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S Conrad

Publications and source records attributed to S Conrad.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic locomotor outcome in dorsal transection of rat spinal cord: predictive value of minimal incision depth.

STUDY DESIGN: Experimental, prospective, blinded, animal study. OBJECTIVES: Subtotal transection models in rodents are widely used in spinal cord injury (SCI) research. In this model, we investigate the effect of the dorso-ventral incision depth (ID) of the spinal cord on functional locomotor outcome using the Basso, Beattie, Bresnahan (BBB) scale. We introduce the minimal incision depth (ID(min)) and the average lesion depth (ID(mean)) as reliable, fast and easily available predictive parameters for intrinsic locomotor function. SETTING: Tuebingen, Germany. METHODS: Dorsal over-hemisection at the level of T8 was performed in male Lewis rats. Functional outcome 4 weeks after SCI and histological analysis of the lesion were studied and correlated in 36 animals. Animals reaching weight support (BBB> or =9) were considered as having reached functional recovery. Data analysis was performed in linear (ordinary least squares; OLS) and nonlinear (logistic) regression models for correlation of histological parameters and functional outcome. RESULTS: BBB scores revealed a strong correlation with ID(mean) and ID(min), showing a higher value in predicting functional outcome for the latter parameter. Based on logistic regression analysis, animals with an ID(min) of 69% would have a 95% probability of reaching weight support. CONCLUSION: These results demonstrate that histological analysis is crucial when functional outcome parameters are used in the dorsal over-hemisection SCI model. A simple and feasible histological evaluation can reliably predict spontaneous functional locomotor recovery in dorsal transection models and could provide a simple tool to identify treatment effects of new experimental therapeutic approaches.

Animals↗
PubMed2006

[Obstructive nephropathy].

Congenital anomalies of the kidney and urinary tract (CAKUT) are regarded as a single entity. The degree of obstruction may have an additional influence on the parenchymal malfunction. Congenital dilatation of the upper urinary tract associated with symptomatic urinary tract infection must be treated early with intensive antibiotic therapy. In some cases temporary urinary diversion is also required. Further diagnostic procedures are then postponed in such cases. In all other cases of dilatation of the upper urinary tract diagnosed prenatally or early in the postnatal period, diuresis renography is still the cornerstone of diagnosis, even though it has definite limitations in young infants and in babies with poor kidney function. Functional gadolinum MR-urography will become the method of choice in the near future, since it combines good functional and excellent morphological presentation. When an obstruction hampering function is definitely present surgical correction is indicated: open and endoscopic surgery yield similarly good results. Molecular markers in CAKUT may soon be used as prognostic indicators. Examination of the molecular alterations that occur in renal and urinary tract anomalies may also lead to medicamentous protection of renal function.

Anti-Bacterial Agents↗
PubMed2006

Living with chronic hepatitis C means 'you just haven't got a normal life any more'.

OBJECTIVE: To explore psychosocial factors that impact on quality of life for people living with self-reported chronic hepatitis C. METHODS: A purposeful sample of 70 people who were self-identified as being hepatitis C virus (HCV)-positive was recruited through a variety of institutions and community agencies. Semi-structured interviews were held with 12 groups and 21 individuals. A qualitative grounded-theory methodology was used for data collection and analysis. Experiences of physical and psychological symptoms, stigma and discrimination, and living with an infectious disease, were explored using matrices. RESULTS: Phenomena emerging from the data included previously undocumented illness 'attacks' that were associated with depressive symptoms and a perception of hepatitis C as fatal. Uncertainty related to disease progression and transmission of the virus were common experiences among participants. A universal experience was fear and anxiety about stigma and discrimination. DISCUSSION: The findings of this study indicate that chronic hepatitis C has a pervasive impact on quality of life with a complexity that has not been explored with quantitative research approaches. Primary healthcare professionals need to be alert to the psychological and social impacts of chronic hepatitis C and to avoid behaviours that lead to perceptions of stigma and discrimination. The research indicates a need for further investigation into the relationship between psychosocial factors, disease management and disease progression.

Adolescent↗
PubMed2004

[Cystectomy for indications other than bladder cancer].

