Penile calciphylaxis: rare necrotic lesions in chronic renal failure patients.

PURPOSE: Calciphylaxis is a rare devastating condition of cutaneous necrosis resulting from calcification of small blood vessels in patients with end stage renal failure and secondary hyperparathyroidism. We describe 5 patients with penile calciphylaxis at a single institution. MATERIALS AND METHODS: From 1992 to 1996, 5 patients had penile calciphylaxis. The charts of these patients were reviewed to determine the nature of the lesions, association with hyperparathyroidism and treatment outcomes. RESULTS: All 5 patients had chronic renal failure, secondary hyperparathyroidism and painful necrotic lesions at multiple sites. Radiographs showed stippled calcification of small vessels, which was confirmed histologically. Three patients had undergone parathyroidectomy with a significant decrease in mean calcium x phosphorus ion products from 86.01 to 45.37 mg.2/dl.2 (p < 0.001), and in 1 calciphylaxis resolved postoperatively. The penile lesions were treated with débridement and aggressive wound care. CONCLUSIONS: The increase in the number of patients with chronic renal failure on dialysis may make penile calciphylaxis more prevalent in the future. Lowering of serum calcium and phosphorus levels, and debridement of these necrotic lesions help to diminish this aggressively destructive process.

Anticoagulant associated hematuria: a prospective study.

We studied prospectively 32 consecutive patients with new onset of gross or microscopic hematuria while on anticoagulant therapy. Of the patients 19 men and 11 women (mean age 65 years) underwent urological evaluation. Of 6 patients with microscopic hematuria 3 with nephrolithiasis subsequently underwent extracorporeal shock wave lithotripsy. Two of 24 patients (7%) with gross hematuria had neoplastic disease invading the bladder, 1 had benign prostatic hyperplasia requiring resection, 1 had urethral stricture, 1 had ureteropelvic junction obstruction and 1 had nephrolithiasis. Thus, significant urinary tract disease was present in 9 patients (30%). Hematuria resolved in more than 90% of the patients after treatment. Based upon these observations, we believe that gross or microscopic anticoagulant associated hematuria is frequently precipitated by a significant genitourinary pathological condition and its prompt evaluation is recommended.

Bilateral spontaneous steinstrasse and nephrocalcinosi associated with distal renal tubular acidosis.

Bilateral spontaneous steinstrasse from the ureteropelvic junction to the distal ureter complicating distal renal tubular acidosis has not been described. We report a case and discuss the clinical presentation, radiographic and metabolic findings, and treatment. Relief of obstructive uropathy with extracorporeal shock wave lithotripsy led to the resolution of the heavy steinstrasse burden.

Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy.

Antibiotic resistance of the resident cutaneous bacterial flora is a well recognized consequence of systemic antibiotic therapy. In this study, we followed the development of antibiotic resistance of coagulase-negative staphylococci (CNS), the most numerous aerobic bacteria found on the skin surface, during treatment with three topical antimicrobial agents used to treat acne vulgaris. Groups of 20 subjects received either topical erythromycin, benzoyl peroxide or a combination of the two for 16 weeks. After 12 weeks of treatment with erythromycin, the aerobic flora was dominated by S. epidermidis which was completely resistant to erythromycin. In addition there was an increase in resistance to clindamycin and tetracycline. Treatment with benzoyl peroxide and the combination of erythromycin and benzoyl peroxide resulted in a significant reduction in the number of aerobic bacteria without any change in the resistance pattern to erythromycin or other antibiotics.

Prostatectomy in patients with bleeding disorders.

Urological surgery is becoming increasingly necessary in patients with acquired or congenital bleeding disorders. We reviewed the management of 10 such patients who required prostatectomy. The average age of the patients at operation was 65.7 years. Seven patients underwent transurethral prostatectomy and 3 underwent suprapubic prostatectomy. Postoperative bleeding occurred in 9 patients who required secondary procedures. Bleeding occurred an average of 13 days postoperatively. The mean hospital stay was 24 days. Partial thromboplastin time when determined was uniformly elevated in all patients preoperatively. The amount of factor and blood replacement is presented. Perioperative management of these patients is discussed in detail. A rational approach for the prevention of postoperative bleeding is presented.

Transuterine resection of fibroids: a new approach to the management of submucous fibroids in selected patients.

