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J D McConnell

Publications and source records attributed to J D McConnell.

At least 19 recordsLinked to original sources
PubMed1996

Smooth-muscle myosin heavy-chain isoform expression in bladder-outlet obstruction.

Bladder-outlet obstruction leads to detrusor smooth-muscle hypertrophy/hyperplasia. Despite this overall increase in muscle mass, smooth-muscle contractility decreases and bladder emptying is impaired. The goal of this study was to determine whether smooth-muscle myosin heavy-chain (MHC) alterations occur in conjunction with partial obstruction of the rabbit bladder. Total MHC and MHC-isoform protein concentrations were determined by quantitative gel electrophoresis in rabbit bladders partially obstructed for 1-4 weeks. MHC gene expression was assessed by Northern and nuclease protection assays. Two MHC isoforms (SM1/SM2) were identified in the normal rabbit bladder. After 2 weeks of obstruction the ratio of SM1/SM2 changed from 0.4:0.6 to 0.5:0.5 (P < 0.01). As compared with sham-operated values, the level of MHC mRNA decreased significantly as of 1 day after obstruction. Quantitation of MHC-isoform mRNA levels revealed a nearly 3-fold increase in the SM1/SM2 ratio. In this animal model of bladder-outlet obstruction, early changes in MHC isoforms as well as an overall decrease of MHC mRNA expression were demonstrated, suggesting that obstruction induces significant alterations in myofilament gene expression.

Animals↗
PubMed1996

Comparison of three assays for total serum prostate-specific antigen and percentage of free prostate-specific antigen in predicting prostate histology.

OBJECTIVES: To determine the statistical performance of three different assays for prostate specific antigen (PSA) and the percentage of free PSA with respect to the differentiation of histologic benign prostatic hyperplasia (BPH) and prostate cancer in men who underwent surgical removal of prostate tissue. METHODS: Serum of 86 men scheduled for prostate surgery (transurethral resection of the prostate [TURP], simple open prostatectomy, radical prostatectomy, cystoprostatectomy) was frozen and subjected to measurement in batches using three different assays for total PSA (Hybritech Tandem-E, Abbott IMx, Tosoh AIA-600) and free PSA by the Hybritech method after a single freeze-thaw cycle. The histologic diagnosis of the removed tissue (35 BPH and 51 cancer) was used as a "gold standard" for classification of disease status. Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were calculated for the three total PSA assays and the free/total PSA ratios for the entire cohort and subsets. Receiver-operating characteristic (ROC) curve analysis was used to compare the performance of the assays and ratios. RESULTS: Mean and median total PSA values differed slightly between the three assays for all patients, and for those with BPH and cancer, but this difference was not significant. Because of a considerable overlap, the differences between the mean PSA values for men with BPH and prostate cancer were not significant. At a cutpoint of 4.0 ng/mL, sensitivity with respect to the differentiation between BPH and prostate cancer was 68.6% for all three total PSA assays; the respective AUCs (0.613-0.625) were not significantly different. While the performance of the free/total PSA ratios was superior, the differences were only significant when subsets of patients were considered with a total PSA between 4 and 10 ng/mL or 4 and 15 ng/mL (AUCs 0.789-0.816). Likewise, sensitivity, specificity, and diagnostic efficiency was better in these subsets of patients. CONCLUSIONS: In this study in which a "gold standard" based on histologic analysis of the entire (or large part of) the prostate gland was used to classify disease status, the three assays for total serum PSA (Hybritech Tandem-E, Abbott IMx, and Tosoh AIA-600) performed very similarly with identical sensitivities (at a cutpoint of 4.0 ng/mL) and comparable AUCs with respect to the differentiation of men with histologic BPH and prostate cancer. The ratios of free/total PSA calculated as free PSA by the Hybritech manual immunoradiometric assay (IRMA) method over all three total PSA assays, performed marginally better in the entire patient population. However, in the subsets of patients with a PSA of 4-10 ng/mL and 4-15 ng/mL, all three ratios performed significantly better than the three total PSA assays. The proper choice of a cutpoint for the ratio (15%, 17%, 19%, or 21%) depends on the desirability of maximizing either sensitivity or specificity while optimizing diagnostic efficiency.