A cystectomy for indications other than transitional cell cancer of the bladder or general bladder cancer is frequently performed in cooperation with other surgical specialties such as general surgery or gynecology. In these cases the urological procedure as well as the oncological and surgical concepts of other specialties have to be combined. We studied our cystectomy patients who had undergone such a combined procedure for a non-urothelial indication concerning perioperative and postoperative complications.A total of 204 cystectomies were performed by the Department of Urology at the University of Hamburg, Germany between 1995 and 2003. Bladder cancer was the indication for cystectomy in 162 patients, but 42 patients had a non-urothelial indication for this procedure. These patients included 12 cases of advanced rectal cancer, 9 cases of advanced cervical cancer, 6 cases of advanced sigmoid cancer, 4 cases of advanced prostate cancer, 1 case of prostate sarcoma, 5 cases of complex vesicointestinal fistulae, 2 cases of urachal cancer, 1 leiomyosarcoma, 1 rhabdomyoma, and 1 rhabdomyosarcoma, respectively. Perioperative and postoperative complications of those patients were compared to patients who underwent cystectomy for transitional cell cancer of the bladder.Those 42 patients who underwent cystectomy for non-urothelial indications included 14 male and 28 female patients. The mean age was 58.2 years with a range of 3-78 years. For urinary diversion 30 ileum conduits, 4 sigma conduits, and 8 ileum neobladders were used. The mean operative time was 6.25 h. The mean blood loss was 2200 ml. An average of four red blood cell concentrates (RBC) had to be given. Postoperative hydronephrosis had to be treated in three (7%) patients unilaterally and in two (5%) patients bilaterally with a temporary nephrostomy. Postoperative urinary leakage lasting more than 30 days was found in two (5%) patients. A deep vein thrombosis as well as an ileus was found in five (12%) patients each, respectively. There was no perioperative mortality in this study. When comparing the complications of those patients with the 162 patients who underwent cystectomy for bladder cancer, the only significant difference ( p=0.033, chi-square test) was a higher ileus rate in the patients with cystectomy for a non-urothelial indication. Complications with cystectomy for non-urothelial indications are in large comparable to those for transitional cell carcinoma of the bladder. The higher ileus rate in non-urothelial patients can be explained by the more radical procedures in this group of patients. Even though the group of patients undergoing cystectomy for indications other than bladder cancer was small in this trial, the procedure is standardized in combination with other specialties. Larger patient numbers and a longer follow-up will lead to more data in this special group of patients.

Adolescent↗
PubMed2004

[Kidney donors and kidney transplantation in the elderly].

The likelihood of terminal renal insufficiency escalates with age, increasing the risk of dying as a patient requiring dialysis. In 1999, Eurotransplant initiated the Eurotransplant Senior Programm (ESP), in which the kidneys of old donors (>64 years) are allocated to recipients 64 years and older. Allocation does not take HLA-matching into account and is performed regionally only according to blood-group-compatibility to keep the storage time short. As a consequence of the short ischemic time, and thus reduced non-immunological damage to the anyways susceptible old kidney, graft-function and graft-survival in the ESP are very good. The results of the initial 5 years of this program show that it successfully utilizes more kidneys from old donors and that more old recipients are being transplanted, with a satisfactory graft-function. Increased donor- and/or recipient age require a thorough evaluation to exclude malignant and other diseases. Furthermore, short term controls on the waiting list and following kidney transplantation are prerequisites for successful transplantation in the aged recipient. If this is guaranteed, kidney transplantation in the old recipient-even with old donor organs-is a good alternative to the morbidity of a prolonged dialysis. Nevertheless, the role of HLA-matching should be reconsidered to reduce rejections.

Aged↗
PubMed2003

[Occurrence, diagnostics and therapeutic management of hydronephrosis in pediatric patients in Germany].

As urinary tract obstruction in children may impair renal function, the early detection and evaluation of the degree of obstruction using adequate diagnostic tools is necessary for the choice of the optimal therapeutic procedure. This study describes diagnostic and therapeutic standards in relation to the quality of management of pediatric hydronephrosis in Germany in the first 6 months of the year 2000. In our study 407 of 711 (57.2%) children with a hydronephrotic condition were detected by routine ultrasound. This, and the fact that 25% of the patients, who were prenatally detected, had a diagnosis of vesicoureteral reflux, underlines the importance of this routine procedure. Our study illustrates the panel of diagnostic and therapeutic procedures used in the management of pediatric hydronephrosis in Germany.

Adolescent↗
PubMed2003

Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats.

