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Biomedical subjects

W M Murphy

Publications and source records attributed to W M Murphy.

At least 91 records · Page 5Linked to original sources

Carcinogenesis in mammalian urothelium: changes induced by non-carcinogenic substances and chronic indwelling catheters.

Carcinogenesis in urinary bladders may not be represented by a continuum of pathological lesions beginning with papillary tumors or flat dysplasias/atypias. In a previous experiment, sterile water and saline continuously infused via catheters connected to ALZA mini-pumps were shown to induce papillary urothelial lesions indistinguishable from tumors considered to be carcinomas in most histological classification schemes. The animals in the initial experiment were followed for relatively brief periods which did not allow for determination of potential reversibility of the process and did not distinguish the effects of the catheters versus those of the infused substances. The present study was designed to control for these variables. Rats were divided into seven groups to examine the urothelial changes after: surgery alone, continuous infusion of the sterile water and mitomycin C, and chronic indwelling catheters with and without infusion. The results indicated that chronic irritation with indwelling catheters was a strong stimulus for the induction of urothelial neoplasms and that continuous infusion of certain substances, even sterile water, might play a small role in the process of carcinogenesis. Comparing the frequencies of papillary urothelial tumors appearing after brief exposure to sterile water and catheters in the initial experiment (75 per cent) and papillary lesions appearing long after removal of the sterile water and catheters in the current study (0 per cent) indicates that these lesions are reversible and probably not neoplastic.

Animals↗

Incidental carcinoma of the prostate. How much sampling is adequate?

A prospective study of 386 consecutive transurethral prostatic resections from 383 patients with clinically benign glands was undertaken to determine the optimal sampling of chips required for the histologic detection of all clinically significant prostatic carcinomas. Cancers were graded according to two systems and staged by counting involved chips as well as estimating volume density. All Stage A2 prostatic carcinomas were detected by histologic examination of 6 g of randomly selected chips. Although additional tumors were detected in direct proportion to the amount of tissue examined, they were small, well-differentiated, Stage A1 lesions. Histologic sampling of 12 g of randomly selected prostatic chips detected almost 90% of incidental carcinomas, including all clinically significant neoplasms.

Adult↗

Aspiration biopsy of the kidney. Simultaneous collection of cytologic and histologic specimens.

Aspiration biopsy of mass lesions of the kidney is a diagnostic procedure whose potential benefit to patients with equivocal radiologic findings, suspected metastases, palpable flank masses, nonfunctioning kidneys and even cortical cysts has not been fully explored. Over the past 7 years 163 renal aspiration specimens from 152 patients have been examined. Diagnostic yield was enhanced by use of modified "fine" needles with notched tips so that tissue fragments for histology as well as smears for cytology were obtained in 89% of solid tumors. The availability of aspirated tissue contributed significantly to pathologic classification and often spared patients additional surgery for confirmation of the cytologic diagnosis. Among the 152 cases, there were 35 with renal cell carcinomas, a sufficient number for detailed semiquantitative evaluation of their cytologic features. The remaining cases comprised metastatic carcinomas, lymphomas, transitional cell carcinomas, oncocytomas, cortical cysts, and miscellaneous conditions, e.g., abscesses, nonfunctioning kidneys, and hematomas. Overall, the aspiration biopsy determined the nature of the renal mass in 141 cases (93%). False-negative interpretations were due to insufficient diagnostic material in all but one instance. There was one false-positive result.

Adenoma↗

Nephrogenic adenoma.

Nephrogenic adenoma is an uncommon, benign, apparently metaplastic response of urothelium to chronic infection or irritation. Endoscopically, these lesions easily can be mistaken for malignant tumors, and their scarcity only heightens the possibility of this error. A case report of nephrogenic adenoma accompanied by endoscopic photographs is presented to improve awareness and avoid inappropriate therapy.

Adenoma↗

An in vitro model for testing biocompatibility of endodontic materials to bone.

Calvaria from 6-day old mice labelled 4 days previously with 45CaCl2 were divided into test and control halves and each half cultured separately in vitro. Eluents from four endodontic materials, endomethasone, zinc oxide/eugenol, AH26 and gutta-percha were added separately to the culture medium of each test half. After 24 and 48 h culturing periods, the 45CaCl2 in the media and calvaria was measured by a standard liquid scintillation counting technique and a resorption ratio between test and control halves was computed. This ratio, based on cell mediated resorption, was an indication of toxicity of soluble components of each endodontic material. In accordance with the literature, endomethasone was found, with our method, to be the most toxic and gutta-percha the least toxic of the materials tested. This shows that our model can be used to test the toxicity of other biomaterials to bone cells in vitro.

