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Biomedical subjects

D F Paulson

Publications and source records attributed to D F Paulson.

At least 145 records · Page 8Linked to original sources

Experience with Gleason's histopathologic grading in prostatic cancer.

The inaccuracy of clinical staging as a predictor of the biologic potential of prostatic cancer has prompted evaluation of additional methods of assessment. We reviewed 228 patients with prostatic adenocarcinoma who presented during a 4-year period. Of the 228 patients 144 with no detectable bony disease underwent staging pelvic lymphadenectomy with or without preliminary bilateral pedal lymphangiography. Histopathologic specimens of the primary diagnostic prostatic biopsy were classified with Gleason's grading system of tumor differentiation. Of the patients with Gleason's sum of 8, 9 or 10, 93 per cent had regional nodal metastases, regardless of preliminary clinical stage. Furthermore, no patient with Gleason's sum of 2, 3 or 4 had nodal metastatic disease. The incidences of falsely positive and falsely negative lymphangiograms were 29 and 35 per cent, respectively, reflecting the unreliability of pedal lymphangiography to predict nodal involvement accurately in patients with prostatic cancer. The Gleason system of histopathologic grading was reliable and reproducible, and afforded an accurate prediction of the surgical stage of disease.

Adenocarcinoma↗

Staging pelvic lymphadenectomy for carcinoma of the prostate risk versus benefit.

A total of 125 patients underwent limited staging lymphadenectomy for adenocarcinoma of the prostate. Of these patients 19 per cent with clinical stage B1 disease, 52 per cent with clinical stage B2 disease and 59 per cent with clinical stages C disease had positive nodes. There was 1 death secondary to myocardial infarction and postoperative complications occurred in 7.2 per cent of the 125 patients. Limited staging pelvic node dissection provides information regarding nodal dissection similar to that identified after more extensive dissection and it can be accomplished with little morbidity.

Adenocarcinoma↗

Predictors of lymphatic spread in prostatic adenocarcinoma: uro-oncology research group study.

There were 122 patients with biopsy-proved adenocarcinoma of the prostate and negative radioisotopic bone scan who were subjected to lymphangiography, determination of serum prostatic acid phosphatase, measurement of the size of the lesion, recent pathologic grading of the needle biopsy of the primary tumor and staging pelvic node dissection. The purpose of this study was to determine which of these variables would be most accurate in predicting the presence or absence of positive nodes. Patients with a Gleason scale of less than 5 had only a 13 per cent chance of having positive nodes, whereas patients with a high Gleason scale of 9 or 10 had a 100 per cent chance of having positive nodes. Lymphangiography, size of the prostatic lesion and serum acid phosphatase were not sufficiently accurate to act as predictors of lymphatic extension and precluded the necessity for staging pelvic node dissection.

Acid Phosphatase↗

In vitro chemotherapy testing of transitional cell carcinoma.

The chemotherapeutic drug sensitivity of live cells freshly isolated from two human bladder tumors was studied. Substantial differences in the sensitivities of the two tumors to various chemotherapeutic drugs as well as different sensitivities of a given tumor to different drugs were found. Such data could be valuable clinically. The therapeutic value of cyclophosphamide, thiotepa and methotrexate was questionable for these two tumors because an increase in thymidine incorporation was seen after treatment with these drugs. A similar increase was observed after treatment with 5-fluorouracil in cells of a tissue-culture cell line derived from a human bladder tumor. Pretreatment of the cells with 5-fluorouracil reduced this effect. Even after 12 to 18 hours of exposure to 5-fluorouracil, the cells formed a confluent monolayer within 9 days. A similar treatment with doxorubicin hydrochloride resulted in detachment of the cells and formation of aggregates. The aggregated cells excluded trypan blue for at least 9 days after the doxorubicin hydrochloride was removed.

Antineoplastic Agents↗

The physiologic consequences of vas ligation.

Although the number of studies involving vasectomized men has been limited there appears to be no significant long-term effects. Endocrine function continues virtually unaltered. With a small number of exceptions spermatogenesis in man, as judged by a return of normal seminiferous tubule morphology, remains unchanged. However, the quality of the sperm may vary. The immunologic consequences of vasectomy have not been investigated fully. Although it is attractive to postulate that cross-reactive antibodies may develop to sperm antigens no autoimmune diseases in man secondary to vasectomy have been demonstrated. The increased incidence of atherosclerosias not been established in man. Presently, vasectomy remains a simple and safe means of permanent contraception.

Animals↗

An in vitro assay procedure to test chemotherapeutic drugs on cells from human solid tumors.

