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Biomedical subjects

C L Parsons

Publications and source records attributed to C L Parsons.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Characterization of microbial presence at the surface of silicone mammary implants.

The purpose of this project was to examine the incidence of microbial presence on the surface of mammary implants and its correlation with clinical presentation. The significance of microbial presence without signs of overt infection is questioned. Several issues are raised, including whether the presence of micro-organisms may immunize the host, trigger autoimmune reactions, or locally change the course of healing (resulting in capsular contracture). A total of 150 explanted silicone mammary implants from 87 patients were cultured. Cultures of 81 devices were positive (54%); the predominant isolate was Staphylococcus epidermidis (found on 68 implants, or 84%). Bacteria were detected on 76% (62 of 82) of implants surrounded by contracted capsules and on 28% (19 of 68) of those without capsular contracture (p < 0.05). Among 40 patients (46%) who had no general health problems, 11 (28%) had positive cultures of explanted devices (15 of 62 explants, or 24%). In the remaining 47 patients (54%) who complained of myalgia (77%), arthralgia (68%), chronic fatigue (38%), skin rashes (21%), cognitive problems (19%), dry mucosal membranes (19%), episodes of low-grade fever (17%), and hair loss (13%), 38 (81%) had positive cultures (66 of 88 explants, or 75%) (p < 0.05). The hypothesis that capsular contracture or problems that might be related to chronic infection and immunization are associated with subclinical infection is supported by this study.

Adult↗
PubMed1995

Transrectal ultrasound-guided transperineal cryoablation in the treatment of prostate carcinoma: preliminary results.

PURPOSE: We studied ultrasound-guided percutaneous cryoablation for treatment of prostate carcinoma. MATERIALS AND METHODS: Our series includes 83 individuals who underwent transrectal ultrasound-guided transperineal percutaneous cryoablation of the prostate. Prostate specific antigen levels, biopsy results and complications were assessed at 3 months. RESULTS: Of 61 biopsies 8 (13.1%) were positive for carcinoma (half showed stage D disease). Of patients with stages T1 to T3 cancer 92.6% were free of disease at 3 months. Prostate specific antigen levels were significantly decreased by an average of 1.90 ng./ml. (p < 0.05). Major complications were infrequent, including bladder perforation in 1 patient, urethral strictures in 3, bladder outlet obstruction in 2 and partial incontinence in 2. Impotence was frequent but transient. CONCLUSIONS: Transrectal ultrasound-guided transperineal percutaneous cryoablation of the prostate produces few major complications and appears at 3 months to be effective in eradicating local prostate tumors. Longer followup is required to test the original hypothesis.

Adult↗
PubMed1995

Selective type IV collagen defects in the urothelial basement membrane in interstitial cystitis.

PURPOSE: The study sought to identify changes in the urothelial basement membrane (UBM) associated with interstitial cystitis (IC). MATERIALS AND METHODS: Immunohistochemical assessment of bladder biopsies from IC patients and controls was compared with clinical and histologic findings. RESULTS: Selective decreases or loss of type IV collagen staining, but not laminin, were found in the UBM of 5 of 11 IC patients with no change in type IV collagen staining of other bladder wall sites. CONCLUSIONS: The loss of type IV collagen may represent a primary or secondary event and could alter the UBM's role in permeability, thereby contributing to the pathogenesis of IC in the subset of IC patients exhibiting this change.

Adult↗
PubMed1995

Production of soluble virulence factor by Escherichia coli.

