5-year continence rates, satisfaction and adverse events of burch urethropexy and fascial sling surgery for urinary incontinence.

PURPOSE: We characterized continence, satisfaction and adverse events in women at least 5 years after Burch urethropexy or fascial sling with longitudinal followup of randomized clinical trial participants. MATERIALS AND METHODS: Of 655 women who participated in a randomized surgical trial comparing the efficacy of the Burch and sling treatments 482 (73.6%) enrolled in this long-term observational study. Urinary continence status was assessed yearly for a minimum of 5 years postoperatively. Continence was defined as no urinary leakage on a 3-day voiding diary, and no self-reported stress incontinence symptoms and no stress incontinence surgical re-treatment. RESULTS: Incontinent participants were more likely to enroll in the followup study than continent patients (85.5% vs 52.2%) regardless of surgical group (p<0.0001). Overall the continence rates were lower in the Burch urethropexy group than in the fascial sling group (p=0.002). The continence rates at 5 years were 24.1% (95% CI 18.5 to 29.7) vs 30.8% (95% CI 24.7 to 36.9), respectively. Satisfaction at 5 years was related to continence status and was higher in women undergoing sling surgery (83% vs 73%, p=0.04). Satisfaction decreased with time (p=0.001) and remained higher in the sling group (p=0.03). The 2 groups had similar adverse event rates (Burch 10% vs sling 9%) and similar numbers of participants with adverse events (Burch 23 vs sling 22). CONCLUSIONS: Continence rates in both groups decreased substantially during 5 years, yet most women reported satisfaction with their continence status. Satisfaction was higher in continent women and in those who underwent fascial sling surgery, despite the voiding dysfunction associated with this procedure.

Tolterodine extended release is well tolerated in older subjects.

OBJECTIVES: To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB). METHODS: This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8-12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65-74 (n = 1059) and > or = 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms. RESULTS: Discontinuation rates were slightly higher among subjects > or = 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65-74 or > or = 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment x age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65-74 years, 16%; > or = 75 years, 15%). The occurrence of all other AEs was < or = 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts. CONCLUSION: The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.

A finite element formulation for atrial tissue monolayer.

OBJECTIVES: Using computer models for the study of complex atrial arrhythmias such as atrial fibrillation is computationally demanding as long observation periods in the order of tens of seconds are required. A well established approach for reducing computational workload is to approximate the thin atrial walls by curved monolayers. On the other hand, the finite element method (FEM) is a well established approach to solve the underlying partial differential equations. METHODS: A generalized 2D finite element method (FEM) is presented which computes the corresponding stiffness and coupling matrix for arbitrarily shaped monolayers (ML). Compared to standard 2D FEM, only one additional coordinate transformation is required. This allows the use of existing FEM software with minor modifications. The algorithm was tested to simulate wave propagation in benchmark geometries and in a model of atrial anatomy. RESULTS: The ML model was able to simulate electric activation in curved tissue with anisotropic conductivity. Simulations in branching tissue yielded slightly different patterns when compared to a volumetric model with finite thickness. In the model of atrial anatomy the computed activation times for five different pacing protocols displayed a correlation of 0.88 compared to clinical data. CONCLUSIONS: The presented method provides a useful and easily implemented approach to model wave propagation in MLs with a few restrictions to volumetric models.

Rapid inactivation of bacteriophage T7 by ascorbic acid is repairable.

Treatment of bacteriophage T7 with ascorbic acid resulted in the rapid accumulation of single-strand breaks in the DNA with double-strand breaks appearing only after incubation times of 20 min or longer. The single-strand breaks were responsible for a rapid inactivation of the phage as assayed by immediate plating of the phage-bacteria mixture on nutrient agar. Incubation of the phage-bacteria mixture in liquid medium prior to plating allowed a host cell reactivation process to repair the nicks and reactivate the phage. Non-reversible inactivation of the phage was a slower process which could be correlated with the appearance of double-strand breaks in the phage DNA. Host cell reactivation of the phage was also manifested in the phenomena of delayed lysis and delayed appearance of the concatemeric DNA replication intermediate.

A psychophysical study of discomfort produced by repeated filling of the urinary bladder.

Psychophysical studies were performed in 10 healthy, female volunteers using urinary bladder distension (UBD) as a visceral stimulus. Stimulus methodology was similar to that used clinically for obtaining cystometrograms with a fixed-rate (100 cc/min normal saline) filling of the urinary bladder, occasional pauses and simultaneous measure of bladder pressure using a catheter-transducer assembly. During bladder filling, subjects were asked to report sensations by verbal report and by using an electronic, hand-held, visual-analog-scale device. Sensations evoked by UBD were generally localized to the suprapubic region. UBD produced cardiovascular responses which increased with repeated trials. Sensation intensity increased with repeated UBDs as indicated by global pain ratings. Intravesical pressure and volume correlated with sensation intensity. The volume of distending fluid needed to produce a report of discomfort was highly variable from trial to trial and did not change significantly with repeated UBDs. The intravesical pressure which produced a report of discomfort was less variable and significantly decreased with repeated UBDs. The change in intravesical pressure and volume needed to produce discomfort was inversely correlated with initial intravesical pressure measures. Similar to findings in other organ systems, these findings demonstrate that repeated presentations of a visceral stimulus may lead to an increase in physiological and perceptual responses to pain.

The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation.

GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.

Instability of microsatellites in radiation-associated thyroid tumours with short latency periods.

