John D. Strandberg

The Role of Androgens and Estrogens in the Pathogenesis of Experimental Nonbacterial Prostatitis

The etiology and pathogenesis of nonbacterial prostatitis remains unclear. This study provides evidence that genetic background, advancing age, and hormonal imbalance are important etiologic factors for prostatitis in rats. It also demonstrates that Lewis and Wistar rats develop a spontaneous nonbacterial prostatitis with advancing age, making them good animal models for the laboratory investigation of this disease. Spontaneous nonbacterial prostatitis is much more common in Lewis rats (72%) than in Wistar rats (27%, p less than .05), and does not occur in Sprague-Dawley rats. The incidence of spontaneous prostatitis is significantly higher in older animals than in younger animals (72% old adult Lewis rats vs. 30% young adult Lewis rats, p less than .05). Administration of exogenous 17 beta-estradiol increases the incidence and severity of prostatitis in old Wistar rats (100% treated vs. 27% control, p less than .01). Castration has a similar effect. Testosterone can block the effect of estradiol on prostatitis, however treatment with an anti-estrogen or an aromatase inhibitor to block estrogen action does not improve prostatitis in the rat. The major finding of this study is the demonstration that severe prostatitis can be induced in young adult Wistar rats by neonatal treatment with 17 beta-estradiol followed several months later in adulthood by testosterone administration. The results of this study suggest that genetic background, advancing age, and hormonal imbalance contribute to the pathogenesis of nonbacterial prostatitis in rats.

Evaluation of venous injury caused by a percutaneous mechanical thrombolytic device

PurposeTo study venous injury caused by a prototype percutaneous mechanical thrombolytic device.MethodsSimulated thrombolysis was performed using the device, or the Fogarty balloon catheter (FBC) as control, in the infrarenal inferior vena cava (IVC) of 40 New Zealand white rabbits. Venous injury was evaluated by cavography, Evans blue dye staining, and histology at 0, 1, and 6 weeks postprocedure.ResultsBoth devices resulted in near complete endothelial denudation acutely. No differences in reendothelialization were noted at any time in the proximal and mid-IVC, but there was significantly greater reendothelialization in the distal IVC in the rabbits treated 6 weeks earlier with the device (p ≤ 0.04). Additionally, the inner luminal diameter at necropsy for the 1-week rabbits treated with the FBC was significantly narrower in the distal and middle sections of the IVC when compared with the device (p ≤ 0.02 for both segments). There was no luminal diameter difference at 0 or 6 weeks.ConclusionBased on a rabbit model, venous injury from the device was found to be similar to, and in the distal IVC less than, the routinely used FBC.

The requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia

A long-term study on the requirement of the testis in establishing the sensitivity of the canine prostate to develop benign prostatic hyperplasia (BPH) was conducted using 23 aging beagles both with and without their testes. The dogs had received long-term restoration of testosterone and estrogen through silicone implants. When young beagles (0.5 to 1 year of age) were castrated and normal serum testosterone and estrogen levels restored during aging to 5 years, only 50% of these dogs developed BPH in the absence of their testes as opposed to 100% BPH development in intact controls. In addition, two-thirds of the prostates in the treated groups were remarkably reduced in size, being smaller than any prostate observed in the intact controls. If, following castration, the steroid restoration was withheld for 4 years during aging and subsequently administered starting at 5 years of age and continuing for a 6-month period, none of the animals developed complex BPH. Moreover, two-thirds of the prostate glands were reduced in size by more than 60% and were atrophied in spite of the maintenance of normal prostatic tissue dihydrotestosterone levels. Regardless of the time of steroid restoration to a castrate beagle, the periurethral zone of the canine prostate exhibits various degrees of atrophy indicating functional regions within the canine prostate that are sensitive to the requirements of the testes during aging. This study implicates the importance of the testis in increasing the probability and/or sensitivity for the full development of canine BPH.

Effect of intrauterine and intravascular quinacrine administration on histopathology, blood chemistry, and hematology in cynomolgus monkeys.

Histopathologic features, blood chemistry, and hematologic features were studied in cynomolgus monkeys following intravascular or intrauterine administration of a 30-mg solution of quinacrine hydrochloride. Intrauterine quinacrine administration resulted in extensive necrosis of the endometrial surface, and lesions were observed at 24 hours after treatment which obliterated the cornual areas of the uterus. Necrosis was also observed on occasion in the ampulla or isthmic portion of the tube. Evidence of repair of the reproductive tract was seen 7 and 28 days following treatment. No lesions were observed in any nonreproductive organ examined, whether quinacrine was administered by the intrauterine or intravascular route. Blood chemistry data revealed moderate and transient increases in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and lactic dehydrogenase (LDH). No other blood chemistry or hematologic changes were noted that could be attributed to quinacrine administration. For the conditions described in these studies, intrauterine administration of quinacrine appears to be a safe procedure. However, the potential toxicity of the drug is discussed.

