Biomedical subjects

Jörg Schubert

Publications and source records attributed to Jörg Schubert.

At least 19 recordsLinked to original sources

PubMed2006

Permanent loss of anti-HBc after reactivation of hepatitis B virus infection in an anti-HBs and anti-HBc-positive patient after allogeneic stem cell transplantation.

BACKGROUND: Reactivation of a hepatitis B virus (HBV) infection after transplantation is associated with a high morbidity and mortality. HBV infections generally result in anti-HBc persisting lifelong. CASE REPORT: A 44-year-old female presented 10 years after allogeneic stem cell transplantation with a chronic hepatitis B. The infection was reactivated from a resolved (anti-HBs and anti-HBc positive) HBV infection acquired some years prior to transplantation. Interestingly, she lost all antibodies to HBV including anti-HBc and is upto now anti-HBc negative. The sequence of the surface and the core gene did not reveal any escape mutations. Thus, the loss of anti-HBc might suggest an immunotolerance of the donor's immune system against HBcAg. CONCLUSION: This data illustrate that an HBV infection might be reactivated despite high anti-HBs levels prior to transplantation. Furthermore, this is the first patient in which a complete loss of anti-HBc could be documented. Moreover, since anti-HBc is often used as a screening marker for HBV it should be kept in mind that anti-HBc negative patients with high viremic HBV infection may occur.

Adult↗

PubMed2006

Differentiation of Potato virus Y strains using improved sets of diagnostic PCR-primers.

Potato virus Y (PVY) is one of the most important viruses of potato world-wide, several strain groups are recognized. In the past two decades, novel PVY variants have appeared causing necrotic symptoms on potato tubers. Implicated are two groups of recombinant strains: PVY(N)W and PVY(NTN), and NA-PVY(NTN). While the first two are recombinants between PVY-N- and O-strains the latter is a recombinant between an N-strain and an unknown PVY strain or other Potyvirus. Available biological and molecular data on PVY suggest that classification of PVY strains has to be revised. Some drawbacks have been found with recently published primers used in RT-PCR based differentiation of PVY strains as some defined isolates could not be identified correctly. Consequently we developed new primers using both recently available sequences and newly generated complete sequences of PVY strains. The reliability of these newly developed primers and procedures was successfully demonstrated on nearly 100 biologically and serologically characterised PVY isolates.

Amino Acid Sequence↗

PubMed2006

The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed. RESULTS: Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae. CONCLUSIONS: Eculizumab is an effective therapy for PNH.

Adolescent↗

PubMed2006

Radical cystectomy with ultrasound-guided partial prostatectomy for bladder cancer: a complication-preventing concept.

OBJECTIVES: Radical cystectomy has been the reference standard for the treatment of muscle-invasive bladder cancer. However, this kind of therapy does have an impact on the patient's quality of life. For this reason, we performed prostate-sparing surgery during radical cystectomy without compromising the oncologic outcome. METHODS: From December 2003 to August 2005, 31 patients with a mean age of 63.6 +/- 8 years (range 48 to 79) underwent apex-sparing radical cystoprostatectomy for invasive bladder cancer. All patients underwent transurethral biopsy in the prostatic urethra to exclude urothelial tumor and transrectal ultrasound-guided biopsy of the prostate to diagnose concomitant prostate cancer. Patients with a prostate-specific antigen level greater than 4 ng/mL were excluded from prostate-sparing cystectomy. The mean follow-up period was 12 months. RESULTS: The postoperative pathologic stage was pTis in 2 patients, pTa in 1, pT1 in 3, pT2 in 20, pT3 in 5, and pN+ in 4 patients. We found no prostate cancer on histopathologic evaluation. Except for 4 patients, no patient had deterioration of sexual function. Except for 2 patients, all patients were fully continent. CONCLUSIONS: Radical cystectomy with prostate-sparing surgery in patients with invasive bladder cancer resulted in improved continence and improved erectile function. Additionally, with apex-sparing radical cystoprostatectomy, we were able to create a wide neovesicourethral anastomosis to prevent strictures, urinary retention, and mucous retention. It is absolutely necessary that this procedure be restricted to highly selected patients.

Aged↗

PubMed2006

Frequent detection of bocavirus DNA in German children with respiratory tract infections.

