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Biomedical subjects

J E Fowler

Publications and source records attributed to J E Fowler.

At least 109 records · Page 6Linked to original sources

Operable prostatic carcinoma: correlations among clinical stage, pathological stage, gleason histological score and early disease-free survival.

We investigated the relationships among clinical and pathological stages, Gleason histological score and early disease-free survival of 75 patients with localized prostatic carcinoma treated by radical prostatectomy. Carcinoma was confined histologically to the prostate in 81 per cent of the patients with clinical stage A2, 79 per cent with B1N, 38 per cent with B1 and 0 per cent with B2 tumors. The Gleason score correlated directly with clinical and pathological stages, estimated extent of intraprostatic tumor and invasive capacity of the primary tumor. Of the tumors with a Gleason score of 8 or more 81 per cent extended beyond the prostatic capsule. Of 12 patients who suffered distant metastases 9 had tumors that extended beyond the prostatic capsule and 5 had tumors with Gleason scores of 8 or more.

Adenocarcinoma↗

Human antisperm monoclonal antibodies constructed postvasectomy.

Sperm and spermatogenic cell antigens, escaping the blood-testis/blood-epididymal barrier, elicit an autoimmune response in patients following vasectomy. In this study, antisperm antibody-positive sera and peripheral blood lymphocytes were obtained 6-9 mo following vasectomy. Serum antisperm antibody levels were assessed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence. Lymphocyte-myeloma hybridomas were constructed by fusing peripheral blood lymphocytes, harvested from antisperm antibody-positive sera, with a hypoxanthine guanine-phosphoribosyltransferase (HGPRT)-negative mouse myeloma line. Immunoglobulin-secreting colonies surviving drug selection were detected by ELISA and screened for antisperm activity. Antisperm antibody-producing cultures were cloned and expanded for bulk antibody production both in culture and as ascites in athymic nude mice. Eight mouse-human fusions yielded 205 hybridomas secreting human monoclonal antibody, of which 11 demonstrated antisperm reactivity by ELISA. Two of these hybridomas are described in detail: HAS-1, which secretes human immunoglobulin M (IgM, kappa)-recognizing epitopes located on the sperm midpiece, and HAS-2 (IgM, lambda), which secretes monoclonal antibody-recognizing epitopes located on the entire sperm tail. The results indicate successful capture of human antisperm autoantibody from the postvasectomy autoimmune state using somatic cell hybridization techniques.

Animals↗

Practical approach to bacteriologic investigation of chronic prostatitis.

Chronic prostatitis is a common disorder sometimes caused by bacterial infection of the prostate. Documentation of such infection requires quantitative culture of carefully collected sequential urine and prostatic fluid specimens (bacterial localization cultures). However, culture of the midstream urine and prostatic fluid alone usually is sufficient to rule out this diagnostic possibility. A practical strategy for the bacteriologic investigation of chronic prostatitis that combines each of these maneuvers--midstream urine and prostatic fluid culture first, then subsequent bacterial localization cultures if pathogenic bacteria are isolated from the initial cultures--is outlined.

Anti-Infective Agents, Urinary↗

Relationship of pretreatment transurethral resection of the prostate to survival without distant metastases in patients treated with 125I-implantation for localized prostatic cancer.

The authors assessed the relationship between transurethral resection of the prostate (TURP) and the probability of survival without distant metastases (survival) in patients with clinically localized prostatic cancer. Fifty-eight patients with obstructive voiding symptoms who underwent TURP within 12 months before pelvic lymphadenectomy and 125I-implantation were compared with 131 patients who did not require TURP before implantation. None received other treatment for the tumor. The overall survivals for the two groups were not significantly different, P greater than 0.1. When stratified by tumor grade or the presence or absence of pelvic lymph node metastases, the survivals for the two groups were also similar, P = greater than 0.1. However, survival associated with Stage C tumors was greater in the No TURP than in the TURP group (P = 0.003), and survival associated with Stage C tumors was greater in the TURP than in the No TURP group (P = 0.005). These data fail to provide convincing evidence that transurethral resection of prostatic cancers has an unfavorable impact on disease progression.

Adenocarcinoma↗

Sentinel lymph node biopsy for staging penile cancer.

Eighteen sentinel lymph node biopsies were performed in 10 patients with invasive squamous carcinoma of the penis. Five of 15 biopsies associated with inguinal lymphadenopathy and 2 of 3 biopsies associated with palpably normal inguinal nodes were positive. Among 7 ipsilateral regional lymphadenectomies undertaken because of a positive biopsy, additional lymph node metastases were uncovered in only 1 instance. Among 5 patients with negative biopsies bilaterally, none had other superficial inguinal lymph node metastases and all but one have remained free of tumor (mean follow-up 26 months). These data support the possibility that the sentinel lymph node is often the first site of regional lymphatic metastasis in penile cancer.