Effect of intrauterine administration of tetracyclines on cynomolgus monkeys

Cynomolgus monkeys were used to screen for chemicals which potentially could be used as tubal occluding agents. Intrauterine administrations of solution or pellets of tetracycline and its analogues (100 mg doses) were tested for their effects on morphologic changes in the reproductive tract of monkeys. These effects were compared to monkeys receiving intrauterine administration of quinacrine pellets (36 mg) since quinacrine has been used successfully in the clinical setting. Blood levels of drugs, blood chemistry and hematology determinations and liver and kidney pathology data were also obtained as indices for toxicity. Morphologic damage to the uterine lining and intramural section of the tube (including necrosis, inflammation or scarring) was elicited by intrauterine tetracycline and doxycycline in the same frequency and severity as quinacrine. In contrast, saline or sham control monkeys showed no morphological damage of the tube or uterus. Although all drugs could be detected in the blood 4 hours after intrauterine administration, levels were near or below the limit of detection by one week. No evidence was found for toxicity of tetracycline or its analogues for the dosage given. Because of these results and the extensive literature on tetracycline toxicity, further studies should be directed toward the use of tetracycline as a sterilizing agent in women.

Specific localization of polychlorinated biphenyls in clams (Mya arenaria) from environmentally impacted sites

Hemocytic neoplasia (HN) develops in soft shell clams (Mya arenaria L.) in coastal locations throughout the world. However, the prevalence of this neoplasm is higher than background levels when clams are collected from a polychlorinated biphenyl (PCB)-contaminated site, New Bedford Harbor (NBH), MA. Immunohistochemistry was used to examine the relationship between the accumulation of PCBs in tissue by M. arenaria and the development of neoplasia in the hemolymph. PCBs preferentially localized in normal and neoplastic hemocytes, in the ovary and in several other tissues. The specific reactivity of tissues with PCB antibodies corresponded to a high reported prevalence (60%) of neoplasia. Understanding the biological implication of PCB accumulation in environmentally impacted animals, particularly in reproductive tissue, is relevant to all species.

Hyperplasia and Pheochromocytoma, Adrenal Medulla, Rat

Adrenal medullary hyperplasia usually cannot be observed grossly, but on occasion the lesion can be seen as unilateral or, more often, bilateral enlargement of the glands. Medullary tumors may be too small to alter the gross appearance of the glands, or they may cause unilateral or bilateral enlargement. The cut surface of the medulla may have a nodular outline and may be fleshy white or reddish-brown due to an extensive vascular network in the tumor. Metastases of malignant pheochromocytomas occur rarely and are usually discovered only upon microscopic examination (Coleman et al. 1977; Anderson and Capen 1978; Goodman et al. 1979; Altman and Goodman 1979).

Hemangiopericytoma and Other Tumors of Urinary Tract of Guinea Pigs

Hemangiopericytoma, transitional cell carcinoma, squamous cell carcinoma and adenosquamous carcinoma developed in the urinary bladder of 6 of 95 guinea pigs of a noninbred stock and 16 of 87 guinea pigs of inbred strains 2 and 13 all gamma or X-ray irradiated. An additional 7 of 66 untreated guinea pigs of the two inbred strains also developed bladder tumors. Twenty-four guinea pigs had multiple tumors of the bladder. In the irradiated animals, the tumors arose significantly earlier but the increase in number of tumor bearing guinea pigs did not reach statistical significance. The tumors extended through the superficial muscularis into the underlying connective tissues and occasionally into lymphatic vessels and veins but none metastasized. Of 29 animals with tumor of the bladder, 21 had papillary proliferation of the renal pelvic mucosa, two papillary transitional carcinoma and one hemangiopericytoma. The EM and light microscopic criteria for the identification of hemangiopericytoma are described.

Focal Hyperplasia, Adrenal Cortex; Rat

The smallest and earliest lesions are grossly inapparent. Larger hyperplasias and adenomas occur as discrete nodular swellings within the cortex of the adrenal gland, resulting in its enlargement. They may be of the same color as the surrounding cortex or contrast with it by being either paler yellow or darker.

Primary Tumors and Adenomatosis Of The Lung In Untreated and In Irradiated Guineá Pigs

The morphology of alveologenic tumor, hemangiosarcoma, lymphangioma, intrabronchial papilloma and adenomatosis observed in the lung of guinea pigs is described. Electron micrographs revealed alveologenic tumor to consist of Type II pneumocytes and the lesion of adenomatosis to consist of distended alveoli lined with ciliated bronchial type epithelial cells. A relationship between the dose of gamma or X-ray irradiation received and the frequency of guinea pigs with lung tumors could not be established. In guinea pigs, which survived over 20 months, the frequency of alveologenic tumors in the inbred strains was 23/107 in irradiated and 11/79 in untreated guinea pigs; this difference was statistically not significant. The frequency of tumor bearing inbred males (11/60) was significantly lower than of tumor bearing noninbred males (23/65). In the irradiated guinea pigs alveologenic tumors occurred earlier and tumor nodules in the lung were more numerous than in the untreated guinea pigs. Primary hemangiosarcoma involved the lung of one untreated and one irradiated strain 2 guinea pig. A single lymphangioma was found in an untreated inbred guinea pig. Intrabronchial papillomas were observed twice in irradiated and once in untreated guinea pigs. Adenomatosis was present in the lung of 2 untreated inbred and 5 irradiated noninbred guinea pigs.