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C L Parsons

Publications and source records attributed to C L Parsons.

At least 19 recordsLinked to original sources
PubMed2000

Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis.

PURPOSE: Tamm-Horsfall protein (THP) is a ubiquitous urinary protein with essentially no known function. We propose that THP is a cytoprotective agent that protects the urothelium from cationic species. To test this hypothesis we isolated THP from normal and interstitial cystitis urine to see if it could protect cultured cells from damage induced by the polyamine, protamine sulfate (PS). METHODS: Tamm-Horsfall protein was extracted from the urine of interstitial cystitis (IC) patients (N=28) and normal volunteers (N=5). Urothelial target cells (T24) were radiolabeled with 51Cr and then exposed to PS (0-1.0 mg/mL) for either 1.5 or 20 h. The resulting cytotoxicity data (dose-response curves) were then compared with the data obtained when PS was preincubated with 0-0.5 mg/mL of THP (IC vs normal), the semisynthetic polysaccharide, pentosan polysulfate (Elmiron), or human serum albumin. RESULTS: Toxicity of PS was significantly reduced by incubation with THP (or Elmiron) prior to evaluation by the chromium release assay, but not reduced by incubating with another protein, albumin. Tamm-Horsfall protein from IC patients' urine was less protective than an equal quantity of THP from normal urine. CONCLUSIONS: These experiments suggest that THP has an important role in bladder mucosal defense mechanisms, protecting the bladder surface from injury. Inability of THP to prevent cytotoxic damage by urinary polyamine or other urinary toxins (cationic species) may be relevant in the etiology of interstitial cystitis, as putative urinary toxic components have been described in the urine of some patients.

Adjuvants, Immunologic↗
PubMed1999

Elevated urinary norepinephrine in interstitial cystitis.

OBJECTIVES: To measure urinary catecholamines and determine the extent to which they may be elevated in urine from patients with interstitial cystitis (IC). METHODS: Random urine samples from patients with IC (n = 111) and urine from normal volunteers (n = 92) were acidified on collection (voided and catheterized specimens) and assayed for catecholamine (norepinephrine or normetanephrine) by enzyme-linked immunosorbent assay. Creatinine levels in these urine samples were also measured. RESULTS: Analysis of the data indicated that patients with IC had a higher urinary level of the neurotransmitter norepinephrine compared with the measured levels in the urine of normal volunteers (89.1 +/- 58.3 versus 54.9 +/- 37.1 microg/g creatinine, P <0.05). The metabolite normetanephrine was similar in the urine samples from these two groups. Urine from patients with bladder outlet obstruction (n = 11) did not have elevated amounts of urinary norepinephrine. The norepinephrine levels were not statistically different in the urine samples from patients with symptomatic and asymptomatic IC. The elevated urinary levels in patients with IC did not decrease after treatment with sodium pentosanpolysulfate (Elmiron), heparinoids, dimethyl sulfoxide, or combinations of these during 1 to 15 months of treatment. CONCLUSIONS: Norepinephrine was found to be elevated in the urine from patients with IC compared with urine from normal controls. This would be consistent with increased sympathetic (adrenergic) activity from the bladders of patients with IC or possibly from increased adrenal activity, since stress is associated with symptom increase in some patients with IC. Norepinephrine levels did not decrease with treatment nor did they differ between symptomatic and asymptomatic patients at the time of urine collection.

Adult↗
PubMed1999

Natural history of interstitial cystitis in 274 patients receiving sulfated polysaccharide therapy.

OBJECTIVES: To assess the natural history of interstitial cystitis in the presence of sulfated polysaccharide treatment. METHODS: This was a longitudinal study of 274 patients. Questionnaires were administered at first visit to obtain information on demographic characteristics, medical history, other risk factors, and type and severity of symptoms. Follow-up questionnaires were administered at subsequent visits to measure symptom progress. Patient status over time was measured for three symptoms: pain, urgency, and nocturia. Changes in symptom and severity were assessed at 6, 12, and 24 months on treatment. Comparisons of symptom change from baseline to 6 and 12 months were assessed for different characteristics among patients with the most severe symptoms. RESULTS: After 1 year of treatment, a decrease of two or more points in symptom score was observed for 33.5% of all patients for pain and 35.4% for urgency. Among patients with the most severe symptoms, a decrease of two or more points was observed in more than 54% for pain and urgency; 55.7% experienced remission to the moderate and mild level (49.2% and 6.5%, respectively). There was no appreciable decrease in nocturia at any severity level. With the exception of feeling heavy and experiencing dull pain at baseline, patients who did not report a specific type of pain improved more than those who did. CONCLUSIONS: The results of this study suggest that treatment with sulfated polysaccharides can help alleviate the symptoms of patients suffering from the most severe stages of interstitial cystitis.

