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Biomedical subjects

K E Whitmore

Publications and source records attributed to K E Whitmore.

15 recordsLinked to original sources

Lack of effect following repeated in vivo exposure of the rabbit urinary bladder to urine from interstitial cystitis patients at low infusion volumes.

We reported previously that substances in interstitial cystitis urine, when infused into the rabbit bladder, induce changes that resemble bladders of interstitial cystitis (IC) patients. Here we report our investigation of the effect of additional molecular weight subfractions of IC urine and lower infusion volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC patients, asymptomatic IC patients (in remission), and normal volunteers. Two fractions of 20x concentrated urine were obtained for each of the 3 groups: a 10-100-kD fraction and a fraction > 100 kD but <0.22 microm. Six rabbits per group were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline as a control. After 6 weeks, each rabbit was cystoscoped before and after hydrodistension, bladder capacity and urea permeability were determined, and the bladder was removed for histologic examination. A questionnaire revealed a significant difference (P < 0.01) regarding voiding symptom severity between symptomatic IC patients and both normal volunteers and IC patients in remission. There was no statistically significant difference among groups of rabbits in cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder histology. If a urine-borne factor is in part responsible for IC symptoms, the rabbit bladder must be filled with urine to near capacity to be able to detect a difference between IC and normal urine in this rabbit bladder bioassay.

Administration, Intravesical

The interstitial cystitis symptom index and problem index.

OBJECTIVES: To develop 2 brief self-administered indices for measuring lower urinary tract symptoms and their impact in patients with interstitial cystitis (IC). METHODS: An initial set of questions was developed and evaluated in focus groups. The index was revised, shortened, and validated with patients diagnosed in 3 large urologic practices with experience in interstitial cystitis (N = 45). Controls were recruited from a group of healthy volunteers in a gynecology clinic (N = 67). Internal consistency, construct validity, and test-retest reliability were evaluated. RESULTS: The IC symptom index and the IC problem index measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls. CONCLUSION: Both indices should be useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important.

Cystitis, Interstitial

Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine the efficacy of transvaginal electrical stimulation in treating genuine stress incontinence. STUDY DESIGN: This was a multicenter, prospective, randomized, double-blind, placebo-controlled 15-week trial comparing the use of an active pelvic floor stimulator with a sham device. Thirty-five women used an active unit and 17 control subjects used sham devices. Weekly and daily voiding diaries were recorded throughout the trial. Urodynamic testing, including pad test and subtracted cystometry, was done before and at the end of device use. Pelvic muscle strength was measured at baseline and at the end of the trial. Patients scored their symptoms on visual analog scales and completed quality-of-life questionnaires before and after therapy. RESULTS: Significant improvements from baseline were found in patients using active devices but not in controls. Comparisons of changes from baseline between active-device and control patients showed that active-device patients had significantly greater improvement in weekly (p = 0.009) and daily (p = 0.04) leakage episodes, pad testing (p = 0.005), and vaginal muscle strength (p = 0.02) when compared with control subjects. Significantly greater improvement was also found for both visual analog scores of urinary incontinence (p = 0.007) and stress incontinence (p = 0.02), as well as for subjective reporting of frequency of urine loss (p = 0.002), and urine loss with sneezing, coughing, or laughing (p = 0.02), when compared with controls. Pad testing showed that stress incontinence was improved by at least 50% in 62% of patients using an active device compared with only 19% of patients using sham devices (p = 0.01). Voiding diaries showed at least 50% improvement in 48% of active-device patients compared with 13% of women using the sham device (p = 0.02). No irreversible adverse effects were noted in either group. CONCLUSIONS: Transvaginal pelvic floor electrical stimulation was found to be a safe and effective therapy for genuine stress incontinence.

Double-Blind Method

Bladder infection.

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ABO Blood-Group System

Self-care regimens for patients with interstitial cystitis.

For those who suffer from interstitial cystitis, living with the condition is a challenge that requires creativity, patience, determination, and a sound set of coping mechanisms. Because of the high percentage of gynecologic and systemic manifestations of interstitial cystitis, a customized treatment regimen is often necessary to achieve the therapeutic goal of a remission in symptoms. Treatment philosophies should be based on the proposed causative mechanisms, and a multimodality approach to therapy is usually successful. Self-care regimens give the patient a sense of control by active participation in treatment, which often improves coping mechanisms. Treatment of the sequelae of chronic pain (anxiety and depression) often improves response to overall therapy. Remission is the goal, coping is the key, and creativity opens the door to treating this most perplexing of conditions.

