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Biomedical subjects

A T Cockett

Publications and source records attributed to A T Cockett.

At least 55 records · Page 3Linked to original sources
PubMed1993

Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer.

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.

Biomarkers, Tumor↗
PubMed1993

Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia.

In previous studies the severity of symptoms of prostatism in men with benign prostatic hyperplasia have not correlated well with prostate size, degree of bladder trabeculation, uroflowmetry or post-void residual volume. As part of a prospective cohort study of benign prostatic hyperplasia treatment effectiveness in 4 university-based urology practices, we correlated symptom severity and these commonly used measures of disease severity. Symptom severity was quantified using the American Urological Association symptom index. Analyses were based on 198 outpatients completing a standardized evaluation (84 of these men have completed 6 months of followup after treatment with prostatectomy, balloon dilation, terazosin or watchful waiting). At baseline, symptom severity was not correlated with uroflowmetry, post-void residual, prostate size and degree of bladder trabeculation. However, symptom severity was much more strongly related to overall health status than the other measures. Reduction in symptoms with treatment did correlate with improvements in uroflowmetry. This poor baseline correlation with symptoms may reflect unreliability in measurement of the physiological/anatomical variables. Alternatively, these parameters may be measuring different pathophysiological phenomena.

Aged↗
PubMed1993

Extracorporeal shock wave lithotripsy for distal ureteral stones.

A retrospective analysis of distal ureteral calculi treated by extracorporeal shock wave lithotripsy (ESWL*) as the primary mode of therapy was performed. Using the Dornier HM3 unit 312 patients underwent a total of 326 ESWL procedures. Several pretreatment procedures, including placement of ureteral catheters were used to help with stone localization. Early fragmentation and 3-month stone-free rates were analyzed. Of the patients 81% were stone-free at 3 months. We reviewed 27 failures, revealing a higher incidence of impacted stones and stones greater than 1 cm. Complications were few and minor. ESWL is a safe and effective treatment option for distal ureteral calculi.

Female↗
PubMed1993

Multiple molecular weight forms of immunoreactive alpha-inhibin in human seminal plasma.

The purpose of these studies was to determine whether the total immunoreactive alpha-inhibin protein concentration in seminal plasma correlated with serum gonadotropin levels or semen characteristics and to identify the forms of alpha-inhibin present in seminal plasma. Thirty-eight serum samples from men being evaluated for infertility were selected for study based on their serum hormone profiles and semen parameters. Serum LH and testosterone levels were normal, but FSH levels ranged from normal to hypergonadotropic (> 20 IU/L). Most semen parameters were within normal ranges, but germ cell numbers ranged from normal to azoospermic. Thus, seminal plasma from these men provided a unique opportunity to examine the antigenic forms of alpha-inhibin in individuals in whom strong correlations between inhibin and FSH levels might be predicted because of the observed ranges of FSH levels and germ cell numbers. Seminal plasma alpha-inhibin was characterized by RIA or Western blotting, using an antiserum directed against the N-terminal of the alpha-subunit of mature [32,000 mol wt (M(r))] inhibin. The antiserum recognized the alpha-subunit of dimeric inhibin as well as free alpha-inhibin and alpha-inhibin precursor proteins. Total immunoreactive alpha-inhibin ranged from 8.21-43.99 nmol/L in seminal plasma. However, alpha-inhibin levels were not statistically correlated with serum FSH levels or any of the measured semen parameters (including germ cell number). In contrast, the immunoreactive alpha-inhibin concentration in seminal plasma was negatively correlated (P < 0.01) with the serum LH level. Western blot analyses revealed that multiple forms of immunoreactive alpha-inhibin are present in seminal plasma. The majority of immunoreactivity was associated with monomeric proteins (ranging from 58,000-95,000 M(r)) that were larger than the alpha-subunit (21,000 M(r)) predicted for mature dimeric human inhibin (32,000 M(r)). The relative amounts of individual forms of immunoreactive alpha-inhibin varied among the patients studied, but could not be correlated with other serum or seminal parameters measured. Our observations demonstrate that various monomeric alpha-inhibin proteins are present in human seminal plasma. It is unlikely that these proteins alone or combined with inhibin beta-subunit proteins have identical biological activities. Thus, until assays specific for each of the various forms of immunoreactive alpha-inhibin are developed, their role as well as that of inhibin in the endocrine or local modulation of testicular function cannot be deduced from RIA data alone.