Transuterine resection of fibroids is an effective alternative to hysterectomy in patients with uterine bleeding secondary to submucous fibroids. To date we have performed this procedure in 3 patients. In 2 patients transuterine resection was performed for uterine bleeding with a successful outcome. In the third patient the procedure was performed to treat infertility and the outcome is not yet known. The procedure should be performed by the combined efforts of a urologist and gynecologist.

Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue.

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.

Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls.

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.

Autoradiographic localization of tritium-labeled dihydrotestosterone in human vas deferens.

The human vas deferens was examined autoradiographically for the presence and distribution of androgen receptors. Samples of vas deferens from the region proximal to the testis and the region at the internal inguinal ring were incubated in vitro with tritium-labeled dihydrotestosterone ([3H]-DHT). Frozen sections of tissue were mounted on autoradiographic emulsion-coated slides and exposed for up to three weeks to demonstrate cells with nuclear accumulations of radioactive hormone. Quantitation of autoradiograms was performed with a Zeiss Videoplan morphometric analysis system. Cells in all five tissue layers of the vas deferens were able to bind androgen receptors in the nucleus, as evidenced by superimposition of silver grains over the nuclei of cells in external, middle, and internal smooth muscle layers, as well as in epithelial and subepithelial stromal cells.

Actin filament organization of the Dunning R3327 rat prostatic adenocarcinoma system: correlation with metastatic potential.

Recently, Volk, Geiger, and Raz (Cancer Res., 44: 811-824, 1984) addressed the question of whether variations in actin organization in clones of the murine K-1735 melanoma tumor correlated with their metastatic capability. Using immunofluorescence techniques, they found that clones which had a more ordered actin network were less metastatic, whereas clones having a diffuse actin staining pattern were more metastatic. Similarly, we have found that in the Dunning rat R3327 prostatic adenocarcinoma tumor system, the non-metastatic (less than 0.1%) H-prostatic tumor cell line has a prominent network of actin filament bundles, whereas the highly metastatic (greater than 90%) MatLyLu cell line has a diffuse actin staining pattern. In the low-metastatic (less than 10%) AT1 cell line an intermediate actin organization between H and MatLyLu was observed. Analysis of cell extracts from H- and MatLyLu-cells revealed differences in the level of activity of cellular proteins which affect actin filament assembly and structure in a manner similar to that of the cytochalasins, fungal metabolites which bind with high affinity to the fast-growing end of actin filaments. Extracts of MatLyLu were significantly more effective than those of H-cells in decreasing the extent of actin filament network formation and in inhibiting the rate of filament assembly by blocking monomer addition onto the fast-growing end. Measurements of spin-lattice nuclear magnetic resonance water proton relaxation times (T1) were made in surgically removed tumor tissue from four sublines (H, AT1, MatLyLu, and MatLu) of the Dunning R3327 tumor system. The highly metastatic cell lines had significantly longer water proton T1 relaxation times than did the lines with low metastatic potential. These differences in T1 may reflect the observed alterations in organization of actin filaments within these various sublines of the Dunning R3327 prostatic adenocarcinoma tumor system.

Historic notes on the development of the computer.

A summary of some of the major historic achievements in the development of the computer is detailed from the ancient efforts represented by Stonehenge through the development of the transistor.

A genetically determined murine model of infantile polycystic kidney disease.

We have evaluated a congenic strain of mice with congenital polycystic kidney disease in which the disease process appears to closely resemble human infantile polycystic kidney disease. Cysts formed first in the proximal tubules of the nephron and appeared, by light microscopy, to be preceded by vacuolization of the cells. These spaces, as seen by electron microscopy, occurred between adjacent cells. The pancreas was severely involved with reduction of both exocrine and endocrine elements. Cyst formation in the liver was minimal. Serum samples evaluated for urea nitrogen and creatinine were significantly elevated in affected mice. Serum glucose was within normal limits.

Autoradiographic localization of estrogen and androgen target cells in human and rat prostate carcinoma.

