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Biomedical subjects

C L Parsons

Publications and source records attributed to C L Parsons.

At least 55 records · Page 3Linked to original sources
PubMed1994

Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo.

We have previously demonstrated that the quaternary amine, protamine sulfate (PS), is bactericidal against Staphylococcus epidermidis. In an attempt to decrease genitourinary prosthesis infection rates, we examined the ability of PS as a wound irrigant to inhibit Staphylococcus epidermidis viability. Eighty-seven Sprague-Dawley rats were studied by implanting a sterile silicone pellet in their dorsum. The pellet was inoculated with Staphylococcus epidermidis and the rats were divided into four groups based on the wound irrigant employed after inoculation: (1) control (sterile water) (2) vancomycin; (3) PS; (4) vancomycin + PS. All rats received perioperative and daily intramuscular vancomycin, and the pellets were explanted on postoperative day 28 and cultured. The infection rates were: (1) control 77%, (2) vancomycin 50%, (3) protamine sulfate 67%, and (4) protamine sulfate and vancomycin 19%. The differences between (2) vancomycin versus (4) vancomycin + PS and (3) PS versus (4) vancomycin + PS were significant (p = 0.05 and p < 0.005). The data suggest that PS potentiates vancomycin as a wound irrigant in prosthesis implantation.

Animals↗
PubMed1994

Decreased expression of a glycoprotein component of bladder surface mucin (GP1) in interstitial cystitis.

Interstitial cystitis is a disease of unknown etiology characterized by unremitting urinary frequency, urgency and suprapubic pain. Recently, a change in urothelial permeability has been identified in interstitial cystitis patients that is presumably mediated by aberrations in bladder surface mucin. For this study we evaluated qualitative changes in a previously defined glycoprotein component of this layer (GP1) as it occurs in interstitial cystitis patients and normal controls. Paraffinized bladder biopsies were obtained from 23 interstitial cystitis patients (all meeting National Institutes of Health inclusion criteria) and 11 normal controls. All biopsy tissue was stained with hematoxylin and eosin, and periodic acid, Schiff reaction. The tissues were examined immunohistochemically for GP1 using an anti-GP1 serum. Periodic acid, Schiff staining clearly identified bladder surface proteoglycans in all specimens. Moderate GP1 reactivity was noted in all normal control specimens. Alternatively, GP1 expression was absent in 35% of the interstitial cystitis patient biopsies and decreased in 61%. These data demonstrate qualitative GP1 changes in a majority of interstitial cystitis patients. It is unknown whether these differences have an impact on the pathogenesis of interstitial cystitis. However, our findings suggest that the absence or decreased expression of GP1 in interstitial cystitis bladder biopsies may serve as a marker to characterize the disease further in conjunction with clinical findings.

Adult↗
PubMed1994

Fibroblast behavior in vitro is unaltered by products of staphylococci cultured from silicone implants.

Our previous clinical study supported the concept that capsular contracture is associated with subclinical infection of silicone implants. If bacterial presence, indeed, contributes to capsular contracture, then fibroblast behavior might be expected to change in the presence of bacteria by-products. Therefore, study of possible alteration of fibroblast behavior by bacteria products was undertaken using an in vitro model with cultured dermal fibroblasts. Coagulase-negative staphylococci from silicone mammary and penile implants were isolated and their phenotypic features were characterized. All represented nonbiofilm-producing strains. Products of isolate cultures were noncytotoxic and did not alter matrix reorganization (collagen gel contraction model) or collagen production by fibroblasts. Isolates from either mammary or penile implants exerted similar effects.

Breast↗
PubMed1994

Treatment of interstitial cystitis with intravesical heparin.

OBJECTIVE: To control the symptoms of interstitial cystitis with chronic self-administered intravesical heparin and determine whether the drug's continued use can sustain remission. PATIENTS AND METHODS: A total of 48 patients were selected to undergo intravesical heparin therapy, 10,000 units in 10 ml sterile water, three times per week for 3 months. For patients who attained a good clinical remission, therapy was available for up to a further 9 months. RESULTS: At 3 months 27 of 48 patients (56%) attained good clinical remissions. All were offered continuous therapy and 23 elected for an additional 3 months. Twenty of the 23 continued in remission. Sixteen of these patients elected to have a further 6 months of therapy (12 months total) and 15 of 16 remained in remission. CONCLUSION: In over half of the patients studied, intravesical heparin controls the symptoms of interstitial cystitis with continued improvement even after one year of therapy.

