Phyllis D. Williams

Clinical significance of erythropoietin levels in renal carcinoma.

The bioassay using the polythemic mice demonstrated persistent erythropoietin (Ep) activity in 24 renal carcinoma patients. Eight patients without clinical evidence of renal carcinoma had Ep levels that were slightly higher than those of controls, suggesting the possibility of occult disease. Increased levels of Ep were noted in 5 patients with other genitourinary carcinomas. This selective study reaffirms the value of Ep as a biologic marker in some renal cell cancers, and occasionally in other genitourinary tumors.

Further study of fibrinogen degradation products in bladder cancer detection

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.

Seminoma at Roswell Park, 1970 to 1979. An analysis of treatment failures.

A retrospective study of all cases of seminoma treated at Roswell Park Memorial Institute from 1970 through 1979 was conducted. Fifty‐six evaluable patients treated initially with radiation therapy were seen during this period, and the overall survival rate at an average follow‐up period of 52 months was 82%. The survival rate in patients with bulky abdominal or supradiaphragmatic metastases was only 33% (4 of 12 patients). Treatment failures were analyzed to determine their apparent causes and the implication of such failures to the future management of seminoma. The use of combination chemotherapy as the initial treatment modality in advanced seminoma is discussed in light of these results.

Experimental bladder tumor induction, propagation, and therapy.

The development of animal bladder tumor models as a research tool for different modes of therapy has been widely evaluated. Recently these tumors have either spontaneously grown or have been propagated in inbred strains. Bladder tumors have also been chemically produced by N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) when orally administered over a long period of time. It has been further reported that these tumors have been inhibited by various chemotherapy regimens. The availability of an experimental bladder tumor model offers an opportunity to evaluate the effectiveness of a prescribed treatment. In our studies FANFT was noted to produce only from 33 to 40% bladder tumors in several experiments in an inbred strain of rats conducted over several years. Reproducible transplantability of these tumors was not demonstrable in the same inbred strain. In addition, treatment with mitomycin C an an effective chemotherapeutic agent was not detectable in part, since comparably the percentage of control bladder tumor growth was low. These findings of a three-year study should be carefully considered when evaluating recommendations for clinical adjuvant chemotherapy based on results obtained with FANFT.

Diagnostic value of lymphocyturia in renal allograft rejection in man.

Abstract Fresh urine specimens in 34 selected renal allograft recipients were examined for the presence of pyronine-positive lymphocytes on 678 occasions during a two-year follow-up period. During the period of observation 15 clinical episodes of allograft rejection diagnosed by a variety of other tests and frequently confirmed by biopsy, correlated 100 per cent with the presence of a significant number of urinary pyronine-positive lymphocytes. No false positive or negative results were noted. These episodes occurred up to nine months after renal allotransplantation. In more than 80 per cent of instances in this carefully selected series, the pyronine-positive urinary lymphocytes were detected two to seven days prior to the clinical diagnosis of renal allograft rejection by other means. Thus this test is a valuable tool for follow-up monitoring of renal allograft recipients.

The treatment of stage III nonseminomatous testicular tumors. Roswell Park Memorial Institute results (1970–1979)

A review of 92 patients with Stage III nonseminomatous tumors treated at Roswell Park Memorial Institute between 1970–1979 was undertaken to verify changes in concepts as related to multiple agent chemotherapy and cytoreductive surgery. Each patient had a minimal follow‐up of 18 months. Fifty‐three patients were seen before 1975. Eighteen had metastasis to the lungs only. These were treated with a variety of single chemotherapeutic agents and cytoreductive surgery. The survival of this group was 38%. Among 35 patients with lung and visceral involvement seen at the same time, only one patient is alive. Thirty‐nine patients were seen after 1975 and treated with multi‐drug chemotherapy and cytoreductive surgery. The current survival rate of 23 patients with lung metastasis only is 69%. Among 16 patients with lung and visceral involvement, the present survival rate is 31%. This report confirms the effectiveness of multi‐drug therapy in conjunction with cytoreductive surgery in the treatment of disseminated testicular tumors.

Evaluation of the Chronic Hepatic Toxicity of 6-Mercaptopurine in the Wistar Rat

The ability of choline (C) to prevent hepatic toxicity due to chronic administration of 6-mercaptopurine (6-MP) was evaluated in male Wistar rats. Two dose levels of 6-MP and two dose levels of C were used. Choline did not prevent or diminish the hepatic accumulation of triglyceride when administered in combination with 6-MP. The 6-MP did impair the growth of the experimental animals, and this effect was antagonized by C administration. The data provided experimental support for the clinical observation of growth impairment in children treated with chronic antimetabolite therapy for acute lymphoblastic leukemia.

The Role of Fibrinolysis in the Therapy of Peripheral Vascular Disease

In vivo thrombolytic studies in stumptailed monkeys indicated that pentoxifylline potentiates thrombolysis induced by urokinase activated human plasmin. Pentoxifylline as well as prostaglandin E1 released plasminogen activators and activated the fibrinolysin system. From this point of view pentoxifylline and prostaglandin E1 synergized with each other. Pentoxifylline potentiated the thrombolytic effect of prostaglandin E1 in vivo.

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.

Unilateral nephrectomy: Its effect on primary murine renal adenocarcinoma☆☆☆

A murine renal adenocarcinoma was implanted unilaterally under the kidney capsule in more than 200 inbred Balb C mice and evaluated in nine groups: controls with and without tumor, and following left nephrectomy of tumorous kidney at seven, fourteen, and thirty-nine days after implant. Mean survival times for tumor-implanted, nephrectomized mice were 60.1, 56.4, 54.1, and 56 days, respectively. Pulmonary metastases were evident between fourteen and forty-five days, 100 per cent in the tumor control non-nephrectomized group, and 36 and 90 per cent in the respective nephrectomized groups. All tumor-implanted animals ultimately died of metastatic disease. Predictable and reproducible disease patterns were noted. This model lends itself to screening chemotherapeutic agents and other modes of therapy for the control of metastatic renal cancer following nephrectomy.