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Biomedical subjects

W M Murphy

Publications and source records attributed to W M Murphy.

At least 109 records · Page 6Linked to original sources

Single and sequential combination intravesical chemotherapy of murine bladder cancer.

We investigated the effectiveness of intravesically administered drugs on the tumor incidence and tumor size in a FANFT-induced animal model for bladder cancer. In the first experiment 106 C3H/He mice were divided into a control and three treatment groups. Therapy consisted of either cis-diamminedichloroplatinum (II) (DDP), mitomycin C, or thio-tepa. There was a reduction in the tumor incidence in all treated groups; this was statistically significant for those receiving mitomycin C (p less than 0.04) and DDP (p less than 0.001). No significant difference in the mean or median tumor weight (an index of tumor volume) between the treated and control groups was found. In a second experiment intravesical combination chemotherapy was compared to single-agent therapy. Animals received either doxorubicin hydrochloride (Adriamycin), mitomycin C, thio-tepa, mitomycin C + doxorubicin, or mitomycin C + thio-tepa. Although there was no significant difference in tumor incidence among the groups with the exception of mice receiving thio-tepa, animals receiving sequential combination chemotherapy had lower mean and median bladder weights suggesting an improved therapeutic effect.

Animals↗

In vitro characterization of four N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced mouse bladder tumors.

Four longterm murine bladder tumor cell lines were established in vitro. The 4 lines were initiated from primary N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced murine bladder tumors arising in C3H/He mice. Each was maintained as a solid tumor in syngeneic mice for at least 30 generations before initiation in tissue culture. The cell lines MBT-2, MBT-8, MBT-409 and MBT-683, have been subcultured over 75 times in vitro for 18 months. They are all epithelial, grow in islands on plastic Petri dishes before confluent growth and form colonies in soft agar suspension culture. Morphologic studies indicate that all 4 lines have epithelial characteristics and karyotypic studies indicate that all lines have polyploidy and marker chromosomes. Population doubling times range from 10 to 26 hours and are consistent for each line.

Animals↗

Aluminum-containing dense deposits of the glomerular basement membrane: identification by energy dispersive X-ray analysis.

Heavy metals, including gold, mercury, lead, bismuth, and cadmium, have the potential to cause renal disease. With the development of X-ray microanalysis, these heavy metals can now be identified in tissue deposits. This report describes a case of renal failure, probably related to dysproteinemia, in which granular, electron-opaque dense deposits were present in the glomerular basement membranes. Energy dispersive X-ray analysis demonstrated that these dense deposits contained aluminum. An analysis of this patient's history in relation to the current knowledge of aluminum metabolism suggests that the aluminum deposition occurred secondary to previous glomerular injury. This case emphasizes the need to utilize heavy metal identification technology whenever granular, electron-opaque dense deposits are identified and represents, to our knowledge, the first study to document aluminum deposits within the glomerular basement membrane of humans.

Acute Kidney Injury↗

A laboratory and clinical study of Trevalon denture base material.

Trevalon is a denture base material which can be cured by three basic alternative curing cycles, thus providing a choice of processing technique which can be selected to suit laboratory or clinical needs. The flexibility of working properties is probably due to the interaction between on the one hand, the high molecular weight of the powder and on the other hand, the particle size distribution which are important factors influencing the doughing time (14 min), working time (40 min) and the exothermic reaction. The effect of each curing cycle upon the following properties of the material was investigated; dimensional accuracy, Young's modulus, modulus of rupture, impact resistance, water sorption, indentation resistance, creep and transverse bend behaviour. The particle size and molecular weight distribution of the powder were also evaluated. A clinical investigation of Trevalon was carried out by constructing complete dentures for a sample of patients, divided into three groups, each group having dentures processed by one of the three alternative curing cycles. Although some laboratory tests demonstrated that there were statistically significant differences between specimen bases, no clinical differences were recorded between dentures 1 year after construction.

Chemical Phenomena↗

Renal disease after mitomycin C therapy.

