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Biomedical subjects

U Ulmsten

Publications and source records attributed to U Ulmsten.

At least 37 records · Page 2Linked to original sources

Validation of cough-induced leak point pressure measurement in the evaluation of pharmacological treatment of stress incontinence.

To improve routines in clinical practice and research, it is important that new tests are thoroughly evaluated before they gain widespread application. This includes establishing the reliability and validity of the new test. The purpose of this study was to establish the construct and criterion validity of cough-induced leak point pressure (CILPP) measurement. Data on CILPP, maximum urethral pressure (MUP), and a short-term pad test from a phase-I trial of a new pharmacological agent (LS 4416), developed for the treatment of stress incontinence, was used to test the validity of CILPP. Fifteen post-menopausal women with stress incontinence were studied. Phenylpropanolamine (PPA) was used as a positive control. Administration of PPA produced a statistically significant increase in MUP and CILPP. There was a significantly better effect of treatment, expressed as an increase in MUP at 1.5 hr, when PPA was used than with placebo or LS 4416. When CILPP was used to detect change after therapy, PPA produced a significantly greater increase in CILPP than did placebo (least square mean of difference 17.25, P = 0.0202). There was a moderate but statistically significant correlation between CILPP and the short-term Pad Test. Construct validity was demonstrated by the ability of CILPP to detect limited improvement in patients with stress incontinence. Criterion validity was established by the correlation of CILPP to a short-term Pad Test. We propose that, thanks to its greater methodological qualities, leak point pressure measurement should be adopted as a standard method to ascertain the effect of treatment in patients with stress incontinence. Neurourol. Urodynam. 18:591-602, 1999.

Aged↗

An anatomical classification--a new paradigm for management of urinary dysfunction in the female.

A new classification specifies anatomical defects in the anterior, middle and posterior zones of the vagina as causing urinary dysfunction. An external musculoelastic mechanism stretches the vagina to open and close the outflow tract. The same pelvic floor muscles provide a peripheral control mechanism for micturition. The stretched vagina prevents the filling bladder from activating the stretch receptors. Vaginal laxity may weaken the transmission of muscle forces, interfering with the mechanical process of opening and closure. Laxity may also destabilize the peripheral control mechanism, a neurological process, causing bladder control to swing between the open and closed modes, i.e. bladder instability. Specific symptoms, signs and urodynamic tests were arranged into a pictorial algorithm as a practical guide for locating the three zones of anatomical defects. It was possible to reinterpret almost all the definitions and descriptions of the International Continence Society in terms of this classification, and to explain how vaginal laxity may cause premature activation of the micturition reflex (detrusor instability), stress incontinence and abnormal emptying (dribble, overflow). This convergence in anatomical and urodynamic (ICS) concepts explains many previously unexplained phenomena, and potentially opens up an entirely new approach to management, non-surgical strengthening of specific ligaments, or surgical reinforcement thereof with ambulatory 'keyhole' methods which do not require catheterization.

Algorithms↗

Connective tissue in female urinary incontinence.

An effective closure of the female urethra in stress situations is dependent on an integrated action of various anatomical structures connected to the organ. The most important of these structures - from a functional aspect - are the suburethral vaginal wall, the pubourethral ligaments, the pubococcygeus muscles and the paraurethral connective tissues. In all these structures connective tissue is an essential ingredient. Hence, defects in the actual connective tissue - in particular the paraurethral connective tissue that connects the aforementioned structures to each other and to the urethra - will bring about an ineffective urethral closure. Female urinary incontinence may then be caused by defective connective tissue per se and/or by a disconnection of the aforementioned structures, whereby the urethra cannot be 'kinked' - that is, closed off in stress situations.

Collagen↗

A three-year follow up of tension free vaginal tape for surgical treatment of female stress urinary incontinence.

