Differences between intrinsic and extrinsic ureteropelvic junction obstruction related to crossing vessels: histology and functional analyses.

PURPOSE: In children, ureteropelvic junction obstruction (UPJO) is mostly caused by intrinsic factors (IUPJO); extrinsic UPJO are rare and often due to crossing vessels (CVs). METHODS: We retrospectively reviewed all data of children with UPJO that underwent surgery in our institution from 2004 to 2011. Analyses included age at surgery, gender, preoperative and postoperative results of ultrasound and renal scans [differential renal function (DRF); signs of obstruction], and pathology reports. Available histological specimens of cases with CV were compared to a random selection of intrinsic cases in a blinded fashion. After additional Masson's trichrome staining, the specimens were scored for fibrosis, muscular hypertrophy, and chronic inflammation. RESULTS: Out of 139 patients with UPJO, 39 cases were associated with CV. Median age at surgery was 68 months (range 2-194) in the CV group and 11.5 months (range 0-188) in IUPJO group. Laparoscopic dismembered pyeloplasty (LDMP) was carried out in 134 and open DMP in five patients. Preoperative ultrasound identified 28/39 cases with CV. DRF below 40 % was more frequently seen in CV patients (p = 0.020). Histological analyses revealed no differences between the CV and IUPJO specimens in total. CV patients with higher grades of muscular hypertrophy had lower preoperative DRF, compared to those with higher preoperative DRF (p = 0.026). Functional recovery after (L)DMP was excellent in both groups. CONCLUSION: We could not find any significant histological differences between CV and IUPJO in children. To obtain excellent functional recovery, surgical procedures with a definite correction of the UPJ should be preferred in paediatric patients with CV.

Induction of antibodies binding to the membrane proximal external region of gp36 of HIV-2.

OBJECTIVE: The ability to induce neutralizing antibodies may be the most important feature of an antiretroviral vaccine, preventing infection of target cells and subsequent integration of the virus into the cellular genome where the virus may persist. Broadly neutralizing antibodies directed against conserved epitopes in the membrane proximal external region (MPER) of the transmembrane envelope (TM) protein gp41 of HIV-1 such as the monoclonal antibodies (mAb) 2F5 and mAb 4E10 have been found in infected individuals; however, all attempts to induce such antibodies failed. In individuals infected with HIV-2 such antibodies were not yet reported. METHODS: Two recombinant proteins corresponding to the ectodomain of the TM protein gp36 of HIV-2 were produced, rats were immunized and sera were analyzed for binding and neutralizing antibodies. RESULTS: Although binding antibodies were induced, none of the sera neutralized HIV-2. Most interestingly, epitope mapping showed specific binding of the antibodies to the MPER of gp36, to a region homologous to the binding site of the mAb 4E10 in gp41 of HIV-1. CONCLUSIONS: Although MPER-specific antibodies were induced by vaccination with gp36, these antibodies did not neutralize HIV-2. This is similar to the situation with HIV-1, but in contrast to that with gammaretroviruses.

[Post-traumatic and psychotic symptoms in severely traumatised patients]. / Posttraumatische und psychotische Symptome bei schwer traumatisierten Patienten.

BACKGROUND: Severely traumatised patients may show a variety of impairments, including psychotic symptoms. The therapist's specific professional background (e. g., trauma-focussed psychotherapy or general psychiatry) may impede adequate diagnosis and treatment of these patients. METHODS: Three case reports show the development and change of post-traumatic and psychotic symptoms over time and the influence of specific interventions. CONCLUSIONS: It is important not to jump to conclusions and interpret perceptual disturbances (flashbacks, dissociative or psychotic ones) too quickly in an one-sided way. Further scientific investigations are mandatory in order to understand and treat patients in an adequate way.

[Normokalaemic primary aldosteronism due to an aldosterone-producing adrenal adenoma--Case 06/2009]. / Normokaliämischer primärer Hyperaldosteronismus infolge eines Aldosteron-produzierenden Nebennierenadenoms--Fall 06/2009.

