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Biomedical subjects

A J Wein

Publications and source records attributed to A J Wein.

At least 19 recordsLinked to original sources
PubMed1992

Effect of outlet obstruction on pyruvate metabolism of the rabbit urinary bladder.

Bladder function is dependent upon cellular metabolism of substrates and the adequate generation of high-energy phosphate compounds. Partial outlet obstruction induces a marked decrease in bladder function which is associated with a significant decrease in the oxidative metabolism of glucose. The current investigation was designed to determine whether the time course of the decrease in mitochondrial oxidation in the hypertrophied urinary bladder is similar to the time course of the contractile dysfunction observed. In these studies we determined: 1) the rate of 14C-pyruvate metabolism to 14CO2 in control and obstructed tissue (1, 3, 5 and 7 days), and 2) the mitochondrial enzymatic activities of malate dehydrogenase and citrate synthase. The results can be summarized as follows: 1) The rate of pyruvate metabolism decreases by over 50% within one day following partial outlet obstruction, and remains at this level for the seven day period of study. 2) Kinetic analysis demonstrates that the change in enzymatic activity is related to a decrease in Vmax; the Kd for pyruvate is similar for control and after all time periods of obstruction. 3) The enzymatic activity of malate dehydrogenase and citrate synthase is reduced by over 50% within one day following partial obstruction, and remains at this level throughout the 7 day study period. These metabolic results correlate in time and duration with the decreased ability of the bladder to empty following partial outlet obstruction.

Animals↗
PubMed1992

Secondary malignant neoplasms in patients with bladder carcinoma.

At the University of Pennsylvania and its affiliates, 292 patients with bladder carcinoma treated with a variety of definitive regimens were observed for the incidence of secondary malignancies. The cumulative incidence at fifty-four months, including synchronous primary neoplasms, was 24 percent. Hazard function analysis reveals a relatively constant risk of new neoplasms to be approximately 1.5 percent per year over a period of forty-eight months after diagnosis.

Humans↗
PubMed1992

KTP-532 laser ablation of urethral strictures.

In 1988 the KTP-532 laser was used to ablate a series of benign urethral strictures. Rather than using a single incision as in urethrotomy, strictures were treated with 360-degree contact photoradiation. Thirty-one male patients, average age 53.2 years, received thirty-seven treatments; 6 patients underwent a second laser treatment. Stricture etiology was commonly iatrogenic (32%), traumatic (16%), and postgonococcal (10%). Stricture location included mainly bulbar (49%), membranous (20%), and penile (12%) areas. The surgical technique consisted of circumferential ablation, followed by Foley catheter placement (mean, 10 days). Follow-up on 29 of 31 patients ranged from one to sixteen months (mean 9.7). Complete success occurred in 17 patients (59%) who had no further symptoms or instrumentation. Partial success was seen in 6 patients (20.5%) with symptom, but not stricture, recurrence. Six patients (20.5%) failed therapy, requiring additional surgery or regular dilations. No complications were seen. Although longer assessment is required, KTP-532 laser ablation of urethral strictures appears efficacious.

Follow-Up Studies↗
PubMed1992

Effect of outlet obstruction on 3H-thymidine uptake: a biochemical and radioautographic study.

Experimental outlet obstruction in the rabbit is characterized by a rapid and substantial increase in urinary bladder mass. Although it is clear that both the smooth muscle and connective tissue compartments are increasing in mass, there is little information on the mechanisms by which this increase in mass occurs. As an initial investigation in this process, urinary bladders from normal and obstructed NZW rabbits were exposed in vitro to tritiated thymidine (3H-TdR) in order to determine which populations of cells are induced to synthesize DNA following outlet obstruction, and when, after obstruction, such synthesis occurs. Biochemical analysis of nucleic acids was performed on each specimen to determine total and radioactive DNA. These analyses showed a marked increase in DNA synthesis at 24 hours following obstruction which remained relatively high through seven days after obstruction. There was a decline in labelling at 14 days. Incorporation of radioactive label peaked at three days and declined to control levels by 14 days. Samples of tissue were taken from each subject and processed for radioautography. At 24 hours after obstruction, significant numbers of cells of the basal cell layer of the urothelium are observed to be actively involved in DNA synthesis, while the other two tissue compartments (muscularis and connective tissue) show no significant changes when compared to normal specimens. Connective tissue, on the other hand, showed significantly increased levels of labelling above control level from three to 14 days after obstruction. Smooth muscle cells were observed to be frequently labelled in only one of the experimental bladders observed three days after obstruction.

