[Clinical and urodynamic experience with intravesical hyaluronic acid in painful bladder syndrome associated with interstitial cystitis]. / Experiencia clínica y urodinámica con ácido hialurónico intravesical en el síndrome de vejiga dolorosa asociado a cistitis intersticial.

INTRODUCTION: few studies have been carried out on therapeutic options in patients with painful bladder syndrome associated with interstitial cystitis. The aim is to verify the safety and effectiveness of treatment with sodium hyaluronate through intravesical instillation in patients with painful bladder syndrome. MATERIALS AND METHODS: a series of 18 female patients is presented, with a mean age of 51 years and prior diagnosis of painful bladder syndrome, who were treated by means of the weekly infusion of an intravesical solution of 40mg of sodium hyaluronate in sterile solution, over a period of eight weeks. The patients were examined clinically and urodynamically prior to their inclusion in the study and eight months after the instillations had concluded. RESULTS: there was a statistically significant improvement in the urodynamic parameters and in the symptoms measured quantitatively by means of the questionnaire "Pelvic Pain and Urgency/Frequency" between the baseline situation and after the vesical instillation of sodium hyaluronate in patients with painful bladder syndrome. There was no toxicity arising from the treatment, given that no adverse effects were recorded in relation to it. CONCLUSION: the clinical use of intravesical hyaluronic acid in patients with painful bladder syndrome possibly associated with interstitial cystitis has been demonstrated. The clinical improvement is also associated both with increased bladder capacity and improved bladder sensitivity. Tolerance was excellent. Clinical tests that more profoundly evaluate the therapeutic potential of this drug in this type of patients are required.

The heterogeneity of segmental dynamics of filled EPDM by (1)H transverse relaxation NMR.

Residual second moment of dipolar interactions M(2) and correlation time segmental dynamics distributions were measured by Hahn-echo decays in combination with inverse Laplace transform for a series of unfilled and filled EPDM samples as functions of carbon-black N683 filler content. The fillers-polymer chain interactions which dramatically restrict the mobility of bound rubber modify the dynamics of mobile chains. These changes depend on the filler content and can be evaluated from distributions of M(2). A dipolar filter was applied to eliminate the contribution of bound rubber. In the first approach the Hahn-echo decays were fitted with a theoretical relationship to obtain the average values of the (1)H residual second moment and correlation time <τ(c)>. For the mobile EPDM segments the power-law distribution of correlation function was compared to the exponential correlation function and found inadequate in the long-time regime. In the second approach a log-Gauss distribution for the correlation time was assumed. Furthermore, using an averaged value of the correlation time, the distributions of the residual second moment were determined using an inverse Laplace transform for the entire series of measured samples. The unfilled EPDM sample shows a bimodal distribution of residual second moments, which can be associated to the mobile polymer sub-chains (M(2) ≅ 6.1 rad (2) s(-2)) and the second one associated to the dangling chains M(2) ≅ 5.4 rad(2) s(-2)). By restraining the mobility of bound rubber, the carbon-black fillers induce diversity in the segmental dynamics like the apparition of a distinct mobile component and changes in the distribution of mobile and free-end polymer segments.

[Overactive bladder symptoms in pregnancy and puerperium: is there a relationship between the symptoms score and quality of life?]. / Síntomas de vejiga hiperactiva en mujeres en fase gestacional y puerperal: ¿existe correlación entre los síntomas y la percepción de la calidad de vida?

INTRODUCTION AND OBJECTIVE: During pregnancy, hormonal change, increase in the body mass index and the pressure caused by the enlarged uterus over the bladder and pelvic floor, are some factors involved in lower urinary tract symptoms (LUTS). This study was made to evaluate the correlation between pregnancy and delivery way with LUTS. MATERIAL AND METHOD: This open prospective study was carried out using the overactive bladder questionnaire short form (OABq-SF). A total of 60 patients enrolled this study. The mean age was 24 year, raging from 14 to 40 years. The patients were evaluated during the third trimester and 6 months after delivery. Statistical analysis of the OABq-SF scores was made using the Pearson method. RESULTS: Mean OABq-SF score during pregnancy was 35.2 and 6 months after delivery decreased to15. Quality of life was 82.9 during pregnancy and increased to 88.4 at 6 month after delivery. Patient's perception, that is correlation, was 55.02 (p=0.0001) during pregnancy and 36.1% (p=0.0046). Clinical correlation index was 6.7%. CONCLUSIONS: Our study demonstrated that in spite of LUTS being more important during pregnancy, there is no significant clinical correlation in patient's perception.

