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Biomedical subjects

D F Paulson

Publications and source records attributed to D F Paulson.

At least 91 records · Page 5Linked to original sources

Does transurethral resection of the prostate promote metastatic disease?

Previously published data have suggested that transurethral resection of the prostate might promote the subsequent appearance of metastatic disease. To confirm or deny these observations 145 patients underwent radical prostatectomy, after having had the disease diagnosed either by transurethral resection of the prostate or transrectal needle biopsy. Of the 145 patients 6 were excluded from analysis since they had had transurethral resection of the prostate and transrectal needle biopsy. In 33 patients the disease was diagnosed by transurethral resection of the prostate only and in 106 it was diagnosed by transrectal needle biopsy only. The relative distribution of Gleason grade and the positive versus negative margins among the 2 populations were similar. Using time to first evidence of distant disease as the endpoint of the study no difference in failure rates could be detected between the 2 populations. It is concluded that transurethral resection of the prostate does not enhance the appearance of metastatic disease.

Adenocarcinoma↗

Radiotherapy versus surgery for localized prostatic cancer.

Current data from randomized and nonrandomized clinical trials would indicate that radical prostatectomy offers the optimum method of disease control. The benefit of radical surgery is related to the extent of local disease. Gleason sum of the prostatic primary predicts for the probability of tumor extent.

Adenocarcinoma↗

Treatment of bacterial prostatitis. Comparison of cephalexin and minocycline.

The relative safety and efficacy of minocycline and cephalexin were examined in patients with acute or chronic prostatitis. The multicenter study was of single-blind, parallel-group design. Forty-two men received minocycline (200-mg initial dose followed by 100 mg twice daily) and 44, cephalexin (500 mg four times daily); each antibiotic was administered orally for four weeks. A follow-up period of patient assessment extended for an additional six weeks. Evaluable data were available for 20 minocycline-treated patients and for 24 cephalexin-treated patients. Clinical cure or improvement without recurrence was seen in 65 per cent of the patients who received minocycline and in 46 per cent of those given cephalexin. Bacteriologic cure without relapse or reinfection occurred in 45 per cent of the minocycline-treated men and in 21 per cent of the cephalexin-treated men. Serious adverse clinical experiences were not encountered in either treatment group. Although several factors, mainly the small number of patients, precluded a statistical analysis of comparative efficacy, it was evident that more patients in the minocycline-treated group had both clinical and bacteriologic cures (35%) than did those in the cephalexin-treated group (21%).

Adolescent↗

Radical prostatectomy: anatomical predictors of success or failure.

A total of 143 patients underwent radical prostatectomy. Surgical specimens were evaluated with respect to local extent of disease, Gleason grade of the primary and relative nuclear roundness of the surgical specimen. The probability of disease control in the total population was 88 per cent at 5 years. Only 8 per cent of the patients who had disease confined to the specimen failed compared to 14 per cent of those who demonstrated extension outside of the surgical margins. The incidence of failure increased as a function of seminal vesicle involvement. Seminal vesicle involvement was greatest among patients with a Gleason grade greater than 7. Postoperative radiation did not offer any apparent advantage in patients with positive margins.

Adenocarcinoma↗

Overview of first-line amikacin therapy for urologic infections.

Severe infections in urologic patients are frequently and effectively treated with aminoglycoside medications. Because of the frequency of nosocomial gram-negative infections in urologic patients, antimicrobial therapy with broad-spectrum antibiotics, such as aminoglycosides, is an integral part of management of urinary infections. Amikacin, because of its activity against infections caused by Pseudomonas, Serratia, and other frequently resistant bacteria, as well as its ability to achieve high blood and tissue levels, provides a significant advantage over other aminoglycoside agents in hospitalized urologic patients with suspected nosocomial infections. Although amikacin remains the most expensive of the aminoglycoside agents, its use is prudent in infections in which the causative organism is suspected but not definitively identified and when treatment must be started before specific culture and sensitivity information is available. In these situations, the most potent antibiotic agent with the broadest spectrum for eliminating infections caused by suspect organisms must be chosen, and amikacin is an ideal choice.

Amikacin↗

Lethal complications of standard self-retaining ureteral stents in patients with ileal conduit urinary diversion.

While standard commercially available pigtail ureteral stents are used commonly in the obstructed patient, particularly when metastatic disease has been identified, our recent experience suggests caution in the use of such stents for patients with ileal conduits. Rapid obstruction of these stents occurs with unacceptable frequency, which has resulted in urosepsis and death, and they do not appear to be cost-effective even for palliation. Although these standard pigtail stents have physical properties that allow easy placement by angiographic wire guidance, they are not to be recommended. Safe internal ureteral diversion in patients with an ileal conduit awaits further evolution in stent technology.

Aged↗

Advanced prostatic carcinoma: pulmonary manifestations.

To clarify the role of standard chest radiography in prostatic adenocarcinoma, the pulmonary manifestations of 198 patients with Stage D disease were evaluated. All patients were treated with chemotherapeutic protocols allowing for adequate clinical and radiographic correlation. Retrospective interpretation of serial chest radiographs revealed that 35% of our patients had visible intrathoracic abnormalities; however, only 24% of the patients had abnormalities attributable to intrathoracic metastases. Twenty-two percent of patients had pleural effusions, 16% reticular opacities, 3.5% reticulonodular opacities, 8% isolated or discrete pulmonary nodules, and 4.5% adenopathy. Etiologies of these opacities included metastatic disease in 93.5% of those with adenopathy and nodular or reticulonodular opacities, but 39% of pleural effusions and 52% of reticular opacities were best attributed to concomitant processes. Four patients had intrathoracic metastases without bone metastases. Standard chest radiography is a valuable screening procedure that should be correlated with clinical data to differentiate metastases from concomitant processes.