Animals↗
PubMed1992

Comparative autonomic responses of the cat and rabbit bladder and urethra.

The cat and the rabbit have both been utilized extensively in the study of lower urinary tract function. Previous studies have demonstrated that although both the cat and rabbit bladder are approximately the same weight, the in-vitro cat bladder can generate over 6 times the intravesical pressure of the rabbit bladder. The current study was designed to compare the ability of the isolated bladder to generate pressure with the pressures required to maintain flow through the isolated urethra for both the cat and the rabbit. The results can be summarized as follows. 1) The cat bladder is visibly much thicker than the rabbit bladder, and in vitro cystometry demonstrates that it is far less compliant than the rabbit bladder. 2) Over 20 cm.H2O pressure is required to begin flow through the isolated cat urethra preparation, whereas 5 cm.H2O begins flow through the rabbit urethra. 3) Increasing the flow rate (up to 7-fold) through both the isolated cat and rabbit urethra increases intraurethral pressure only slightly. 4) Both the isolated cat and rabbit urethra respond strongly to field stimulation and alpha-adrenergic stimulation (relative to the opening pressure required to begin flow), but not to cholinergic stimulation. 5) Field stimulation following pre-stimulation by methoxamine induces a strong relaxation of the pre-stimulated cat urethra, but an additive contraction in the pre-stimulated rabbit urethra. These studies demonstrate that in order for the cat to empty its bladder, it must generate a comparatively high intravesical pressure, whereas the rabbit is required to generate a relatively low intravesical pressure.

Animals↗
PubMed1992

Studies on experimental bladder outlet obstruction in the cat: long-term functional effects.

Experimental bladder outlet obstruction in cats induces a significant increase in the in vivo leakage pressure. The effects of obstruction on the detrusor function were analyzed, using control, 3, 6 and 12 month obstructed cats. The in vivo leakage pressures were substantially increased in all obstructed groups. From a previous study on the short-term effects of obstruction in the cat; although there was an immediate increase in pressure, there were no significant differences between control bladders and two week obstructed bladders in: bladder weight, peak pressure response to field stimulation and bethanechol, and emptying of the in vitro whole bladder model. In this current study, although there was no direct relationship between duration of obstruction and severity of the impaired pharmacological response of the isolated whole bladder, there was a direct relationship between the magnitude of the increase in bladder weight, leakage pressure, and impaired functional response of the in vitro whole bladder. In this regard the cats were separated into four groups: controls and shams (average bladder weight 2.95 gm.), obstructed group 1 with bladder weights less than 6.0 gm. obstructed group 2 with bladder weights between 6 and 10 gm., and obstructed group 3 with bladder weights greater than 10 gm. The results can be summarized as follows: A) In vivo leakage pressures were significantly increased in all obstructed groups, and progressively higher in proportion to the bladder weights. B) Bladder capacity significantly increased in all, being greatest in obstructed group 3. C) The magnitude of the response to field stimulation of obstructed groups 1 and 2 were significantly greater than the response of control bladders at virtually all frequencies. The frequency response curve of obstructed group 3 was similar to control. D) The ability of the bladder to empty in response to field stimulation was significantly reduced in all obstructed groups. The magnitude of the decrease was proportional to the increase in bladder weight. E) There were no differences between control and obstructed bladders in the pressure response to bethanechol or KCl; the ability of both bethanechol and KCl to empty the bladder was reduced in the obstructed groups. In general, the presence of bladder enlargement was accompanied by significant alterations in the ability of the in vitro bladder to empty in response to field stimulation, bethanechol, and KCl.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation.

The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1992

Effects of sensitization on the permeability of urothelium in guinea pig urinary bladder.