[Impact of sacrospinous vaginal vault suspension on the anterior compartment]. / Impacto de la suspensión de la cúpula vaginal al ligamento sacroespinoso sobre el compartimiento anterior.

OBJECTIVES: A prospective study was conducted to assess the efficacy of sacrospinous vaginal vault fixation and its impact on the anterior compartment. The Pelvic Organ Prolapse Quantification (POP-Q) system was used to quantify pelvic organ prolapse in the apical and anterior vaginal compartments. METHODS: Fifty-eight patients underwent a procedure to correct apical prolapse from March 2003 to February 2006. Mean preoperative and postoperative POP-Q scores were respectively: Aa (+0.74; -1.45); Ba (+3.17; -1.36); C (+3.41; -7.71) (p<0.001). RESULTS: Cure rate was 93.1%. Preoperative and postoperative evaluation of the anterior vaginal compartment was respectively: stage 1 (5.2%; 48.3%), stage 2 (6.9%; 34.5%), stage 3 (74.1%; 5.2%), and stage 4 (13.8%; 0%). De novo cystocele occurred in 87.9% of cases. An improvement was seen in lower urinary tract symptoms of urgency, nocturia, and urge incontinence. CONCLUSIONS: Sacrospinous vaginal vault suspension is effective for the treatment of apical prolapse and leads to formation of cystocele in most cases.

Impact of pregnancy and childbirth on female rats' urethral nerve fibers.

This study aims to evaluate the urethral nerve fibers of adult female rats during pregnancy and after vaginal birth, cesarean section or simulated birth trauma. For immunohistochemical analysis of nerve fibers, 70 female rats were distributed in seven groups of ten female rats: group 1, control; group 2, pregnant; group 3, cesarean section; group 4, vaginal birth; group 5, virgin female rats with simulated birth trauma; group 6, cesarean section followed by simulation of birth trauma; and group 7, vaginal birth followed by simulation of birth trauma. The number of nerve fibers in groups 1, 2, and 3 were significantly higher than the other groups. Pregnancy and cesarean section did not cause alterations in the nerve fibers number. Vaginal birth and simulated birth trauma significantly decreased the number of nerve fibers in the female rats' middle urethra.

The impact of pregnancy and childbirth in the urethra of female rats.

The aim of this study was to evaluate the modifications in the amount of collagen, muscular, and elastic fibers in the mid-urethra of adult female rats during the pregnancy and after the natural childbirth, cesarean, and after simulated trauma of childbirth. The authors evaluated the histomorphometric aspects (collagen, muscular, and elastic fibers) in the mid-urethra of 70 animals distributed in seven groups: group 1 (n = 10)--control, group 2 (n = 10)--pregnant female rats, group 3 (n = 10)--female rats submitted to cesarean, group 4 (n = 10)--female rats with natural childbirth, group 5 (n = 10)--virgin female rats with simulated trauma of childbirth, group 6 (n = 10)--female rats submitted to cesarean followed by simulation of childbirth trauma, and group 7 (n = 10)--female rats with natural childbirth followed by simulation of childbirth trauma. The average concentration of collagen and elastic fibers and the collagen/muscular fiber correlation in groups 1, 2, and 3 were similar and significantly inferior to groups 4, 5, 6, and 7. The average of muscular fibers was similar in groups 1, 2, and 3 and significantly superior to groups 4, 5, 6, and 7. Pregnancy and cesarean did not induce alterations in collagen, muscular, and elastic fibers. However, the vaginal delivery and simulation of childbirth trauma determined the decrease in muscular fibers and the increase in collagen and elastic fibers and the correlation collagen/muscular fiber.

Prevalence and correlates of stress urinary incontinence during pregnancy: a survey at UNICAMP Medical School, São Paulo, Brazil.