Administration, Topical↗

IgA nephropathy. A comparative study of the clinicopathologic features in children and adults.

A comparative study of the clinicopathologic features of IgA nephropathy in 24 children and 46 adults was undertaken. In children, microscopic hematuria was present in all cases and was associated with gross hematuria in 83% and proteinuria in 58%. In adults, microscopic hematuria was present in 91%, gross hematuria in 25%, and proteinuria in 80%. During followup, renal failure was recorded among 5.5% of children and 10% of adults. Biopsy specimens were obtained from all patients and were examined by light, electron, and immunofluorescence microscopic technics. Morphologic changes in the glomeruli were classified according to the degree of mesangial hypercellularity, sclerosis, and crescent formation into four groups. The most common glomerular pattern in children was diffuse, mesangial hypercellularity, while mesangial proliferation associated with focal segmental glomerulosclerosis predominated among adults. These observations suggest that glomerular morphology correlates with age at diagnosis and influences the clinical outcome of the disease.

Adolescent↗

Importance of urinary cytology and future role of flow cytometry.

A study recently completed in our laboratory evaluated the role of flow cytometry in comparison with urinary cytology in a clinical practice setting to ascertain the utility of this new method in routine diagnostic pathology. In patients being followed up for known bladder cancer, urinary cytology yielded a positive result in 85 per cent of cases. Flow cytometry yielded a 74 per cent positivity rate. The diagnostic accuracy of the two modalities combined was 98 per cent. The lower diagnostic yield from flow cytometry occurred in patients treated with topical chemotherapy for bladder cancer. This apparent false negative result of flow cytometry may be due to paucity of cells from epithelial denudation by the topical agents, inhibition of tumor growth by the chemotherapeutic agent, or masking of small aneuploid cell populations by a large inflammatory cell population. Our results suggest that urinary cytology and flow cytometry are complementary laboratory tests in the diagnostic evaluation of bladder cancer patients in clinical practice.

Administration, Topical↗

Urinary cytology and bladder cancer. The cellular features of transitional cell neoplasms.

Urinary cytology is increasingly accepted as a diagnostic tool in the detection and follow-up of patients with bladder cancer. Its potential value has been reduced, however, by the relative inexperience of most pathologists in the examination of urinary specimens, and by the lack of cellular criteria specifically reflecting the morphology of low-grade papillary and flat lesions of bladder epithelium. The cytologic features of urothelial lesions, including papillary transitional cell carcinomas and flat urothelial dysplasias have been studied in both experimental systems and clinical situations and their application to a selected patient population is presented. Overall, the cytohistologic correlation for patients with bladder cancer was 92%. Positive cells reflecting the morphology of the tumor occurred in 62% of patients with grade I transitional cell carcinomas, and cells suspicious for malignancy were identified in an additional 14% of these individuals. Using the criteria presented, a positive cytology can correlate with a papillary grade I bladder tumor, and should not necessarily indicate the presence of another neoplasm. Dysplastic cells in cytologic specimens are often identified in patients having urothelial dysplasia as the most serious bladder lesion, but the cytologic diagnosis of dysplasia may represent an under-interpretation of a low-grade papillary bladder tumor. The cells of urothelial neoplasms, including low-grade transitional cell carcinomas and dysplasias, differ morphologically both from normal and reactive/reparative elements, and can be detected in cytologic samples. The changes are often subtle and require experience and a cautious approach for accurate interpretation.

Biopsy↗

Surveillance of stage O, grade I bladder cancer by cytology alone--is it acceptable?

Although the high incidence of subsequent tumors is well established there is accumulating evidence that few cases of low grade, low stage transitional cell carcinomas will progress in stage. Since the purpose of intensive endoscopic monitoring following initial tumor resection is to detect potentially lethal new tumors as soon as possible, we reviewed retrospectively the course of 36 patients with an initial grade I, stage O (Ta) transitional cell carcinoma to determine whether cytology was capable of achieving this goal. Of these patients 10 (28 per cent) had a subsequent tumor of a higher grade or stage. Cytology performed at or before recurrence was positive in 8 patients (80 per cent) and 2 (20 per cent) had grade II, noninvasive transitional cell carcinoma with negative cytology. Subsequent tumors in these 2 patients have been grade I. All 36 patients are alive. Given the patient inconvenience, expense and risk of infection of cystoscopy compared to cytology, this retrospective review suggests that when an experienced cytopathologist is available patients with grade I, noninvasive transitional cell carcinoma may be monitored primarily by urinary cytology with less frequent endoscopy. A prospective study must be performed to confirm this approach.