Permeability of the guinea pig urinary bladder was investigated in a model of experimental cystitis induced by intravesical antigen challenge following sensitization. Guinea pigs were sensitized by intraperitoneal injections of ovalbumin (10 mg./kg.) given on days 1, 3, and 5. The studies described were done four weeks after the last injection. Controls (injected with saline) were used at the same time as sensitized animals. Each group (control and sensitized), was divided into two subgroups; guinea pigs challenged with intravesical ovalbumin (10 mg./ml., one ml.) and those receiving one ml. saline intravesically. Immediately following the antigen (or saline) challenge, one ml. of 14C-urea urea was placed into the bladder for two hours. We examined the peripheral blood concentrations of 14C-urea at periods of time up to 120 minutes. There was a progressive increase in the blood level of 14C-urea with time only in the sensitized group challenged with antigen (ovalbumin). There was no 14C-urea present in the blood of the sensitized group without antigen challenge, or in either unsensitized group. We also measured isotope concentration in the bladders and found a significantly higher concentration of isotope in the bladders from ovalbumin-treated sensitized guinea pigs. We believe that this animal model of cystitis is an improvement over previous models because of its physiological relevance. In this model, cystitis is produced without mechanical or chemical damage to the bladder mucosa. A discussion of the model in relation to interstitial cystitis is presented.

Animals↗
PubMed1992

Effect of partial obstruction of the rabbit urinary bladder on malate dehydrogenase and citrate synthase activity.

Previous studies have demonstrated that partial outlet obstruction in rabbits induced a significant decrease in oxidative metabolism in urinary bladder smooth muscle. The current experiments were designed to determine whether the decreased oxidative metabolism of obstructed bladder tissue is associated with alterations in the activities of specific mitochondrial enzymes. The activities of two important enzymes in the tricarboxylic acid cycle, malate dehydrogenase and citrate synthase, were measured in samples of bladder body and base from normal bladders and in bladders from rabbits in which partial outlet obstruction had been produced seven days prior to the experiments. The results can be summarized as follows: malate dehydrogenase activity was similar in bladder body and base isolated from control rabbits; and decreased by approximately 40% in both segments of the bladder isolated from obstructed rabbits. In contrast to malate dehydrogenase, citrate synthase activity was significantly higher in the bladder body than in the base of normal rabbits. Outlet obstruction caused about a 50% decrease in activity of this enzyme in the bladder body, but had no significant effect on citrate synthase activity of the bladder base. These findings demonstrate that the deficiency in bladder function following partial outlet obstruction is associated with a marked decrease in the activities of two essential enzymes in oxidative metabolism: malate dehydrogenase and citrate synthase. This decrease in enzyme activity is consistent with the previously observed decrease in oxidative metabolism and would be expected to lead to an inability of the tissue to supply sufficient metabolic energy for proper contractile function.

Animals↗
PubMed1992

Effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine and KCl.

The contractile response of the bladder can be divided into two phases: an initial rapid increase in tension and a prolonged period of sustained tension (plateau phase). The bladder empties primarily during the plateau phase of the contractile response. These two phases can be differentiated using both pharmacologic and metabolic agents, indicating that the two phases have independent energy requirements. The present study compares the phasic (peak) and tonic (plateau) components of the responses of isolated strips of bladder body and base to field stimulation, bethanechol, methoxamine and KCl administration. New Zealand White rabbits were anesthetized with pentobarbital, and the bladder was removed. The bladder was divided between body and base at the level of the ureteral orifices. Three strips of bladder body and three strips of bladder base were mounted in separate baths containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effects of anoxia on the responses to field stimulation, bethanechol, methoxamine and KCl were determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows: (1) Anoxia induced time-dependent plateau phases of the response to field stimulation (2 and 32 Hz). (2) The rate of inhibition of the plateau phase was significantly and substantially greater than that of the peak phase in both the bladder body and base. (3) Similarly, anoxia inhibited the plateau phase of the bladder body's response to bethanechol to a significantly and substantially greater degree than anoxia inhibited the peak contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of pinacidil on spontaneous and evoked contractile activity.

Uninhibited bladder contractions have been associated with a variety of bladder dysfunctions including outlet obstruction, neurogenic bladder, incontinence, and other neurologic and nonneurogenic bladder disorders. One class of compounds that is gaining popularity and support for the treatment of hyperreflexia is potassium channel openers, such as pinacidil and cromakalim. In general, these agents act by hyperpolarizing the smooth muscle membrane, resulting in an increase in membrane stability which in turn would be expected to inhibit spontaneous and evoked contraction. It is the purpose of this study to compare the potency and selectivity of pinacidil at inhibiting both hyperreflexia in vivo, and several forms of in vitro contractile stimulation in the rabbit. The following is a summary of the results. (1) Pinacidil is an effective inhibitor of hyperreflexia in the in vivo rabbit model. (2) Pinacidil is a substantially more potent inhibitor of the amplitude of the hyperreflexia than the frequency. (3) Pinacidil was substantially more potent at inhibiting the contractile response to 2-Hz stimulation than to 32-Hz stimulation, but was equally effective at inhibiting field stimulation of the bladder base and body. (4) Pinacidil was significantly more potent at inhibiting the peak response to field stimulation than the rate of tension generation. (5) Pinacidil was equally potent and effective at inhibiting the phasic and tonic components of the response to field stimulation. (6) Pinacidil was a more potent inhibitor of methoxamine stimulation of the bladder base than bethanechol stimulation of the bladder body. (7) Pinacidil was a noncompetitive or mixed inhibitor of both methoxamine and bethanechol stimulation, whereas it was a competitive inhibitor of KCl stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Influence of the bathing medium on the contractile responses of the rabbit urinary bladder.