HISTORY AND ADMISSION FINDINGS: A 39-year-old patient presented with normokalaemic therapy refractory arterial hypertension despite of four antihypertensive drugs for further diagnostics. INVESTIGATIONS: Ultrasound displayed no evidence of renal artery stenosis. Furthermore, the kidneys were normal sized and morphologically without pathological findings. Renal function was normal. Free cortisol and catecholamine levels in a 24-hr-urine sample were within the normal range. Plasma renin activity was reduced and both the plasma aldosterone concentration and the aldosterone to renin ratio were elevated. A saline infusion test showed no suppression of the plasma aldosterone concentration, nor did an orthostatic testing show an increase. MRI revealed an adenoma of the right adrenal gland. DIAGNOSIS, TREATMENT AND COURSE: The results were consistent with primary aldosteronism due to an aldosterone-producing adenoma of the adrenal gland. The patient underwent laparoscopic adrenalectomy. The histological findings confirmed an adenoma of the adrenal gland. Three months later, blood pressure was normal under a single treatment regimen with an AT(1) receptor blocker. CONCLUSIONS: Screening for endocrine causes of hypertension is recommended in young patients, therapy refractory hypertension, and in hypokalaemic hypertension. Normokalaemia does not exclude primary aldosteronism as the underlying cause of hypertension.

A neutralization assay for HIV-2 based on measurement of provirus integration by duplex real-time PCR.

Specific, effective and rapid neutralization assays are crucial for the development of an HIV vaccine based on the stimulation of neutralizing antibodies and the development of such an assay for the human immunodeficiency virus-2 (HIV-2) is described. Virus neutralization was measured as the reduction of provirus integration using a duplex real-time PCR with high efficiency (99.4%). This PCR uses primers and a probe specific for the proviral LTR. Amplification and quantitative analysis of the cellular GAPDH gene was carried out in parallel to control for toxic or growth-inhibitory components in the sera. The neutralization assay was used to screen sera from 23 HIV-2 infected patients. 21 sera were able to neutralize HIV-2(60415K), 20 sera neutralized HIV-2(7312A) and 7 sera cross-neutralized HIV-1 IIIB. In contrast, when 14 of these sera were tested in parallel with a conventional neutralization assay based on a p27Gag capture ELISA, only one was found to neutralize HIV-2(60415K) and 11 to neutralize HIV-2(7312A) compared with 12 and 13 sera respectively using the PCR-based assay.

[Quality of scientific advice to politics. Lecture at the Berlin-Brandenburg Academy of Science and Humanities]. / Was ist gute Wissenschaftliche Politikberatung? Akademievorlesung bei der Berlin-Brandenburgischen Akademie der Wissenschaften.

Scientific advice to politics is a primary function of governmental research. The advisory process is, in the ideal situation, a collective duty of science and politics. The final decision rests ultimately with politicians. An understanding of the differences between science and politics is necessary for successfully providing advice to politicians. The requirements necessary to allow politics to substantially follow the advice of scientists are multifarious. The first of these is trust from the side of politics and the public and from the side of science competitive research, respect and communication skills, neutrality and integrity. From these requirements it is possible to derive criteria for quality assurance in advice to politics. The maintenance of scientific expertise at the competitive international level demands independent, qualified and adequately financed research. Governmental institutes have an antenna function: they have to recognize in good time whether risks are increasing, whether the government has to be informed and whether there is a need for action. The continuing maintenance of excellence requires measures of quality assurance at all levels. Evidence for the quality of advice to politics can, for example, be found in the good reputation of an institution and its prominent representatives. Success in research is an indirect quality criterion that can be and should be measured to a certain extent. The influence of advisory activities on political decisions is direct evidence for the quality of the advice. A classic example of highly successful policy advice is the development of the German AIDS policy.

Inhibition of porcine endogenous retroviruses (PERVs) in primary porcine cells by RNA interference using lentiviral vectors.