Adult↗
PubMed1996

Smooth-muscle physiology.

In the last several years, significant advances have been made in the understanding of bladder smooth muscle physiology. This article provides a summary for the clinician of current knowledge about the detrusor smooth muscle cell structure, function, and the relationship of structure to function in terms of bladder storage and physical properties such as compliance. The integration of this basic science knowledge into clinical practice is illustrated in discussion of two common disorders: detrusor instability, and outflow obstruction.

Action Potentials↗
PubMed1996

Increased expression of early growth response-1 messenger ribonucleic acid in prostatic adenocarcinoma.

PURPOSE: We isolated genes whose expression differs between normal and malignant prostate. MATERIALS AND METHODS: Differential display polymerase chain reactions revealed a messenger ribonucleic acid (mRNA) with higher expression in prostatic adenocarcinoma versus age matched normal tissue. Deoxyribonucleic acid sequencing identified this mRNA as the product of the early growth response-1 gene. RESULTS: Early growth response-1 mRNA levels were elevated in 12 of 12 intraprostatic adenocarcinomas but not in breast or ovarian cancers, or in rapidly dividing rat ventral prostate cells. Early growth response-1 mRNA was detected in epithelial and stromal cells at tumor margins but not in lymph node metastases. CONCLUSIONS: Early growth response-1, a nuclear transcription factor, is implicated in the growth and invasion of intraprostatic cancers.

Adenocarcinoma↗
PubMed1996

Is screening for prostate cancer necessary in men with symptoms of benign prostatic hyperplasia?

In this report, we review the critical issues concerning the early detection of prostate cancer in patients presenting with symptoms of benign prostatic hyperplasia (BPH). Only with the recent introduction of serum prostate-specific antigen (PSA) testing and transrectal ultrasonography (TRUS)-guided biopsy has the question arisen to what extent the treating physician has a responsibility to rule out prostate cancer before recommending treatment-or watchful waiting-for men with clinical BPH. Uneasiness and uncertainty also result from the development of alternative therapies that do not provide tissue for pathological analysis, or alter serum PSA levels in a poorly predictable fashion. Current early detection strategies, in this clinical situation, pose unique problems, largely because of the great degree of overlap in serum PSA among men with localized prostate cancer and BPH. The underlying goal is to distinguish patients with BPH alone from those with clinically significant, but organ-confined and potentially curable prostate cancer. Treatment for prostate cancer may take precedence over BPH management strategies, while at the same time address the symptoms associated with coexistent clinical BPH. The issues discussed in this report should aid the clinician in the evaluation of patients with clinical BPH. Further studies are clearly needed that may ultimately enhance our ability to discriminate patients with clinically significant organ-confined prostate tumors from those with BPH alone.

Adult↗
PubMed1995

Molecular aspects of bladder outlet obstruction.

In an animal model of obstruction, increasing load induces significant smooth muscle hypertrophy which is associated with a down-regulation of myosin heavy chain expression. This undoubtedly contributes to the decreased smooth muscle contractility seen in this model. Moreover, obstruction-induced hypertrophy leads to the development of a dedifferentiated smooth muscle phenotype, as evidenced by a revision of the cell to fetal (of non-muscle) gene expression patterns. Similar alterations are seen in atherosclerotic vessels and other pathologic smooth muscle systems. In these systems, dedifferentiation is also associated with significant alterations in extracellular matrix expression. It seems likely that obstruction in the bladder induces dedifferentiation of the smooth muscle cell which alters contractility as well as extracellular matrix expression, leading to altered bladder performance and decreased compliance.

Animals↗
PubMed1995

The outcome of suprapubic prostatectomy: a contemporary series in the developing world.