Biopsy↗

Difficulties in quantitating the contribution of urethral bacteria to prostatic fluid and seminal fluid cultures.

A greater than 10-fold increase in the concentration of a bacterium in expressed prostatic secretions or seminal fluid compared to the first voided urine specimen generally is considered as evidence of prostatic infection. To test the validity of this criterion serial culture studies using expressed prostatic secretions and/or seminal fluid were done in 6 men with no clinical evidence of genitourinary infection. In each case during the study period prostatic infection by at least 2 different bacteria that commonly colonize the urethra was suggested by the culture results. Concurrent expressed prostatic secretions or seminal fluid cultures suggesting prostatic infection by the same organism occurred in only 1 of 14 culture studies. These observations suggest that expressed prostatic secretions and seminal fluid are more susceptible to contamination by urethral bacteria than urine and that this phenomenon, rather than infection of the prostate, was the cause of culture results suggesting prostatic infection.

Bacterial Infections↗

Localized amyloidosis of the ureter.

The deposition of amyloid fibril proteins as localized tumor-like masses (amyloid tumors) is a relatively rare phenomenon in the spectrum of amyloid-related disease. These tumors have a particular tendency to occur in the genitourinary tract and are often mistaken clinically for malignancies. We report a case of primary amyloidosis of the ureter. A cause for the amyloid deposition could not be identified.

Aged↗

Bacteriology of branched renal calculi and accompanying urinary tract infection.

We determined the bacteriology of apparently infected renal calculi and accompanying urinary tract infections, and assessed the potential clinical value of the culture results. Twenty-two branched renal calculi from 16 patients were cultured. Fifteen calculi were infected with 1 or more urease-producing gram-negative enteric bacterium, 2 were infected with a urease-producing bacterium and a nonurease-producing organism, and 5 were sterile. Immersion of infected stones in antimicrobial solutions before culture reduced or eliminated surface bacteria but usually did not eradicate bacteria within the stone. The bacteriology of a stone or stones could be predicted on the basis of available urine culture results in only 2 of the 16 cases. These data suggest that branched renal calculi associated with bacteriuria usually are infected but that documentation of infection and identification of the infecting organism require culture of the stone.

Anti-Bacterial Agents↗

Longitudinal studies of prostatic fluid immunoglobulin in men with bacterial prostatitis.

To better characterize the apparent secretory immune response of the prostate to bacterial infection of the genitourinary tract, we assayed serial expressed prostatic secretion (EPS) specimens for total and antibacterial immunoglobulin. Three men with bacterial prostatitis, including 2 otherwise healthy men with chronic infections and 1 man with IgG multiple myeloma and an acute infection, were studied. In the former 2 cases the infections were associated with greater increases in total EPS IgA than total EPS IgG or IgM. The patient with multiple myeloma had markedly elevated serum IgG levels and subnormal serum IgA and IgM levels and the acute infection was accompanied by increases in total EPS IgG and IgM but consistently low total EPS IgA. Antibacterial EPS IgA, which was measurable in each case, was always quantitatively greater than antibacterial EPS IgG. Antibacterial IgM was never detectable. Alterations in the concentrations of antibacterial EPS IgG and IgA were generally not associated with comparable alterations of total EPS IgG and IgA, respectively, and the concentrations of antibacterial EPS IgG and IgA did not correlate well with the clinical or bacteriologic response to antimicrobial therapy. The concentration of antibacterial IgA expressed as a function of total IgA was as much as 1550 times greater in the EPS than in the serum. However, the relative concentrations of antibacterial IgG and IgM were similar in the EPS and serum. These data suggest local synthesis of antibacterial IgA in the prostate that persists following eradication of the infection and that is regulated independent of both the systemic immune response and the concentration of total prostatic fluid immunoglobulin.

Adult↗

Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer.

We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.

Adult↗

Bacterial infection and male infertility: absence of immunoglobulin A with specificity for common Escherichia coli 0-serotypes in seminal fluid of infertile men.

We used an indirect solid phase radioimmunoassay to detect and quantitate immunoglobulin A (IgA) in male genital secretions with specificity for Escherichia coli (E. coli) antigen. We assayed the seminal fluid and expressed prostatic secretion (EPS) of a patient with chronic bacterial prostatitis (CBP) due to an 01 E. coli, the seminal fluid of 24 fertile men, and the seminal fluid of 62 men of infertile marriages. IgA directed apparently against the 0-antigen of the infecting E. coli was measurable in both the seminal fluid and EPS of the CBP patient. IgA in these specimens also bound to antigen in a mix of 8 common E. coli 0-serotypes that included an 01 E. coli. IgA with specificity for antigen in the mix of common E. coli 0-serotypes could not be detected in the seminal fluid of the fertile men or the men of infertile marriages. These data suggest that subclinical E. coli infections of the male reproductive tract are not commonly associated with infertility.