The aim of this study was to evaluate the prevalence of stress urinary incontinence (SUI) in women in the third trimester of pregnancy. In total, 340 patients attending the Antenatal Clinic at the State University of Campinas (UNICAMP) were interviewed. Overall, 170 women (50%) presented SUI. Stress urinary incontinence did not correlate to either body mass index (BMI) or race. There was no correlation between parity and SUI, but when considering distinct types of effort, urine leakage on coughing (P = 0.0478) and laughing (P = 0.0046) were highly more frequent in multiparous women. One hundred eleven women had had only vaginal deliveries and 68 delivered by cesarean section. There was no difference between the two groups concerning incontinence, but multiparous women (> or = 4) who delivered exclusively vaginally demonstrated 2.0 times more chances to leak urine when compared to nulliparous women. This fact strongly suggests parity to be more relevant than delivery route as a risk factor to stress urinary incontinence. Nulliparous women presented with a high percentage (45.5%) of the symptom, emphasizing the elevated risk of SUI during first pregnancy.

[Transobturator correction of cystocele]. / Corrección transobturatoria de los cistoceles.

OBJECTIVE: We present our initial experience with the Perigee system for anterior vaginal wall prolapses repair. MATERIAL AND METHOD: 15 patients with anterior vaginal wall prolapse (mean age: 62 years old) underwent implanted with Perigee system which is composed by a mesh for correcting central defect and four self-attached horns for correcting lateral defect. The implanted procedure consist of four steps: 1) lateral vaginal wall dissection as far as isquiopubic branch; 2) performance of two upper marks at genitofemoral fold and two lower marks at 2 cm laterally and 3 cm lower; 3) insertion of the upper needles parallel to the isquiopubic branch and connection with the mesh's "arms" plus insertion of the lower needles vertically and connection with mesh's "legs"; 4) to adjust the mesh free tension. The system POP-Q was used as an objective measure of correction rate. RESULTS: Preoperatively, the point Aa was 0.09. After 6 weeks and three months postoperatively was -3.00 and -2.73 respectively. Preoperatively, the point Ba was 1.73. After 6 weeks and three months postoperatively was -2.82 and -2.82 respectively. No major complications were presented. No vascular damage or significant bleeding was observed. CONCLUSION: The transobturator correction of cystocele is an attractive alternative. The initial good outcome may be expected to be long lasting.

Urethral resistance measurement: a new method for evaluation of stress urinary incontinence in women.

The aim of this study was to evaluate a new method to measure urethral resistance among 66 women with urinary incontinence. A stainless steel sphere attached to a guide wire was developed. The sphere is inserted into the bladder and withdrawn through the urethra at a steady rate. Serial measurements with spheres of 5, 6 and 7 mm were performed. The mean urethral resistance as measured by the largest sphere (0.07+/-0.03) was significantly greater than that measured by the medium sphere (0.06+/-0.02, p<0.0001), which was significantly larger than that measured by the smallest sphere (0.04+/-0.01, p<0.0001). There was good correlation of urethral resistance with maximum urethral closure pressure (MUCP) by this technique, but no correlation with Valsalva leak point pressure (VLPP).

[SAFYRE. A new concept for adjustable minimally invasive sling for female urinary stress incontinence]. / SAFYRE. Un nuevo concepto de cabestrillo ajustable mínimamente invasivo para la incontinencia urinaria por estrés femenina.

INTRODUCTION: SAFYRE is a new readjustable and minimally invasive sling for the treatment of stress urinary incontinence (SUI). Attempts to restore the normal suburethral hammock using an anatomical approach have been made in recent years. The authors report their experience with this device, which associates the efficacy of slings with readjustability. MATERIAL AND METHODS: A total of 100 consecutive patients with clinical and urodynamic diagnosis of SUI underwent SAFYRE sling procedure. The age range was from 40 to 71, mean age 63 years. Seventy-five patients (75%) presented previous failed anti-incontinence procedures. Physical clinical examination, stress test, pad use and a urodynamic study were performed before the surgery. All the patients presented symptoms of SUI and 30% also reported mild urgency. RESULTS: The average follow up period was 14 months (12-30 months). The mean operative time was of 25 minutes. Dystopia repair was performed whenever necessary, during the same procedure. The average hospital stay was 24 hours. In 3% of the implants, bladder perforation occurred. During the postoperative period, 26 patients developed urgency symptoms. During that follow up period, 92% were found to be continent, 3% reported an improvement and 5% were dissatisfied. CONCLUSION: SAFYRE is a safe and quick procedure that allows for postoperative readjustment. This technique may be an attractive alternative if the good result obtained so far proves to be long lasting.

Urodynamics in climacteric women with urinary incontinence: correlation with route of delivery.