Experimental evidence suggests that adherence is a prerequisite for bacterial infection. We demonstrated that transitional cells at the surface of the bladder are coated with glycosaminoglycans (proteoglycans and mucus) whose presence efficiently decreases bacterial adherence to the mucosa. Exposure of mucus to protamine sulfate, a quaternary amine (known to form salts with glycosaminoglycans and inactivate them) significantly increases the bacterial adherence to the bladder. Investigators have primarily focused on bacterial surface factors (that is pili or fimbriae, glycocalix) in relation to the ability to adhere. We explored the hypothesis that Escherichia coli produces a soluble virulence factor that increases the infection rate in rabbits by promoting bacterial adherence to the bladder mucosa. In addition, it was proposed that this factor is a quaternary amine similar to protamine. For these studies an in vivo bacterial infection assay (which we described previously in rabbits) was used to examine E. coli metabolic products (soluble virulence factor) that could promote bacterial persistence in the bladder by perturbing mucus (glycosaminoglycans), and promote bacterial adherence and virulence. E. coli was grown in human urine and a bacterial-free supernatant was collected. Rabbit bladders were then exposed to either this supernatant or to the same human urine that was not infected with E. coli. Results show a significantly higher bacterial persistence (bacterial count) in bladders pretreated with urine containing the E. coli supernatants compared to controls pretreated with uninfected urine (p = 0.03). The molecular weight of the putative soluble virulence factor is less than 3.5 kD. (p = 0.056) based on dialysis studies and binds to heparin agarose affinity chromatography matrix, suggesting that it is cationic and capable of adhering to the highly anionic bladder mucus (glycosaminoglycans).

Animals↗
PubMed1994

Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis.

The urgency-frequency syndrome (UFS) (non-bacterial cystitis, interstitial cystitis) may well represent a heterogenous group with several etiologies. This study was based on the hypothesis that one subset of UFS patients has a leaky (to solutes) epithelium and cations such as potassium could thereby diffuse subepithelially and provoke symptoms. It was also hypothesized that normal impermeable transitional epithelium would not allow cations to diffuse across the cells during the K+ provocation test and no symptoms would be experienced. If the epithelium was permeable ("leaky"), diffusion would occur and provoke symptoms. Water or 0.4 M KCl was placed intravesically into normal volunteers and interstitial cystitis (IC) patients. Water did not provoke symptoms in either group but KCl provoked 4.5% of normals and 70% of IC patients. Differences were significant (P < 0.0001). This test provides a valuable diagnostic tool for UFS and a valuable research tool to separate epithelial permeability problems from other subsets of patients. A third group, consisting of 11 IC patients in remission on heparinoid therapy, was also tested and only 18% were provoked by KCl. Four patients with radiation cystitis were also examined and all four (100%) were provoked by the potassium.

Administration, Intravesical↗
PubMed1994

Proteoglycan core protein syndecan in bladder biopsies.

The etiology of interstitial cystitis (IC) may be related to a dysfunctional epithelium caused by an abnormal permeability barrier. The presence of deleterious urinary substances (quaternary amines) that alter an otherwise normal epithelium may also be contributory. IC disease could reflect an inability of the bladder to repair its protective surface-coat material (glycosaminoglycans and proteoglycans), which is constantly exposed to a toxic urine environment. Bladder biopsy tissue from IC patients and derived explant cells were investigated to determine if mRNA for a proteoglycan core protein could be extracted and evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Syndecan was chosen for this investigation because the available sequence information permitted PCR primers to be synthesized. The results indicated that biopsy tissue and explant cells could be utilized for the isolation of syndecan core protein mRNA. This proteoglycan was also demonstrated in mouse bladders by immunostaining and immunoblotting (but not in human tissues) using a syndecan-specific monoclonal antibody (281-2). Quantitative differences in IC tissues versus normal bladder tissue with respect to gene expression for this proteoglycan core protein can now be determined.

Animals↗
PubMed1994

A model for the function of glycosaminoglycans in the urinary tract.

Investigations into the antibacterial defense mechanisms of the urinary tract revealed an important function for cell surface glycosaminoglycans (GAG), that of a generalized antiadherent activity. This activity was found to prevent bacterial, protein, and ionic adherence to the cell membrane. A model was developed to explain mechanically the activity of sulfated polysaccharides at the bladder surface. The model predicted injurious effects of quaternary amines and also that the mucus would be the so-called blood-urine barrier. It also led to the hypothesis that exogenous polysaccharides may be important in treating bladder disease such as infection and interstitial cystitis. For the first clinical test of these concepts, a polysaccharide was employed in several double-blind studies and was shown to ameliorate significantly the symptoms of interstitial cystitis. These discoveries suggest new methods to manipulate the microenvironment between the transitional cell surface and the urine, leading to novel therapies in regulating disease of the genitourinary tract. They also stress the importance of understanding the mechanisms by which GAGs exert their effect in the urinary tract and how they are produced, maintained, and even inactivated (e.g., by urinary substances such as protamine).