Adult↗

Immunoglobulin in seminal fluid of fertile, infertile, vasectomy and vasectomy reversal patients.

We measured the concentrations of IgG, IgA, and IgM, in the seminal fluid of 16 fertile men, 77 men of infertile marriages, 21 men who had undergone vasectomy reversal and 5 men who had undergone vasectomy only. The lower limits of sensitivity of the assay was 0.04 mg./dl. IgG (mean concentration 3.29 mg./dl., range 0.48 to 15.41 mg./dl.) and IgA (mean concentration 1.11 mg./dl., range 0.05 to 19.11 mg./dl.) were measureable in all specimens, but IgM (range 0.04 to 0.76 mg./dl.) was measureable in only 20 per cent. Intrasubject variability of IgG and IgA concentrations expressed as the coefficients of variation of serial determinations ranged from 18 to 40 per cent and 29 to 52 per cent, respectively. Discrepancies between the presence or absence of measurable IgM in serial determinations were unusual. The mean concentrations of seminal fluid IgG and IgA in the fertile group were not significantly different from the other patient groups. However, IgM was measurable in only 13 per cent of specimens from the fertile patients but in 62 per cent of specimens from the vasectomy reversal patients (p = 0.003). This suggests disruption of the blood-genital tract barrier following vasectomy and continuing after vasectomy reversal.

Adult↗

Considerations for the use of testosterone with systemic chemotherapy in prostatic cancer.

Among 52 patients with metastatic adenocarcinoma of the prostate who were treated with exogenous testosterone, 45 (87%) experienced unfavorable subjective and/or objective responses. These unfavorable responses were elicited more frequently and after shorter treatment periods in patients in symptomatic relapse following endocrine therapy than in untreated patients or patients in remission following endocrine therapy. Serious morbidity or mortality, seemingly due to the testosterone administration, occurred in eight cases (15%). It is not known if the action of chemotherapeutic agents will be enhanced by concurrent testosterone therapy but any such investigation should be undertaken with extreme caution.

Acid Phosphatase↗

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone.

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationship between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadal function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.

Adolescent↗

Observations on reliability of commercial assay for alpha-fetoprotein.

Thirty patients with nonseminomatous germ cell tumors of the testis were monitored with serum levels of alpha-fetoprotein (AFP). Each patient had at least one AFP determination performed in duplicate: one by the National Institutes of Health (NIH) and one by a commercially available assay. With respect to normal and elevated levels, there was agreement in 60 of the 69 duplicate AFP determinations (87 per cent). Six of the 9 discordant AFP determinations were due to increased sensitivity (a lower normal range) of the NIH assay. There was a close correlation between the quantitative levels of AFP when both the NIH and commercial levels were elevated.

Humans↗

Immunologic response of the prostate to bacteriuria and bacterial prostatitis. I. Immunoglobulin concentrations in prostatic fluid.

We investigated the impact of bacteriuria and bacterial prostatitis on the immunoglobulin content of prostatic fluid. Using an indirect solid-phase radioimmunoassay, we assayed samples of expressed prostatic secretion (EPS) from 20 men with no histories of bacteriuria and from 13 men with histories of culture proven bacteriuria for IgG, IgA and IgM concentrations. Five of the bacteriuric men had culture proven bacterial prostatitis. The concentrations of each immunoglobulin varied widely and were unrelated to age, race, history of urologic instrumentation, presence of benign prostatic hyperplasia, leukocyte content of EPS or EPS aerobic bacterial culture results. The mean concentration of IgG for samples from the bacteriuric patients, 44.3 mg/ml., was similar to that of the uninfected patients, 58.4 mg./dl. (p less than 0.5). The mean concentrations of IgA and IgM for samples from the bacteriuric patients, 89.2 and 1.44 mg./dl., respectively, were greater than those of the uninfected patients, 25.2 and 0.95 mg./dl., respectively. These differences, however, did not achieve statistical significance, p less than 0.025 and p less than 0.3, respectively. However, the mean ratio of IgA:IgG for samples from the bacteriuric patients, 1.67, was significantly greater than that of the uninfected patients, 0.34 (p less than 0.005). The fraction of IgA in the form of secretory IgA was greater than 60 per cent for samples obtained from both the uninfected and bacteriuric patients. These data suggest that bacteriuria is associated with increased secretion of IgA in the prostatic fluid.

Adult↗