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Biomedical subjects

J L Mostwin

Publications and source records attributed to J L Mostwin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Stretch-mediated visceral smooth muscle growth in vitro.

An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5-fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors.

Aging↗
PubMed1992

Detrusor hyperplasia and expression of "immediate early" genes with onset of abnormal urodynamic parameters.

To determine the stimulus for growth of the detrusor with a pathophysiological obstruction to the urinary stream, we studied urodynamic parameters, detrusor weight, detrusor DNA content, and the expression of early growth-related protooncogenes in a model of gradual onset bladder outflow obstruction and reversal of obstruction. Silver jeweler's jump rings were placed loosely round the urethra of immature guinea pigs, allowing an obstruction to develop gradually with animal growth. At 1, 2, 4, and 8 wk after surgery, animals were killed after urodynamic studies under urethan anesthesia. Bladders were removed, and mucosa-free detrusor was weighed and frozen for assay of DNA content and expression of c-fos and c-myc protooncogenes. Results were compared with sham-operated age-matched control animals. One week after surgery there was no change in the urodynamic parameters, detrusor weight, or DNA content. At 2, 4, and 8 wk after placement of the silver rings, animals developed obstructive voiding patterns, an increase in detrusor weight, and total DNA content. The onset of obstructive voiding patterns correlated with transient increased levels of c-fos and c-myc mRNA by Northern blot analysis. Autoradiography of in vivo [methyl-3H]thymidine-labeled detrusor muscle from obstructed animals showed myocyte DNA synthesis and mitosis, implying myocyte hyperplasia. After removal of the silver ring, the obstructive voiding patterns resolved and detrusor weight and DNA content returned to levels of the control animals. These results suggest that in the guinea pig bladder subjected to a gradual onset outflow obstruction, detrusor growth is initiated by the development of obstructive voiding patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Changes in electrical properties of guinea pig smooth muscle membrane by experimental bladder outflow obstruction.

The changes in membrane electrical properties of guinea pig bladder smooth muscle following experimental bladder outflow obstruction were studied by means of an intracellular microelectrode technique. The results of this study can be summarized as follows. 1) Bladder outflow obstruction resulted in a threefold increase in bladder weight after 4-8 wk. 2) The resting membrane potential was unchanged with obstruction; however, the obstructed smooth muscle membrane was more quiescent, with less spontaneous electrical activity compared with control tissue. 3) The membrane constants, space constant and time constant, were both reduced in the obstructed bladders. 4) There was no detectable difference in membrane depolarization induced by high extracellular K+ solution between control and obstructed bladders. 5) Both the membrane depolarization induced by K(+)-free solution or ouabain-containing Krebs solution and ouabain-sensitive membrane hyperpolarization by K(+)-containing solution after application of K(+)-free solution were significantly increased in the obstructed bladders. 6) Low extracellular Cl- solution evoked greater membrane depolarization in obstructed bladders. These results suggest that bladder outflow obstruction results in suppression of the cell-to-cell transfer of electrical activity and activation of a membrane electrogenic Na(+)-K+ pump mechanism in guinea pig detrusor.

Animals↗
PubMed1992

Effect of pinacidil on the membrane electrical activity of guinea pig detrusor muscle.

The effects of pinacidil on the guinea pig detrusor smooth muscle membrane were studied to investigate the electrophysiological mechanisms by which this drug relaxes smooth muscle tissue and, thus, might be of value in the treatment of detrusor instability. Pinacidil (> or = 3 x 10(-7) M) hyperpolarized the membrane in a concentration-dependent manner, with a reduction in spontaneous spike discharges. The membrane hyperpolarization induced by pinacidil was consistently associated with an increase in membrane ionic conductance. Glybenclamide (10(-6) M) completely inhibited the membrane hyperpolarization induced by pinacidil (up to 10(-5) M). Membrane hyperpolarization with pinacidil was consistently greater in a low-K+ solution, and it decreased in the presence of a high-K+ solution, compared with that measured in normal Krebs solution. Pinacidil consistently suppressed carbachol-induced depolarization of the membrane, with a reduction in the frequency of spontaneous action potentials. Glybenclamide (10(-6) M) did not inhibit the effect of pinacidil on increased action potential frequency induced by carbachol but blocked the membrane hyperpolarization induced by pinacidil (10(-5) M). In addition, the amplitude and maximum velocity of depolarization of carbachol- and current-induced action potentials were significantly decreased by pinacidil in the presence of glybenclamide. These results suggest that pinacidil blocks action potential generation in detrusor smooth muscle by inducing membrane hyperpolarization secondary to an increase in K+ permeability. Pinacidil, at high concentrations (> or = 10(-5) M), might block action potentials by inhibiting the voltage-sensitive Ca++ influx independently of hyperpolarization of the membrane. These mechanisms might be of benefit therapeutically in relaxation of unstable detrusor contractions.

