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Biomedical subjects

C L Parsons

Publications and source records attributed to C L Parsons.

At least 19 recordsLinked to original sources

Profiles of grammatical morphology and sentence imitation in children with specific language impairment and Down syndrome.

The purpose of the present study was to examine the grammatical morphology and sentence imitation performance of two different groups of children with language impairment and to compare their performance with that of children learning language typically. Expressive use of tense-bearing and non-tense-related grammatical morphemes was explored. Children with specific language impairment (SLI), with Down syndrome (DS), and with typical language development (TL) were matched on mean length of utterance (MW). Performance was compared primarily on composite measures of tense, tense inflections, and non-tense morphemes, as well as on the Sentences subtest of the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R; D. Wechsler, 1989). Exploratory analyses were completed on a set of 11 individual grammatical morphemes as a follow-up to the principal analyses. As predicted, the children with SLI performed significantly more poorly than the children with TL on all three composite measures. In addition, the DS group exhibited significantly weaker performance than did the TL group on the tense inflections and non-tense morpheme composites. Although there were no statistically reliable differences between the SLI and DS groups on any morpheme measure, the groups were not comparably weak in their use of the regular post, -ed; the irregular third person singular morphemes (e.g., has, does); the present progressive, -ing; or the use of modals. The SLI and DS groups both performed more poorly than did the TL group on the sentence imitation task.

Child↗

Estrogenic regulation of HSP90 kD synthesis in rat urinary bladder.

The role of heat shock protein (HSP90 kD) has been investigated in regard to its association with steroid receptors. HSP90 kD may play a role in steroid receptor stabilization and activation. Oophorectomized Sprague-Dawley rats (n = 25) were placed into five groups and injected subcutaneously with 30 microg beta-estradiol 17-benzoate in sesame oil, with one group injected with carrier oil (control). After estrogen administration, the rats were killed, and their bladders removed for immunostaining, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis demonstrated a 90-kD band in bladder homogenates, even in the absence of estrogen. However, the bands were more intense 12 and 24 h after administering estrogen. ELISA showed significant differences in HSP90 kD synthesis as early as 6 h compared to controls (P< 0.05). After 48 h the estrogen-treated rats and controls were identical. The above results were confirmed by immunostaining for HSP90 kD. HSP90 kD synthesis in the rat urinary bladder is under estrogenic regulation. These findings may be relevant in the etiology and pathobiology of interstitial cystitis and menopausal voiding dysfunctions since the bladder is enriched with estrogenic receptors and is under estrogenic influence.

Animals↗

Gynecologic presentation of interstitial cystitis as detected by intravesical potassium sensitivity.

OBJECTIVE: To document the initial clinical diagnoses, determine the prevalence of urinary symptoms, and test for intravesical potassium sensitivity in gynecologic patients with chronic pelvic pain. METHODS: Gynecologists at three United States medical centers administered the Potassium Sensitivity Test to consecutive unselected pelvic pain patients. Before testing, each patient was given an initial clinical diagnosis based on the patient's chief symptomatic complaint(s) and surveyed for urologic symptoms. RESULTS: Of 134 patients, 114 (85%) had positive potassium sensitivity. Positive potassium sensitivity rates were similar across all three sites and all clinical diagnoses including endometriosis, vulvodynia (vulvar vestibulitis), and pelvic pain. A total of 75% of the subjects reported urologic symptoms, but only 2.9% received an initial diagnosis of interstitial cystitis. CONCLUSION: A significant majority of gynecologic patients presenting with pelvic pain have a positive Potassium Sensitivity Test, indicating their pain may have a bladder component (interstitial cystitis). Interstitial cystitis deserves greater consideration in the differential diagnosis of chronic pelvic pain.

Administration, Intravesical↗

Intravesical potassium sensitivity in patients with interstitial cystitis and urethral syndrome.

OBJECTIVES: To examine populations with diagnosed clinical interstitial cystitis (IC) and urethral syndrome and normal controls using the potassium sensitivity test (PST), to determine the incidence of PST-provoked pain and/or urgency, and to document the type and location of IC and urethral syndrome pain, association of pain with sexual intercourse, and family history of female urgency/frequency problems. METHODS: The PST and a questionnaire were administered to 466 patients with clinical IC, 116 patients with urethral syndrome, and 42 controls. RESULTS: The PST was positive in 78% of patients with clinical IC, in 55% of patients with urethral syndrome, and in 0% of the controls. Of the patients with clinical IC, 9% responded to the PST with pain only and 8% with urgency only. Patients with clinical IC reported the pain as dysuria (58%), urethral/vaginal (76%), above the pubic bone (53%), lower abdomen (47%), lower back (35%), vaginal (51%), and inguinal (28%). The results were similar for patients with urethral syndrome. Of the sexually active men and women, 71% with clinical IC and 59% with urethral syndrome reported pain associated with intercourse. Urgency/frequency problems in female relatives were reported by 35% of patients with IC and 33% of those with urethral syndrome. CONCLUSIONS: The significant potassium sensitivity in both patients with clinical IC and those with urethral syndrome and the absence of potassium sensitivity in normal controls indicates that a positive PST suggests the presence of an abnormal bladder epithelium. The lower rate of positive PSTs in patients with urethral syndrome reflects the less severe, more intermittent, nature of the symptoms in urethral syndrome (early IC). Pelvic pain of bladder origin may occur anywhere in the pelvis. Finally, IC appears to have a genetic component.

