[Urinary incontinence in older women: what can a GP do?]. / Incontinence urinaire chez la femme âgée: que faire au cabinet?

Urinary incontinence (UI) is frequent in older women but remains often neglected when they consult their physician. It is associated with numerous health and social consequences that impact on these older persons' quality of life, as well as on their health care costs. Primary care physicians should become more familiar with this frequent condition. A clinical pathway is proposed to guide them in diagnosing and managing of this debilitating condition.

Synthesis of alpha- and beta-globin directed by messenger ribonucleoprotein from rabbit reticulocytes.

The translation of globin messenger ribonucleoprotein (mRNP) obtained from high salt-washed rabbit reticulocyte ribosomes by treatment with EDTA was investigated using a cell-free system from mouse Krebs II ascites tumour cells. The messenger activity of the mRNP and the mRNA derived from it by mild deproteinization was compared in the presence and absence of reticulocyte initiation factors. Both forms gave identical products over a wide range of messenger concentration and there was no qualitative or quantitative difference in their efficiency as messengers. It is concluded that the proteins associated with polysomal mRNA do not alter the specificity of translation of alpha- and beta-globin messengers or the requirement for initiation factor.

Risk factors for the intermediate outcome of morbid obesity after laparoscopically placed adjustable gastric banding.

BACKGROUND: The overall long-term results of medical treatment for morbid obesity are poor. Surgery is the only treatment option to obtain long-term weight reduction. Analysis of risk factors for treatment success of laparoscopically placed gastric banding (LGB) has not been available until now. METHODS: Prospective study with 99 patients with LGB between January 1997 and July 2003. The parameters assessed as risk factors included onset of obesity, feeling of postprandial satiety, and initial body mass index (BMI). RESULTS: Median follow-up was 36 months (3 to 72). Independent prognostic factors of excess body weight reduction (>25%) were for the first postoperative year: onset of obesity as an adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m(2) (RR 4.76), and a BMI between 45.1 and 50 kg/m(2) (RR 3.23). After the second year, independent prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and an initial BMI <45 kg/m(2) (RR 3.03). CONCLUSION: LGB is suitable to achieve intermediate weight reduction in patients with morbid obesity. To obtain the best results, patients should be treated before they achieve a BMI >45 kg/m(2). Additionally a postprandial feeling of satiety after LGB is mandatory for good long-term results.

Expression of 1,25-dihydroxyvitamin D3 receptors in normal and psoriatic skin.

Increasing evidence suggests an immunoregulatory function of the potent steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) which has been successfully applied for treatment of psoriasis. The skin is both a site of production and a target of 1,25(OH)2D3. In vitro, 1,25(OH)2D3 inhibits proliferation and stimulates differentiation of keratinocytes. We investigated the in situ expression of vitamin D-receptors (VDR) in normal and psoriatic skin by immunochemical methods. The VDR were visualized using the monoclonal antibody (MoAb) 9A7g to the VDR and the labeled avidinbiotin technique. Immunoreactivity was consistently confined to nuclei in all skin biopsies. In normal skin specimens (n = 10) VDR antigens were expressed in keratinocytes of all epidermal layers (except those of the stratum corneum) and in cells of the epidermal appendages. Double labeling experiments with MoAb to cluster-defined antigens indicated that melanocytes and approximately 75% of Langerhans cells exhibit 1,25(OH)2D3 receptors in normal skin biopsies (n = 5). Depending on their localization in skin compartments 42-62% of CD11b+ positive macrophages and 45-75% of CD3+ T lymphocytes expressed VDR. Non-lesional psoriatic skin specimens (n = 8) revealed nearly identical staining patterns. Lesional psoriatic skin specimens (n = 8) exhibited a significant increase of VDR expression both in basal and suprabasal epidermal layers as measured by computer-assisted morphometry and showed a remarkable change of the immune cell pattern: the densitity and proportion of VDR positive T lymphocytes and macrophages were higher in the epidermal and the perivascular papillary loop compartment. These in vivo findings strongly support the hypothesis that 1,25(OH)2D3 modulates immune response and cell proliferation/differentiation in human skin.

Molecular genetics of primary congenital glaucoma in Brazil.

PURPOSE: To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG). METHODS: PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments. RESULTS: Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5'-C-C-G-G-T-A-3' as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing. CONCLUSIONS: Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5'-C-C-G-G-T-A-3' was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers.

A nitric oxide-releasing polydiazeniumdiolate derived from acetonitrile.

Acetonitrile, frequently used as a solvent in reactions of nitric oxide (NO) with amines and other nucleophiles to introduce the [N(O)NO](-) (diazeniumdiolate) functional group, has itself been shown to react with NO in the presence of strong base to yield methane trisdiazeniumdiolate (1), presumably via an intermediate trisdiazeniumdiolated imidate. Aqueous hydrolysis of 1 does not follow simple first-order kinetics and produces mixtures of NO and nitrous oxide in ratios that vary with solution pH. [reaction: see text]

[Roentgen morphological aspects of the structure of the oesophagus (author's transl)]. / Röntgenmorphologische Aspekte zum Aufbau des O sophagus.

