PubMed Health⌕ Search

Biomedical subjects

G P Murphy

Publications and source records attributed to G P Murphy.

At least 19 recordsLinked to original sources
PubMed1992

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

Adult↗
PubMed1992

Relapsing disease.

Explore the source record for details and available documents.

Antigens, Neoplasm↗
PubMed1992

The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The participating institutions of the American Cancer Society National Prostate Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A total of 88 cancers were confirmed pathologically, 93% of which clinically were organ confined. In 324 men (62.3%), a recommendation for biopsy was made based solely on the results of transrectal ultrasonography (TRUS); in 69 patients (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%), on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on cancer detection increased as the serum level increased above 4 ng/ml. The positive predictive values of both the DRE and TRUS were influenced significantly by the presence of an elevated PSA level (P = 0.044 and P less than 0.001, respectively). The results of this ongoing multicenter study support the following statements: (1) the prostate cancer detection rate is influenced by this diagnostic triad and (2) the detection rate of organ-confined disease can be improved substantially by early detection programs.

Aged↗
PubMed1992

Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.

Age Factors↗
PubMed1992

Two mechanisms for growth inhibition by elevated transport of sugar phosphates in Escherichia coli.

The Escherichia coli uhp T gene encodes an active transport system for sugar phosphates. When the uhp T gene was carried on a multicopy plasmid, amplified levels of transport activity occurred, and growth of these strains was inhibited upon the addition of various sugar phosphates. Two different mechanisms for this growth inhibition were distinguished. Exposure to glucose-6-phosphate, fructose-6-phosphate or mannose-6-phosphate, which enter directly into the glycolytic pathway, resulted in cessation of growth and substantial loss of viability. Cell killing was correlated with the production of the toxic metabolite, methylglyoxal. In contrast, addition of 2-deoxyglucose-6-phosphate, galactose-6-phosphate, glucosamine-6-phosphate or arabinose-5-phosphate, which do not directly enter the glycolytic pathway, resulted in growth inhibition without engendering methylglyoxal production or cell death. Inhibition of growth could result from excessive accumulation of organophosphates in the cell or depletion of inorganic phosphate pools as a result of the sugar-P/Pi exchange process catalysed by UhpT. The phosphate-dependent uptake of glycerol-3-phosphate by the GlpT antiporter was strongly inhibited under conditions of elevated sugar-phosphate transport. There are thus two separate toxic effects of elevated sugar-phosphate transport, one of which was lethal and related to increased flux through glycolysis. It is likely that the control of uhpT transcription by catabolite repression exists to limit the level of UhpT transport activity and thereby prevent the toxic events that result from elevated uptake of its substrates.

Bacterial Proteins↗
PubMed1991

The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men.

The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary, multicenter effort to assess the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) assay. By June 1990, 2425 men not previously suspected of having prostate cancer had been examined in ten participating clinical centers according to the project protocol. Three hundred ninety-six men (16.3%) were recommended for biopsy on the basis of TRUS or DRE. An analysis of the results of 330 completed biopsies showed 52 cancers detected by DRE and/or TRUS. Forty-four (84.6%) of the men with cancer had positive TRUS examination results compared with 33 (63.5%) with positive DRE. Five additional cancers were discovered as a result of elevated PSA levels. The overall detection rate was 2.4% and this rate varied by age. The detection rate in men 55 to 60 years of age was 1.3% and this rose to 3.3% in men older than 65 years of age. The estimated sensitivity was significantly greater for TRUS compared with DRE (77.2% versus 57.9%; P less than 0.05). The estimated specificity of DRE was greater than that of TRUS (96.3% versus 89.4%; P less than 0.01). The positive predictive value (PPV) for the tests varied as a function of patient and disease characteristics. The overall PPV was 28.0% for DRE and 15.2% for TRUS. The occurrence of elevated PSA levels significantly increased the PPV of both TRUS and DRE. The majority of cancers detected were at early stages. These preliminary data suggest the feasibility of using these techniques to promote cancer control, but additional data and follow-up are needed to assess the significance of the results.

Age Factors↗
PubMed1991

Lucy Wortham James Basic Research Award. Markers of prostatic carcinoma.

Markers of human prostatic cancer are important diagnostic aids in the management of this most common tumor among US men. A rapidly expanding body of basic and clinical knowledge about the properties and behavior of these unique organ-specific macromolecules bridges the gap between sophisticated immunochemistry and everyday practice. As a consequence, the patient benefits, because greater opportunities for early detection of prostatic cancer provide more freedom in selecting the most effective treatment modalities. Parallel improvement in quantitative assessment of an existing tumor mass allows earlier and more precise monitoring of the positive therapeutic responses and/or disease progression, as well as better overall prognosis. In addition, marker molecules can provide specific targets for antibody-directed therapeutic compounds active against prostatic cancer. This study focused on three such markers: prostatic acid phosphatase, prostate-specific antigen, and a new membrane-associated marker defined by a monoclonal antibody called 7E11-C5. A critical evaluation of clinical usefulness and prospects for future developments are presented.

Acid Phosphatase↗
PubMed1979

The histology of liver tumors in oral contraceptive users observed during a national survey by the American College of Surgeons Commission on Cancer.