INTRODUCTION: Resuscitation from cardiac arrest (CA) often results in a poor neurological outcome possibly due to an incomplete understanding of the pathophysiology of brain injury following CA-induced global cerebral ischemia. Brain edema is an important manifestation after CA and is associated with significant morbidity and mortality. The matrix metalloproteinases (MMPs) contribute to brain edema formation following focal cerebral ischemia. The objective of this study was to investigate the role of an MMP inhibitor, GM6001, in CA-elicited brain edema. METHODS: Eighteen rats were subjected to normothermic (37.5 +/- 0.5 degrees C) CA induced by eight minutes of asphyxiation and assigned to a CA-control group (CA), an alcohol-placebo group (CA + ETOH), or a GM6001-treated group (CA + GM6001). GM6001 in 100% alcohol or a vehicle was given i.v. before CA to achieve a whole blood concentration of 10 microM. Animals were resuscitated with CPR, ventilation and epinephrine. Brain edema was determined by brain wet-to-dry weight ratio at one hour after resuscitation. FINDINGS: Brain wet-to-dry weight ratio was 4.86 +/- 0.09 in CA, 4.76 +/- 0.12 in CA + ETOH (p = 0.30 vs. CA), and 4.72 +/- 0.03 in CA + GM6001 (p = 0.17 vs. CA and 0.42 vs. CA + ETOH). INTERPRETATION: MMPs are not involved in brain edema formation one hour following CA.

Animals↗
PubMed2002

Haptic interaction with highly detailed objects.

Haptic exploration of detailed models from patient specific anatomical structures places high demands on computational resources. Constant collision detection and correct calculation of forces fed back to the operator quickly exceed available processing power with increasing level of detail of the represented objects. To alleviate the strain on computational resources optimisation schemes are employed to speed up processing and guarantee glitch-free operation as well as smooth haptic feedback. Among these are the generation of a local haptic model, a look-ahead strategy to increase its range of validity, small world-shift operations and force extrapolation algorithms for smooth feedback.

Algorithms↗
PubMed2001

Do serum C-reactive protein measurements help to discriminate episodes of renal dysfunction in patients after renal transplantation?

INTRODUCTION: This study investigated whether serial daily measurements of serum C-reactive protein (sCRP) could help differentiate episodes of transplant dysfunction due to rejection, infection, cyclosporine A (CsA) nephrotoxicity, or acute tubular necrosis (ATN) in renal-allograft recipients. MATERIALS AND METHODS: Morning serum was obtained daily from 134 patients during the first 30 days after renal transplantation. All episodes of graft dysfunction were recorded and differentiated with transplant biopsies. CRP concentrations were correlated with post-operative graft function and the various causes of graft dysfunction. RESULTS: All patients showed an increase in sCRP in response to surgery, with a maximum on day 2 after transplantation. The sCRP concentration was significantly higher in patients with delayed graft function (mean 61.50 microg/ml) than in patients with primary graft function (mean 38.01 microg/ml) (p=0.001). Bacterial infections other than asymptomatic bacteriuria (mean sCRP 33.98 microg/ml), interstitial graft rejection (mean sCRP 16.43 microg/ml), and ATN (mean sCRP 30.50 microg/ml) were accompanied by significant increases in sCRP compared with uneventful courses. sCRP was unchanged in the presence of viral infections or CsA toxicity. CONCLUSION: Serial sCRP measurements help to identify renal-transplant dysfunction of different origins. However, rejection, infection and ATN show similar patterns of sCRP increase. Thus, sCRP is unable to discriminate the causes of renal-graft dysfunction. Biopsy remains the gold standard for the differential diagnosis of renal-allograft dysfunction.

Adolescent↗
PubMed2001

Sequencing and tissue distribution of the canine MRP2 gene compared with MRP1 and MDR1.

The effects of xenobiotic drugs and toxic compounds depend largely on their kinetic properties, which can be influenced by transmembrane drug transporters like MDR1/P-glycoprotein and the drug-conjugate transporters multidrug resistance protein (MRP) 1 and 2. As the dog is a preferential species used in the pharmacological and toxicological evaluation of new drugs, we sequenced the canine MRP2 cDNA and investigated its expression in various canine tissues compared with the related transporters MRP1 and P-glycoprotein. The tissue distribution pattern of these ABC-transporters differs partially from the distribution described in humans. So we found relatively high renal and low hepatic canine MRP2 expression levels, relatively high hepatic canine MRP1 expression levels, and quite high levels of MRP1 and P-glycoprotein in the dog brain. The knowledge of the tissue distribution pattern of these transporters will aid to interpret pharmacokinetic and toxicokinetic data gained from dog studies and to extrapolate them to humans.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

[Side-fire laser coagulation of the prostate with the neodymium:YAG-laser. Long-term outcome].