BACKGROUND: In a substantial proportion of respiratory tract diseases of suspected infectious origin, the etiology is unknown. Some of these cases may be caused by the recently described human bocavirus (hBoV). The aim of this study was to investigate the frequency and the potential clinical relevance of hBoV in pediatric patients. METHODS: We tested 835 nasopharyngeal aspirates (NPA) obtained between 2002 and 2005 from pediatric in-patients with acute respiratory tract diseases at the University of Würzburg, Germany, for the presence of hBoV DNA. The specificity of positive PCR reactions was confirmed by sequencing. RESULTS: HBoV DNA was found in 87 (10.3 %) of the NPAs. The median age of the infants and children with hBoV infection was 1.8 years (mean age 2.0 years; range 18 days - 8 years). Infections with hBoV were found year-round, though most occurred in the winter months. Coinfections were found in 34 (39.1 %) of the hBoV positive samples. RSV, influenza A, and adenoviruses were most frequently detected as coinfecting agents. Sequence determination of the PCR products in the NP-1 region revealed high identity (99 %) between the nucleotide sequences obtained in different years and in comparison to the Swedish viruses ST1 and ST2. An association of hBoV with a distinct respiratory tract manifestation was not apparent. CONCLUSION: HBoV is frequently found in NPAs of hospitalized infants and children with acute respiratory tract diseases. Proving the clinical relevance of hBoV is challenging, because application of some of Koch's revised postulates is not possible. Because of the high rate of coinfections with hBoV and other respiratory tract pathogens, an association between hBoV and respiratory tract diseases remains unproven.

Adenoviruses, Human↗

PubMed2006

Case report: primary carcinoid tumor of the testicle without metastases in combination with testicular atrophy and testosterone deficiency.

The first case of testicular carcinoid was represented as an element of a benign cystic teratoma by Simon et al. J Urol 1954; 72: 892-894. It is a rare disease accounting for less than 1% of all testicular neoplasms. We report a case of carcinoid of the testis without carcinoid syndrome and metastasis but with testosterone deficiency based on a bilateral testicular atrophy, which has not been previously reported.

Adult↗

PubMed2006

Prediction of renal allograft rejection by urinary protein analysis using ProteinChip Arrays (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry).

OBJECTIVES: To develop a noninvasive method for the detection of renal transplant rejection using ProteinChip Arrays (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry). METHODS: A total of 23 urine samples were collected from 13 patients showing biopsy-proven renal allograft rejection and from 10 patients without histologic signs of rejection. All 23 patients had clinical symptoms and signs of acute allograft rejection and underwent renal biopsy. Samples were centrifuged, and supernatants were directly spotted onto the ProteinChip arrays with different chromatographic surfaces. The obtained spectra in a range from 2 to 200 kDa were subjected to bioinformatic analysis using the method of Fuzzy c-means, followed by the establishment of rule bases and evaluation using the relevance index according to Kiendl. RESULTS: Several protein peaks were identified allowing differentiation between rejection and no rejection. Using two different ProteinChip surfaces, we found two biomarkers at 25.71 kDa and 28.13 kDa that gave a diagnostic sensitivity of 90% and 93% and a specificity of 80% (SAX2) and 85% (CM10), respectively. CONCLUSIONS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry appears to be a promising new diagnostic tool for distinguishing renal transplant patients with no rejection from those with acute rejection.

Graft Rejection↗

PubMed2006

Penile prosthetic surgery in neurologically impaired patients: long-term followup.

PURPOSE: Penile prosthetics are a viable option for erectile dysfunction in neurologically impaired patients. Penile implants can also be used to facilitate the management of urinary drainage when penile retraction has made this difficult. MATERIALS AND METHODS: Between 1980 and 1996, 245 neurologically impaired patients with a mean age of 40.8 years (range 16 to 75), including 188 with paraplegia, 57 with quadriplegia and 197 with spinal cord injuries, were treated for erectile dysfunction and/or urinary incontinence with penile prosthesis implantation. The mean history of paralysis was 11.2 years (range 1 to 52). After neuro-urological evaluation all patients included in this study were considered candidates for penile prosthesis implantation. A followup program for treatment success, patient satisfaction, problems and complications was subsequently initiated. RESULTS: During 17 years a total of 293 surgical procedures in 245 patients were done with the implantation of 147 semirigid (Jonas), 113 self-contained inflatable (Dynaflex) and 33 inflatable 3-piece (AMS 700) prostheses. There were 3 patient groups based on the indication for penile prosthetic surgery, namely group 1-134 patients with urinary management only, group 2-60 with erectile dysfunction only, and group 3-51 with urinary management and erectile dysfunction. At a mean followup of 7.2 years (maximum 17) 195 patients were reevaluated in clinic. In 122 patients (90.3%) urinary management problems were resolved. Erectile dysfunction treatment was successful in 76 patients (82.6%). There were 43 revisions for technical reasons and infections. The infection rate was 5% (12 patients). The perforation rate was different for different implant devices, that is 18.1% (15 of 83 cases) for semirigid devices, 2.4% (2 of 84) for self-contained inflatable devices and 0% (0 of 28) for inflatable 3-piece devices. CONCLUSIONS: The implantation of a penile prosthesis is a safe procedure for erectile dysfunction and/or urinary incontinence in neurologically impaired patients. Based on technical advances the complication rates significantly decreased during the years. The implantation of an inflatable 3-piece penile prosthesis in a neurologically impaired patient is a safe and viable procedure. Indications include the management of erectile dysfunction and problematic urinary collection.