Adult↗
PubMed1998

The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis.

PURPOSE: We determined whether intravesical potassium absorption in normal bladders correlates with increased sensory urgency, and corroborated the hypothesis that mucus is important in the regulation of epithelial permeability. We compared sensory nerve provocative ability of sodium versus potassium, and determined whether intravesical potassium sensitivity discriminates patients with interstitial cystitis from normal subjects and those with other sensory disorders of the bladder. MATERIALS AND METHODS: A total of 231 patients with interstitial cystitis and 41 normal subjects underwent intravesical challenge with 40 ml. water and then 40 ml. of 40 mEq./100 ml. potassium chloride. Subjective responses of urgency or pain stimulation were recorded on a scale of 0 to 5. In 19 normal subjects potassium absorption was measured at baseline, after injury of the bladder mucus with protamine, after heparin treatment to reverse mucus damage and then for a final time. These subjects simultaneously recorded the symptoms of sensory urgency and pain at baseline, after protamine and after heparin. Another group of normal volunteers underwent a challenge with sodium versus potassium to determine which cation was more provocative. Patients with bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), detrusor instability, and acute and chronic urinary tract infection but no current infection were also evaluated for potassium sensitivity. RESULTS: Neither normal subjects nor patients with interstitial cystitis reacted to water administered intravesically. There was marked sensitivity to intravesical potassium in 75% of patients with interstitial cystitis versus 4% of controls (p <0.01). Only 1 patient with BPH responded to potassium and none of the 5 with chronic urinary tract infection responded. All 4 patients (100%) with a current acute urinary tract infection reacted positively to the potassium challenge. Of 16 patients with detrusor instability 25% responded. Normal subjects had minimal sensitivity to potassium before (11%) and markedly increased sensitivity after (79%) protamine treatment, and these symptoms were reversed by heparin in 42%. Potassium absorption directly correlated with symptoms (0.4, 3.0 and 1.3 mEq. before and after protamine, and after heparin reversal, respectively). In regard to sodium versus potassium provocation, potassium was far more provocative for causing urgency after protamine (10 versus 90%). Neither group underwent provocation before protamine. CONCLUSIONS: Chronic diffusion of urinary potassium into the bladder interstitium may induce sensory symptoms, damage tissue and be a major toxic factor in the pathogenesis of interstitial cystitis. Intravesical potassium sensitivity is a reliable method for detecting abnormal epithelial permeability. It discriminates between patients with interstitial cystitis and normal subjects with intact epithelial function, and it is a useful diagnostic test for interstitial cystitis. Potassium sensitivity correlates with increased potassium absorption in normal subjects, and potassium is far more provocative than sodium. Potassium sensitivity is also present in acute urinary tract infection and occasionally detrusor instability but not in BPH or chronic urinary tract infections.

Adult↗
PubMed1998

New indications for radical prostatectomy.

PURPOSE: Radical prostatectomy is considered the gold standard for treatment of localized prostate cancer, either as primary or salvage therapy. Recently with the advent of increased organ transplantation, use of prostatic specific antigen for cancer detection and cryoablation as an alternative treatment, more men with prostate cancer can be considered for radical surgery. We review these new indications. MATERIALS AND METHODS: Clinically localized untreated prostate cancers were identified in 3 men being considered for cardiac or lung transplantation (group 1), and 4 men originally treated with transperineal cryoablation had local relapse (group 2). All 7 men underwent radical prostatectomy. RESULTS: Organ confined cancer (pT2C) was found in all 3 patients in group 1. All 3 men underwent successful cardiac or lung transplantation 1 to 12 months after radical prostatectomy, and they are disease-free at short-term followup. Of the group 2 patients 2 had organ confined disease (pT2b and c) and 2 had extensive extraprostatic disease (pT3cN1 and pT3cN0). Only 2 patients remain disease-free and do not require adjuvant endocrine therapy. Major perioperative complications of rectotomy and total incontinence occurred only in group 2 patients. CONCLUSIONS: Patients being considered for heart and lung transplantation need to be free of concurrent malignancy because of immunosuppressive therapy. Radical prostatectomy can achieve this goal in select patients. Cases of failed cryoablation can be salvaged with radical prostatectomy but with less chance of success and with greater risk of complications.