Animals↗
PubMed1991

Ileocolic neobladder post-cystectomy: continence and potency.

Incontinence and impotence are 2 of the primary complications associated with total bladder reconstruction after cystectomy for carcinoma. These and other features are addressed in 25 patients who underwent total neobladder reconstruction following cystectomy for transitional cell carcinoma. Of these patients 20 had a urethral anastomosis. No patient had to wear a pad or device. Enuresis was rare. When the radical cystoprostatectomy population was contrasted with a radical prostatectomy patient population, continence was achieved more rapidly in the neobladder group. Potency was maintained in 15 of 21 (71%) evaluable patients. This ileocolic neobladder produces a large volume and low pressure, and provides excellent day and night continence. With preservation of the neurovascular bundle potency can be maintained in the majority of patients.

Carcinoma, Transitional Cell↗
PubMed1991

The guinea pig as a model of gradual urethral obstruction.

We developed a new model of partial urethral obstruction using the guinea pig. We placed jeweler's jump rings loosely around the proximal urethra of immature guinea pigs and allowed the obstruction to develop gradually as the animal grew. After four or eight weeks of obstruction, we studied the filling and emptying characteristics of the bladder during continuous repetitive cycling under urethane anesthesia. Following this examination, bladders were removed and weighed. Wet weight was compared to urodynamic findings. We identified four abnormal urodynamic patterns: high pressure voiding, instability, poor compliance and decompensation. All obstructed bladders showed weight gain associated with muscle hypertrophy, but the degree of weight gain was different for each of the various urodynamic categories. High pressure voiding was associated with the least weight gain, whereas instability and decompensation showed the most weight gain. The results are consistent with a thesis that partial urethral outlet obstruction in the guinea pig gives rise to several distinct forms of abnormal voiding characterized by high pressure in the early stages, and progressing to more advanced forms of dysfunction characterized by instability and decompensation in the later stages.

Animals↗
PubMed1991

Transesophageal echocardiography in renal cell carcinoma: an accurate diagnostic technique for intracaval neoplastic extension.

Between 4 and 10% of patients with renal cell carcinoma have tumor involving the inferior vena cava and many of these patients have suprahepatic extension. In patients with intracaval neoplastic extension precise definition of the superior aspect of the tumor thrombus is critical. Transabdominal ultrasonography, computerized tomography (CT), magnetic resonance imaging (MRI) and inferior venacavography are all currently used to evaluate the inferior vena cava in these patients. Intraoperative transesophageal echocardiography was used to image the inferior vena cava in 5 patients with renal cell carcinoma and intracaval neoplastic extension. In each patient transesophageal echocardiography correctly revealed the superior extent of tumor thrombus. In 3 patients tumor thrombus was found at a higher level by transesophageal echocardiography than by CT, MRI and inferior venacavography. In all patients tumor imaging by transesophageal echocardiography correlated well with the gross appearance and extent of tumor found at operation. Echocardiography also documented the absence of residual gross tumor after resection. Transesophageal echocardiography was also useful to assess left ventricular function. Although each of these patients had a pulmonary artery catheter as well transesophageal echocardiography can be useful in situations when right atrial tumor thrombus prevents right heart catheterization. This small series demonstrates that intraoperative transesophageal echocardiography can accurately evaluate the extent of tumor thrombus and provides a means to assess myocardial function complementary to the pulmonary artery catheter.