Blotting, Western↗
PubMed1992

Prostate specific antigen predominantly forms a complex with alpha 1-antichymotrypsin in blood. Implications for procedures to measure prostate specific antigen in serum.

BACKGROUND: Prostate specific antigen (PSA) is a zymogen of a 33-kilodalton (kD) serine proteinase with extensive similarity to glandular kallikreins. The mechanism responsible for converting the zymogen into active proteinase has not been defined, but active PSA may be irreversibly inactivated in vitro by two of the major proteinase inhibitors in blood: alpha 1-antichymotrypsin and alpha 2-macroglobulin. METHODS: Procedures have been designed to characterize the different molecular forms of PSA in serum. One assay detects PSA epitopes available on both PSA binding to serine proteinase inhibitors and PSA not binding to a proteinase inhibitor. A second assay only detects PSA in complex with alpha 1-antichymotrypsin. A third assay mainly detects PSA not binding to a proteinase inhibitor. RESULTS: In serum samples, an 80-kD to 90-kD species of PSA in complex with alpha 1-antichymotrypsin is the predominant molecular form and a minor molecular form of serum PSA was an approximately 30-kD fraction not binding to a proteinase inhibitor. CONCLUSIONS: The benefits of detecting different molecular forms of serum PSA should be investigated regarding possibilities to facilitate differential diagnosis of carcinoma of the prostate (CAP) and benign prostatic hyperplasia (BPH).

Antigens, Neoplasm↗
PubMed1992

Indications for treatment of benign prostatic hyperplasia. The American Urological Association Study.

BACKGROUND: In 1990, a pilot study was begun that evaluated benign prostatic hyperplasia (BPH) at five clinical institutions. Data management and coordination of this study was performed at the Medical Practices Evaluation Center at Massachusetts General Hospital. Because of decreased patient enrollment, one institution was dropped. This was a randomized, prospective, clinical study that provided an initial overview of the trial and a rationale for the project. METHODS: Patients with clinically significant signs and symptoms of BPH were enrolled in this study. A symptom index consisting of seven items was used to document patient complaints of prostatic enlargement. Prostate size was determined using ultrasonography. Uroflowmetry (peak flow and mean flow) and residual urine volumes were documented. Abdominal ultrasonography was performed to rule out the presence of a dilated upper urinary tract. Cystoscopy was completed to determine the extent of prostatic and bladder neck obstruction. Trabeculations or cellules in the bladder, if present, were also documented. Conclusions. Preliminary results were obtained. The operative and nonoperative options depending on prostate size are shown in the figures of this article. The use of an interactive video disc has been beneficial in explaining the risks and benefits of each treatment option applicable to the patient in this randomized, controlled study.

Aged↗
PubMed1992

The effect of varicocelectomy on testicular volume in 89 infertile adult males with varicoceles.

The presence of a varicocele has been associated with reduced testicular volumes both in the adult and pediatric patient populations. An increase in testicular volume after varicocelectomy, however, has been documented only in the latter group and then only in the ipsilateral testicle. We present our experience with 89 infertile male patients with varicoceles who underwent operative repair. An increase in testicular volume was observed in 72 of the 89 patients, with the right side showing a greater increase, regardless of whether bilateral or unilateral left varicoceles were present preoperatively. No greater increase in testicular volume was noted among the patients who went on to achieve a pregnancy with their spouses. In addition, the age of the patient did not influence the observed change in testicular volume. No correlation between varicocele grade and pregnancy nor between improvement in semen parameters and improvement in testicular volume could be demonstrated.

