation in urban areas are discussed, and a stepwise introduction of source-separation, starting with hotel and restaurant waste, is suggested. For rural areas, the implementation of home composting is recommended.

[Fetal bladder development. A current overview]. / Kindliche Blasenentwicklung. Eine aktuelle Standortbestimmung.

Human fetal bladder development starts in the 9th to 10th week of gestation. Smooth muscle cell formation is induced by Hedgehog proteins and their signaling in the surrounding mesenchyma of the fetal bladder cavity. Bladder wall thickness increases significantly with advancing gestation, mediated by linear growth patterns irrespective of the related sex. lt is the aim of this article to address new insights into bladder development to enhance our knowledge about normal and pathological conditions that occur when developmental processes are disturbed.

[Urological problems in patients with meningomyelocele. Diagnostic studies and management]. / Urologischer Erkrankungen bei Patienten mit Meningomyelozele. Diagnostik und Management.

Since the 1980s the management of children and adolescents with meningomyelocele has undergone major changes. The introduction of pharmacotherapy with antimuscarinic agents, clean intermittent catheterization (CIC) and antibacterial prophylaxis has revolutionized the management of children with neurogenic bladder. The co-operation between neonatologists, neurosurgeons, paediatric neurologists, paediatricians, paediatric urologists, paediatric nephrologists, paediatric orthopaedists and paediatric surgeons is necessary to achieve an optimized therapy in each individual patient. In this interdisciplinary consensus paper we provide definitions and classifications as well as a timetable for the appropriate investigations. The conservative and surgical options are explained in detail. A short review is given concerning orthopaedic management, incidence of latex allergy, options for bowel management, diagnosis and treatment of urinary tract infections, problems with sexuality and fertility as well as the long-term compliance of these patients and their relatives.

Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen-glucose deprivation.

The survival of rat Purkinje cell (PCs) cerebellar cultures was used to test the hypothesis that progesterone is protective against oxygen-glucose deprivation through potentiation of GABA(A) receptor activity. Electrophysiological recordings confirm that PCs develop robust excitatory and inhibitory synapses in culture. Exposure of cultured PCs to increasing concentrations of progesterone during oxygen-glucose deprivation revealed a concentration-dependent protection by progesterone, with significant protection observed at physiological concentrations, as low as 10 nm. The concurrent application of the GABA(A) receptor antagonist picrotoxin (100 microm) completely abolished the neuroprotection afforded by progesterone, indicating that progesterone is neuroprotective through activation of GABA(A) receptors. Progesterone potentiates GABA(A) receptor activity indirectly through its metabolites, such as allopregnanolone (ALLO). Therefore, ALLO was applied to PC cultures and was observed to produce significant protection at all concentrations tested, from 10 to 1000 nm. Finally, the inhibition of progesterone metabolism with finasteride abolished the protection afforded by progesterone without having any effect on the neuroprotection caused by ALLO. These data indicate that progesterone protects cerebellar PCs at physiological concentrations through a GABA-active metabolite.

[Health-related quality of life in children with spina bifida]. / Gesundheitsbezogene Lebensqualität bei Kindern mit Spina bifida.

BACKGROUND: There are no studies on the health-related quality of life (HRQoL) in German children with a myelomeningocele (MMC). This study aims to obtain generalizable epidemiological data on the HRQoL of such children. PATIENTS AND METHODS: KINDL-R questionnaires were filled out and clinical findings on typical MMC disabilities were also documented. Of the 115 families contacted, 70 MMC families responded (response rate 61%). Normative KINDL-R data from a sample of healthy children served as reference. RESULTS: No differences in clinical data were found when comparing responders and non-responders. KINDL total scores as well as scores across all scales were highly concordant for parental reporting and self-reporting. CONCLUSIONS: Despite the fact that children with MMC often suffer from severe physical limitations, their HRQoL is not necessarily lower than that of healthy children.

Behaviour of biodegradable plastics in composting facilities.