The clinically most important disturbance of the function of esophagus is that of esophago-gastric area. Because there is up till now no recognized opinion about the mechanism of the esophago-gastric sphincter, there are a lot of theories about that. In our own radiologic studies of the esophagus we were able to demonstrate in a low percentage the intern muscularis mucosae. The structure of these intern folds of the muscularis mucosae are like a spiral line or a screw, this is in accordance with the direction of muscle bundles of the theories of "Muscular Stretch Closure Function of the Terminal Esophagus".

The Trauma Symptom Checklist for Young Children (TSCYC): reliability and association with abuse exposure in a multi-site study.

OBJECTIVE: The Trauma Symptom Checklist for Young Children (TSCYC) is a 90-item caretaker-report measure of children's trauma- and abuse-related symptomatology. It contains two reporter validity scales and eight clinical scales [Post-traumatic Stress-Intrusion (PTS-I), Post-traumatic Stress-Avoidance (PTS-AV), Post-traumatic Stress-Arousal (PTS-AR), Post-traumatic Stress-Total (PTS-TOT), Sexual Concerns (SC), Dissociation (DIS), Anxiety (ANX), Depression (DEP), and Anger/Aggression (ANG)], as well as an item assessing hours per week of caretaker contact with the child. This paper introduces the TSCYC and describes its psychometric properties in a multisite validity study. METHOD: A total of 219 TSCYCs administered by six clinician/researchers across the United States were analyzed for scale reliability and association with several types of childhood maltreatment. RESULTS: The TSCYC clinical scales have good reliability and are associated with exposure to childhood sexual abuse, physical abuse, and witnessing domestic violence. The PTS-I, PTS-AV, PTS-AR, and PTS-TOT scales were most predictive, followed by SC in the case of sexual abuse and DIS in the case of physical abuse. There were a small number of age, sex, and race effects on TSCYC scores. CONCLUSIONS: The TSCYC appears to have reasonable psychometric characteristics, and correlates as expected with various types of trauma exposure. Subject to continued validation and the development of general population norms, its use as a clinical measure is supported.

Matrix metalloproteinase-9 derived from polymorphonuclear neutrophils increases gut barrier dysfunction and bacterial translocation in rat severe acute pancreatitis.

BACKGROUND: The role of polymorphonuclear neutrophil granulocytes (PMNs) and the PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on gut barrier dysfunction in rat SAP. METHODS: SAP was induced by the injection of 5% sodium taurocholate, and anti-rat PMN serum or BB-94 were administered 48 h and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four hours after the induction of acute pancreatitis, the gut barrier dysfunction and the incidence of bacterial translocation (BT) and PMN transmigration were investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive oxygen species were evaluated by spin trap assay. RESULTS: The mucosal injury and the infiltration of PMNs into the gut tissue of rats with SAP were significantly increased in comparison with rats treated with anti-rat PMN serum or BB-94. The levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were significantly higher than those of the rats treated with anti-rat PMN serum or BB-94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in SAP. CONCLUSION: The incidence of BT in SAP was prevented by the depletion of PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in both BT and PMN transmigration in rat SAP.

Mixed-valence states formation in conformationally flexible metal-free 5,10,15,20-tetraferrocenylporphyrin and 5,10-bisferrocenyl-15,20-bisphenylporphyrin.

Metal-free 5,10,15,20-tetraferrocenylporphyrin and 5,10-bisferrocenyl-15,20-bisphenylporphyrin have been prepared and characterized by UV-Vis, MCD, (1)H, (13)C, and variable-temperature NMR, APCI- and ESI-MS, and Mössbauer spectroscopy, while their redox properties were investigated using electrochemical (cyclic voltammetry and differential pulse voltammetry), spectroelectrochemical, and chemical oxidation approaches. The electronic structure calculations at Density Functional Theory level reveal that both compounds adopt saddle conformations and the HOMOs in both complexes are predominantly metal-centered, while the LUMOs predominantly consist of porphyrin pi* orbitals. In spite of the rotational freedom of ferrocenyl substituents at room temperature, both metal-free 5,10,15,20-tetraferrocenylporphyrin and 5,10-bisferrocenyl-15,20-bisphenylporphyrin are able to form mixed-valence states upon the successive ferrocene-based two- and one-electron oxidations, respectively, as confirmed by UV-Vis, MCD, Mössbauer, electro-, and spectroelectrochemical methods, and thus, the earlier suggested (Boyd et al. Chem. Commun., 1999, 637) requirements for the formation of mixed-valence states in ferrocene-containing porphyrins should be revised.