Adolescent↗

PubMed2006

Successful renal transplantation in a patient with heterozygous prothrombin gene, factor V Leiden mutation and heparin-induced thrombocytopenia using r-hirudin as anticoagulant.

Vascular complications remain the most common cause of early renal allograft loss in patients with end-stage renal failure. Underlying thrombophilic disorders increase the risk of early graft thrombosis. A male adolescent with high-risk thrombophilia because of combined heterozygous factor V Leiden (G1691A) and prothrombin gene (G20210A) mutation developed HIT II. Hemodialysis and subsequent renal transplantation were undertaken using recombinant hirudin, a direct and selective thrombin inhibitor, as an anticoagulant. Primary function in the transplanted kidney was excellent. No thrombotic or hemorrhagic events have occurred and follow-up showed excellent long-term graft survival. Patients on HD have an increased risk for the development of HIT, and therefore, they need repetitive screening for the development of acquired thrombotic risk factors (e.g. HIT II or lupus anticoagulant). R-hirudin is efficacious and safe on both HD and following renal transplantation.

Adolescent↗

PubMed2006

Frequency and nocturia after successful renal transplantation: a normal situation?

OBJECTIVE: To analyse lower urinary tract function before and after successful renal transplantation and compare the data with those from a healthy control group. PATIENTS AND METHODS: Data were gathered by retrospective analysis of 331 charts of patients transplanted between March 1998 and May 2003, using written questionnaires and personal interview, and investigation of 150 patients. The control group consisted of 150 urologically healthy volunteers. RESULTS: Frequency and nocturia were the main lower urinary tract symptoms. Frequency of more than six voids/day was reported by 87% and nocturia of more then one void/night by 93% of all patients after successful renal transplantation. There was no significant correlation with fluid intake, diuretic medication, gender or age. Over the years the number of voids tended to decrease but remained higher than in the control group. However, 94% of all patients were happy with the quality of life after renal transplantation. CONCLUSION: Frequency and nocturia are the two main characteristics of lower urinary tract function after renal transplantation, probably through a combination of high fluid intake, a long-term defunctionalized urinary bladder during renal replacement therapy, a denervated donor kidney, concomitant diseases and psychosocial distress. Quality of and satisfaction with life were not compromised.

Adolescent↗

PubMed2005

No influence of the P-glycoprotein polymorphisms MDR1 G2677T/A and C3435T on the virological and immunological response in treatment naïve HIV-positive patients.

BACKGROUND: In a retrospective study of HIV-infected patients, we investigated the influence of the MDR1 genotype (G2677T/A and C3435T) on the virological and immunological response of treatment naive patients. METHODS: The MDR1 genotype was analysed from 72 patients in whom antiretroviral therapy was initiated between 1998 and 2004. Data were obtained at week 4, 12, 24 and 48 and were analysed by the Kruskal-Wallis test. RESULTS: During the first 48 weeks of antiretroviral therapy, there were no significant differences in the virological and immunological response with respect to the MDR1 2677 and 3435 genotypes and the 2677/3435 haplotype. CONCLUSIONS: In view of different results from several studies concerning the influence of MDR1 polymorphisms on the immunological and virological response to antiretroviral therapy, further studies with larger patient groups and longer follow-up are necessary in order to resolve conflicting issues.

Adult↗

PubMed2005

Is there a relationship between chronic bladder dysfunction and somatic symptoms in other body regions? 2. An experimental neuroanatomical approach.