Composting is a preferred treatment strategy for biodegradable plastics (BDPs). In this sense, the collection of BDPs together with organic household wastes is a highly discussed possibility. Under the aspect of the behaviour of BDPs in composting facilities, a telephone survey was carried out with selected composting facility operators. They were interviewed with respect to treated wastes, content of impurities, processes for impurity separation, experiences with biodegradable plastics and assumptions to the behaviour of biodegradable plastics in their facility. Forty percent of the facilities had some experiences with BDPs due to test runs, and also since the occurrence of BDPs in their waste was known. The majority of the operators expressed apprehension regarding an increase of impurities resulting from a combined collection of biowaste and BDPs. In the facilities, measures for the impurity separation from the biowaste were used in common practice - in 33% of the cases, separation of disturbing plastics was done before composting, in 33% after composting, and in 13% before and after composting. The most important separation processes for conventional plastics were sieving and manual sorting. In two cases air classification was also used. When asked about the separation possibility of the conventional but not of the biodegradable plastics in their facilities, the majority of operators were not in a position to comment or they replied that it was not an option. No problems were seen in most cases if the impurity separation follows composting. If impurity separation takes place before composting it was often assumed that the BDPs are mainly separated by sieving. In conclusion, in more than half of the cases, BDPs would not be composted if delivered to a composting facility. Under the actual conditions regarding the collection and the treatment/disposal possibilities, an application of BDPs seems to only be reasonable for clean (i.e., source separated on their own) fractions of BDPs.

[Clinical and economical outcome evaluation of dental care services received by German patients in countries outside the EU]. / Klinische und ökonomische Evaluation der Inanspruchnahme zahnärztlicher Leistungen im Ausland.

PURPOSE: During the past decade German patients developed an increasing tendency to dental health tourism in countries outside the European Union. The present investigation aimed at evaluating both clinical and economic outcome of dental care in these countries with regard to German directive standards. METHODS: Based on physical examinations performed by the Medizinische Dienst der Krankenversicherung Rheinland-Pfalz in the context of reimbursement or regress requests after dental care in countries outside the European Union, an individual treatment concept was designed and its direct costs from the patient's perspective were estimated according to German standards. Furthermore, the clinical outcome was evaluated and treatment concepts for the correction of clinically relevant findings were simulated; the corresponding costs were estimated. A descriptive cost-cost analysis has been performed from the patient's perspective and a secondary one from the health service's perspective. RESULTS: A total of 60 examinations (january 2001 to october 2002) were analysed. 29 of these 60 patients showed clinically relevant findings affording post treatment correction, among which 23 treatment concepts significantly disagreed with German directive standards. From the 60 patients' perspective median costs of 942 euro; for treatment outside the EU versus hypothetical costs of 750 euro; for treatment in Germany were observed. In addition, the 29 patients with clinically relevant findings affording corrective treatment implied median costs of 1,383 euro;. From the health service perspective, median costs of 761 euro; could be avoided due to treatments outside the EU, whereas median costs of 1,220 euro; were simulated due to necessary corrective treatments. CONCLUSION: From the patients' perspective dental care outside the EU has to be reconsidered both from a clinical and an economic point of view.

Investigation and optimization of composting processes-test systems and practical examples.

To determine the optimal course of composting it is useful to carry out experiments. The selection of the right experimental set-up depends on the question of concern. Each set-up is useful for a particular application and has its limits. Two test systems of different scales (up to 1500 ml; up to 100 l) are introduced. The purpose and importance of each system design shall be highlighted by application examples: (1). Suitability of a liquid industrial residue as composting accelerator; (2). Determination of the compost maturity; (3). Behaviour of odor-reducing additives during waste collection and composting; (4). Production of tailor-made compost with respect to Nitrogen (5). Suitability of O(2)-enriched air for acceleration of composting. Small-scale respiration experiments are useful to optimize parameters which have to be adjusted during substrate pre-treatment and composting, with the exception of particle size and temperature, and to reduce the number of variants which have to be investigated in greater detail in larger scale experiments. As all regulation possibilities such as aeration, moistening, turning can be simulated with the technical scale set-up, their complex cooperation can be taken into consideration. Encouraging composting variants can be tested, compared and optimized.

Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on CD34(+) progenitor cells during differentiation into antigen presenting cells.