OBJECTIVE: To study the long term results of tension-free vaginal tape, a new ambulatory surgical procedure for treatment of female stress urinary incontinence. STUDY DESIGN: A prospective open study using a standardised protocol for pre- and post-operative evaluation. PARTICIPANTS: Fifty consecutive women participated in the study. All suffered from genuine stress incontinence. The mean age was 57 years (SD 11), 42 women (84%) were multiparous, 8 (16%) nulliparous. SURGICAL METHOD: Tension-free vaginal tape implies the implantation of a prolene tape around mid-urethra via a minimal vaginal incision. The procedure is carried out under local anaesthesia, allowing the surgeon to check intra-operatively that continence has been obtained. RESULTS: All the women except one could be operated on an ambulatory basis under local anaesthesia. Mean operation time was 29 minutes (range 1647). Ninety percent of the women were able to micturate spontaneously within 24 hours with insignificant residual volumes. In another 10% of the women an in-dwelling catheter had to be used temporarily. There was no need for long term postoperative catheterisation (> 14 days). Post-operative evaluation was carried out after 2 to 6, 12, 24 and 36 months. According to the protocol, 86% of the women were completely cured and another 11% were significantly improved. No signs of deterioration of the results over time were observed. No defect in healing or rejection of the tape occurred. CONCLUSION: We consider the tension-free vaginal tape operation to be a safe and effective surgical procedure for the treatment of female urinary stress incontinence. The technique can be considered as an ambulatory procedure performed under local anaesthesia, allowing the majority of the women to be discharged from the clinic the same day or the day after the procedure.

Adult↗

Low myometrial glycogen content compared with rectus muscle in term pregnant women before labor.

Glycogen, glucose, some nucleosides and purine base derivatives were determined in biopsies from 10 term pregnant women undergoing elective cesarean sections before labor. The concentrations were compared in the biopsies which were cut from isthmus and fundus of the uterus and m. rectus abdominis. M. rectus biopsies had 1.5 and 2 times higher concentration of glycogen than the isthmic and fundal uterine biopsies, respectively. The glucose concentration in the striated muscle was on the other hand only half that in the myometrium. The uterus displayed regional differences in concentrations of glycogen (higher in isthmus). A relatively low glycogen content in term pregnant uterine smooth muscle compared with striated muscle signifies the restricted energy demands of pregnant myometrium.

Adenosine↗

DiHA Dextran Copolymer, a new biocompatible material for endoscopic treatment of stress incontinent women. Short term results.

BACKGROUND: This study was undertaken to investigate the safety and effect of DiHA, dextranomers in hyaluronan, a new biocompatible material for endoscopic treatment of stress incontinence, and to further develop the injection technique. METHODS: Twenty women aged 38 to 90 years with genuine stress incontinence participated. Seventeen were followed for a minimum of 6 months after treatment and three for a minimum of 3 months. The DiHA implants were administrered by transurethral endoscopically controlled submucosal injections under local anesthesia. Safety was assessed mainly in terms of infection, need for catheterization, residual urine and dysuria. The treatment efficacy was estimated objectively by a short-term pad test with standardized physical exercise and a 48 h pad-test, 7 days, and 1, 3 and 6 months after treatment. The patient's subjective experience of the effect was also studied. RESULTS: The implantation procedure was well accepted by the patients. Four patients required catheterization due to voiding problems during the first 24 postoperative hours. One patient had urinary retention 14 days postoperatively. No UTI or local infection was detected. Some patients had transient urgency. In 17 or 20 patients the treatment resulted in objective cure or improvement. CONCLUSIONS: This substance shows promising qualities for endoscopic treatment of stress incontinence.

Adult↗

A multicenter study of tension-free vaginal tape (TVT) for surgical treatment of stress urinary incontinence.

The aim of the study was to evaluate the safety and efficacy of TVT (tension-free vaginal tape) for the surgical treatment of stress urinary incontinence. The design was a prospective open multicenter study including six centers, each operating an approximately 20 patients. In total 131 patients suffering from genuine stress incontinence were included. They were followed for at least 1 year using a specific protocol for objective and subjective evaluation of the outcome. All patients underwent the operation under local anesthesia. Mean operation time was 28 minutes (range 19-41 minutes); 119 (91%) of the patients were cured according to the protocol and another 9 (7%) were significantly improved. There were 3 (2%) failures. The majority of the patients (about 90%) were operated upon on a day-care basis, which implied that they were released from the hospital within 24 hours, with no postoperative catheterization. No defect healing and no tape rejection occurred. Three patients needed an indwelling catheter for 3 days. In 1 patient catheterization was necessary for more than 10 days. Two uncomplicated hematomas and one uncomplicated bladder perforation occurred. Based on the results, we conclude that TVT is a safe and effective ambulatory procedure for surgical treatment of genuine stress urinary incontinence.

Ambulatory Surgical Procedures↗

Ineffectiveness of oxytocin on intercellular communication between term pregnant human myometrial cells before labor.