Animals↗
PubMed1994

Activation of urinary kallikrein in patients with interstitial cystitis.

A potential pathophysiological role for the urinary kallikrein-kinin system is suggested by the prominent symptoms of bladder pain and urinary frequency in interstitial cystitis. Kallikrein activity in the urine of 84 patients with interstitial cystitis and 33 normal volunteers was determined by cleavage of the synthetic substrate Val-Leu-Arg-pNA. Interstitial cystitis patients had significantly higher levels of kallikrein activity than did the normal volunteers. Kallikrein activity was correlated with symptoms of bladder pain and voiding frequency. The percentage of total urinary kallikrein in the active form correlated with active kallikrein levels and was also increased in interstitial cystitis patients, particularly those with higher levels of pain. Patients who underwent hydrodistention and subsequently experienced relief from the bladder symptoms had a decrease in urinary kallikrein levels, whereas patients who failed to improve following hydrodistention did not.

Adult↗
PubMed1994

A new method for cytodestruction of bladder epithelium using protamine sulfate and urea.

Bladder epithelium relies primarily on the presence of a surface glycosaminoglycan (GAG) layer and the structural integrity of cell-cell contact to maintain impermeability to toxic urinary wastes. Previous clinical studies evaluating bladder permeability characteristics in interstitial cystitis patients had indicated that epithelial desquamation occurs after treatment with protamine sulfate (PS) followed by hypertonic urea. The following study was performed using rabbits to further investigate this finding. The urinary bladder was evaluated for optimal treatment conditions for epithelial removal. Protamine sulfate (1 to 10 mg./ml.) and urea (100 to 200 gm./ml.) were instilled into the bladder at volumes ranging from 5 to 60 ml. to that required for near maximum distention. After incubation at room temperature for 15 minutes, the bladders were fixed and evaluated histologically for epithelial removal. The maximum epithelial removal occurred when the bladders were distended, and when PS concentration was 5 to 10 mg./ml. and urea at 200 gm./l. There was greater epithelium removal after repeated treatments. Epithelial cells that were removed were not viable based on Trypan blue staining. There was no significant increase of C14 labeled urea in the plasma after 15 minutes. Rabbits that were followed for 6 weeks after treatment did not show any histological evidence of increased collagen deposition and/or fibrosis. This procedure may have important clinical value since it may remove sufficient bladder epithelium in patients with transitional cell carcinoma to have therapeutic benefit. This offers a realistic option for selective, nontoxic destruction of bladder epithelium.

Administration, Intravesical↗
PubMed1994

Inflammatory mediator profile in urine and bladder wash fluid of patients with interstitial cystitis.

Interstitial cystitis is a syndrome of urinary urgency, frequency and suprapubic pain. We investigated the role of inflammatory mediators in 96 patients with histories and symptoms consistent with interstitial cystitis, and 13 controls from The New York Hospital-Cornell Medical Center, University of Washington and University of California at San Diego. Patients were classified into either group A (meets all criteria of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases for inclusion in research studies), group B (meets all of these criteria but without glomerulations) or an "other" group. A small number of group A patients had detectable interleukin-6 in the urine. Urinary concentrations of tumor necrosis factor, prostaglandins E2, D2 and F2 alpha, and thromboxane B2 were not different among either patient groups or controls. Urine specimens contained inhibitors of the bioactivity of interleukin-6 and tumor necrosis factors but no differences between patients or controls were found. No factors chemotactic for human neutrophils were detected in a small patient sample. Bladder wash fluid concentrations of prostaglandins E2, D2 and F2 alpha, and thromboxane were much lower than urinary levels. Bladder wash fluid interleukin-6 and tumor necrosis factor were not detectable. The results suggest that while a small subset of patients may have elevated levels of interleukin-6 the majority of patients do not appear to have elevated levels of inflammatory mediators in the urine or bladder wash fluid. Evaluation of patient bladder tissue may indicate changes not detectable in urine or bladder wash fluid. Alternatively, other etiologies must be considered in those patients.

Adult↗