The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor family that regulates T cell activation and function. ICOS binds to a newly identified ligand on antigen presenting cells different from the CD152 ligands CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is first expressed on myeloid antigen presenting cells, we examined ICOSL expression on CD34(+) cells in bone marrow. We found that CD34(bright) cells regardless of their myeloid commitment were ICOSL(-), whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared. However, acute myeloid leukemia cells were ICOSL-negative, whereas among B-cell malignancies only some cases of the most mature tumors such as prolymphocytic leukemia and hairy cell leukemia were positive. Next, we investigated purified CD34(+) hematopoietic progenitor cells that did not constitutively express ICOSL but were induced to express ICOSL within 12 h after granulocyte/macrophage colony-stimulating factor/tumor necrosis factor alpha (TNF-alpha) stimulation. Interestingly, ICOSL was induced prior to CD80/CD86 induction on CD34(+) cells so that ICOSL was expressed in the absence of CD80/CD86. This suggests that ICOSL is an early differentiation marker along the monocytic/dendritic maturation pathway. Induction of ICOSL was dependent on TNF-alpha and was regulated via NF-kappa B as revealed by use of inhibitors specific for I kappa B alpha phosphorylation such as BAY 11-7082 and BAY 11-7085. The antigen presenting capacity of TNF-alpha stimulated CD34(+) cells was strongly inhibited by ICOSIg fusion proteins or by NF-kappa B inhibition. Thus, TNF-alpha-induced ICOSL expression seemed to be functionally important for the costimulatory capacity of CD34(+) hematopoietic progenitor cells.

The use of isosulphan blue to identify lymphatic vessels in high retroperitoneal ligation of adolescent varicocele--avoiding postoperative hydrocele.

OBJECTIVE: To assess whether identifying and preserving the lymphatic vessels, using vital dyes, avoids postoperative hydrocele in adolescents with varicocele undergoing high retroperitoneal ligation (Palomo procedure). PATIENTS AND METHODS: The results were assessed from 28 consecutive adolescent patients undergoing varicocelectomy, treated between 1998 and 1999 by the Palomo procedure. The lymphatic vessels were identified and preserved using vital dyes, to avoid postoperative hydrocele formation. RESULTS: In 24 of the 28 patients (86%) the identification and preservation of lymphatic vessels was feasible. Over a mean (range) follow-up of 14 (4-24) months there were no postoperative hydroceles and no clinical recurrences. CONCLUSION: Identifying and preserving the lymphatic drainage of the testis and tunica vaginalis using vital dyes prevents the development of postoperative hydrocele in adolescents undergoing the Palomo procedure.

Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning.

Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin. However, the cellular signal transduction cascades resulting in ischemic tolerance and the mechanisms involved in neuronal survival in the tolerant state still remain unclear. The current study investigated the mRNA and protein expression of the antiapoptotic bcl-2 and the proapoptotic bax. two antagonistic members of the bcl-2 gene family, in response to a single dose of 3-NPA, to global cerebral ischemia-reperfusion. and to the combination of both 3-NPA-pretreatment and subsequent global cerebral ischemia-reperfusion. Brain homogenates of adult Wistar rats (n = 25) were analyzed for bcl-2 and bax mRNA expression using a new highly sensitive and quantitative polymerase chain reaction (PCR) technique that allows real-time fluorescence measurements of the PCR product (LightCycler; Roche Diagnostics, Mannheim, Germany). Animals for mRNA analysis received 3-NPA (20 mg/kg, intraperitoneal; "chemical preconditioning") or vehicle (normal saline), and were either observed for 24 plus 3 hours or were subjected to 15 minutes of global cerebral ischemia 24 hours after the pretreatment and observed for 3 hours of reperfusion. Immunohistochemistry was applied to serial brain sections of additional rats (n = 68) to determine amount and localization of the respective Bcl-2 and Bax protein expression in various brain areas. One set of animals was injected with 3-NPA and observed for 3, 12, 24, and 96 hours; a second set was exposed to 15 minutes global cerebral ischemia, 3, 12, and 24 hours reperfusion; and a third set was pretreated with 3-NPA or saline 24 hours before the ischemic brain insult and observed for 96 hours of reperfusion. The authors found single dose 3-NPA treatment to be associated with an elevated bcl-2:bax ratio (increased bcl-2 expression, decreased bax expression), both on the transcriptional (mRNA) and the translational (protein) level. The differential influence of 3-NPA was maintained during early recovery from global cerebral ischemia (3 hours), when 3-NPA pretreated animals showed higher bcl-2 and lower bax mRNA levels compared with rats with saline treatment. Respective changes in protein expression were localized predominately in neurons vulnerable to ischemic damage. Compared with baseline, Bcl-2 protein was significantly higher in surviving neurons at 96 hours after the insult, whereas Bax protein remained unchanged. However, at this late time of postischemic recovery (96 hours), the protein expression pattern of surviving neurons was not different between animals with and without 3-NPA pretreatment. To the authors' knowledge, the current study is the first report on the differential expression of pro- and antiapoptotic genes after a single, nonlethal dose of 3-NPA. The current results suggest alterations in the balance between pro- and antiapoptotic proteins as a potential explanation for the reported protection provided by chemical preconditioning using 3-NPA in rats.

Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.

In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl+ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin-, CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c. vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC-based vaccination strategies are a promising clinical approach, particularly as postremission immunotherapy in the setting of autologous stem cell transplantation.

Long-term follow-up of female patients with congenital adrenal hyperplasia from 21-hydroxylase deficiency, with special emphasis on the results of vaginoplasty.

OBJECTIVE: To assess, in a long-term follow-up, female patients with congenital adrenal hyperplasia (CAH), with special emphasis on vaginal functional outcome and sexual activity after vaginoplasty. PATIENTS AND METHODS: Twenty-seven patients with CAH (aged 14-33 years; six Prader grade II, 14 grade III, six grade IV and one grade V) underwent surgery between 1972 and 1988. Three of the patients underwent clitoridectomy, 24 clitoroplasty and 25 vaginoplasty (24 with a Fortunoff flap and one a 'pull-through' procedure). In 20 patients the vaginoplasty was a one-stage procedure, undertaken at a mean (range) age of 3.6 (1-9) years, and in five patients a two-stage operation. The analysis was based on the patients' history and examination; the patients also completed a questionnaire, including a psychological profile. RESULTS: Nine of the 25 patients (36%) who underwent vaginoplasty developed intravaginal stenosis; of these nine, six were Prader grade III and three grade IV. All had undergone a single-stage procedure at a mean (range) age of 4.7 (2-9) years. Of the 16 patients who answered the questionnaire, 14 had problems with their overall body image; patients in whom vaginal stenosis was corrected were particularly anxious about sexual intercourse and had problems with orgasm. CONCLUSION: The main problem during the long-term follow-up was intravaginal stenosis; all the affected patients had undergone a single-stage procedure early in life to correct ambiguous genitalia. This high rate of vaginal stenosis suggests that vaginoplasty should be undertaken at the beginning of puberty, because higher oestrogen levels may prevent stenosis and, if necessary, dilatation can be performed by the patient. These data also underscore the importance of psychological support in the treatment of children with CAH.

Comparison of the perimeatal-based flap (Mathieu) and the tubularized incised-plate urethroplasty (Snodgrass) in primary distal hypospadias.

OBJECTIVES: To determine whether the perimeatal-based flap technique or the tubularized incised-plate repair is the more appropriate treatment for distal hypospadias in terms of fistula rate, cosmesis of the meatus and operative duration. PATIENTS AND METHODS: Between July 1997 and August 1998, 60 children (none of whom had previously undergone a procedure for hypospadias) underwent primary distal hypospadias repair in a prospective randomized trial. Thirty patients were allocated to undergo a Mathieu repair (mean age 24.9 months, range 9-72) and 30 a Snodgrass procedure (mean age 23.1 months, range 7-19). The mean follow-up was 15.4 months. RESULTS: The mean duration of surgery was significantly lower for the Snodgrass procedure than for the Mathieu repair (75 vs 115 min, P < 0.05). Three children undergoing a Mathieu repair had complications (two a urethrocutaneous fistula and one a meatal stenosis), compared with only one in the Snodgrass group (glanular dehiscence). The resultant meatus was slit-like in all patients undergoing the Snodgrass repair whereas those with a Mathieu repair had a rounded and horizontal meatus. CONCLUSION: The overall complication rate was lower and the surgery significantly quicker with the Snodgrass urethroplasty, which also had a better cosmetic outcome. The Snodgrass technique is recommended as a primary treatment for distal hypospadias.