Aged↗
PubMed1998

Elevated stress protein in transitional cells exposed to urine from interstitial cystitis patients.

BACKGROUND: It has been hypothesized that urine from interstitial cystitis (IC) patients may contain one or more toxic factors not present in "normal" urine. Bladder tissues exposed to these toxic factors could have elevated stress proteins. If this assumption is correct, stress protein levels could be a useful marker for identifying patients at risk for developing this syndrome. METHODS: To experimentally investigate this possibility, a sensitive assay (ELISA) was used to measure levels of the 72 kDa stress protein in urothelial target cells after in vitro exposure to urine from IC patients. RESULTS: We observed a modest 12% increase in 72 kDa stress protein in cells treated with urine from IC patients compared to cells exposed to normal urine (1.12 compared to 0.99 ng/microg extracted protein; P < 0.05). In addition, it was possible to demonstrate the 72 kDa stress protein in histologic sections obtained from mucosal biopsies of IC patients. Stress protein was located primarily in the surface urothelial cells of the mucosa. CONCLUSIONS: These results seem to indicate that stress protein could play an important protective role at this particular site. They further suggest that IC urine is more toxic than normal urine and, in contact with underlying urothelial and deeper bladder tissue, may upregulate genes involved in stress protein responses. This may be an important concept in the etiology of IC.

Biomarkers↗
PubMed1997

Epithelial coating techniques in the treatment of interstitial cystitis.

OBJECTIVES: To review the newer methods of treatment of interstitial cystitis using techniques that coat the epithelium to maintain its integrity relative to permeability. METHODS: The technique of employing sulfated polysaccharides in the treatment of interstitial cystitis both orally and intravesically were reviewed as well as the concepts supporting the use of such technology, including a review of the role glycosaminoglycans (mucus) play in the regulation of epithelial permeability. Also reviewed were the methods that can be employed to detect aberrations of epithelial permeability as seen in the interstitial cystitis syndrome. RESULTS: The techniques of detecting epithelial permeability problems and appropriate therapy for this using polysaccharides, such as heparin and pentosanpolysulfate, are presented. This article also discusses the point that these techniques will result in long-term remissions in patients with the IC syndrome who respond to these treatments. CONCLUSIONS: The use of sulfated polysaccharides, both orally and intravesically, is an effective long-term treatment for many people with the interstitial cystitis syndrome.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Associations among cystoscopic and urodynamic findings for women enrolled in the Interstitial Cystitis Data Base (ICDB) Study.

OBJECTIVES: Interstitial cystitis is a symptom complex characterized by pelvic pain, urinary urgency, urinary frequency, and nocturia. Patients with these symptoms, at the 5 clinical centers participating in the National Interstitial Cystitis Data Base (ICDB) Study, have been evaluated with history and physical exams, questionnaires, and urodynamic studies. METHODS: Of the 388 female subjects entered in the study as of December 31, 1995, 150 women have undergone cystoscopy with hydrodistension. The data from the endoscopic procedures and the urodynamic studies were analyzed. The associations among cystoscopic and urodynamic findings were reviewed. RESULTS: Patient demographics of this subgroup show a predominance of Caucasians 139/150 (92.7%), with the average age being 43 (+/-13.2) years. Of the total, 17 patients (11.3%) had a Hunner's patch (HP). The prevalence by center varied from a low of 2/38 (5.3%) to a high of 3/9 (33.3%). Bloody effluent following hydrodistension was present in 113/150 (75.3%). Glomerulations appeared in varying degrees (mild, moderate, severe) in 91.3% of the 150 patients. There was a strong inverse relationship (P < 0.001) between bladder capacity under anesthesia and the presence of a HP (mean of 845 cc with HP absent versus a mean of 531 cc when present). The incidence of HP varied from 67.6% among women with a bladder capacity at hydrodistension of < 400 cc to 3.8% for those with a bladder capacity of at least 800 cc. The presence and increasing severity of glomerulations was positively associated (P < 0.003) with the presence of HP, ranging from 0/13 (0%) when glomerulations were not present to 6/31 (19.4%) when glomerulations were graded as severe. Of the patients with HP, 17/17 (100%) had glomerulations after hydrodistension. HP is more closely associated with the moderate to severe range of glomerulations (P < 0.01). Nearly half of the patients with HP or 8/17 (47.1%) had "moderate" glomerulations, while 6/17 (35.3%) had "severe" glomerulations. The volume at first sensation to void on urodynamics (mean 87 cc without HP versus 34.7 cc with HP) was highly inversely associated (P = 0.002) with the presence of HP, but not with any of the other cystoscopic findings. Of patients with HP, 94% had a volume at first sensation to void of < or = 50 cc where only 36% of patients without HP had a volume at first sensation to void of < or = 50 cc. The volume at maximum capacity on urodynamics was positively associated with the volume at hydrodistension (P < 0.001). CONCLUSIONS: Overall, patients with HP had lower bladder capacities, lower volumes at first sensation to void, and more severe glomerulations. Thus, the presence of HP would imply a more severe case of interstitial cystitis. Logically, a higher bladder capacity on cystometrogram is associated with a higher volume at the time of hydrodistension, and bloody effluent is associated with more severe glomerulations.