Aged↗

Bladder cancer induced by noncarcinogenic substances.

Chemical carcinogenesis is currently regarded as a complicated series of events requiring initiation and promotion in specific sequences. Carcinogens are thought to be chemicals which can induce both initiation and promotion so that few if any additional host or environmental factors are required in the production of neoplasms. Most experimental studies to date have investigated bladder cancer using these highly active agents and the role of other substances in urothelial neoplasia has not been emphasized. We have examined the role of a variety of solutions, including water and saline, in pilot studies of urothelial carcinogenesis using the ALZA mini-pump for continuous infusion. Bladder tumors indistinguishable morphologically from papillary transitional cell carcinomas were induced. Although experimental induction of bladder cancer with powerful carcinogens may completely overwhelm host defenses and result in more and higher grade neoplasms, similar tumors may occur after exposure to substances not generally considered to be carcinogenic. This process, which probably requires cofactors and host-chemical interaction, may be more representative of environmental carcinogenesis than systems using powerful carcinogens and should be further investigated.

Administration, Topical↗

Comparative carcinogenicity of N-butyl-N-(3-carboxypropyl)-nitrosamine and N-butyl-N-(4-hydroxybutyl)nitrosamine for the urinary bladder of (C57BL/6 X DBA/2)F1 mice.

The carcinogenicity of N-butyl-N-(3-carboxypropyl)-nitrosamine [CAS: 38252-74-3; 4-(N-butyl-N-nitrosamino)butyric acid] in male and female (C57BL/6 X DBA/2)F1 mice was determined. N-Butyl-N-(3-carboxypropyl)nitrosamine given in the drinking water at a concentration of 3 mM (0.056%) for 13 weeks induced only carcinoma of the urinary bladder in both sexes. At 22-28 weeks, the incidences of bladder cancer in the male and female mice were 100 and 88%, respectively. These bladder tumors were classified histologically according to the frequency (%) of tumor type: pure transitional cell carcinoma, 42%; mixed (transitional cell carcinoma with squamous or glandular differentiation, or both), 28%; squamous cell carcinoma, 27%; and carcinoma in situ, 3%. No significant sex differences were observed. In comparative studies, the incidence of bladder cancer was 100% for both sexes after administration of 3 mM (0.052%) N-butyl-N-(4-hydroxybutyl)nitrosamine [CAS: 3817-11-6; 4-(butylnitrosoamino)-1-butanol] in the drinking water. The frequency of pure transitional cell carcinoma was 47%, which was not significantly different from that observed for the carboxypropyl compound. The frequencies of other types of bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine were the following: mixed, 8%; squamous cell carcinoma, 42%; and carcinoma in situ, 3%.

Animals↗

Papillomavirus structural antigens in condyloma acuminatum of the male urethra.

Current developments in the technology of viral identification have rekindled interest in the relationship of human papillomaviruses, condylomata acuminata and neoplasia. Although important observations are being reported in the female genital system the association of human papillomavirus and mucosal condylomata in male patients has not been well documented. Using the horseradish peroxidase technique and antisera to papillomaviruses, viral antigens were identified in 62 per cent of male patients with urethral condylomata acuminata. The implications of this relationship are discussed briefly.

Adult↗

The effect of disulfiram on the carcinogenicity of N-butyl-N-(3-carboxypropyl)nitrosamine in the rat.

N-Butyl-N-(3-carboxypropyl)nitrosamine (BCPN) is a proximate carcinogenic metabolite of the bladder specific carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN). The objective of this study was to determine if disulfiram would inhibit the induction of bladder cancer in rats given BCPN, as reported for BHBN (Cancer Res., 39, 3040, 1979). Two groups of 30 male Wistar rats were given 1.5 mM BCPN (0.028%) in the drinking water for 12 weeks. The total dose of BCPN/rat was 5 mmol (0.95 g). During administration of the BCPN, one group of rats was fed a diet containing 0.5% disulfiram, while the other group was maintained on control diet. At the end of 12 weeks, the animals were maintained on control diet without BCPN for an additional 18 weeks, at which time the animals were sacrificed. It was found that 0.5% disulfiram significantly reduced the incidence of bladder cancer, decreasing from 30/30 (100%) in the group receiving BCPN alone to 3/30 (10%) in the group fed the disulfiram diet. The inhibition of BHBN-induced bladder cancer by disulfiram, previously reported, was also confirmed in these experiments.

Animals↗