Transurethral laser prostatectomy has been widely used in patients with benign prostatic obstruction (BPO) with good short-term results and an excellent safety profile. We investigated how stable the results of side-firing visual laser coagulation of the prostate are during long-term follow-up to evaluate whether laser prostatectomy can really be an alternative to transurethral resection of the prostate (TURP). Between January 1993 and December 1995 a total of 59 patients underwent visual transurethral side-firing laser coagulation of the prostate (Urolase, Bard Inc., Murray Hill, NJ, USA). The patients were monitored at 1, 3, 6, and 12 months and then reevaluated after a mean of 33 months. As expected, at the 1-year follow-up there was a significant improvement in peak flow rate, post-void residual urine, international prostate symptom score (IPSS) and quality of life index (QoL). After a mean of 33 months, 15% of the patients required reoperation due to persistent BPO. In the remaining patients, peak flow rate and post-void residual urine were stable. However, the QoL index increased during long-term follow-up and no longer differed from the preoperative value after 33 months. The side-firing laser coagulation of the prostate does not seem to be a sufficient therapeutic alternative to TURP in the treatment of BPO.

Aged↗
PubMed2001

Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution.

The multidrug resistance protein 1 (MRP1) belonging to the ATP-binding cassette (ABC) superfamily of transport proteins can confer resistance to multiple natural product drugs and methotrexate in human tumor cells. In addition, MRP1 is expressed in normal tissues acting as an efflux pump for glutathione, glucuronate, and sulfate conjugates and may thus influence the pharmacokinetic properties of many drugs. Using polymerase chain reaction-single-strand conformation polymorphism analysis, we screened 36 Caucasian volunteers for mutations in the coding exons of the MRP1 gene, including the adjacent intron sequences. Among several mutations found, two are expected to cause amino acid substitutions. One of these mutations (G671V) was of special interest because it is located near the first nucleotide binding domain. To determine whether this mutation caused a change in the MRP1 phenotype, a mutant MRP1 expression vector was constructed and transfected into SV40-transformed human embryonic kidney cells (HEKSV293T) and the transport properties of the mutant protein were examined. Transport of the MRP1 substrates leukotriene C4, 17beta-estradiol 17beta-(D)-glucuronide, and estrone sulfate by membrane vesicles prepared from transiently transfected HEKSV293T cells was comparable to that of wild-type MRP1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction.

AIM: To develop a fast fluorometric screening assay based on vincristine resistant Caco-2 cells (Caco-2VCR) in order to elucidate potential P-glycoprotein (Pgp) interactions of compounds, and to characterise Caco-2VCR cells with regard to their expression of the efflux transporters Pgp, MRP1 and MRP2. METHODS: We applied the Caco-2VCR cells to a 96-well plate-based calcein AM extrusion assay. The Caco-2VCR cells were cultured as monolayers and incubated with calcein AM with/without addition of Pgp modulators. Fourteen known Pgp modulators were tested in the assay (chloropromazine, cyclosporin A, domperidone, digoxin, ivermectin, ketoconazole, loperamide, metoprolol, propranolol, progesterone, quinidine, quinine, verapamil and vincristine). For each compound an EC50 value was calculated. Protein and mRNA levels of the efflux transporters were analysed by Western blot and polymerase chain reaction techniques. RESULTS: All compounds with the exception of digoxin displayed increased calcein levels. Protein and mRNA analysis showed increased levels of Pgp after vincristine exposure, while expression of the efflux transporters MRP1 and MRP2 remained unchanged. CONCLUSIONS: The calcein AM extrusion assay applied to Caco-2VCR cells can be a valuable tool as a screening assay for new compounds and their potential interaction with P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Frequent p16/MTS1 inactivation in early stages of urothelial carcinoma of the bladder is not associated with tumor recurrence.