An in vitro assay was developed to measure the chemotherapeutic drug susceptibility of cells from human tumors. The assay utilized live cells, freshly isolated from tumor tissue, which were incubated for a short period in vitro. The drug-induced inhibition of incorporation of radiolabeled precursor into DNA, RNA, and protein was measured. The assay is sensitive to concentrations of chemotherapeutic drugs in the therapeutic range and is reproducible when tested with replicates of the same tumor cell population.

Animals↗

Activation of cyclophosphamide for in vitro testing of cell sensitivity.

Two methods are described for the activation of cyclophosphamide by a liver microsome preparation. These procedures were applicable to an assay in vitro which tests the sensitivity of tumor cells to the drug. Satisfactory results were obtained either by pretreatment of the cyclophosphamide and removal of the microsomes before testing or by the somewhat simpler procedure of mixing drug, microsomes, and test cells for the assay. Microsome treatment of bleomycin gave a smaller increase in activity, and much smaller effects were seen on some other drugs.

Animals↗

The prognostic role of lymphadenectomy in adenocarcinoma of the prostate.

Lymphatic extension to the pelvic nodes is best identified by pelvic lymphadenectomy, although pathologic grading of the prostatic primary lesion may allow identification of nodal extension in a small number of patients. The treatment data indicate that prostatic adenocarcinoma, as with virtually all other cancers, has limited potential for cure by local treatment when lymph node extension has occurred. Categorical statements promoting lymphadenectomy as a therapeutically beneficial procedure must be tempered by the observed adverse prognostic impact of identified nodal extension. Lymphadenectomy, as it has little therapeutic impact, should be used to select patients for treatments designed for control of localized disease. Patients with identified nodal extension might best be managed by design and application of a treatment regimen that has a systemic rather than a local or regional effect. It seems reasonable to conclude that pelvic node dissection in prostatic carcinoma offers limited therapeutic benefit and should be considered only as an aid in treatment selection.

Adenocarcinoma↗

Complications of Small-Carrion penile prosthesis.

Seventy-six patients with impotence have undergone insertion of the Small-Carrion penile prosthesis at Duke University Medical Center. Twenty patients experienced postoperative complications. Seven of these 20 patients lost one or both prostheses either by spontaneous extrusion or surgical removal. Although success with this procedure is well documented, complications may be significant when they occur and awareness of these problems is essential for proper management. The benefits of this procedure are reviewed, and reported complications and their management are discussed.

Erectile Dysfunction↗

Primary non-urachal adenocarcinoma of the bladder.

The clinical course of 34 patients with non-urachal adenocarcinoma of the bladder was reviewed and compared to the world experience. The 5-year survivorship was 19 per cent, with only 1 patient being free of disease. Metaplasia with formation of glandular elements reflects the unstable potential of the transitional cell and may be associated with the biologic aggressiveness of the tumor.

Adenocarcinoma↗

Cortisone acetate versus clomiphene citrate in per-germinal idiopathic oligospermia.

Long-term, low dose clomiphene citrate (25 mg./day for 25-day cycles with 5-day rest periods) and long-term, low dose cortisone acetate (5 mg. twice daily) were compared in equivalent populations of men with idiopathic oligospermia. Clomiphene citrate seemed to be more effective than cortisone acetate in enhancing spermatozoal number and the likelihood of pregnancy. In addition, clomiphene citrate increased serum testosterone levels and provided an indicator of hypothalamic-pituitary-testicular axis responsiveness.

Clomiphene↗

C-type virus particles in human urogenital tumours after heterotransplantation into nude mice.

C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.

Animals↗

Treatment of metastatic endocrine-unresponsive carcinoma of the prostate gland with multiagent chemotherapy: indicators of response to therapy.

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.

Acid Phosphatase↗

Isolation of a human prostate carcinoma cell line (DU 145).

A long-term tissue culture cell line has been derived from a human prostate adenocarcinoma metastatic to the brain. The cell line, DU 145, has been passaged 90 times in vitro over a period of 2 years. The cells are epithelial, grow in isolated islands on plastic Petri dishes, and form colonies in soft agar suspension culture. Karyotypic analysis demonstrates an aneuploid human karyotype with a modal chromosome number of 64. Distinctive marker chromosomes (a translocation Y chromosome, metacentric minute chromosomes and three large acrocentic chromosomes) have been identified. Electron microscopy of the original tumor tissue and of the tissue culture cell line show a remarkable similarity in cell organelle structure.

Acid Phosphatase↗