Cystitis

Effect of repeated instillation of interstitial cystitis urine on the rabbit urinary bladder.

One theory for the etiology of interstitial cystitis (IC) proposes toxic substances in the urine. This hypothesis was tested in our laboratory by infusing urine into the bladders of rabbits twice weekly for six weeks. For the first study rabbits were treated by one-hour biweekly intravesical exposure to urine from a symptomatic interstitial cystitis patient, a normal volunteer, or physiologic saline. For the second study, animals were exposed to both a high and a low molecular weight fraction of urine pooled from 7 interstitial cystitis patients, 7 normal female volunteers, and physiologic saline. At the end of six weeks the animals were cystoscoped and the bladder was removed the following day for histologic and contractile studies. Post-distention glomerulations were observed in 3 of the 4 whole IC urine-treated animals and an ulcer identical to the classic "Hunner's ulcer" was seen in one of these animals. Post-distention petechial hemorrhages were also noted in all 5 of the high molecular weight IC urine-treated animals but in none of the others, suggesting a difference between IC and normal urine. These IC urine-treated groups also showed the greatest degree of histologic changes including edema and plasma cell infiltrates in the lamina propria, submucosa and perivascular tissue. However, there was no statistically significant difference in bladder capacity, micturition patterns, or contractile response of bladder strips. These results indicate that there are substances with nominal molecular weight greater than 10 kD in interstitial cystitis urine that induce changes in the rabbit bladder that resemble bladders of interstitial cystitis patients.

Administration, Intravesical

Bladder purinergic receptors.

In rabbits the contractile response of the urinary bladder is only partially due to cholinergic innervation since atropine does not completely block neuronally mediated contractions. In the human bladder this atropine resistance is controversial with some reporting atropine resistance in vitro while others have stated that the atropine resistance is also tetrodotoxin resistant. Results of the present investigation demonstrate that an atropine resistant, tetrodotoxin sensitive contraction can be evoked in some, but not all human bladder strips. Evidence accumulated over the past few decades indicates that this atropine resistant contraction may be mediated by ATP or a related purine compound. Studies presented herein are designed to develop a radioligand assay for this purinergic receptor. Initial studies indicated that the hydrolysis resistant ATP analog beta, gamma methylene ATP offers several advantages over ATP as a potential radioligand. It is only slowly hydrolyzed by endogenous ATPase and does not inhibit the hydrolysis of ATP indicating that it probably does not bind to the active sites of endogenous ATP hydrolyzing enzymes. In addition beta, gamma methylene ATP is 10-100 fold more potent than ATP itself in stimulating contractions of the urinary bladder in-vitro. The radioligand binding assay herein described can be used to quantitate the density of purinergic receptors, an essential step for determining the role of this system in urinary bladder function and dysfunction. Application of this assay could form the foundation for development of a new class of therapeutic agents for the treatment of urinary bladder dysfunction based on modulation of the purinergic nervous system.

Adenine Nucleotides

Traumatic rupture of the corpus cavernosum: evaluation and management.

Rupture of the corpus cavernosum is a rare but probably under-reported entity. It truly represents a urological emergency and current recommendations are for early surgical intervention. We review 5 cases with evaluation, treatment and followup. Delays in treatment lead to long-term complications, such as erectile dysfunction and penile curvature.

Adult

Masson's tumor of the kidney: a new renal lesion.

Intravascular papillary endothelial hyperplasia (Masson's tumor) is a rare benign reactive lesion usually found in thrombosed subcutaneous blood vessels. We report a case of Masson's tumor of the kidney, and discuss the relevant clinical, radiographical and pathological aspects.

Endothelium, Vascular

Xanthogranulomatous pyelonephritis and amyloidosis: a rare association.

The coincidence of systemic amyloidosis and xanthogranulomatous pyelonephritis has been reported previously only once. Clinical findings, such as the nephrotic syndrome, cardiac and autonomic nervous system dysfunction, and adrenal insufficiency, are suggestive and a thorough investigation to rule out other causes of secondary amyloidosis is warranted. We report a case of xanthogranulomatous pyelonephritis associated with secondary systemic amyloidosis and the nephrotic syndrome. Treatment consisted of nephrectomy and intensive supportive care. The unique clinical, radiographic and pathological aspects of this case are discussed.

Amyloidosis

Functional and biochemical alterations in the rabbit urinary bladder following ileocystoplasty.