Adult↗
PubMed1992

The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association.

A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols.

Adult↗
PubMed1992

Suramin inhibits gonadotropin action in rat testis: implications for treatment of advanced prostate cancer.

Suramin is being evaluated for the treatment of metastatic prostate cancer based on its inhibition of growth factor action. In addition, suramin may inhibit the endocrine control of androgen production, which was explored herein. Adult Sprague-Dawley rats were injected (i.p.) daily with varying doses of suramin. At a cumulative dose of 200 mg., suramin significantly depressed serum testosterone (p less than 0.05), and follicle stimulating hormone (p less than 0.002) levels. In vitro studies showed that suramin-mediated suppression of androgen production might be secondary to inhibition of gonadotropin action. In MA-10 cell cultures, suramin inhibited a maximum stimulatory dose of human chorionic gonadotropin with an ED50 of 4.4 microM. Studies in rat Sertoli cell cultures showed that follicle stimulating hormone action was also inhibited by suramin, with an ED50 of 8.6 microM. Using receptor binding assays with calf testis membrane, we showed that suramin inhibited 125I-hFSH binding to receptor in a dose dependent fashion with an ED50 of 10.4 microM; comparable to the ED50 of suramin inhibition of follicle stimulating hormone action in Sertoli cell culture cells. Thus the mechanism of suramin's suppression of androgen production may involve multiple sites of action, including inhibition of gonadotropin binding to its receptor and suppression of pituitary gonadotropin levels in serum. This inhibition of androgen production may be useful in the treatment of advanced prostate cancer.

Animals↗
PubMed1991

DNA slit-scan flow cytometry of bladder irrigation specimens and the importance of recognizing urothelial cells.

DNA slit-scan flow cytometry was used to analyze 150 bladder irrigation specimens from 83 patients. Specimens were categorized into groups based on cystoscopy, histology, and cytopathology. Cells were stained for DNA with propidium iodide using a whole cell protocol. Non-specific fluorescence in the cytoplasm of some urothelial cells together with differential DNA staining of cell types in certain specimens was noted. DNA frequency distributions were analyzed using a semi-automated technique. Data were gated using slit-scan morphological features to remove cellular debris, multiple nuclei, and cells exhibiting nonspecific cytoplasmic fluorescence. Specimens were classified abnormal if they were aneuploid or had a hyperdiploid fraction (HDF) greater than 8%. The sensitivity to abnormality was 89% for grade 3 transitional cell carcinoma (TCC), 70% for grade 2 TCC, and 67% for grade 1 TCC. Specificity was 61%. Specimen data were then reprocessed using slit-scan morphological features to enrich for urothelial cells. The urothelial cells were identified by the ratio of nuclear diameter to cell diameter. This method was found to be in good agreement with immunofluorescent labeling of urothelial cells using the urothelium-selective T16 monoclonal antibody. The sensitivity to abnormality remained 89% for grade 3 TCC and 70% for grade 2 TCC, but fell to 52% for grade 1 TCC. Specificity for the urothelial cell enriched data increased to 77%. Reprocessing of data to enrich for urothelial elements resulted in 16 fewer specimens with an aneuploid DNA distribution and 2 fewer specimens with increased HDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1991

Bacillus Calmette-Guerin and interleukin-2 for treatment of superficial bladder cancer.

A total of 22 patients with bladder cancer received bacillus Calmette-Guerin (BCG) and interleukin-2. Significant bladder tumor remissions were noted in 15 of 17 patients (88%). Of 5 patients with carcinoma in situ 1 was noncompliant and he died of carcinoma in situ. The other 4 patients are in remission. BCG alone was instilled in 22 additional patients with superficial bladder cancer. The remission rates were encouraging. Of the 22 patients 13 (59%) had remission of the bladder tumor. A half dose of BCG (60 mg.) is adequate when given weekly for 6 weeks. Maintenance therapy is important as noted in both of our clinical arms. BCG and interleukin-2 therapy results in a higher remission rate.