Carcinoma, Renal Cell↗
PubMed1991

Pelvic floor descent in women: dynamic evaluation with fast MR imaging and cinematic display.

The authors present a new method for assessing pelvic prolapse with dynamic fast magnetic resonance (MR) imaging. Twenty-six women with signs and symptoms suggesting pelvic prolapse and 16 control subjects were studied with a series of fast (6-12-second) MR images. Sagittal and coronal images were obtained with graded increase in voluntary pelvic strain, allowing for dynamic display and quantification of the pelvic prolapse process. The distance from the pubococcygeal line was used as an internal reference for measurement of descent in the maximal strain position. With use of control results for normal limit values, prolapse involving the anterior pelvic compartment (cystocele), the middle compartment (vaginal prolapse, uterine prolapse, and enterocele), and the posterior compartment (rectocele) was easily demonstrated. Significant differences between control subjects and patients with prolapse were seen at maximal strain but not in the relaxed state. Quantification of the pelvic descent process with use of fast MR imaging may be of value in surgical planning and postsurgical follow-up.

Adult↗
PubMed1991

Current concepts of female pelvic anatomy and physiology.

The female urinary bladder and urethra are situated on the intrapelvic surface of the anterior vaginal wall, firmly anchored to the distal vagina by the urogenital diaphragm and to the superior vagina at the vesicocervicouterine junction. The anterior surface of the proximal urethra is firmly anchored to the posterior aspect of the symphysis pubis by the pubourethral ligaments and to the remaining distal vagina by the lower two thirds of the urogenital diaphragm. The lateral bladder wall derives its support from the anterior vaginal wall attachments to the pelvic sidewall. The anterior vaginal wall is strongly supported by pubococcygeus muscle fibers inserting on the vaginal wall and the genital hiatus and by the cardinal and uterosacral ligaments. Vaginal detachment from the lateral pelvic sidewall can result in herniation, with accompanying secondary posterior bladder descent. Levator ani weakness or injury may be a contributing etiologic factor in the genesis of vaginal wall detachment and the development of stress incontinence.

Female↗
PubMed1990

Local recurrence and survival following nerve-sparing radical cystoprostatectomy.

From March 1982 through July 1988, 76 men underwent nerve-sparing radical cystoprostatectomy for carcinoma of the bladder at our hospital. Of the 76 patients 2 (2.6%) had positive surgical margins (dome of the bladder and left ureter) and neither had positive margins at the site of nerve-sparing modifications. Of 3 patients (3.9%) who had local recurrence none had positive surgical margins. The 5-year actuarial local recurrence rate is 7.5%. Thirteen of 76 patients (17%) died of transitional cell carcinoma and 7 (9%) died of other causes, while 53 (70%) are alive without evidence of disease with a mean followup of 38.4 months. The 5-year actuarial survival rates are 64% over-all, 68% without disease and 78% disease-specific. Of the 42 evaluable men who underwent cystoprostatectomy alone 27 (64%) are potent, compared to 2 of the 12 men (17%) who also underwent urethrectomy. We conclude that the nerve-sparing modifications do not compromise cancer control, that local recurrence and survival rates are at least comparable to those achieved with standard radical cystoprostatectomy, and that it is possible to preserve potency in most men undergoing this procedure.

Actuarial Analysis↗
PubMed1989

Intracorporeal pressure monitoring during artificial penile erection.

In an effort to determine if artificial penile erection has any harmful effect in children intracorporeal pressures were measured in 12 boys (mean age 18 months) with mid shaft hypospadias. Using a solid state intracompartmental pressure monitoring system, intracorporeal pressures were obtained during full penile erection and after removal of the tourniquet at detumescence. The mean intracorporeal pressure obtained was 85.9 mm. Hg during erection and 21.6 mm. Hg at detumescence. The systemic arterial pressure obtained was 102 mm. Hg at full erection. The pressure studies would suggest that the intracorporeal pressures achieved during full artificial erection would not be harmful to the cavernosal tissue in the hypospadiac child.