Fourteen patients with adenocarcinoma of the gastrointestinal tract and pancreas treated with mitomycin C(MMC) and 5-fluorouracil (5-FU) had renal impairment 6-11 months from the beginning of MMC therapy. Two clinical entities were recognized: an acute fulminating renal failure that was rapidly fatal and a chronic slowly progressive renal impairment. The first entity showed a microangiopathic hemolytic profile with anemia, thrombocytopenia, and erythrocyte fragmentation. Light microscopy and electron microscopy examination of the kidney revealed a primary vascular disease with musculomucoid intimal hyperplasia of arteries and rare fibrin thrombi in arterioles. Interstitial fibrosis, tubular atrophy, and widespread glomerular necrosis were also seen. The disease was ultimately fatal within three to four weeks. The second entity showed a chronic course of renal failure with similar pathologic findings but less pronounced, and a microangiopathic hemolysis was absent. The course in the second group was ultimately fatal between three to eight months.

Acute Kidney Injury↗

The morphologic effects of mitomycin C in mammalian urinary bladder.

This investigation was intended to determine the morphologic changes of mitomycin C. It is part of a series of experiments designed to evaluate the cytologic and histologic effects of topical chemotherapeutic agents using the FANFT experimental model system in mice. The results for mitomycin C are very similar to those previously reported for thio-tepa. The indicate that these chemicals produce few, if any, drug-specific light microscopic alterations. Rather, mitomycin C and thio-tepa apparently act as toxic substances, causing increased exfoliation, degeneration, and necrosis of urothelial cells. The implications of these findings and suggestions for future investigations are discussed.

Administration, Topical↗

The cellular features of developing carcinoma in murine urinary bladder.

Bladder cancer often results from a widespread reaction of urothelial cells to carcinogenic stimuli. Although developing carcinoma is widely considered to progress through various grades of epithelial atypia, well-controlled prospective studies detailing the morphologic features of these lesions at the cellular level have not appeared in the literature. This study was designed to document the cellular features of developing urothelial carcinoma in experimental animals using the BHBN model system. Developing lesions were monitored by periodic collection of urine and tissue. The specimens were coded and examined by cytology and histology using multiple discriminators. The morphologic changes in the treated bladders were statistically different from those in control tissue. They could be divided into three stages: 1) The earliest abnormalities were an increase in the number of cell layers, loss of polarity, and slight crowding of nuclei in the tissue sections. Among the cellular features, there were increased nuclear size and sharply angulated indentations (notches) in the nuclear borders. A few nuclei exhibited a finely granular pattern, but dusty chromatin predominated. 2) In the intermediate stage, nuclear crowding became more prominent, and there were numerous areas with finely granular, regularly distributed chromatin. A few nucleoli were identified. Mitoses were prominent in the tissue sections. 3) In the late stage, as papillary tumors developed elsewhere, the urothelium of the flat areas changed significantly. Nuclear crowding and notching remained constant but were overshadowed by the appearance of nucleoli and irregularly distributed chromatin. The pattern was finely granular in some cases but coarsely granular in most. Nuclear size decreased markedly as the cells became smaller and more numerous. Cytologically, it was not possible to distinguish these cells from neoplastic cells emanating from the papillary areas. This experimental study tends to confirm deductions made from clinical material that urothelial carcinoma develops through an orderly sequence of morphologic severity. It further indicates that invasive carcinoma can arise from neoplastic cells that neither occupy the full thickness of the epithelium nor represent lateral migration from an adjacent full thickness lesion. The detailed cellular features documented can be used to identify atypical cells in correlative cytologic preparations. Studies such as this could provide an experimental basis for future evaluations of the cytologic characteristics of human urothelial atypia.

Animals↗

Evaluation of cystography for detection of bladder carcinoma in mice: comparison with urinary cytology.

Cystography was compared to urinary cytology in an effort to determine whether or not this modality might be useful in the detection of FANFT-induced bladder tumors in mice. Compared to gross examination of the bladders in 24 mice, cystography had the same degree of accuracy as urinary cytology--79.2 per cent. Comparison of the cystographic and cytologic diagnoses with histology revealed that cytology was more accurate, 79.2 vs 66.6 per cent. Cystography was especially helpful in detecting papillary tumors while cytology was more accurate in the detection of high-grade, high-stage tumors or carcinoma in situ (CIS). Cystography in mice can complement cytology as an additional useful technique for detection of bladder carcinoma.

Animals↗

Poststreptococcal crescenteric glomerulonephritis in children: comparison of quintuple therapy versus supportive care.