Although the use of ileocystoplasty has increased significantly in recent years, very little is known concerning the smooth muscle properties of the implanted bowel segment. In a previous study, preliminary evidence was presented which indicated that the pharmacological response of the cytoplastic ileal segment to autonomic agonists changed toward that of the bladder. The present study extends and expands these preliminary observations on the physiology and pharmacology of augmentation cystoplasty. Augmentation cystoplasty with detubularized ileum was carried out in 16 rabbits. In vivo and in vitro physiological and pharmacological studies were carried out one and three months after surgery. The results can be summarized as follows: 1) in-vivo CMG at one month was similar to that of the preoperative bladder, but at three months there was a 24% increase in capacity, with the presence of multiple phasic contractions beginning at a volume of approximately 65% of capacity. 2) The frequency and magnitude of spontaneous activity in the cystoplastic ileum did not significantly alter from that of the normal ileum. 3) Cystoplastic ileum responded to muscarinic stimulation differently from the normal ileum. The bladder responded with an increase in the tension whereas the ileum responded with an increase in the frequency and amplitude of phasic contractions. The cystoplastic ileum responded with a pronounced sustained contraction with phasic contractions superimposed. The tonic contraction at three months was of a significantly greater magnitude than that at one month. 4) The qualitative and quantitative response to field stimulation of the cystoplastic ileum was altered from that of the ileum towards that of the bladder. 5) The normal bladder contains greater amount of creatine phosphate and lesser amounts of creatine than the normal ileum. Cystoplasty, after three months induced a change in the ileal segment towards the bladder (increased creatine phosphate and decreased creatine). 6) The normal ileum was found to have greater number of muscarinic receptors than the normal bladder whereas the cystoplastic ileum at three months was intermediate.

Animals

Vascular integrity of the distal ureter following combined tapering and cross trigonal reimplantation.

Massive unilateral hydroureteronephrosis was created in 20 female dogs by ligating the urographically normal prevesical ureter. Over a 14-day period the obstructed ureter dilated to an average of 15.3 mm. A ureteral tapering procedure was performed by lateral darting and posterior folding of the resultant flap, followed by a cross-trigonal reimplantation. One anastomotic stricture resulted; in the remaining 19 animals, ureteral peristalsis was restored, the ureteral diameter was reduced 61.9 per cent and hydronephrosis was resolved. Histological studies on the tapered segments of these 19 animals showed that the subadventitial blood supply was preserved with fibrotic occlusion of the folded flaps. These results demonstrate that no significant vascular compromise after ureteral tapering and cross-trigonal reimplantation occurs. Success rates comparable to those of conventional ureteral tailoring can be achieved by this technically simplified form of reconstructive surgery.

Animals

Bladder calculi in women after urethrovesical suspension.

There have been a number of reports recently on vesical calculi in women with a history of gynecological procedures. Within 1 year we encountered 2 patients with vesical calculi after vesicourethral suspension performed with concomitant hysterectomy. These calculi formed on a retained intravesical suture and a monofilament knitted polypropylene pledget, and they produced interesting pathological and radiographic findings.

Adult

Office urodynamics.

Each urologist can best form his or her own set of indications for and techniques of urodynamic evaluation or referral. Thus, what constitutes "office urodynamics" in one practice does not in another. The practicing urologist should at least have access to filling cystometry, flowmetry, residual urine determination, and voiding cystourethrography. All but the last named are certainly compatible with any office practice.

Ambulatory Care

Murine hybridoma antibodies against human transitional carcinoma-associated antigens.

Spleen cells from mice immunized with the human urinary bladder transitional cell carcinoma cell line 647V have been fused with a syngeneic myeloma cell line to produce hybridomas. Screening of supernatants from 40 hybridomas which reacted with the immunizing cell line identified antibodies recognizing a variety of common, shared and tumor-associated antigens as well as newborn calf serum dependent antigens. Three hybridoma antibodies, 9A7 , 2E1 and 2A6 , recognize antigens found on all the human transitional cell carcinoma cell lines and tissue preparations tested, but the antigens were not found on normal human tissue (including urothelium), thus demonstrating the capability of the antibodies to distinguish normal from malignant bladder transitional epithelium. These antibodies, however, otherwise differ in their patterns of reactivity, with 1 recognizing an antigen which is also expressed on highly anaplastic malignant non-transitional cell carcinoma cell lines and tumors, while the other 2 demonstrate reactivities which are far more restricted to transitional cell carcinoma.

Animals