The distribution of estrogen target cells within the Dunning R3327-H rat prostate tumor following intravenous injection of tritiated estradiol into rat hosts was compared to the distribution obtained following incubation of a 2 mm. sample of the tumor with tritiated estradiol in organ culture. No difference was observed, indicating that the in vitro method was an effective approach for autoradiographic analysis of tumor biopsy samples. Subsequently, tumor samples were excised from solid tumors of R3327-H and R3327-MAT LyLu tumors growing in Copenhagen rats. These tumor models were chosen as representatives of hormone sensitive (R3327-H) and hormone insensitive (R3327-MAT LyLu) tumors. Normal rat dorsal prostate and human tumor biopsy samples were also studied. Autoradiographic studies were performed in vitro utilizing tritiated estradiol and tritiated dihydrotestosterone to compare the distribution of estrogen and androgen target cells. The present research demonstrated that 1) similar patterns of nuclear uptake of steroids are obtained with in vivo and in vitro autoradiographic techniques, 2) estradiol receptors occur primarily in extra-acinar epitheloid cells in both rat and human prostate carcinomas, 3) these epithelioid cells are not characteristic of the normal rat dorsal prostate, 4) androgen receptors occur in both acinar and stromal epithelioid cells in rat and primarily in acinar epithelial cells in human tumors and 5) in vitro autoradiographic methods can provide insight into differences in sensitivity to steroids which may be of diagnostic importance in the treatment of cancer.

Dimethylsulfoxide-induced changes in a rat prostate adenocarcinoma.

A variety of agents can induce mammalian tumor cell lines to acquire characteristics of the normal cell counterpart. Dimethylsulfoxide (DMSO) has been an effective differentiating agent in many tumor cell lines. In the present study a Dunning rat prostate tumor subline, MAT LyLu, available as an in vitro continuous cell culture was treated with 2.25% DMSO (vol/vol). Treated MAT LyLu cells had a decreased growth rate, saturation density, and clonogenicity, an increased doubling time, and alterations in enzyme activity and tumorigenicity when compared to untreated MAT LyLu cells. The cell viability of treated cells at the saturation density was greater than 90%. MAT LyLu cells treated with DMSO and then removed from DMSO (posttreated) when compared to untreated cells had similar growth rates, doubling times, clonogenicities, enzyme activities, and tumorigenicities. Posttreated MAT LyLu cells had a different growth pattern than untreated MAT LyLu cells. Posttreated cell viability at saturation density was greater than 90%. This investigation demonstrated that a rat prostate adenocarcinoma grown in medium containing 2.25% DMSO acquired characteristics consistent with differentiated prostate cells. Posttreated MAT LyLu cells were similar in many characteristics to untreated cells but were not identical. The alterations noted were not cytotoxic and were not completely reversible. The results of this study correlated with the observations of other investigators who have studied mammalian tumor cell lines exposed to DMSO.

In vitro characterization of MAT LyLu: a Dunning rat prostate adenocarcinoma tumor subline.

Prostate carcinoma has been a therapeutic challenge. The Dunning tumor, a rat prostate adenocarcinoma tumor model, has been used to evaluate prostate carcinoma treatment protocols. The Dunning tumor subline, MAT LyLu , as described in this report, has been established and characterized as an in vitro continuous cell culture. The cell culture has been stable for greater than 60 passages. The in vitro characteristics of the MAT LyLu cell culture, such as growth rate, loss of contact inhibition, clonogenicity, morphology and tumorigenicity, are consistent with the malignant characteristics of the Dunning tumor subline. The MAT LyLu cell culture has enzyme activities which can be used to characterize the cell line. The establishment of MAT LyLu as a continuous cell culture should provide a controlled approach to evaluate the etiology and treatment of prostate carcinoma.

Spontaneously acquired anti-factor VIII antibodies: report of a patient with adenocarcinoma of the prostate.

Anti-factor VIII antibodies, inherited or acquired inhibitors of the factor VIII molecule, have not been reported previously in the urological literature. Although more common in hemophiliac patients who have received multiple transfusions, this anticoagulant may be the cause of severe hemorrhage in nonhemophiliac patients. We describe a patient with carcinoma of the prostate and an unsuspected anti-factor VIII antibody, who experienced excessive postoperative bleeding and prolonged hospitalization following a vesicolithotomy and bilateral orchiectomy. A prolonged partial thromboplastin time and a significant decrease in measurable factor VIII clotting activity in a patient with no history of bleeding problems are essential clues in making the diagnosis of a factor VIII inhibitor. This coagulation defect is treated best with prothrombin complex concentrates, which contain vitamin K dependent clotting factors.