OBJECTIVE: Based on clinical description of associated dysfunctional symptoms in patients with non-neurogenic lower urinary tract dysfunction an experimental setup was created in order to investigate the neuroanatomical basis for the clinical phenomena observed. METHODS: Using 24 male adult Sprague-Dawley rats for retrograde mapping of the spinal cord and brain, a pseudorabies virus (PRV) tracer was subsequently injected into four pertinent locations; (a) the trigone, (b) the masseter muscle (c) the forepaw and (d) the hindpaw. RESULTS: PRV tracing demonstrated clearly overlapping of labeled areas in the brain stem, diencephalon and thoracic-lumbar cord, from all injection sites of the rats. CONCLUSION: There is a diffuse overlap within the brain stem and spinal cord, of autonomic innervation to peripheral tissues based on the presented animal experiments. The described autonomic network allows an understanding of the occurrence of symptoms in distant regions of the body associated to chronic bladder dysfunction.

Animals↗

PubMed2005

Is there a relationship between chronic bladder dysfunction and somatic symptoms in other body regions? 1. Clinical observations.

OBJECTIVE: Investigation of patients with chronic bladder dysfunction regarding associated general symptoms and complaints in the cervico-facial, upper and lower extremity regions. PATIENTS AND METHODS: We retrospectively evaluated history, physical and special neurourological examination and urodynamic studies in 213 patients with non-neurogenic bladder dysfunction. RESULTS: 22 patients out of 213 patients with chronic bladder dysfunction reported reproducible associated symptoms involving the temporo-mandibular joint, the distal forearm/hand or feet and headache. There was an obvious clinical connection regarding the severity of bladder dysfunction and associated symptoms and possible relief of both by successful treatment. CONCLUSION: Symptomatic lower urinary tract dysfunction may accompanied by specific muscular and or sensory disturbances in different areas of the body. These associated pathologies in patients without neurological disease can be explained by functional changes in a complex autonomic peripheral and central nervous network.

Adolescent↗

PubMed2005

Molecular aspects of declining sperm motility in older men.

OBJECTIVE: To investigate the molecular mechanism for declining sperm motility in older men. DESIGN: Retrospective and prospective study. SETTING: University-based andrology unit. PATIENT(S): Semen was collected from 2,111 patients and sperm donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, sperm concentration, ejaculate volume, sperm motility (including velocity average path, velocity straight line, velocity curvilinear, linearity, and lateral head displacement), normal sperm morphology, percentage of abnormally blue-stained flagella, and total and free T, FSH, and LH concentrations were analyzed. In addition, the zinc concentration in the seminal fluid, flagella, and the whole spermatozoa was measured by means of atomic absorption spectrometry. RESULT(S): Patient age correlated negatively with T concentration and sperm motility, including velocity, but positively with the percentage of abnormally stained flagella and the flagellar zinc. Whereas the percentage of abnormally stained flagella correlated negatively with motility and sperm velocity, there was a positive relationship with the flagellar zinc content. Flagellar zinc content was negatively correlated with motility. Testosterone showed a positive relationship with motility and sperm concentration. CONCLUSION(S): Because the epididymis is functionally T-dependent, our data suggest that the removal of zinc from the outer dense fibers during epididymal sperm maturation is affected in aging men, which in turn will result in decreased sperm motility.

Adolescent↗

PubMed2005

Central autonomic innervation of the kidney. What can we learn from a transneuronal tracing study in an animal model?

PURPOSE: Renal sympathetic innervation is involved in the maintenance of fluid homeostasis, modulation of renal secretion from juxtaglomerular cells, sodium resorption from renal tubular cells and renal hemodynamics. The understanding of central innervation and neuronal connections is important for studying the consequences of renal disease and surgical interventions compromising renal nerves. MATERIALS AND METHODS: A total of 38 individual adult male Sprague-Dawley rats were used for retrograde transneuronal mapping of the spinal cord and brain stem after pseudorabies virus (PRV) injection into the left kidney in 30 and control experiments in 8. After a survival time of 72, 96 or 120 hours the animals were sacrificed. Exploration of the abdominal and pelvic visceral organs was done, and the brain and spinal cord were harvested via dorsal laminectomy. After cutting on a freezing microtome the tissue was immunostained for PRV. RESULTS: After kidney injection inspection of the abdominal and pelvic cavity revealed an enlarged bladder with hemic urine. The urine was sterile and the bladder wall showed signs of neurogenic inflammation. Other organs were not affected. PRV positive cells were primarily found within the ipsilateral nucleus intermediolateralis of thoracic spinal cord segments T6 to T13. At the supraspinal level PRV positive cells were found within certain regions, namely the nuclei raphes, rostral ventromedial and ventrolateral medulla, A5 noradrenergic cell region, locus coeruleus and nucleus paraventricularis of the hypothalamus. CONCLUSIONS: This investigation demonstrates the anatomical basis for broad central sympathetic innervation of the kidney. The neurogenic inflammation within the spinal cord inherent to the PRV tracing method causes an inflammatory reaction within the bladder. This can be due to increased sympathetic nerve activity, followed by peripheral, neurogenically mediated inflammation.