A potential risk in pig-to-human xenotransplantation is the transmission of PERVs to human recipients. Here we show for the first time the inhibition of PERV expression in primary porcine cells by RNA interference using lentiviral vectors. Cells were transduced with lentiviral vectors coding for short hairpin (sh) RNAs directed against PERV. In all primary porcine cells studied and in the porcine kidney cell line PK-15, expression of PERV-mRNA was significantly reduced as measured by real-time PCR. Most importantly, expression of PERV proteins was almost completely suppressed, as shown by Western blot analysis. Thus, lentiviral shRNA vectors could be used to knockdown PERV expression and create transgenic pigs with a reduced risk of PERV transmission during xenotransplantation.

Who benefits from inpatient short-term psychotherapy in the long run? Patients' evaluations, outpatient after-care and determinants of outcome.

BACKGROUND: Little work has been published on short-term inpatient treatments combining the virtues of inpatient treatments and short-term psychotherapy. The purposes of this study are to (a) determine the outcomes of short-term psychodynamic inpatient psychotherapy from patients' and therapists' perspectives, (b) assess the stability of changes, and (c) identify predictors of long-term outcome. METHODS: 83 consecutive inpatients (76% of those eligible) were assessed at intake, discharge, and 1 year follow-up by standardized questionnaires regarding symptoms (SCL-90R), interpersonal problems (IIP), object relationships (IPO), and the therapeutic relationship (HAQ). Diagnoses and functioning (GAF) were assessed by the therapists. RESULTS: Psychological distress (effect size S = 1.14) and physical complaints (ES = 1.03) decreased strongly from intake to discharge, the majority of patients moving from the pathological to the normal range of the global severity index GSI (SCL-90R). At follow-up, average distress remained at a low level, and the majority of patients, and their therapists and physicians, regarded their well-being as improved. In a multivariate approach, a substantial proportion of variance of the distress at follow-up (42%) was explained by an infantile object relationship pattern (IPO), social avoidance (IIP), negative vocational changes, and a lack of a confidant at follow-up. A delayed start of subsequent ambulatory psychotherapy was another negative outcome predictor. CONCLUSIONS: Attention should be given to maladaptive interpersonal relationship patterns, to vocational reintegration, and a confiding relationship as potential predictors of long-term outcome. Also, patterns of ambulatory after-care following inpatient treatment need further scrutiny.

Neutralising antibodies against the transmembrane protein of feline leukaemia virus (FeLV).

Neutralising antibodies specific for feline leukaemia virus (FeLV) were induced by immunisation with recombinant FeLV transmembrane envelope protein p15E. Epitope mapping revealed two epitopes located in similar regions to those previously identified for the porcine endogenous retrovirus (PERV). One of the epitopes has partial homology and both are located in regions corresponding to epitopes recognised by neutralising antibodies in patients infected with HIV-1.

[The emergence of old and new epidemics as a consequence of human actions]. / Das Auftreten alter und neuer Seuchen als Konsequenz menschlichen Handelns.

In the era of antibiotics and vaccines and prior to the appearance of AIDS, well-known infectious diseases received decreasing clinical attention. Occasionally, the opinion was also expressed that new types of infectious diseases could no longer be expected. However, a more detailed analysis of the state of infectious diseases yields quite a different picture. A variety of new infectious diseases has clinically been defined over the last few decades. New viruses, bacteria, and parasites with pathogenic potential for humans have been detected and well-known microorganisms have spread beyond their original geographic areas. Infectious agents, in particular viruses, permanently alter their genomes and may thus gain new clinical relevance. This article demonstrates that primarily the behavior of man influenced the nature and distribution of infectious diseases in the past and will affect the spread of infectious diseases in the future.

Clinical evaluation of a new intracranial pressure monitoring device.