Aged↗

Management of metastatic prostatic cancer.

Current management techniques for metastatic prostatic cancer have given rise to controversies regarding the optimal timing, form, and degree of androgen deprivation. Low-dose diethylstilbestrol (DES) or orchiectomy decrease serum testosterone levels while posing less cardiovascular risk than high-dose DES. LH-RH analogues, such as leuprolide or buserelin, also inhibit testosterone production. Some studies suggest that some tumor cells may be relatively, rather than absolutely, androgen dependent. This has been the rationale for the combined use of a pure antiandrogen and an LH-RH agonist. Unfortunately, while this combination has been found effective in previously untreated patients, it has not been equally effective in those who have undergone prior therapy and demonstrated disease progression.

Adenocarcinoma↗

Staging lymphadenectomy should not be an antecedent to treatment in localized prostatic carcinoma.

The current controversy focusing on regional node evaluation in patients with prostatic carcinoma has been engendered by the enhanced biologic risk created by regional lymph node extension. The data indicate that node-positive disease is a systemic disorder and, as such, is not controlled by local treatment, such as lymphadenectomy combined with either radical removal of the primary malignancy or local radiation therapy. If lymphadenectomy is only prognostic and not therapeutic, it is reasonable to argue that any form of anatomic staging that permits the identification of nodal extension is a replacement for staging lymphadenectomy.

Biopsy↗

Evidence for a novel hybrid immunotoxin recognizing ricin A-chain by one antigen-combining site and a prostate-restricted antigen by the remaining antigen-combining site: potential for immunotherapy.

We have used cell fusion technology to produce second-generation hybridomas which secrete a population of murine monoclonal antibodies (MABs), a portion of which are bifunctional antibodies. The bifunctional hybrid MABs produced are capable of recognizing ricin A-chain (RAC) via one antigen-combining site and a prostate-restricted antigen via the other antigen-combining site of the IgG molecule. The second-generation hybridoma described in this report resulted from the fusion of spleen cells from mice immunized with purified RAC to hybridoma cells which secrete prostate-directed alpha Pro 15 monoclonal antibody. We have demonstrated that the MAB population secreted by the second-generation hybridoma can be physicochemically separated into distinct populations exhibiting differential binding to the cultured prostatic carcinoma cell surface and to RAC immobilized in a solid phase; specifically, a subset of the monoclonal antibody population which exhibits high binding to both prostatic carcinoma cells and to solid-phase RAC can be enriched by physicochemical methods. Binding of hybrid immunotoxin (HIT) MAB population to RAC can be quantitatively reduced by prior adsorption of the antibody population with prostate carcinoma cells; conversely, hybrid MAB binding to prostate carcinoma cells can be quantitatively reduced by prior adsorption with RAC. The biologic impact of the HIT has been evaluated by the ability of the HIT-RAC conjugate to reduce the uptake of 14C-amino acids into cellular protein. This effect is selective, since HIT-RAC conjugates do not exert an effect on labeled amino acid uptake by a cell line that does not express the target antigen recognized by the prostate-directed component of the hybrid MAB. Furthermore, depression of labeled amino acid uptake by prostate carcinoma cells exhibits a stoichiometric relationship with respect to both the concentration of HIT-MAB and to RAC to which the cells are exposed. The biologic impact of HIT-RAC conjugates on prostate carcinoma cells is enhanced markedly in the presence of lysosomotropic amines.

Adsorption↗

1,10-Phenanthroline reversibility inhibits proliferation of two human prostate carcinoma cell lines (PC-3 and DU145).

The metal chelator 1,10-phenanthroline reversibly inhibits proliferation of two human prostate carcinoma cell lines, PC-3 and DU145. Inhibition is dose-dependent, and persists for several days after removal of the chelator. The ability to induce reversible quiescence in human prostate carcinoma cells in vitro may facilitate the study of their growth cycle biochemistry.

Antigens, Surface↗

Characterization of prostate-tissue-directed monoclonal antibody, alpha-Pro 13.

The alpha-Pro 13-secreting hybridoma was produced by immunizing mice with an equal mixture of PC-3, DU145, and LNCaP established prostatic carcinoma cell lines. The specificity of alpha-Pro 13 monoclonal antibody was evaluated by the criteria of differential binding to cultured cells; differential binding to extracts of malignant prostate, nonmalignant prostate, and malignant and nonmalignant tissues of various histiotypes in solid phase radioimmunoassay; and by immunoperoxidase staining of primary surgical tissues of varied histiotypes. The data generated by multiple assay investigation indicate that alpha-Pro 13 exhibits preferential binding to the ductal epithelium of prostate tissue; immunoperoxidase evaluation indicates a considerable heterogeneity of staining of ductal epithelial cells. The most prevalent cross-reactivity of alpha-Pro 13 monoclonal antibody with non-prostate tissue occurs with blood vessel endothelium of restricted tissues. Electrophoretic analysis of immunoprecipitates from radioiodinated prostatic tumor extracts indicates that the molecule recognized by alpha-Pro 13 is of 120,000 dalton apparent nonreduced molecular weight. Under reducing conditions, the antigen (p40) consists of a major component of 40,000 dalton apparent MW and a minor component of 17,000 dalton MW. p40 has an isoelectric point of 3.5-4.5. The antigen is intrinsically stable on the PC-3 cell surface; its release into spent culture medium is negligible. p40 is also stable upon complexation with alpha-Pro 13 antibody in that it is not shed from the cell surface as an immune complex nor is it endocytosed to any extent as an immune complex.

Antibodies, Monoclonal↗