OBJECTIVE: p16, located at chromosome 9p21, is a negative regulator of G1 cell checkpoint and functions as tumor suppressor gene. Only few data are available on the frequency and clinical relevance of p16 alterations in Ta, T1 transitional cell carcinoma (TCC) of the bladder. We investigated 40 patients with Ta, T1 TCC of the bladder for p16 alterations (mutations, homozygote deletions, allelic loss) or reduced p16 immunoreaction. PATIENTS AND METHODS: DNA was prepared from microdissected tumor tissue from 40 patients with pTa, pT1 TCC of the bladder (pTa: 18 patients; pT1: 22 patients; grade 1: 7 patients; grade 2: 28 patients; grade 3: 5 patients). Mutation screening was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing at exon 1 and exon 2. Detection of homozygote deletions was performed using multiplex PCR. Immunohistochemistry (IHC) was performed using an anti-human monoclonal antibody (p16, Pharmingen). Allelic loss was detected by PCR using three different microsatellite markers (D9S161, D9S171, D9S319). RESULTS: SSCP and direct sequencing revealed 3 cases of base substitution which turned out to be natural polymorphisms. Homozygote deletions were not detected in any case. p16 IHC revealed reduced p16 expression (<5% positive nuclei) in 10 patients; 30 patients had a positive reaction (> or =5% positive nuclei) and 10 patients a strong positive reaction (> or =50% positive nuclei). Thirteen of 37 informative cases revealed loss of heterozygosity (LOH) with at least one marker. After a median follow-up of 23 months, 15 patients suffered from disease recurrence. Statistical analysis using Kaplan-Meier analysis and the log-rank test did not reveal significant association of recurrence-free interval and detection of LOH (p = 0.34) or p16 IHC (p = 0.9). CONCLUSIONS: We present a comprehensive evaluation of chromosome 9p21 alterations including p16 analysis and clinical follow-up data. Although p16 mutations and homozygote deletions are rarely detectable in Ta, T1 TCC, the reduction of p16 expression and the frequent hemizygote deletions at 9p21 suggest an early involvement of chromosome 9p and p16 in superficial TCC.

Carcinoma, Transitional Cell↗
PubMed2001

Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder.

PURPOSE: The prognostic relevance of p53 protein accumulation in muscle-invasive bladder carcinoma is well documented, but the prognostic relevance of p53 alterations in superficial bladder tumors remains uncertain. Immunohistochemical data are divergent, possibly because of the use of nonstandardized techniques. We therefore investigated the relevance of p53 gene point mutations and loss of heterozygosity (LOH) for tumor recurrence. The results of this molecular analysis were compared with accumulation of the p53 protein as shown by immunohistochemistry. MATERIAL AND METHODS: Representative tumor tissue was selected and microdissected from 40 patients (pTa, 18 patients; pT1, 22 patients; grade I, 7 patients; grade II, 28 patients; grade III, 5 patients). Polymerase chain reaction (PCR) was carried out with exons 5-8. All PCR products were screened for p53 mutations with temperature-gradient gel electrophoresis (TGGE). When mobility shift was observed, direct nucleotide sequencing was performed. Detection of LOH was performed with nonradioactive microsatellite analysis using three markers (TP 53, D17S513 and D17S786) on chromosome 17p. Immunohistochemistry was performed with the DO 7 antibody. Tumor samples with p53 accumulation of 5% or more positive nuclei were classified as positive. Univariate analysis for disease-free survival was performed using Kaplan-Meier analysis and the log-rank test. RESULTS: TGGE and direct sequencing detected mutations in 10 of 40 patients (2 of 18 pTa and 8 of 22 pT1 patients). LOH was detected in 11 patients. Both a mutation and LOH were detected in 3 patients. p53 immunohistochemistry detected at least 5% positive nuclei in 28 of 40 patients (70%). After a median follow-up of 26 months 14 patients suffered disease recurrence. Whereas disease-free survival did not correlate with a mutation (p = 0.77, log-rank test), LOH (p = 0.2) or a mutation in combination with LOH (p = 0.23), a positive p 53 immunoreaction was significantly associated with short disease-free survival (p = 0.009). CONCLUSION: Despite the relatively high percentage of patients with p53 gene alteration in this population no significant correlation between the detection of molecular alteration and disease recurrence could be found. We conclude that, in contrast to immunohistochemical accumulation, gene alterations play only a minor role in tumor recurrence of p53 in patients with superficial transitional cell carcinoma of the bladder, and that immunohistochemical accumulation of the p53 protein has to be explained by mechanisms other than gene mutations.

Carcinoma, Transitional Cell↗