OBJECTIVE: The effects of the uterotonic agent oxytocin on intercellular communication between term pregnant human myometrial cells before labor were studied to investigate its contribution to the synchronicity of uterine contractions. STUDY DESIGN: The membrane potential and the input resistance of myometrial cells were measured with intracellular micropipettes, and dye-coupling assays were concomitantly performed while the tissues were perfused with three concentrations of oxytocin (10(-8) mol/L, 10(-7) mol/L, and 10(-6) mol/L). The results were compared with those obtained from tissues perfused with gap junctional uncoupling agent octanol and those with Tyrode's solution (control). RESULTS: Octanol increased input resistance and inhibited dye coupling but did not affect membrane potential compared with controls. Oxytocin depolarized membrane potential at all studied concentrations. The mean input resistance values and detectable dye propagation with oxytocin were similar to controls. CONCLUSION: Oxytocin does not contribute to gap junctional intercellular communication in term pregnant human myometrium before labor but may affect contractions by depolarizing membrane potential.

Cell Communication↗

Identification of two further gap-junctional proteins, connexin40 and connexin45, in human myometrial smooth muscle cells at term.

The powerful synchronous contractions of the uterus in labor depend on electrical coupling of myometrial smooth muscle cells by gap junctions. In humans and other mammals, gap junctions are scarce in the myometrium of the non-pregnant uterus, but become abundant at term and/or with the onset of labor. Previous work has shown that the gap-junctional protein (connexin) expressed by human myometrial smooth muscle cells is connexin43, the same connexin type that predominates in cardiac muscle. Here we show that two further gap junctional proteins, connexin40 and connexin45, are expressed by the myometrial smooth muscle cells of the human uterus at term. Transcripts encoding the human isoforms of these connexins were demonstrated by Northern blot analysis, and immunoconfocal microscopy enabled precise localization of the corresponding proteins to punctate contact points (i.e., gap junctions) between interacting smooth muscle cells. Double labeling demonstrated that, while some fluorescent spots comprise only connexin43, both connexin40 and connexin45 predominantly colocalize to connexin43-positive fluorescent spots. Triple labeling revealed that where all three connexin types were expressed, they frequently localized to the same gap junction spot. As gap-junctional channels composed of different connexin types have been demonstrated in vitro to have different functional properties, multiple connexin expression may contribute to modulation of gap junction function in human myometrial smooth muscle cells in vivo.

Blotting, Northern↗

An anatomical classification--a new paradigm for management of female lower urinary tract dysfunction.

A new anatomical classification specifies anatomical defects in the anterior, middle and posterior zones of the vagina as the cause of female lower urinary tract dysfunction. An external musculoelastic mechanism stretches the vagina to open and close the outflow tract. The same pelvic floor muscles provide a peripheral control mechanism for micturition. The stretched vagina prevents the filling bladder from activating the stretch receptors in the bladder neck. Vaginal laxity may weaken transmission of muscle forces, interfering with urethral opening and closure, a mechanical process. Laxity may also destabilize the peripheral control mechanism, a neurological process, causing bladder control to swing between the open and closed modes urodynamically interpreted as bladder instability. Specific symptoms, signs, and urodynamic tests can be arranged into a pictorial algorithm. This acts as a practical guide for locating the three zones of anatomical defects. It has been possible to reinterpret almost all the definitions and descriptions of the International Continence Society (ICS) in terms of this classification, and to explain how vaginal laxity may cause premature activation of the micturition reflex (detrusor instability), stress incontinence and abnormal emptying (dribble, overflow). This convergence in anatomical and urodynamic (ICS) concepts explains many previously unexplained phenomena, and potentially opens up a new approach to management, nonsurgical strengthening of specific ligaments, or surgical reinforcement thereof with ambulatory "microinvasive" methods which do not require catheterization.

Biomechanical Phenomena↗

Intravenous nitroglycerin for rapid uterine relaxation.

BACKGROUND: To investigate the effect of nitroglycerin in vitro and in vivo on human uterine contractile activity. METHODS: In vitro myometrial strips were obtained from six pregnant women at term who underwent elective cesarean section. The biopsies were mounted in tissue baths. After spontaneous or oxytocin-induced activity had been accomplished, nitroglycerin in various concentrations was added to the baths and the effects were continuously registered. In vivo, in an open study nitroglycerin was administered as a bolus injection of 100-200 micrograms intravenously to 32 women at cesarean section when uterine relaxation was urgently needed; to 22 other women after vaginal delivery for facilitation of manual removal of retained placentas, and to one patient at vaginal delivery of premature twins. RESULTS: In vitro nitroglycerin induced a dose-dependent inhibition of spontaneous as well as oxytocin-induced myometrial contractile activity. Complete muscular relaxation was obtained at a concentration of 25-50 micrograms/ml. In vivo all patients had rapid effective uterine relaxation after intravenous injection of 100-200 micrograms nitroglycerin. CONCLUSION: Nitroglycerin administered intravenously seems to be a rapid and effective uterine muscle relaxant agent without overt adverse effects on mother or fetus.