As part of the national survey on the tumorigenesis of oral contraceptive drugs conducted by the American College of Surgeons' Commission on Cancer, a histologic study was made of 94 cases of liver tumors in users and non-users of oral contraceptives. Pathologic criteria were established and then the slides were studied; the results were tabulated to determine the significance of each of the criteria as related to the use of contraceptives. These criteria included tumor size, peliosis hepatis, hemorrhage, necrosis, fibrosis, thrombosis, and vascular alterations of the intima and media. Cases of focal nodular hyperplasia in pill users exhibited greater vascular alterations, fibrosis, peliosis, and tumor size as compared to focal nodular hyperplasia observed in non-pill users. In addition, hemorrhage, necrosis, and peliosis were much more common in hepatic cell adenoma than in focal nodular hyperplasia. In the material reported in this series there were no hepatic cell adenoma cases observed in non-pill users. Focal nodular hyperplasia cases exhibited an overwhelmingly greater degree of vascular intimal and medial alterations than hepatic cell adenoma. The results suggest that the effects of oral contraceptives on the liver may be primarily upon the vasculature.

Carcinoma, Hepatocellular↗
PubMed1979

A report of the workshops on the current status of the histologic grading of prostate cancer.

A national multidisciplinary study of four major systems for the histological grading of primary prostatic cancer was completed during 1978. In a series of workshops culminating in a final review, criteria of grading were critically assessed against the background of patient survival data. The overall consensus was that the Gleason system should tentatively be adopted as the pathologic reference point for classifying patients. This system can be used in conjunction with other systems. It seems definable, reproducible, reasonably simple, and has clinical relevance as judged by correlations with patient survival. Further study may demonstrate advantages from incorporation of the nuclear or cytologic characteristics of tumor cells into the Gleason system. New techniques of acid phosphatase determination, bone scans, and assessment of the regional lymph nodes should provide better staging criteria for correlation with primary tumor histology in the furture. These workshops presented a unique opportunity for representative clinicians and pathologists in the United States to express their viewpoints in a comprehensive fashion on this timely and important topic.

Anaplasia↗
PubMed1979

Comparison of intramural 5-fluorouracil and more conventional routes of drug administration on concentrations in gastric regional lymph nodes: a potential for trans-endoscopic adjuvant chemotherapy.

Intramural injection of 20 muCi (2-14C) 5-fluorouacil (5-FU) into the gastric submucosa of dogs and baboons was employed to evaluate the kinetics of 5-FU distribution following this route of administration and to compare these results with those following intraluminal, intravenous, and local intraarterial injections. Measurements of radioactivity taken over a six-hour period after injections demonstrated that the greatest concentration of isotope in samples of gastric wall and perigastric lymph nodes was found after administration of the drug directly into the stomach wall. Clinical application of intramural injections of 5-FU into the stomach wall under direct gastroscopic visual control, may be worthy of trial in patients with gastric cancer.

Animals↗
PubMed1979

Two new, direct, and specific methods of acid phosphatase determination. National field trial.

A national study of the new specific assays for prostatic acid phosphatase was conducted by the National Prostatic Cancer Project. The results of the study have confirmed that the counterimmunoelectrophoretic method is easily reproducible, highly specific, and sufficiently sensitive. Based on tests as performed by different institutions, the counterimmunoelectrophoretic (CIEP) method was also shown to have high reproducibility and was found to be of much greater sensitivity than the conventional biochemical methods for the detection of earlier stages of prostatic cancer. The national study of the radioimmunoassay (RIA) has shown that although being a highly sensitive method, it could not be readily distributed at this time from one specialized center. It requires highly specific, expensive technical assistance and is not yet available nationwide. CIEP is recommended at this time to be used as the preferred method in the evaluation and diagnosis of prostatic cancer. The value of counterimmunoelectrophoresis in detecting early prostatic cancer as a screening method is promising, but still under study.

Acid Phosphatase↗
PubMed1979

Insulin-induced growth hormone responses in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH) response was studied in 12 patients with prostatic carcinoma. Three patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. The patients subsequently presented clinically with rapidly progressing disease. Such observations are compatible with the viewpoint that abnormally high or low GH levels systemically present, may be associated with a particularly bad clinical prognosis. Further studies will clarify this relationship.

Adenocarcinoma↗
PubMed1979

Paradoxical increase of renal blood flow in anesthetized hypertensive dog treated with indomethacin.

To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.

Animals↗
PubMed1979

Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.

Aged↗
PubMed1979

Steroid hormone receptors in the prostate.

Specific receptors for dihydrotestosterone and estradiol-17-beta have been identified in cytosols of the human and baboon prostate. Binding of radioactive estradiol-17-beta to the 0.4 M potassium chloride extractable component of human prostate nuclei also was demonstrated. Cyproterone acetate and diethylstilbestrol, agents of known high affinity for dihydrotestosterone and estradiol-17-beta receptors, respectively, did not bind significantly to sex hormone binding globulin and, therefore, were useful as competitors in distinguishing binding of dihydrotestosterone and estradiol-17-beta to sex hormone binding globulin and to their specific receptors. Displacement of [3H]-estradiol-17-beta binding by diethylstilbestrol in cytosols of 11 needle biopsy specimens (mean equals 16.8 mg.) from prostatic cancer patients was analyzed. These preliminary data indicated a trend towards greater competition by diethylstilbestrol for high affinity binding sites in differentiated tumor specimens from men who were not receiving estrogen therapy. Objective and subjective responses to hormone therapy were recorded in these patients, whereas the disease in those men with low displacement assay values progressed.

Aged↗
PubMed1979

Prostate cancer.

Explore the source record for details and available documents.

Humans↗