Humans↗
PubMed1989

The rat as a model for the study of penile erection.

A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection.

Animals↗
PubMed1989

Electrical and mechanical responses of guinea-pig bladder muscle to nerve stimulation.

1 The electrical and mechanical responses to transmural stimulation of intrinsic nerves have been recorded from smooth muscle strips dissected from the dome of the guinea-pig bladder, by use of intracellular microelectrodes, and conventional tension recording techniques. 2 Stimulation of intrinsic nerves evoked action potentials in all cells studied. Hyperpolarization of the cells by extracellular current injection revealed subthreshold excitatory junction potentials (e.j.ps) in about a quarter of the cells studied. 3 Action potentials could still be evoked in the presence of atropine and neostigmine, but were abolished after desensitization of the cells to alpha, beta-methylene ATP, a stable analogue of ATP. 4 In the presence of neostigmine, the evoked action potential was followed by a slow depolarization of the membrane. The mechanical response increased in amplitude and duration. 5 The contractile response to transmural nerve stimulation was reduced but not abolished in the presence of either atropine or desensitizing doses of alpha, beta-methylene ATP. Atropine was more effective at high frequencies of stimulation (greater than or equal to 30 Hz), and alpha, beta-methylene ATP at low frequencies (less than or equal to 15 Hz). In combination the drugs abolished the response. 6 The results suggest that the mechanical response to excitatory nerve stimulation is biphasic. The early transient response is elicited by e.j.ps and evoked spikes, is resistant to atropine, but sensitive to desensitization of purinoceptors. The late response is mediated through muscarinic receptors, involves little membrane depolarization, and is unaffected by desensitization of purinoceptors. These responses are analogous to the responses seen in rabbit bladder, and in the sympathetically innervated rat tail artery and guinea-pig vas deferens.

Acetylcholine↗
PubMed1986

The action potential of guinea pig bladder smooth muscle.

The smooth muscle of the guinea pig bladder demonstrates in vitro spontaneous electrical activity in the form of action potentials which are associated with contraction. The action potential frequency is highly voltage-sensitive. The relative contributions of Na, Ca and K to the action potential elicited by depolarizing current have been studied using intracellular microelectrodes. In solutions in which NaCl is replaced by sucrose, the membrane hyperpolarizes and the rate of rise and after-hyperpolarization of the elicited action potential is increased. The amplitude is unaffected. In Ca-deficient solutions, the membrane depolarizes, the rate of rise and amplitude of the action potential is reduced, and the after-hyperpolarization is decreased. Nifedipine reduces amplitude and rate of rise but does not affect after-hyperpolarization. In the presence of the K-channel antagonist TEA, the duration of the action potential is prolonged, but the amplitude and rate of rise are unaffected. After-hyperpolarization is not reduced. It is concluded that the action potential of guinea pig bladder muscle, like many other smooth muscles studied, is Ca-based. Repolarization depends on changes in K conductance. The after-hyperpolarization is voltage-sensitive.

Action Potentials↗
PubMed1985

Receptor operated intracellular calcium stores in the smooth muscle of the guinea pig bladder.

Study of the in vitro behavior of strips of guinea pig bladder and taenia coli demonstrated that: Both bladder and taenia temporarily retain their ability to contract in Ca-free solutions, but the magnitude of this response decays with time. Carbachol is capable of producing contraction in Ca-free solution for a longer period of time than K depolarisation. Once lost, the ability of carbachol (but not K) to contract the tissues in Ca-free solution can be temporarily restored by a brief application of high Ca. The size of the carbachol contraction in Ca-free solution is reduced in Na-free solution, suggesting that membrane-bound Ca may not play a major role in this response. In depolarised bladder exposed to nifedipine 2 X 10(-7) M, carbachol can only elicit 1 large contraction, suggesting depletion of an intracellular source. It is concluded that whereas the response of the bladder to depolarisation depends primarily on extracellular Ca, the response to carbachol may also involve release of stored Ca and that the bladder, like other smooth muscles, appears to contain agonist-releasable intracellular Ca stores.

Animals↗