Partial purification and characterization of heat stable protein phosphatase inhibitor-2 from rabbit reticulocytes.

Previous studies indicated that the species of type 1 and type 2 protein phosphatases (PP-1, PP-2) in rabbit reticulocytes are similar to those of rabbit skeletal muscle and rabbit liver. Reticulocyte PP-1 was found to be selectively inhibited by the heat stable protein phosphatase inhibitor-2 (I-2) from rabbit skeletal muscle. Of interest was the observation that muscle I-2 appeared to regulate protein synthesis in reticulocyte lysates by inhibiting an eIF-2 alpha phosphatase with type 1 properties. In this study we have characterized reticulocyte inhibitor-2 (I-2) and find that its properties are similar to those of skeletal muscle I-2. (i) Both I-2 species are stable to boiling and to acid treatment, and have similar chromatographic profiles on DEAE-cellulose and on Blue Sepharose CL-6B. (ii) The two I-2 species migrate electrophoretically as 26-28,000 dalton polypeptides in SDS-acrylamide gels. (iii) Both skeletal muscle I-2 and reticulocyte I-2 selectively inhibit isolated reticulocyte PP-1 and endogenous PP-1 in the lysate. (iv) Reticulocyte I-2 co-chromatographs with PP-1 on DEAE-cellulose, and over 90% of lysate I-2 can be isolated from this partially purified PP-1. (v) Both inhibitor-2 species are active in the unphosphorylated state, but upon addition to lysates, both are phosphorylated by endogenous cAMP-independent protein kinase(s). In addition a preliminary analysis using a polyclonal antibody against muscle inhibitor-1 confirmed biochemical analyses which indicate that lysates are deficient in inhibitor-1.

Inhibition of protein synthesis in reticulocyte lysates by a double-stranded RNA component in HeLa mRNA.

Double-stranded RNA (dsRNA) inhibits protein synthesis initiation in rabbit reticulocyte lysates by the activation of a latent dsRNA-dependent cAMP-independent protein kinase which phosphorylates the alpha-subunit of the eukaryotic initiation factor eIF-2. In this study, we describe a dsRNA-like component which is present in preparations of HeLa mRNA (poly A+) isolated from total cytoplasmic RNA. The inhibitory species in the HeLa cytoplasmic mRNA was detected by (a) its ability to inhibit protein synthesis with biphasic kinetics in reticulocyte lysates translating endogenous globin mRNA, and (b) by the inefficient translation of HeLa cytoplasmic mRNA in a nuclease-treated mRNA-dependent reticulocyte lysate. The inhibitory component was characterized as dsRNA by several criteria including (i) the ability to activate the lysate dsRNA-dependent eIF-2 alpha kinase (dsI); (ii) the prevention of both dsI activation and inhibition of protein synthesis by high levels of dsRNA or cAMP; (iii) the reversal of inhibition by eIF-2; and (iv) the inability to inhibit protein synthesis in wheat germ extracts which lack latent dsI. By the same criteria, the putative dsRNA component(s) appears to be absent from preparations of HeLa mRNA isolated exclusively from polyribosomes.

[Immunologic studies for the diagnosis of chronic prostatitis]. / Immunologische Untersuchungen zur Diagnose der chronischen Prostatitis.

A prospective study comparing the results of Antibody-Coating-Test (ABC) in semen and aspiration biopsy of the prostate with immunodiffusion of the former was carried out. In 143 patients with clinical signs of prostatitis only 98 showed a positive ABC in their ejaculates. IGA-specific ABC was positive in 75%, IGG-specific ABC in 48%, and IGM-specific ABC in 9.6% respectively. Specimens gained by aspiration biopsy of the prostate were also demonstrating positive ABC. Consistently negative was the ABC in 15 healthy male who served as a control. In 30 patients the ABC-Test of ejaculate speciments was compared with complement (C3) and coeruloplasmin content of the ejaculates using immunodiffusion technique. Contrary to the reports in the literature, however, elevated levels of complement (C3) and coeruloplasmin were not correlated with local infection of the prostate proven by ABC.

In situ phosphorylation of the alpha subunit of eukaryotic initiation factor 2 in reticulocyte lysates inhibited by heme deficiency, double-stranded RNA, oxidized glutathione, or the heme-regulated protein kinase.