OBJECTIVES: To assess the appropriateness of the technique of suprapubic prostatectomy using a removable bladder neck partition suture for use in a developing world hospital and to provide contemporary open prostatectomy outcome data currently lacking in the world's literature. METHODS: From 1984 to 1994, 240 consecutive patients presenting to a developing world hospital with acute urinary retention underwent suprapubic prostatectomy using a removable bladder neck partition suture. The average length of time from bladder decompression until operation was 2.5 months. The outcome of these cases was retrospectively analyzed. RESULTS: The overall early complication rate was 19.6%. There were no deaths. The transfusion rate was 4.6%. Clot retention occurred in 6.7%, and 2.9% required return to the operating room for evaluation. For the second half of the series, the early complication rate decreased to 8.3%, the clot retention rate to 0.8%, and the transfusion rate to 1.7%. Other early and late complications were minimal. The length of delay from decompression until operation did not affect outcome. CONCLUSIONS: The technique of suprapubic prostatectomy using a removable bladder neck partition suture is appropriate for use in developing world hospitals because of its low morbidity and mortality rates. The outcome in this contemporary series of open prostatectomy cases compares favorably with the outcome from reported contemporary transurethral resection of the prostate (TURP) series. These data demonstrate that suprapubic prostatectomy is an acceptable option when the patient's anatomy or the state of local medical facilities precludes TURP.

Adenocarcinoma↗
PubMed1995

Benign prostatic hyperplasia. Hormonal treatment.

Androgen withdrawal therapy appears to produce a 20% to 30% decrease in the volume of the hyperplastic prostate after 3 to 6 months of therapy. Longer periods of treatment do not result in further prostatic regression, but further growth of the gland is not apparent in men treated with finasteride for 4 years. Although biopsy studies indicate that epithelial regression occurs to a much more significant degree than stromal regression, this may simply reflect the relatively longer turnover of the stromal cell population. The significant placebo effect of oral medication in patients with BPH makes interpretation of clinical symptomatology and uroflow data difficult. Analysis of symptom improvement is further complicated by the relatively slow improvement of patients on hormonal therapy, as opposed to surgery, where relief is immediate. In addition to limited stromal involution and inadequate treatment duration, other biologic factors may limit the clinical efficacy of androgen withdrawal therapy. Most importantly, partial involution may not necessarily decrease urethral resistance. In addition, obstruction-induced detrusor dysfunction may persist after relief of outflow obstruction in some patients, as it does following surgery. Incomplete blockade of androgen action, as well as compliance issues, may also limit efficacy. Long-term studies validate a modest but significant clinical response rate of finasteride therapy with preservation of sexual function in most men. Of the available hormonal therapeutic agents, only finasteride appears to have an acceptable risk-benefit ratio. Other 5 alpha-reductase inhibitors in the "pipeline," such as episteride, may have similar benefits. In the long term, this class of drugs may have a much larger role in patients who present with the early signs of BPH, to prevent any further progression of the disease. Presently, no form of antiandrogen therapy is as effective as transurethral resection of the prostate in relieving symptomatology. Because of patient preferences, however, medical therapy will play an increasingly important role in the management of patients with BPH.

Androgen Antagonists↗
PubMed1995

The effect of zanoterone, a steroidal androgen receptor antagonist, in men with benign prostatic hyperplasia. The Zanoterone Study Group.

PURPOSE: Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment. RESULTS: Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly. CONCLUSION: Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.

Aged↗
PubMed1994

Expression and regulation of steroid 5 alpha-reductase 2 in prostate disease.

The androgen dihydrotestosterone is synthesized by the enzyme steroid 5 alpha-reductase, and it is required for growth and development of the prostate. We used immunohistochemistry to examine the expression of the type 2 isozyme of 5 alpha-reductase in benign prostatic hyperplasia and prostate cancer. The type 2 isozyme is highly expressed within stromal cells in both disease states. No type 2 isozyme is detectable in a lymph node metastasis. Immunoblotting studies show that androgen ablation therapies substantially decrease isozyme expression in the epididymis but have a lesser effect on expression in the prostate. Finasteride therapy (2 weeks to 3 years) did not abolish expression of the prostatic type 2 isozyme nor did this drug treatment induce expression of the type 1 isozyme.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Cell type specific expression of steroid 5 alpha-reductase 2.