Cesarean Section↗

Different organization of collagen fibrils in stress-incontinent women of fertile age.

OBJECTIVE: The objective was to test the hypothesis that stress urinary incontinence in women is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism. METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in women of fertile age with stress urinary incontinence and in matched continent controls. All the stress-incontinent women were characterized with urodynamic investigation. In the biopsies, collagen concentration, measured as hydroxyproline, and the degree of extraction by pepsin digestion were quantified. Proteoglycan composition and concentration were analyzed using Alcian blue precipitation, followed by electrophoretic separation and quantification. Using Northern blots mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen organization was examined with transmission electron microscopy and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron). RESULTS: The biochemical and morphological analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women. Also the organization of the collagen fibrils differed, with considerably higher cross-linking. A higher level of mRNA for collagen I and III in the incontinent group indicates that the differences can be related to an altered collagen metabolism. No change of proteoglycan amount or composition was observed, resulting in a significantly lower proteoglycan/collagen ratio in the incontinent group of women. CONCLUSION: Stress urinary incontinence in fertile women is associated with a change in collagen metabolism resulting in an increased concentration of collagen and larger collagen fibrils. These alterations should result in a more rigid form of extracellular matrix, suggesting a connective tissue with impaired mechanical function.

Adult↗

Paraurethral connective tissue in stress-incontinent women after menopause.

OBJECTIVE: To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism. METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron). RESULTS: No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group. CONCLUSION: The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.

Aged↗

Progesterone increases cAMP release and accumulation in isolated term human myometrium.

OBJECTIVE: To study the relationship between the action of progesterone on term human myometrial contractile activity and cAMP alterations. STUDY DESIGN: Myometrial tissues were obtained from 13 term pregnant women who underwent elective cesarean section. The contractile activity of muscle strips was recorded isometrically, and the level of cAMP in both superfusion media and experimental biopsies was measured by radioimmunoassay. RESULTS: An increased cAMP release into the superfusion media and an increased accumulation of cAMP in myometrium were observed after the addition of progesterone (3, 15 and 150 microM). Simultaneously, the frequency and tonus of contractions were increased, while the amplitude and activity area of contractions were decreased. CONCLUSIONS: The data indicate that an increase in cAMP concentration plays a role in the action of progesterone on the regulation of term human myometrial contractile activity.

Adult↗

Role of the pelvic floor in bladder neck opening and closure II: vagina.

The aim of the study was to examine the role of vaginal stretching during bladder neck opening and closure. The study group comprised 12 patients with GSI and 4 controls. The position of the bladder neck relative to the vagina was assessed in the resting, straining and 'squeezing' positions using video-radiological studies. Radio-opaque dye was instilled into the bladder, vagina, rectum and levator plate. Vascular clips applied to the midurethral, bladder neck and bladder base parts of the anterior vaginal wall assisted in determining differential movements of these parts of the vagina during bladder neck opening and closure. The suburethral vagina (hammock) was shown to stretch downwards and forwards during straining, and downwards and backwards during micturition. The bladder neck, upper part of the vagina and the rectum were stretched backwards and downwards in an identical manner during straining and micturition, apparently in response to backward contraction of the levator plate and downward angulation of its anterior lip. All organs were stretched upwards and forwards during 'squeezing'. The findings support the hypothesis that, during stress and micturition, selective pelvic floor contractions stretch the vagina against intact pubourethral and uterosacral ligaments to assist opening and closure of the urethra and bladder neck.

Aged↗

Role of the pelvic floor in bladder neck opening and closure I: muscle forces.

The aim of the study was to identify the striated muscle forces hypothesized to assist bladder neck opening and closure in females. Cadaveric dissection was used to identify the levator plate (LP), the anterior portion of pubococcygeus muscle (PCM), the longitudinal muscle of the anus (LMA), and their relation to the bladder, vagina and rectum. X-ray video recordings were made during coughing, straining, squeezing and micturition in a group of 20 incontinent patients and 4 controls, along with surface EMG, urethral pressure and digital palpation studies. During effort, urethral closure appeared to be activated by a forward muscle force corresponding to PCM, and bladder neck closure by backward muscle forces corresponding to LP and LMA. During micturition the PCM force appeared to relax, allowing LP and LMA to pull open the outflow tract. The data appear to support the hypothesis of specific directional muscle forces stretching the vagina to assist bladder neck opening and closure.

Adult↗