Protein synthesis initiation in reticulocyte lysates is inhibited by heme deficiency, low levels of double-stranded RNA (dsRNA), oxidized glutathione (GSSG), or the purified kinase (HRI) that acts on the alpha polypeptide of eukaryotic initiation factor 2 (eIF-2alpha). The phosphoprotein profiles produced in lysates in response to these various conditions have been monitored directly in lysates after labeling for brief periods with pulses of [gamma-(32)P]ATP. The [(32)P]phosphoprotein profiles were analyzed by electrophoresis in sodium dodecyl sulfate/polyacrylamide slab gels under conditions in which the HRI and eIF-2alpha polypeptides were clearly distinguished. All four modes of inhibition produced a rapid phosphorylation of eIF-2alpha compared to control lysates, which displayed little or no phosphorylation of eIF-2alpha. In heme-deficient lysates, phosphorylation of eIF-2alpha occurred rapidly both before and after the shut-off of protein synthesis; the delayed addition of hemin to these lysates resulted in a decrease in the phosphorylation of eIF-2alpha and the subsequent restoration of protein synthesis. These data suggest that rapid turnover of phosphate occurs at the site(s) of eIF-2alpha phosphorylation. In lysates inhibited by heme deficiency, GSSG, or added HRI, the phosphorylation of eIF-2alpha was accompanied by the rapid in situ phosphorylation of HRI. The inhibition of initiation induced by dsRNA was accompanied by the phosphorylation of eIF-2alpha and a 67,000-dalton polypeptide but not HRI. These observations in situ indicate that (i) the phosphorylation of eIF-2alpha is the critical event in these inhibitions of protein chain initiation, and (ii) the phosphorylation of HRI is associated with its activation in heme deficiency.

Oxidative capacity distribution in the cardiac myocytes of hypermetabolic rats.

To study the distribution of oxidative capacity in the cardiac myocyte in control and in hypermetabolic (hyperthyroid) rats, we evaluated mitochondrial volume density (Vv,mi) distribution by morphometry and oxidative capacity, cytochrome a + a3 concentration and protein yield of isolated subsarcolemmal and interfibrillar mitochondria by biochemical techniques. In control animals Vv,mi underneath the sarcolemma was higher than in the center of the myocytes and it decreased linearly with increasing distance from the capillaries. Interfibrillar mitochondria showed a greater oxidative capacity and a high concentration of cytochrome a + a3 than subsarcolemmal mitochondria. Values of Vv,mi and its distribution were not changed by the hypermetabolic condition. Oxidative capacity and cytochrome a + a3 concentration were higher in the interfibrillar mitochondria but not in the subsarcolemmal mitochondria of the hypermetabolic rats. The product of the oxidative capacity of the mitochondria times the Vv,mi indicated that the oxidative capacity of the interfibrillar zone is 30% higher than that of the subsarcolemmal zone. In the hypermetabolic rats, due to the increase in oxidative capacity of the interfibrillar mitochondria, the oxidative capacity of this zone was 80% higher than that of the subsarcolemmal zone.

Separation and identification of type 1 and type 2 protein phosphatases from rabbit reticulocyte lysates.

Protein phosphatase type 1 and type 2 activities (designated PP-1 and PP-2, respectively) from rabbit reticulocyte lysates have been identified and characterized based on criteria previously established for similar activities in rabbit skeletal muscle and rabbit liver. These include (a) chromatographic separation on DEAE-cellulose, (b) substrate specificity toward glycogen phosphorylase a and the alpha- and beta-subunits of phosphorylase kinase, (c) differential sensitivity to the heat-stable protein phosphatase inhibitors-1 and -2, and (d) sensitivity to MgATP. When total lysate phosphatases are assayed in the presence of 1 mM MnCl2, protein phosphatase type 2 represents 84% of lysate phosphorylase phosphatase activity. However, when phosphatase assays are carried out with MgATP concentrations similar to those in the lysate, type 2 activity is diminished, and the levels of type 1 (41%) and type 2 (59%) phosphatase activities are comparable. A small proportion (6%) of total lysate phosphatase is tightly bound to the ribosomes, where type 1 phosphatase predominates. At least five species of protein phosphatases can be identified in lysates. These constitute two forms of protein phosphatase type 1, one of which (designated FC) is dependent on MgATP and a lysate activator protein FA; both FC and FA have been identified previously in skeletal muscle. Three species of protein phosphatase type 2 have been identified and designated PP-2B, PP-2A1, and PP-2A2 based on criteria recently established for rabbit skeletal muscle and rabbit liver phosphatases, which display similar phosphatase profiles. Lysate protein phosphatases types 1, FC, 2A1, and 2A2 can all act on phosphorylase a and the alpha- (type 2) or beta-(type 1) subunit of phosphorylase kinase. PP-2B, a Ca2+/calmodulin-dependent phosphatase, specifically dephosphorylates the alpha-subunit of phosphorylase kinase, but does not act on phosphorylase alpha. The heat-stable protein phosphatase inhibitor-2 from skeletal muscle completely blocks the activity of the two type 1 phosphatases (PP-1, FC), but has no effect on the three species of type 2 protein phosphatase. A preliminary assay of the two heat-stable phosphatase inhibitors in lysates indicates significant levels of inhibitor-2, but little or no detectable inhibitor-1.