Adult↗
PubMed1996

Cryoablation for carcinoma of the prostate.

Percutaneous transperineal cryoablation of the prostate is now available in the armamentarium for treatment of prostate cancer. Technical advances in real-time transrectal imaging of the prostate and improvements in cryosurgical equipment have brought this modality into the limelight of available prostate cancer management. Cryosurgery can be offered to many patients with prostate cancer. However, the main indications for its use include primary treatment for localized disease, salvage therapy after failure of traditional methods, and relief of local symptoms. A historical background, description of the technique, and clinical experience at several medical centers including the University of California San Diego, Allegheny General Hospital, University of Texas M.D. Anderson Cancer Center, and Crittenton Hospital, are presented.

Biopsy↗
PubMed1996

Electrophysiologic monitoring of the effects of soluble virulence factors produced by Escherichia coli infection in urine.

OBJECTIVES: The presence of soluble virulence factors in urine infected by Escherichia coli has been postulated by recent studies in a rabbit bladder model. These substances may enhance bacterial adherence by damaging the glycosaminoglycan (GAG) layer that normally blocks both bacterial adherence and diffusion of solutes to the level of the epithelial membrane. We evaluated the effects of E. coli-infected urine on New Zealand white rabbit bladder mucosal permeability by measuring conductance (g) and current (I) and then calculating resistance (R) using the formula R = I divided by g. METHODS: Forty-five rabbit bladders were prepared and mounted in Ussing chambers. The group was divided equally into three smaller cohorts (n = 15). The first cohort (NL) was exposed to uninfected sterile-filtered urine, the second cohort (PS) was a positive control exposed to uninfected sterile-filtered urine containing protamine sulfate, and the final cohort (INFX) was exposed to supernatants of E. coli-infected (more than 10(7) colony-forming units) sterile-filtered urine. The average time of exposure was 160 minutes, and the previously mentioned electrophysiologic parameters were measured and recorded. RESULTS: The results of the PS group showed statistically significant differences in conductance, current, and resistance compared with the NL group. The decline in resistance accompanied by elevation in both current and conductance was an indirect indication that the GAG layer was functionally disturbed with a secondary increase in mucosal permeability. In a similar fashion, the INFX group also showed a statistically significant rise in conductance as well as a decline in resistance. CONCLUSIONS: These data support the concept that E. coli-infected urine contains soluble factors that can damage the GAG layer. Although these substances appear to be less potent than quaternary or polyamines such as protamine sulfate, their mechanism of action appears similar and may enhance bacterial virulence.

Animals↗
PubMed1996

A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis.

