W.B. Gill

Association of Diethylstilbestrol Exposure in Utero With Cryptorchidism, Testicular Hypoplasia and Semen Abnormalities

Epididymal cysts and/or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero, compared to 7.8 per cent of 307 placebo-exposed controls. Analyses of the spermatozoa have revealed severe pathological changes (Eliasson score greater than 10) in 134 diethylstilbestrol-exposed men (18 per cent) and 87 placebo-exposed men (8 per cent). Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism. Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent. Although none of our Diekmanns lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid. A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism.

Protective Effects of Heparin and Other Sulfated Glycosaminoglycans on Crystal Adhesion to Injured Urothelium

Heparin was found to prevent calcium oxalate crystal adhesion to chemically injured rat bladder urothelium. Heparin was the only polysaccharide tested which restored injured urothelium to the functional status of normal, uninjured urothelium with respect to anticrystal adhesion properties. Other sulfated glycosaminoglycans, sulfated polysaccharides and monosaccharides were without restorative or protective effects. 3H-heparin was found to bind to injured urothelium but not to normal urothelium.

The influence of bladder fullness on upper urinary tract dimensions and renal excretory function.

Nearly full bladders (375 ml.) produced significantly greater dimensions of the renal calices, pelves and ureters on excretory urograms compared to nearly empty bladders. These dimensions were frequently to the point of being considered pathological dilatations. On planimetry the urographic areas of the pelviocaliceal systems decreased by 43 per cent on the right side and 38 per cent on the left side when the nearly full bladder was compared to the nearly empty bladder in 10 patients. Renal excretory function also was affected by nearly full bladders. Urea clearances after 1 hour were 24 per cent lower and creatinine clearances were 9 per cent lower when starting with a nearly full bladder as compared to starting with an empty bladder. The implications of these findings are of potential significance with respect to 1) interpretation of excretory urograms and 2) chronic urine holding in patients with recurrent urinary tract infections, impaired renal function and/or urolithiasis.

Selective surface staining of bladder tumors by intravesical methylene blue with enhanced endoscopic identification

Intravesical instillation of methylene blue resulted in selective surface staining of bladder tumors in vivo without staining the background of normal urothelium. Staining of human bladder tumors in vivo was accomplished by the intravesical instillation of 0.1% methylene blue in 0.9% saline through a foley catheter under 20 cm of hydrostatic pressure up to a maximum volume of 400 ml. After 5 minutes contact time, the methylene blue solution was drained, and the bladder was washed with saline. Thereafter, either endoscopic or open surgery was performed. The transitional cell carcinomas in 45 of 48 patients bound methylene blue to the surfaces of the tumors but not to normal urothelium. Higher grade tumors usually bound the dye more extensively than lower grades. The three patients, whose tumors did not bind methylene blue, had received previous chemotherapy, which might account for their being falsely negative. Carcinoma in situ and dysplasia did stain blue. Areas of hyperplasia and cystitis, however, did not bind methylene blue. In vivo intravesical staining with methylene blue has been a simple and safe procedure which has enhanced the endoscopic localization for biopsy and fulguration/resection of transitional cell carcinomas.

Angiomyolipoma with regional lymph node involvement and long-term follow-up study

The first long-term follow-up study of a patient who had renal angiomyolipoma with regional lymph node involvement is reported. The absence of recurrence after 15 years favors the view that regional lymph node involvement represents a multicentric hamartomatous change and is not a metastasis from a malignant renal tumor.

Urolithiasis Update: Biophysical and Radiologic Advances Enhance Antistone Therapy

Understandings of the molecular mechanisms of urolithiasis and rationale antistone therapy have undergone significant advances with the application of biophysical theories and techniques to urine, uroliths, and the urinary tract. In addition, the development and combinations of radiologic and surgical techniques have dramatically improved the treatment of existing stones in both the upper and lower urinary tracts. This review is designed to cover the biophysical advances in diagnosis and antistone preventive therapy, plus the technical advances in stone removal by endoscopic, radiographic-enhanced manipulative and dissolution techniques, and open surgical procedures which maximize nephron preservation.

Experimental Cytoxan Cystitis and Prevention by Acetylcysteine

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).

Calcium Oxalate Crystallization in Urothelial-Lined Systems

The liquid/solid interface is of fundamental importance in the crystallization of solutes from aqueous systems. Nucleation preferentially occurs at interfaces that inherently present energetically favored sites for the initiation of crystallization1,2. Most crystallization studies have dealt with the nature of the solute and/or the solvent2,4 and have usually ignored consideration of the containers and the nature of the solid surfaces enclosing the systems.

In Vivo Urothelial Surface Histology by Microscopic Chromocystoscopy

Microscopic chromocystoscopy is a new in vivo procedure that we have developed to aid in the detection and treatment of bladder tumors. Intravesical ionic dye chromocystoscopy was introduced by our group to permit cystoscopic viewing with ordinary light of selectively stained malignant urothelial surfaces by the cationic dye, methylene blue. With the recent availability of the Hamou hysteroscope, a microscopic endoscope, we have combined intravesical ionic dye chromocystoscopy with microscopic cystoscopy to give in vivo urothelial surface histology, with resolution of cytological detail. We herein describe our new method and preliminary results with this procedure, which we have designated in vivo urothelial surface histology by microscopic chromocystoscopy.

FOLLOW-UP STUDY OF MALE AND FEMALE OFFSPRING OF DES-EXPOSED MOTHERS

This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind, placebo-controlled investigation during 1951 and 1952 aimed at determining the effect of DES on pregnancy. Epididymal cysts, hypotrophic testes, and capsular induration were the more common genital lesions found in 25% of 163 DES-exposed males as compared to 6% in 168 control males. Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26% of the DES-exposed group produced an ejaculate volume under 1.5 ml; no such cases were observed in the control group. The average values for sperm density and total motile spermatozoa per ejaculate, although in the normal range, were more than two times lower in the DES-exposed group as compared to the controls. A quality score of > 10 (“severely pathologic semen”) was found in 28% of the DES-exposed group as compared to 0 in the control group. An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group. Two cases of azoospermia, one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group. Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles (oligomenorrhea) as compared to 10% of 136 controls. The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group (18%) than in the control group (33%). Circumferential ridges of the vagina and cervix were seen in 40% of 229 DES-exposed females but in none of 136 controls. Colposcopic findings in the vagina revealed adenosis in 66.8% of the DES-exposed females and in 3.6% of the control group. Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects. No cases of cancer were observed in either the male or female offspring.