Administration, Intravesical↗
PubMed1994

The therapeutic role of sulfated polysaccharides in the urinary bladder.

Polysaccharide therapy for bladder disease is a novel therapy based on the model of bladder mucus activity and the belief that mucus and exogenous glycosaminoglycans (GAG) have protective properties. Interstitial cystitis is the first disease explored for the potential use of polysaccharide therapy, which appears to be effective in some patients with this syndrome.

Animals↗
PubMed1993

A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate.

A randomized, prospective, double-blind, placebo-controlled study was conducted at 7 clinical centers on 148 patients. Patients received orally either 100 mg. pentosanpolysulfate (a synthetic polysaccharide) 3 times per day or a placebo. Of the patients on drug therapy 32% showed significant improvement compared to 16% of those on placebo (p = 0.01). This study provides a model to assess this disease quantitatively in a prospective manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0, 25, 50, 75 or 100%. Patients on drug therapy also experienced a significant decrease in pain and urgency (p = 0.04 and 0.01) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml. in voided volume than did placebo patients (p = 0.02). All adverse effects were minor, with 7 in the drug group and 10 in the placebo group. The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans.

Aged↗
PubMed1993

Evaluation of urothelial Tamm-Horsfall protein and serum antibody as a potential diagnostic marker for interstitial cystitis.

Demonstration of adherence of Tamm-Horsfall protein to bladder epithelium has been suggested as a potential diagnostic test for interstitial cystitis. Bladder specimens from 18 interstitial cystitis patients were evaluated by indirect immunoperoxidase techniques using a Tamm-Horsfall protein specific monoclonal antibody to determine the diagnostic value of the staining results. The study population consisted of 7 severely diseased patients who required cystectomy with urinary diversion and 11 other patients meeting National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis. We were unable to detect intraepithelial or surface-bound Tamm-Horsfall protein in any of the biopsy tissues. Human kidney tissue, similarly fixed and processed, consistently demonstrated Tamm-Horsfall protein staining of the kidney tubules. The monoclonal antibody also reacted on Western blots against urinary Tamm-Horsfall protein. Although antibody (alpha-Tamm-Horsfall protein) reactivity was measured by enzyme-linked immunosorbent assay in sera from interstitial cystitis patients, the titers did not differ statistically from those measured in sera from those without interstitial cystitis. Together, these results make it unlikely that immunohistochemical detection of Tamm-Horsfall protein will have diagnostic value in interstitial cystitis. Whether Tamm-Horsfall protein has a role in the pathogenic processes involved in this disease is not yet known. These findings do not eliminate the possibility that some interstitial cystitis patients will have abnormalities associated with the biochemical and physiological functions of Tamm-Horsfall protein.

Adult↗
PubMed1993

Urinary glycosaminoglycan excretion as a laboratory marker in the diagnosis of interstitial cystitis.

Urinary macromolecular uronate and glycosaminoglycan uronate concentrations were determined in 209 urine specimens obtained from 192 interstitial cystitis patients, 47 asymptomatic normal individuals and 32 spinal cord injury patients. As a group the concentration of macromolecular uronate or glycosaminoglycan uronate was significantly less in the interstitial cystitis patients than in the normal controls. Some interstitial cystitis patients showed low values of macromolecular uronate and glycosaminoglycan uronate. Analysis of the population distributions suggested that macromolecular uronate may have significant value in diagnosis of interstitial cystitis.

Adult↗
PubMed1993

Diagnosis and therapy of subclinically infected prostheses.

We believe 5 to 7 percent of prosthetic devices are "subclinically" infected by Staphylococcus epidermidis. These infections are manifested by chronic pain, migration and late extrusion of the devices. To examine this problem, we cultured penile and mammary prostheses. For the experimental arm, we cultured painful penile and mammary prostheses that were being removed because of symptoms (pain). For patients in a control group, we cultured penile prostheses being replaced because of mechanical failure (no pain) and mammary tissue expanders that were temporarily installed. Actual parts of the device were cultured in Trypticase Soy Broth. There were 14 and 12 painful penile and mammary prostheses, 13 and ten, respectively, were cultured positive, for an infection rate of 88 percent. The primary organism identified was S. epidermidis. The nonpainful penile prostheses (zero of five and three of 22 mammary prostheses) grew S. epidermidis. The differences were highly significant (p < 0.001), suggesting that the painful prosthesis is infected. In an attempt to resolve the problem of the painful prosthesis, ten prosthesis were removed and exchanged for new devices. Patients received preoperative and postoperative antibiotics. All ten had positive cultures and nine of ten were successfully exchanged (no pain).