Animals↗

PubMed2005

The accuracy of 250 fine needle biopsies of renal tumors.

PURPOSE: In some cases of uncertain lesions in the kidney it would be helpful to perform biopsies for preoperative histopathological evaluation. In this study we evaluated the accuracy of and the impact on tumor management of core biopsy for histopathological evaluation of small solid renal masses. MATERIALS AND METHODS: After radical or partial nephrectomy 250 renal tumor biopsies were performed in 50 patients. All biopsies were performed by 1 urologist after preparation of the kidney ex situ on back table visually guided. Formalin fixed paraffin embedded biopsies were evaluated by 1 pathologist. RESULTS: In 49 of 50 cases (98%) we could define the malignant behavior of the tumor when performing 1 central and 4 peripheral biopsies of each tumor. In 85.2% the grading was correctly defined. A benign lesion was revealed in 4 cases (8%, all oncocytoma). In renal tumors 4 cm or smaller in diameter the accuracy of 1 central and 1 peripheral biopsy each regarding definition of tumor origin, tumor grading and cell type/growth pattern was 96% and 95.5%, 84% and 84.4%, and 87.5% and 89.5%, respectively. In renal tumors more than 4 cm in diameter the accuracy was 100% and 98.1%, 85% and 94.3%, and 71.4% and 88.7%, respectively. CONCLUSIONS: Core biopsy of renal lesions is accurate enough for histopathological evaluation and determination of therapeutic procedure. Additionally, biopsy could be used for identifying benign renal lesion for observation.

Biopsy, Needle↗

PubMed2005

Successful treatment of disseminated aspergillosis with the combination of voriconazole, caspofungin, granulocyte transfusions, and surgery followed by allogeneic blood stem cell transplantation in a patient with primary failure of an autologous stem cell graft.

The treatment of disseminated aspergillus infections in neutropenic patients remains a major challenge in spite of several new antifungal drugs. We report the case of a patient with multiple myeloma in prolonged neutropenia after primary failure of an autologous stem cell graft who developed invasive aspergillosis despite voriconazole monotherapy. He responded to a combination of voriconazole and caspofungin, supported by granulocyte transfusions and surgery. A subsequent allogeneic peripheral blood stem cell transplantation did not lead to recurring aspergillus infection. The patient is well and free of clinical disease with respect to the fungal infection and myeloma more than 18 months after the allogeneic transplantation.

Antifungal Agents↗

PubMed2005

Molecular clonal analysis of recurrent bladder cancer.

In order to select the optimum therapy for patients at risk of recurrent bladder cancer, it is necessary to know the pathway of recurrence development. However, the origin of recurrent bladder cancer is controversially discussed. Therefore, the aim of our study was to define the clonal origin of recurrent tumors of the bladder using molecular genetic markers. Thirty cases with recurrent bladder cancer (1-4 recurrences per case) were investigated by microsatellite analysis using 4 markers for chromosome 9. PCR was performed according to standard protocols followed by gel electrophoresis and automated analysis using an automated DNA-Sequencer (LI-QOR). In 25 of 30 cases, loss of heterozygosity (LOH) occurred in at least 1 tumor. Identical LOH was detected in 20 cases. In all these cases the same allele was affected. Different LOH patterns were found in 4 cases showing LOH in only 1 tumor and in 1 case with alterations of different markers. In 5 cases, no alterations were detected using these markers. Our results show that the majority of bladder cancer recurrences are characterized by monoclonal origin. These data indicate that recurrence is caused by cell dissemination from the original tumor. For that reason, an early instillation therapy should be performed after transurethral resection.

Chromosomes, Human, Pair 9↗