This study examined contractile responses of the in vitro rabbit whole-bladder preparation to field stimulation, bethanechol and KCl in Tyrode's solution and minimum essential medium (MEM). We found frequency-dependent increases in intravesical pressure in bladders incubated in Tyrode's solution and MEM. However, bladders incubated in MEM consistently responded with greater increases in intravesical pressure compared to those incubated in Tyrode's solution. Similarly, there were frequency-dependent increases in the rate of pressure generation in bladders incubated in Tyrode's solution and MEM, and bladders incubated in MEM responded with greater rates of pressure generation than those incubated in Tyrode's solution at frequencies of 1, 2 and 4 Hz. In addition, there were significant increases in intravesical pressure generated in response to administration of 500 mmol/l bethanechol and 186.4 mmol/l KCl in bladders incubated in MEM compared to Tyrode's solution but no changes in the rate of pressure generation. The influence of L-methionine, one of the constituents of MEM, on the responses of whole bladders to nerve stimulation was also investigated. L-methionine at concentrations of 0.1 and 1.0 mmol/l had no effects on the increase in intravesical pressure or rate of pressure generation following nerve stimulation. It is speculated that the increases in contractile responsiveness of bladders incubated in MEM are related to the combination of amino acids, vitamins and other constituents of the cell culture medium.

Animals↗
PubMed1992

Effect of ryanodine on mitochondrial respiration.

Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation.

Animals↗
PubMed1991

Bladder outlet obstruction treated with transurethral ultrasonic aspiration. One-year follow-up on 59 patients.

Fifty-nine males with bladder outlet obstruction were treated with transurethral ultrasonic aspiration of the prostate. Utilizing a 26.5F urethral sheath, surgery was accomplished with a 10F, 0-700-micron-vibration-level ultrasonic tip with an excursion rate of 39 kHz. Complete removal of the adenoma was accomplished followed by transurethral electrocautery biopsies of both lateral lobes to compare pathologic specimens. One year follow-up revealed satisfactory voiding patterns in 57 of 59 men (96%). Bladder neck contractures developed in 2 men. Pathologic comparisons showed 100 percent correlation between aspirated and TUR specimens (56 BPH, 3 adenocarcinoma). Forty-seven men were active sexually preoperatively (6 with inflatable penile prostheses). Post ultrasonic aspiration, 46 men had erectile function similar to preoperative levels with 1 patient suffering erectile dysfunction. Forty men (85%) had antegrade ejaculation while 7 (15%) experienced retrograde or retarded ejaculation. No patients were incontinent.

Adenocarcinoma↗
PubMed1991

Effect of anoxia on in vitro bladder function.

Previous studies have demonstrated that the ability of the in vitro whole bladder to empty in response to bethanechol administration was inhibited by anoxia while its ability to generate pressure decreased only slightly. One question was not addressed by these early studies: Is the anoxic effect selective for receptor-mediated contractile stimulation (as opposed to non-receptor-mediated contractile stimulation)? The present study was designed to compare the effect of anoxia on the ability of the in vitro bladder to generate pressure, sustain pressure, and empty in response to field stimulation (FS), bethanechol and KC1 administration. Each New Zealand white rabbit was anesthetized with pentobarbital and the bladder removed. The bladder was mounted as a whole-bladder preparation in a 300-ml isolated bath containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effect of anoxia on the response to FS, bethanechol, and KCl was determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows. (1) Anoxia induced a time-dependent decrease in the rate of pressure generation, the magnitude of pressure generation, and the percent volume emptied in response to FS and bethanechol. (2) At all time periods of anoxia, the ability of the bladder to empty was inhibited to a significantly greater degree than either the rate of magnitude of pressure generation (for both FS and bethanechol administration).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