Adult↗
PubMed1992

Subclinical infection of the silicone breast implant surface as a possible cause of capsular contracture.

In order to reexamine the possible association between bacterial presence and capsular contracture, 55 silicone devices (mammary implants or tissue expanders) were cultured at the time of their removal from 40 patients. Special culture techniques were used in an attempt to recover bacteria adhering to the smooth-surfaced implant and encased in glycocalyx biofilm. Bacteria were detected on 56% (15 of 27) of implants surrounded by contracted capsules and on 18% (5 of 28) of those without capsular contracture (p less than 0.05). Only three implants tested positive using routine plating techniques. The predominant isolate was Staphylococcus epidermidis. The concept that capsular contracture is associated with subclinical infection of silicone implants is supported by this study. With changes in the microbiological technique, bacterial recovery and growth occurs at a frequency greater than previously thought.

Adult↗
PubMed1992

Prevention of acrolein-induced bladder injury by pentosanpolysulfate.

The active metabolite of cyclophosphamide, acrolein, which is capable of damaging the transitional epithelium of the bladder, was evaluated in both in vivo and in vitro models to determine if its damaging effect could be reduced by the presence of a sulfated polysaccharide pentosampolysulfate. It was discovered that in all models pentosanpolysulfate was capable of reducing transitional cell injury due to acrolein.

Acrolein↗
PubMed1991

The production of antibodies to pentosanpolysulfate (ELMIRON, SP-54).

Pentosanpolysulfate (PPS) represents the product obtained after sulfation of xylan and is composed of beta 1----4-D-xylopyranose residues sulfated at C2 and C3. Studies have shown that this compound can often be effective in relieving the symptoms of interstitial cystitis (IC). In order to elucidate the mode of action of PPS in IC, a sensitive and reliable assay was needed. To this end we prepared an immunogenic form of PPS by coupling it to methylated bovine serum albumin (MBSA). This complex was used to immunize NZW rabbits (1 mg, IM). Four of five animals responded with anti-PPS antibodies, three of which had high titer (greater than 1/2000) as measured by an enzyme-linked immunosorbent assay (ELISA). All sera were routinely absorbed with an MBSA-Sepharose immunoadsorbent to remove anti-MBSA antibodies. ELISA inhibition tests were used to determine the sensitivity and specificity of the sera. At least 50 ng/ml of PPS could be routinely detected by this assay. A number of naturally occurring proteoglycans, polysaccharides, monosaccharides and disaccharides were examined for reactivity with the antibodies but only heparin was an effective inhibitor. Absorption with heparin immunoadsorbents reduced, but did not eliminate, the ability of heparin to inhibit anti-PPS binding. This activity could be destroyed by treatment with heparinase without affecting PPS inhibition. Normal urine did not affect the ELISA or ELISA inhibition tests and thus allowed the determination of PPS levels in IC patient urines. Initial analysis of seven IC patients receiving oral PPS revealed urine concentration of 0.8-16.0 micrograms/ml. No inhibition could be detected in pre-treatment urine samples.

Animals↗
PubMed1991

Interstitial cystitis: successful management by increasing urinary voiding intervals.

A variant of the interstitial cystitis (IC) syndrome, minimal or no pain or significant pain that has been lessened by another therapy, can be clinically improved by retraining of the individual's voiding pattern. Patients with greater pain but capable of completing this protocol also may be helped. While this group of patients fills the diagnostic criteria of IC and has many of the classic changes, many differ in that they have minimal or no pain, while simultaneously they have a dysfunctional bladder as expected from long-term low-volume voiding. All patients were placed on a protocol which focused on progressively increasing intervals between voids. Fifteen to thirty minutes initially were added to their present voiding time. The same increase was added to the voiding pattern every three or four weeks until an interval of three to four hours between voids was achieved. Twenty-one patients fit the criteria to be entered into this study. Overall 71 percent (15/21) had successful management of their symptoms and reported a 50 percent decrease in their symptoms of urinary urgency, frequency, and nocturia. Nineteen percent (4/21) reported 25 percent decrease in symptoms and 10 percent had no change. Presence of significant pain adversely affects outcome, 3/7 (with pain) improvements versus 12/14 (without pain). For all patients there was a significant increase in bladder capacity (92 mL average before study and 179 mL after) and average daily voids (13.2/day prestudy and 7.4 post-therapy). These differences in voided profiles were statistically significant (p value less than 0.01).