The aim of this study was to compare the urodynamic findings among climacteric women complaining of urinary incontinence who had only vaginal deliveries with those who had only cesarean sections. The study group comprised 30 climacteric women with complaints of urinary incontinence consulting at the Menopause Outpatient Clinic, State University of Campinas, submitted to anamneses and complete urodynamic testing. Nineteen women had had only vaginal deliveries and 11 were delivered only by cesarean section. Vaginal delivery was significantly associated with a reduced normal and strong desire to void and maximum cystometric capacity compared to women who delivered only by Cesarean section. Detrusor instability was four to five times more frequent among women who had had only vaginal deliveries. There was no difference between the two groups concerning uroflowmetry parameters. Climacteric women with urinary incontinence who had had only vaginal deliveries are at a higher risk of urodynamic abnormalities.

Urinary tract infections: pathogenesis and related conditions.

This paper deals with main aspects of pathogenesis of urinary tract infection (UTI). Bacterial and host-related factors such as defense mechanisms and predisposing factors are described. Special aspects of UTI in elderly patients and during pregnancy are discussed. Recurrent cystitis and prophylactic measures are also reported.

Pancytopenia after removal of copper from total parenteral nutrition.

Patients who develop cholestatic jaundice during chronic total parenteral nutrition (TPN) can develop significant hematologic complications due to hypocupremia if copper supplementation is withheld. A 36-year-old female with short bowel syndrome developed progressive liver dysfunction 6 months after initiation of TPN. Trace elements were omitted from her TPN because of cholestasis and persistent hyperbilirubinemia. Despite chronic diarrhea, absorption of some dietary copper was anticipated from her oral diet. Fifteen months later, the patient became red cell transfusion dependent, and her neutrophil and platelet counts steadily declined. After 19 months of receiving TPN without trace elements, her serum copper level was 25 microLg/dL (normal: 70 to 155 microg/dL). Provision of trace elements for 2 months was associated with increased serum copper, neutrophil and platelet counts and independence from red cell transfusions. When the serum copper level reached 186 microg/dL, copper supplementation was discontinued. Over the next 3 months, serum copper level fell to 10 microg/dL, neutrophil and platelet counts fell precipitously, and red cell transfusions were resumed. Once again, copper, neutrophil and platelet levels promptly rebounded with parenteral copper supplementation. Although anemia and neutropenia are well-recognized hematologic consequences of copper deficiency, thrombocytopenia rarely has been reported. This is the first report of pancytopenia secondary to TPN-related copper deficiency in which the association was confirmed when hypocupremia recurred.

beta-adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells.

beta-Adrenergic receptor (betaAR) activation and/or increases in cAMP regulate growth and proliferation of a variety of cells and, in some cells, promote cell death. In the current studies we addressed the mechanism of this growth reduction by examining betaAR-mediated effects in the murine T-lymphoma cell line S49. Wild-type S49 cells, derived from immature thymocytes (CD4(+)/CD8(+)) undergo growth arrest and subsequent death when treated with agents that increase cAMP levels (e.g., betaAR agonists, 8-bromo-cAMP, cholera toxin, forskolin). Morphological and biochemical criteria indicate that this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells, which lack G(s)alpha and functional protein kinase A (PKA), respectively, betaAR activation of G(s)alpha and cAMP action via PKA are critical steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cAMP-induced apoptosis. We conclude that betaAR activation induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while overexpression of Bcl-2 prevents cell death. betaAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.

Comparative pharmacodynamics and pharmacokinetics of candesartan and losartan in man.