Isozymes of steroid 5 alpha-reductase (5 alpha-reductase) have crucial roles in androgen physiology by synthesizing the potent hormone dihydrotestosterone. The expression pattern of the 5 alpha-reductase type 2 isozyme was determined in genital and extragenital tissues by developing an immunohistochemical assay using formalin-fixed tissue and affinity purified polyclonal antibodies that specifically recognize this isozyme. Expression was detected in basal epithelial and stromal cells of the normal prostate but not in luminal epithelial cells. Stromal cells of the seminal vesicle also expressed the type 2 isozyme. In contrast, staining was detected in epithelial cells of the epididymis but not in the surrounding stroma. Myofibroblasts in foreskin samples of normal and hypospadiac individuals expressed antigen and were distributed in bands throughout the prepuce, suggesting a clonal origin. In most cells the type 2 isozyme exhibited a perinuclear subcellular distribution. However, in liver hepatocytes the protein was distributed throughout the intracellular membrane compartment.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Analysis of factors contributing to success or failure of 1-stage urethroplasty for urethral stricture disease.

We reviewed charts with adequate documentation and followup (mean 24.6 months) between 1970 and 1987 of 110 patients who had undergone 1-stage urethroplasty for urethral stricture disease at our institutions. Two age peaks were observed, 1 in the younger population (21 to 30 years old) with traumatic strictures (50% of all strictures) and 1 in elderly men (61 to 70 years old) with mainly post-inflammatory strictures (28.2% of all strictures). The majority of all strictures (63.6%) were in the bulbous urethra. Only strictures induced by trauma were located in the membranous urethra (total 28.2%). A patch graft repair was used in 49.1% of all cases, an end-to-end technique in 29.1% and a transpubic repair in 21.8%. Overall, a 57% rate of excellent results was observed with 24% failures. The results were best for patch graft repairs (65% excellent), followed by end-to-end repairs (56% excellent) and transpubic repairs (42% excellent). The choice of the surgical approach in urethral stricture surgery is dictated by the location of the stricture. The location in turn is dependent on the etiology of the stricture. Consequently, the cause of the stricture affects the location and character of the stricture and, therefore, has an immediate impact on the choice of the surgical approach and, thus, the outcome of the patient. The failure rate doubled overall when the patients had a previous manipulation for the stricture disease or if the urine was infected preoperatively despite antibiotic coverage. While our patient population may not be representative for other institutions, some general conclusions regarding proper management and treatment selection can be drawn from our experience.

Adolescent↗
PubMed1994

Benign prostatic hyperplasia: diagnosis and treatment. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains highlights from the Clinical Practice Guideline of Benign Prostatic Hyperplasia: Diagnosis and Treatment. The Benign Prostatic Hyperplasia Guideline Panel, a private-sector panel of health care providers, developed the guideline after comprehensively analyzing the research literature. As a result, this guideline comprises the most current scientific knowledge of the development, diagnosis, and treatment of benign prostatic hyperplasia (BPH). The guideline makes specific recommendations to identify both the most effective methods for diagnosing BPH and the most appropriate treatments for BPH based on patient preference and clinical need. BPH affects quality of life and is very rarely a life-threatening disease. Motivation to seek active treatment will, for most patients, depend on how much their symptoms bother them. Many patients choose a regimen of "watchful waiting." The guideline details the relative benefits and harms associated with all diagnostic and treatment approaches. Treatment options discussed include watchful waiting, alpha blocker and finasteride medications, balloon dilation, and the surgical options of transurethral incision, transurethral resection, and open prostatectomy.

Adrenergic alpha-Antagonists↗
PubMed1994

Effects of obstruction on bladder contractile proteins.

In an animal model of obstruction, increasing load induces significant smooth muscle hypertrophy which is associated with a down-regulation of myosin heavy chain expression. This undoubtedly contributes to the decreased smooth muscle contractility seen in this model. Moreover, obstruction-induced hypertrophy leads to the development of a dedifferentiated smooth muscle phenotype. Similar alterations are seen in atherosclerotic vessels and other pathologic smooth muscle systems. In these systems, dedifferentiation is also associated with significant alterations in extracellular matrix expression. It seems likely that obstruction in the bladder induces dedifferentiation of the smooth muscle cell which alters contractility as well as extracellular matrix expression, leading to altered bladder performance and decreased compliance.

Animals↗