OBJECTIVES: To investigate the abundance of chondroitin sulfate proteoglycans at the bladder lumenal and subepithelial surfaces in bladder biopsies derived from patients with interstitial cystitis (IC) and controls. METHODS: Tissue sections derived from biopsies from 31 IC patients and 24 pathologically normal control sections were labeled for proteoglycans using the 2B6 anti-"stub" antibody and detected by immunohistochemistry. RESULTS: On the lumenal surface, 5 of 31 (19%) IC sections were positive for proteoglycans versus 14 of 24 (58%) control sections (P = 0.00011). At the basal surface, 5 of 19 IC patients were positive versus 7 of 12 controls (P = 0.032). CONCLUSIONS: A deficit of bladder lumenal and basal proteoglycans is associated with IC. The deficit in basal layer proteoglycans suggests an altered urothelial differentiation program. The lumenal deficit suggests that the charge-dependent exclusion of ions from the bladder surface is compromised in IC.

Chondroitin Sulfates↗
PubMed1996

Bladder injury model induced in rats by exposure to protamine sulfate followed by bacterial endotoxin.

PURPOSE: A bladder injury model was developed using protamine sulfate (PS) and endotoxin lipopolysaccharide (LPS) administered intravesically to female Sprague-Dawley rats. MATERIALS AND METHODS: Experimental and control animals were catheterized and intravesically exposed to PS-LPS, PS, LPS, or phosphate buffered saline. After 4, 24 or 72 hours, rats were sacrificed. Urines and bladder tissues were then obtained. Bladder mucosal permeability was evaluated by measuring 14C-urea uptake 24 hours after injury. Repeated instillations of PS/LPS were also made in another group of rats over a period of 5 weeks to attempt to establish a more serious mucosal injury, possibly reflected by altered staining of the collagen IV component of the urinary basement membrane (UBM). RESULTS: Histological examination of the tissues indicated a maximal inflammatory response in the mucosa 4 hours after instillation of PS/LPS. Neutrophils and macrophages in close proximity to the UBM and intraepithelially could be demonstrated. Bladder permeability was significantly altered (26.9% 14C-urea uptake) in rats assayed 24 hours after the PS/LPS treatment, but not after exposure to PS or LPS alone (11.9 and 17.5%, respectively). Protease activity detected in urines from experimental, but not control, animals coincided with the appearance of inflammatory cells in the lamina propria. Inflammatory injury did not appear to alter the collagen IV staining of the UBM. CONCLUSIONS: This rat bladder injury model is useful for examining controversial issues regarding bladder wall structure-function alterations induced by inflammation and possibly important in the pathobiological mechanisms involved in some patients with interstitial cystitis.

Animals↗
PubMed1996

Potassium sensitivity test.

Intravesical potassium sensitivity can readily elicit abnormal epithelial permeability responses in subjects with diseased bladder, primarily interstitial cystitis. The technique involves eliciting responses in each subject to 40 cc of plain water or 40 cc of potassium chloride solution (40 mEq per 100 cc water). The subjects are asked to rate their subjective responses 3-5 minutes after instillation of the test solution and told to compare the water and potassium. An abnormal provocation to potassium but not water is considered a positive response and a useful way to delineate people with epithelial dysfunction and loss of permeability control. On the other hand, normal subjects will not respond to either the water or potassium.

Administration, Intravesical↗
PubMed1995

Intestinal de-epithelialization and augmentation cystoplasty: an animal model.

OBJECTIVES: An animal model of augmentation cystoplasty was developed in New Zealand rabbits to study the effects of intestinal de-epithelialization on subsequent re-epithelialization by bladder urothelium. METHODS: Twenty-four rabbits underwent augmentation cystoplasty using intestinal segments that were either treated with protamine sulfate and urea solution or else anastomosed with an intact epithelium. Half of the rabbits receiving the de-epithelialized intestinal segments were subjected to glycosaminoglycan replacement therapy by administration of intravesical heparin. Experimental and control rabbits were sacrificed at 1-, 2-, and 3-month intervals. RESULTS: Histologic examination of the augmented sections showed small areas of urothelium growing over the intestinal epithelium (approximately 15%). The heparin-treated group demonstrated the greatest amount of re-epithelialization. There was no obvious histologic difference in the amount of collagen present in the augmented tissues in any of the experimental groups. CONCLUSIONS: In a preliminary study, New Zealand rabbits appear to be satisfactory as an experimental animal for studying the augmentation cystoplasty procedure and for the development of therapeutic interventions for enhancing epithelial growth. Protamine and urea will de-epithelialize the bowel and heparin may promote epithelialization of augmented intestinal segment by transitional epithelium.

Anastomosis, Surgical↗