The angiotensin II antagonistic effects of candesartan and losartan were compared in-vivo after single and repeated doses. Effects were related to antagonistic activity in plasma. In this double-blind, crossover study, 12 healthy male volunteers received, in random order, daily oral doses of 8 mg candesartan cilexetil or 50 mg losartan for seven days. On day 1 and day 8, dynamics and kinetics were assessed up to 48 h after dosing. Antagonistic effect was determined from the antagonist-induced rightward shifts of the diastolic blood pressure response curves to exogenously administered angiotensin II measured as the dose ratio (DR). The antagonistic activity in plasma was measured using an ex-vivo/in-vitro radioreceptor assay. Specific high-performance liquid chromatography assays determined plasma concentrations of candesartan, losartan and its active metabolite EXP-3174. The pharmacokinetic properties of candesartan and losartan were comparable and antagonistic activity in plasma almost identical (ratio candesartan: losartan = 0.97 and 1-2 after single and multiple doses, respectively). However, the antagonistic effects of candesartan and losartan in-vivo were quite different. Twenty-four hours after single dosing with candesartan a clinically relevant rightward shift in the angiotensin II dose-response curve (DR= 3.2) occurred that was more pronounced than that following losartan administration (DR=2.1, ratio candesartan: losartan= 1.65). Twenty-four hours after multiple doses of candesartan or losartan, the values of the DR were 4.8 and 2.3, respectively (ratio candesartan: losartan = 1.94). The values of DR for candesartan were significantly higher compared with losartan between 6 and 36h after a single dose and between 3 and 24 h post-dose following multiple dose administration. A counter-clockwise hysteresis was apparent between antagonistic activity in plasma and antagonistic effect. Despite equivalent angiotensin II antagonistic activity in plasma, the pharmacodynamic effect of candesartan cilexetil was greater than that of losartan. Candesartan appeared to have a slower off-rate from the angiotensin AT1-receptor compared with losartan, nevertheless differences in distributional phenomena or the extent of insurmountable antagonistic activity cannot be ruled out.

Beta2-adrenergic receptor polymorphisms at codon 16, cardiovascular phenotypes and essential hypertension in whites and African Americans.

Beta2-adrenergic receptors (beta2-AR) contribute to cardiovascular regulation by influencing several functions and previous studies suggest that a decreased function of the beta2-AR may be involved in essential hypertension. Beta2-AR are polymorphic and certain polymorphisms of these receptors are of functional importance. We focus here on the Arg16-->Gly16 beta2-AR polymorphism, which shows enhanced agonist-promoted downregulation of the receptor and which, in two recent studies, yielded opposite results in terms of association with essential hypertension: an increased frequency of the Gly16 variant in African-Caribbean hypertensives and of the Arg16 variant in offspring of Norwegian white hypertensive parents. In the current study, we genotyped 243 subjects, including both African-American and white individuals, for codon 16 polymorphism and assessed blood pressure and cardiovascular function using impedance cardiography and pressor sensitivity to phenylephrine. We found similar patterns of cardiovascular function and expression of hypertension with the two genotypes of codon 16. There was no statistically significant difference in the overall allelic distribution of the two genotypes: among African-Americans, 51% of the hypertensives and 50% of the normotensives carried the Arg16 allele, whereas among the white subjects 40% of the hypertensives and 47% of the normotensives were carriers of the Arg16 allele. Although we observed a statistically significant increase in the Arg16/Gly16 heterozygotes in the African-American population, the Gly16 allele was not significantly increased in the African-Americans compared to whites. These findings indicate that the codon 16 polymorphisms are not associated with hypertension in a mixed American study population nor do they appear to substantially impact on a variety of hemodynamic variables.

Variability in phenylephrine response and essential hypertension: a search for human alpha(1B)-adrenergic receptor polymorphisms.

Genetic polymorphisms in drug receptors, in particular adrenergic receptors, may contribute to intersubject differences in pharmacologic response. We tested patients and first-degree normotensive and hypertensive relatives of patients with essential hypertension and found substantial intersubject variability in blood pressure response to infusion of the alpha(1)-adrenergic agonist phenylephrine. Because response to phenylephrine depends upon interaction with alpha(1B)-adrenergic receptors, we tested whether polymorphisms in this receptor contribute to the variable responses. Accordingly, we developed a polymerase chain reaction-based method, generating four exon-spanning fragments, to identify polymorphisms in the coding sequence of the two exons of the human alpha(1B)-adrenergic receptor. We sequenced the entire coding sequence of exon 1 from 51 subjects and exon 2 from 16 of these 51 subjects. Compared with the published sequence for the alpha(1B)-adrenergic receptor, we found one amino acid addition in exon 2 at position 368 (Arg) and one substitution (Arg371Gly) in all subjects. We thus suggest we have defined the correct coding sequence of the human alpha(1B) receptor. We found two "silent" polymorphisms in exon 1, one of which occurred in 3 of 51 subjects. These polymorphisms were unrelated to blood pressure status or response to phenylephrine. The 95% confidence intervals for expression of polymorphisms in exons 1 and 2 were 0 to 11%. Our data reveal that although phenylephrine response varies in humans, frequent polymorphisms in the coding sequence of the human alpha(1B)-adrenergic receptor appear not to account for this variation or for the increased blood pressure in patients with essential hypertension.