PURPOSE: To determine the instability of microsatellite sequences in post-Chernobyl thyroid tumours from children and young adults, and to ascertain whether they correlated with the age of the patient at the time of the accident and the tumour latency period. MATERIALS AND METHODS: The stability of 26 microsatellite markers was investigated in 122 radiation-associated thyroid tumours (96 children, 26 adults) from Belarus and 39 spontaneous thyroid tumours (adults) from Munich without radiation history. RESULTS: A significant correlation between patient age at the time of the accident and the instability of microsatellite sequences was established. Also, a high instability of microsatellite sequences was found in 28 early thyroid tumours from Belarus with latency periods of 6-8 years, in contrast to a low instability of microsatellites in 94 tumours emerging 9-11 years after the accident. Microsatellite instability in the reference group from Munich proved similar to the early thyroid tumours from Belarus. CONCLUSION: Early, fast-growing and aggressive post-Chernobyl thyroid tumours are characterized by an increase in microsatellite instability.

Protein metabolism in chicken muscle cell cultures treated with cimaterol.

Primary muscle cell cultures were prepared from the leg muscle of 12-d broiler chicken embryos. The partitioning agent cimaterol (10(-6) to 10(-10) M) was added on d 1 and each day thereafter, and cells were studied after 7 d in culture. Cimaterol had no effect at any level either on the percentage of nuclei within multinucleated myotubes or on the total number of nuclei within myotubes. At 10(-7) M cimaterol, the quantity of the myofibrillar protein fraction was increased by 25.1 +/- 8.0% (P less than .05) and the quantity of myosin heavy chain was increased by 30.9 +/- 4.5% (P less than .05). To understand the basis for the increase in myofibrillar protein, the incorporation rate of [3H]Leu was measured in pulse labeling experiments. The apparent synthesis rate of the soluble protein fraction and the crude myofibrillar fraction was not significantly increased by cimaterol; however, cimaterol levels greater than 10(-8) M caused a 10 to 12% increase (P less than .05) in the incorporation rate of [3H]Leu into myosin heavy chain. The effect of cimaterol on release of [3H]Leu from prelabeled protein also was assessed in pulse-chase experiments; the apparent rate of protein degradation was inhibited by 10 to 15% (P less than .05) at the higher levels of cimaterol. Dot blot analysis indicated that the quantity of myosin heavy chain mRNA was elevated in cimaterol-treated cultures. Thus, the increased quantity of myofibrillar proteins in embryonic broiler muscle cell cultures is the combined result of a stimulation in the rate of protein synthesis and an inhibition in the rate of protein degradation.

Expression pattern and partial sequence analysis of a fetal bovine myosin heavy-chain gene.

A fragment of a bovine myosin heavy-chain (MHC) gene approximately 15 kbp in size (designated MHC 67) was isolated from a bovine genomic DNA library. The direction of transcription was determined, and preliminary experiments indicated that the gene was expressed in fetal skeletal muscle. The expression pattern of this gene was, therefore, evaluated in detail using northern blots containing RNA from eleven different bovine muscle and nonmuscle tissues at three developmental ages. A restriction fragment of clone MHC 67 containing the 3' untranslated sequence (which is specific for each MHC gene) was used as a probe. This gene fragment hybridized predominantly to RNA from fetal skeletal muscles and did not hybridize to RNA from either neonatal or adult skeletal muscles (red or white), smooth muscle tissue, or nonmuscle tissue. A 7-kb EcoRI fragment containing both translated and untranslated regions surrounding the 3' end of the gene was subcloned into pBluescript II KS+ and partially sequenced. When these bovine sequences were aligned to that of the human and rat skeletal and cardiac MHC genes, we found that these sequences corresponded to exons 31, 32, and 33, and that they had homology with human perinatal and fetal MHC as high as 90% at the nucleotide level and 97% at the amino acid level. Comparison of the nucleotide sequences of isoform-specific 3' nontranslated regions from bovine, human, and rat genes further verify that the MHC 67 clone encodes the bovine fetal or perinatal MHC isoform.

Screening of a bovine genomic library for myosin heavy-chain genes.

Restriction enzyme digests of bovine genomic DNA were hybridized against a .37-kilobase (kb) quail embryonic myosin heavy-chain (MHC) copy deoxyribonucleic acid (cDNA) probe; containing both translated and nontranslated regions surrounding the 3' end of the gene. These experiments revealed seven to eight different bands of hybridization, indicative of multiple genes of MHC in the bovine genome. Additionally, a bovine genomic recombinant DNA library was screened with the .37-kb probe. Of the 10(6) phage screened, 11 clones containing portions of the MHC genome were identified, and four were selected for further analyses. Characterization of these four clones was carried out by constructing partial restriction enzyme maps of the inserts using six restriction enzymes singly or in combination. Orientation of the inserts with respect to the arms of the vector and with respect to direction of transcription was determined by hybridizing the DNA fragments against either the .37-kb Pst 1 fragment of pcC128 or to the .23-kb Pst I fragment of pcC128. The .23-kb fragment is located upstream from the .37-kg fragment and contains only coding sequence. Therefore, the differential hybridization pattern of these two probes provided a means for determining the probable direction of transcription. These data provide evidence for a myosin multigene family in cattle, as well as illustrating that the organization of these genes around the 3' end is unique for each of the genes analyzed.

[Self-criticism and reconciliation capacity]. / Selbstkritik und Versöhnungsfähigkeit.

With reference to empirical socio-psychological studies conducted by the author himself (on prejudices in connection with AIDS, inquiries into attitudes displayed by German and Russian students) and the results of opinion polls on xenophobia, racism and nationalism, the author demonstrates that reconciliation with oneself and others is proportional to the propensity for self-criticism and the ability to recognize and acknowledge personal guilt. Where, by contrast, self-hatred and self-devaluation prevail, the tendency towards projection and hatred of others will also be dominant.