Clinical Protocols↗
PubMed1991

Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis).

Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease.

Absorption↗
PubMed1990

Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study.

Pentosan polysulfate sodium (PPS) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind, multicenter study. A total of 110 patients were enrolled and treated for three months. In this study, overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients (p = 0.03). The investigators' overall evaluation provided similar results, 26 percent vs 11 percent in favor of PPS (p = 0.04). Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance (p = 0.07 and 0.08). The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group. All adverse reactions were minor, and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group. In this study, PPS was found to be significantly more effective than, and equally as safe as, placebo.

Adult↗
PubMed1990

Bladder surface glycosaminoglycans: an epithelial permeability barrier.

Sulfated polysaccharide's ability to modulate the movement of small molecules was examined both in vivo and in vitro. For the in vivo test, the rabbit bladder was utilized and C-14 labeled urea 45-Ca, or 3H2O was placed into the lumen of control bladders, bladders pretreated with protamine sulfate (20 mg./cc) and bladders pretreated with protamine sulfate (20 mg./cc) plus pentosanpoly-sulfate (PPS), 10 mg./cc. After 45 minutes, the controls absorbed 21% of the urea, 16% of the calcium, and 38% of the 3H2O; the protamine treated group 40% urea, 23% calcium, and 51% H2O; the PPS only group 22% urea and the protamine plus PPS group absorbed 24% of urea, 18% calcium, and 44% water. Differences between the control and protamine groups were statistically significant, p less than 0.01 for urea 45-Ca and 3H2O. The bladder mucosa contained a significantly higher concentration of urea and calcium after protamine treatment which were both reversed by PPS (p less than 0.01) while 3H2O content went down significantly (p = 0.03), reflecting a loss of the hydrophilic effect of bladder GAG. The control mucosas had 250 cpm/mg. tissue urea for Ca 64 cpm/mg. and water 262 cpm/mg., the protamine group urea 498 cpm/mg., Ca 190 cpm/mg., and H2O 139 cpm/mg.; the protamine plus PPS group urea 344 cpm/mg., Ca 129 cpm/mg., and water 168 cpm/mg. For the in vitro studies, an Ussing chamber was employed. Normal rabbit bladder membranes were placed in the chambers and the potential difference was zeroed across the membrane. There were three groups, membranes that were treated only with the irrigating solution, membranes pretreated with protamine, and membranes pretreated with protamine plus PPS. At the end of 40 minutes, there was an approximately 1.2% movement of urea across the control membrane, a 3.5% movement across the protamine treated membrane (a significant increase p less than 0.001) and a 1.1% movement across the protamine plus PPS treated membrane. It would appear that the surface polysaccharide may play an important role as a bladder permeability barrier in modulating both charged and uncharged small molecule movement in that its ability to impair such movement can be inhibited by protamine and this protamine effect can be reversed by a treatment with an exogenous sulfated polysaccharide.

Animals↗
PubMed1990

Decreased urinary uronic acid levels in individuals with interstitial cystitis.

The pathogenesis of interstitial cystitis currently is unknown. A possible etiology is that the transitional epithelium is defective, leading to molecular leaks that initiate the disease complex. An important surface defense mechanism is the glycosaminoglycans or polysaccharides that line the bladder epithelium and act as a nonspecific antiadherence factor blocking access of bacteria, microcrystals, proteins and ions to the underlying transitional cells. We examined the excretion of urinary macromolecular uronic acid and glycosaminoglycans in normal individuals and those with interstitial cystitis. A total of 37 controls had a mean macromolecular uronic acid level of 56 nmol. per mg. creatinine, compared to 40.2 nmol. per mg. creatinine in 43 patients with active disease (differences were significant, p equals 0.03). The median excretions of glycosaminoglycan uronate for controls and patients were 15.1 and 11.1 nmol. per mg. creatinine, respectively. (There was an over-all tendency to decrease excretion in patients with a p value of 0.06.) Specimens obtained at cystoscopy from patients with active interstitial cystitis had ureteral macromolecular uronic acid levels of 40.5 nmol. uronate per mg. creatinine compared to 43.6 nmol. uronate per mg. creatinine from the bladder. Interstitial cystitis patients had 16.0 nmol. glycosaminoglycan uronate per mg. creatinine compared to 14.6 nmol. per mg. creatinine in normal controls. Neither of these differences was statistically significant. It would appear that there is a tendency to lower macromolecular uronic acid and polysaccharide excretion in individuals afflicted with this syndrome.

Creatinine↗