Crescenteric glomerulonephritis preceded by a streptococcal infection with creatinine clearance CCr of less than 30 ml/minute/1.73 m2 was treated by supportive care plus three months of quintuple therapy (prednisone, azathioprine, cyclophosphamide, dipyridamole, and heparin followed by warfarin) in five children (Group A) or by supportive care alone in five others (Group B). Of the glomeruli examined, 69.8 +/- 11.7% (mean +/- SE) in Group A and 64.4 +/- 10.6% in Group B had crescents which involved 54.0 +/- 10.8% and 60.0 +/- 10.5% of glomerular circumference, respectively. Clinical and histologic findings supported a recent streptococcal infection in every patient. Two patients from Group A had mild proteinuria and normal CCr at 12 months; one died abruptly of pulmonary hemorrhage after maintaining a normal CCr for 25 months. Following a second episode of poststreptococcal acute glomerulonephritis seven months after the first, one patient from Group B had persistent mild proteinuria for 41 months and hypertension through 56 months of follow-up. Nine surviving patients have maintained normal CCr for eight to 60 months (mean 29.5 months). The findings of this study suggest that this quintuple therapy offers no advantage over supportive care in the clinical management and outcome of children with severe crescenteric glomerulonephritis when an antecedent streptococcal infection is confirmed by serologic and histopathologic criteria.

Adolescent↗

The diagnostic value of urine versus bladder washing in patients with bladder cancer.

In a prospective, critical appraisal of simultaneously collected cystoscopic urine and bladder cancer washing for the evaluation of patients with bladder cancer little consistent difference in cellular yield or preservation could be documented between the 2 techniques. Diagnostic cells usually occurred in both types of specimens but in 20 to 30 per cent of the cases they could be identified only in cystoscopic urine. Over-all, 13.1 per cent of the cancers would have been missed had cystoscopic urine not been examined cytologically. Although bladder washing alone has a greater diagnostic yield than cystoscopic urine alone urine remains a valuable source of diagnostic information and should be evaluated, even when simultaneously collected bladder washings are available.

Cystoscopy↗

Pathological changes associated with topical chemotherapy for superficial bladder cancer.

With use of previous observations in experimental animals as a basis for comparison the cytologic and histologic changes in human patients who underwent topical chemotherapy for superficial bladder cancer were documented. Despite the potential for inhibition of deoxyribonucleic acid replication these drugs apparently act in vivo as toxic substances, causing increased exfoliation with denudation of papillary and/or flat urothelium. Multinucleation was common but confined to superficial cells. Atypical cells, such as those observed after systemic chemotherapy with cyclophosphamide, rarely were present and could be distinguished readily from neoplastic elements. Although topical chemotherapy may suppress tumor growth and progression it apparently does not eradicate the neoplastic process.

Administration, Topical↗

The effect of mitomycin C on superficial bladder cancer.

A course of intravesical mitomycin C, consisting of 8 weekly doses of 30 or 40 mg., was evaluated in 16 patients with superficial bladder cancer (stages O and A). Cystoscopically documented tumor was destroyed completely in 11 patients (69 per cent), while 3 patients exhibited partial tumor regression. Two patients had only multifocal, grade 3 carcinoma in situ and both had a complete response with negative biopsies and cytology at the 12-week evaluation. Toxicity was minimal. Further data, including longer followup, are needed to define the potentially promising role of this agent in the over-all management of superficial bladder cancer.

Aged↗

The effect of thio-TEPA on developing and established mammalian bladder tumors.

The inhibitory effect of thio-TEPA on both developing and established mammalian bladder cancer was tested in the FANFT model system using female C3H/He mice. This model allows the histologic evaluation of the entire target organ, a major advantage over clinical trials, which have relied largely on endoscopic appearance for determination of response. A powerful carcinogen, FANFT is known to cause bladder carcinoma in at least 90% of these animals within 12 months. The tumors develop through a spectrum of morphologic changes including hyperplasia, dysplasia, and carcinoma in situ. Animals were divided into equally sized control and test groups and either thio-TEPA or saline was administered on a schedule designed to correspond to that used in clinical trials. Bladders from 159 mice were evaluated grossly, microscopically and in some instances, ultrastructurally, for the presence of tumor or other intraepithelial lesions. When compared to controls, thio-TEPA had no statistically significant inhibitory effect on either developing or established bladder tumors. The drug did, however, cause a statistically significant decrease in the frequency of high-grade, high-stage lesions when given during tumor development and may retard the evolution of such neoplasms from low-grade noninvasive carcinomas. The correlation of these experimental findings with the reportedly beneficial results of clinical trials is discussed.

Animals↗