Adult↗

The intravesical potassium sensitivity test and urodynamics: implications in a large cohort of patients with lower urinary tract symptoms.

PURPOSE: Bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) is the most common diagnosis in older men with lower urinary tract symptoms. However, these symptoms also can occur with interstitial cystitis. We determine whether the potassium sensitivity test is useful for distinguishing BPH from possible intersitial cystitis in patients with lower urinary tract symptoms. We also test the hypothesis that patients with these symptoms who have a positive test will have urodynamic findings consistent with the diagnosis of interstitial cystitis. MATERIALS AND METHODS: The potassium sensitivity test was performed in 526 (95%) males and 25 (5%) females with lower urinary tract symptoms undergoing urodynamic testing. Urodynamic parameters in the positive and negative potassium sensitivity test groups were compared. % RESULTS: Of the patients 16% (89 of 551) had a positive potassium sensitivity test. Compared with patients who had a negative test, those who had a positive test were younger (61 versus 64 years, p = 0.03), had urgency at significantly lower volumes (108 versus 182 cc, p <0.0001), lower bladder capacity (343 versus 436 cc, p <0.0001) and lower post-void residual (49 versus 95 cc, respectively, p <0.001). Urodynamic parameters in the 24% (6 of 25) of women who had a positive potassium sensitivity test were similar to those in men who also had a positive test. CONCLUSIONS: Urodynamic findings in patients with lower urinary tract symptoms who have a positive potassium sensitivity test are significantly different from those in patients who have a negative test, and are similar to those findings characteristic of interstitial cystitis. Interstitial cystitis should be considered in patients with lower urinary tract symptoms who have a positive test. The potassium sensitivity and urodynamic tests may be a useful combination for screening men with lower urinary tract symptoms to identify those symptoms that may be due to interstitial cystitis versus BPH.

Administration, Intravesical↗

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↗

Pentosanpolysulfate coating of silicone reduces encrustation.

BACKGROUND AND PURPOSE: A significant problem associated with catheterization in the urinary tract is the encrustation of the catheter materials. One approach to reducing encrustation is to alter the surface properties of the catheters. We evaluated the effectiveness of coating with pentosanpolysulfate (PPS), a semisynthetic polysaccharide similar to heparin, in reducing encrustation and the foreign-body inflammatory response to silicone stents in the bladders of male New Zealand White rabbits. MATERIALS AND METHODS: Sixteen rabbits were divided into three groups to receive placement in their bladders of uncoated (N = 7), PPS-coated (N = 7), or sham matrix-processed silicone rings (N = 2) via open cystotomy. After 50 days of maintenance on normal food and water, all rabbits were sacrificed, and the air-dried, unfixed silicone ring surfaces were examined by scanning electron microscopy. Bladders and remaining silicone rings were removed and preserved separately. Silicone rings, cleaned of all encrustation, were stained with toluidene blue to determine the presence or absence of PPS coating on the surface. RESULTS: Histologic examination revealed normal tissue in bladder sections exposed to coated silicone rings and an inflammatory response in sections from bladders having uncoated silicone rings. Coating with PPS was associated with an eightfold reduction in the amount of encrustation of silicone and a marked reduction in the inflammatory response of the bladder wall to the foreign body. CONCLUSIONS: A PPS coating may be useful in reducing the encrustation of long-term indwelling silicone stents or catheters in the human urinary tract.

Animals↗

Cyto-injury factors in urine: a possible mechanism for the development of interstitial cystitis.

PURPOSE: In most of our patients with interstitial cystitis (IC), the disease is associated with an increased urothelial permeability whose cause has not been identified. We postulate that both normal urine and the urine of IC patients contains factors capable of injuring the mucosa and causing an increased permeability that would allow urine components to leak into the bladder muscle. To test this hypothesis, we examined fractions of normal urine for toxic effects on bladder smooth muscle and epithelial cells in vitro. In the same in vitro system, we measured the effects of Tamm-Horsfall protein (THP), a normal urinary glycoprotein that may be a scavenger of injurious agents capable of "detoxifying" normal metabolic products. MATERIALS AND METHODS: Human urothelial cells (T24) and rabbit bladder smooth muscle cells were incubated overnight with various fractions prepared from healthy volunteers' urine. The urine fractions of molecular weights >100 Da were incubated overnight with either urothelial or smooth muscle target cells after no treatment or after heating to 56C, preincubation with THP, exposure to heparin, or elution from heparin. Cytotoxicity was determined for each group using a neutral red uptake assay. RESULTS: Urine fractions of molecular weight 500 to 1000 Da were cytotoxic to smooth muscle cells (39%) and urothelial cells (50%). Cytotoxicity levels for THP-treated fractions were significantly lower than those for untreated fractions in both urothelial cells (7% versus 89%, p <0. 001) and smooth muscle cells (8% versus 70%, p <0.01). Fractions exposed to heparin were less cytotoxic to smooth muscle cells (20%) than were untreated fractions (27%). Fractions eluted from heparin were also cytotoxic to urothelial cells (42%). CONCLUSIONS: Normal human urine contains heat labile, cationic components of low molecular weight that bind to heparin. These components, when separated from the bulk of the urinary wastes, are cytotoxic to urothelial cells as well as underlying smooth muscle cells, indicating their potential for causing bladder mucosal injury. The cytotoxic activity can be blocked by the presence of THP. This urinary cytoprotective activity of THP may play an important but unrecognized role in the development of IC.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