BCG Vaccine↗
PubMed1991

Extracorporeal shock-wave lithotripsy in patients with spinal cord dysfunction.

Patients with spinal cord dysfunction are at an increased risk for urolithiasis. A retrospective study was undertaken to determine the effectiveness of extracorporeal shock-wave lithotripsy (ESWL) in this population. Thirteen kidneys received 19 treatments averaging 2,350 shocks per renal unit. All but one of the stones showed good fragmentation; however, none of the patients was stone-free at three months. Four of 9 patients with long-term follow-up were stone-free at five to fifteen months. Our poor stone-free rate is similar to that found in other studies of patients with spinal cord dysfunction. ESWL was well tolerated in this population, however, the clearance of stones is poor and delayed.

Adult↗
PubMed1991

World Health Organization Consensus Committee recommendations concerning the diagnosis of BPH.

The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.

Clinical Protocols↗
PubMed1990

Influence of intravesical administration of tumor necrosis factor alpha and systemic gamma-interferon on murine bladder cancer: lack of dose response.

The effect of intravesical administration of high dose recombinant tumor necrosis factor-alpha (rTNF) and in combination with systemic recombinant gamma-interferon (rIFN) on murine bladder cancer was studied. RTNF was given at 12.5 micrograms/mouse on days 7, 11 and 15 after tumor instillation or at 2.5 micrograms/mouse on days 7, 9, 11, 13 and 15. Some groups were also injected i.v., 24-h prior to each rTNF treatment with rIFN at a dose of 1.3 micrograms/mouse. RTNF treatment suppressed tumor growth up to 48% of control, although the difference was not statistically significant. Combined administration of rIFN did not provide additional benefit.

Administration, Intravesical↗
PubMed1990

Clonal growth of bladder cancer cells in a double layer soft agar assay: needles addition of multiple culture supplements.

The necessity of multiple culture supplements, characteristic of Hamburger and Salmon (H&S) soft agar assay (1977), for the clonal growth of bladder cancer cells was systematically investigated. One murine and 6 human cell lines were cultivated in different culture supplemented conditions based on the H&S method. All cell lines successfully formed colonies in the absence of supplements. The inclusion of 2-mercaptoethanol to supplement-free medium stimulated the clonal growth of murine (MBT-2) cells, whereas it did not affect the growth of human cell lines. DEAE-dextran suppressed the clonal growth of 5 out of 7 lines. Tryptic soy broth stimulated the growth of 2 human cell lines, whereas it suppressed the other 2 cell lines. The chemosensitivity of MBT-2 cells was not affected by these supplements.

Animals↗
PubMed1990

Cortisone inhibition of tumor angiogenesis measured by a quantitative colorimetric assay in mice.

A simple and quantitative angiogenesis assay was developed. Using this assay, the angiostatic effect of cortisone acetate (CA) on three murine tumors was studied. Tumor cells were inoculated i.d. into the syngeneic or heterogeneic hosts (day 0) and the degree of angiogenesis was quantitated on day 3 by measuring the tumor vascular volumes using an Evan's blue perfusion technique. CA treatment (250 mg/kg for 3 days) significantly suppressed tumor angiogenesis; however, the degree of angiostatic effect was influenced by the tumor types and by the mouse strain used. MBT-2 bladder cancer angiogenesis was suppressed by 77%-80% of controls in C3H/HeN and C57B1/6 mice, whereas MBT-2 angiogenesis in BALB/c mice was significantly less suppressed by CA (65% inhibition) as compared with values obtained for C3H mice. B16 melanoma or Line-1 lung-cell carcinoma-induced angiogenesis was suppressed by 57%-66% in their syngeneic or heterogeneic hosts. The combined administration of CA and heparin (Sigma; 1,000 units/ml in drinking water) did not influence the outcomes. The data suggest that host factor(s) and tumor factor(s) influenced the expression of CA angiostatic activity. This colorimetric assay enabled a quantitative estimation of the degree of angiogenesis in mammalian animals.

Animals↗