BACKGROUND: Continuous monitoring of intracranial pressure (ICP) still plays a key role in the management of patients at risk from intracranial hypertension. Numerous ICP-measuring devices are available. The aim of the present study was to investigate the clinical characteristics and the magnetic resonance imaging (MRI) compatibility of the recently developed Neurovent-P(REHAU AG+CO, REHAU, Germany) ICP monitoring device. METHOD: In a prospective two-center study, a total of 98 patients with severe head injury, subarachnoid haemorrhage, intracerebral haemorrhage, and non-traumatic brain edema underwent intraparenchymal monitoring of ICP using the Neurovent-P. A control group comprising 50 patients underwent implantation of the Camino-OLM-110-4B ICP monitor. The zero drift of the probes was determined before and after the ICP recording period. Technical and medical complications were documented. The MRI compatibility of the Neurovent-P ICP probe was investigated by evaluating artifacts caused by the probe, probe function and temperature changes during MRI, and probe movement caused by the magnetic field. FINDINGS: The mean zero drift was 0.2+/-0.41 mmHg (maximum 3 mmHg) for the Neurovent-P ICP probes and 0.4+/-0.57 mmHg (maximum 12 mmHg) for the Camino-OLM-110-4B ICP probes. No significant correlation was identified between the extent of zero drift following the removal of the probes and the length of monitoring. Intraparenchymal haemorrhage spatially related to the probe occurred in 1 out of 50 (2%) patients with a Camino-OLM-110-4B probe and in 1 out of 98 (1%) with a Neurovent-P. Damage of the probe due to kinking or overextension of the cable or glass fiber occurred in 4 of the 50 (8%) Camino-OLM-110-4B ICP probes and in 5 of the 98 (5%) Neurovent-P probes. On T2-weighted MR images, the Neurovent-P ICP probe induced only small artifacts with very good discrimination of the surrounding tissue. On T1-weighted MR images, there was a good imaging quality but artifact-related local disturbances in signal occurred. There was no temperature change in the Neurovent-P probe and in the surrounding brain tissue during MR imaging. INTERPRETATION: The Neurovent-P ICP measuring system is a safe and reliable tool for ICP monitoring. Handling of the Neurovent-P system is safe when performed properly.

Virus safety in xenotransplantation: first exploratory in vivo studies in small laboratory animals and non-human primates.

For xenotransplantation, the transplantation of animal cells, tissues and organs into human recipients, to date, pigs are favored as potential donors. Beside ethical, immunological, physiological and technical problems, the microbiological safety of the xenograft has to be guaranteed. It will be possible to eliminate all of the known porcine microorgansims in the nearby future by vaccinating or specified pathogen-free breeding. Thus, the main risk will come from the porcine endogenous retroviruses (PERVs) which are present in the pig genome as proviruses of different subtypes. PERVs will therefore be transmitted, with the xenograft, to the human recipient. PERVs can infect numerous different types of human primary cells and cell lines in vitro and were shown to adapt to these cells by serial passaging on uninfected cells. Furthermore, PERVs have high homology to other retroviruses, such as feline leukemia virus (FeLV) or murine leukemia virus (MuLV), which are known to induce tumors or immunodeficiencies in the infected host. To evaluate the potential risk of a trans-species transmission of PERV in vivo, naive and immunosuppressed rats, guinea pigs and minks were inoculated with PERV and screened over a period of 3 months for an antibody reaction against PERV proteins or for the integration of proviral DNA into the genomic DNA of the host's cells. Furthermore, we inoculated three different species of non-human primates, rhesus monkey (Macaca mulatta), pig-tailed monkey (Macaca nemestrina) and baboon (Papio hamadryas) with high titers of a human-adapted PERV. To simulate a situation in xenotransplantation, the animals received a daily triple immunosuppression using cyclosporine A, methylprednisolone and RAD, a rapamycin derivative, presently under development by Novartis. None of the small laboratory animals or the non-human primates showed production of antibodies against PERV or evidence of integration of proviral DNA in blood cells or cells of several organs, 3 months after virus inoculation, despite the observation that cells of the animals used in the experiment were infectible in vitro. This apparent difference in the outcome of the in vitro and the in vivo data might be explained by an efficient elimination of the virus by the innate or adaptive immunity of the animals.