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Biomedical subjects

R L Clark

Publications and source records attributed to R L Clark.

180 records · Page 10Linked to original sources

Primary isolated urethral amyloidosis.

We report an unusual case of primary amyloidosis isolated to the urethra in a patient with tender, periurethral masses and obstructive voiding symptoms. When not secondary to other phenomena, amyloidosis most commonly affects the skin, respiratory, and urinary tracts. Isolated amyloidosis of the urethra should be in the differential diagnosis of a patient with irregular strictures of the penile urethra, a clinical presentation consistent with urethral carcinoma, and no evidence of systemic disease.

Adult↗

Effects of corticosterone on reproduction in male Sprague-Dawley rats.

Corticosterone, the predominant circulating adrenal corticosteroid in rodents, was investigated for its effects on reproduction in male Sprague-Dawley rats. Male rats (in groups of 50, 25, and 50) were administered corticosterone at doses of 0, 10, and 25 mg/kg/d, respectively, by subcutaneous injection once daily for 6 weeks; the highest dose was decreased to 20 mg/kg/d after 15 d. During the last 2 weeks of the 6-week treatment period, 25 males per group were paired with untreated females. The remaining 25 males from the 0 and 25/20 mg/kg/d groups were allowed a 6-week recovery period and, during the last 2 weeks of this period, these males were also paired with untreated females. At the end of the treatment period, the males had markedly elevated plasma corticosterone concentrations and decreased weight gain. They also produced fewer copulatory plugs than controls, which may have been secondary to observed adverse effects on the accessory sex organs (decreased weights and microscopic changes in prostate and seminal vesicles). However, no adverse effects on sperm motility, sperm count, or microscopic features of the testes were observed. Serum testosterone concentration of the high-dose males was elevated, but luteinizing hormone was unaffected. The numbers of embryonic implantation sites and live fetuses in females mated to these males were reduced. All of these effects except decreased prostate weights were reversible upon cessation of corticosterone administration. Thus, exogenous administration of corticosterone to male rats produced reversible effects on implant count and litter size of female rats mated to these males. These effects on male rat reproduction may have been secondary to reduced accessory sex organ function, which resulted in diminished secretions and fewer copulatory plugs.

Animals↗

Microvascular changes in canine renal allograft rejection: a correlative microangiographic and histologic study.

The progressive microvascular changes occurring during unmodified renal allograft rejection were studied in 22 dogs utilizing post-mortem barium sulfate perfusion microangiography. Sixteen dogs (7 autografts, 8 ischemia controls and 1 hydronephrotic animal) made up a control group. The microradiographic findings were correlated with intravenous urography, coagulation profiles and histopathologic studies. Vascular obstruction and obliteration occur from the outer cortex inward and involve sequentially, capillaries, efferent arterioles, glomeruli, afferent arterioles and interlobular arteries. A-V communications develop late and are due to a loss in vascular integrity. Medullary vascular obliteration occurs subsequent to cortical changes. The microangiographic changes mirror the hstologically evident cellular infiltrate, vascular damage and eventual hemorrhagic necrosis. The appearance of fibrin split products in the plasma late in rejection and the dramatic vascular occlusive changes seen microangiographically suggest that localized intravascular coagulation occurs during rejection.

Angiography↗

Lymphatic visualization during renal transplant rejection.

Intrarenal microlymphatic filling was observed during a microangiographic and histologic study of unmodified canine allograft rejection. The extent of lymphatic visualization was correlated with the pathophysiologic state of the allograft. An example of renal lymphatic visualization following arterial perfusion of a human specimen is also presented. During early rejection, as microvascular and histologic alteration became more severe, there was prominent visualization of lymphatics. However, in late rejection, as cortical necrosis developed, lymphatic filling was less evident. Lymphatic visualization following arterial perfusion during rejection depends on progressive loss of microvascular integrity, contrast extravasation and subsequent filling of lymphatics which are acting as an alternate route of drainage for the excess interstitial edema present due to immune injury.

Angiography↗

Pyelovenous and pyelolymphatic backflow during retrograde pyelography in renal vein thrombosis.

Pyelovenous and pyelolymphatic backflow have been observed during retrograde pyelography in three patients with renal vein thrombosis. The radiographic patterns of backflow following experimental unilateral renal vein occlusion in rabbits were analyzed and correlated with the clinical findings. Capsular, perihilar, periureteric, and retroperitoneal collateral vein networks and lymphatic channels were demonstrated on the venous occluded side. The appearance shown in the experimental study correlate well with the clinical observations.

Adolescent↗

Experimental renal papillary necrosis in rats: microangiographic and tubular micropuncture injection studies.

Proposed causes of renal papillary necrosis (RPN) include tubular toxicity due to hyperconcentration of toxins in the renal medulla and vasoconstriction of medullary vessels with ischemic necrosis. The authors studied these mechanisms in bromoethylamine hydrobromide-induced RPN in rats by microvascular and tubular micropuncture injection studies. During early stages of RPN, microvascular studies revealed reduced perfusion of vasa recta, and tubular injection studies showed unobstructed tubules and collecting ducts. In the late stage, medullary vascular obliteration and intratubular debris with tubular obstruction were seen. This evidence suggests that RPN in this model is initiated by vasoconstriction rather than direct tubular toxicity.

Angiography↗

Microangiographic studies of experimental erosive synovitis in rats.

Chronic remittent erosive synovitis, which is clinically, radiologically and pathologically similar to rheumatoid arthritis in man, can be produced in rats by systemic injection of cell wall fragments isolated from Group A streptococci. Because of our desire to study the synovial microvasculature in this experimental model, we developed a reliable microangiographic technique to document these changes. This paper describes the first reported microangiographic studies of rat joints and discusses the microvascular changes that parallel the previously reported radiographic and histologic findings. As the arthritis progresses, as judged by clinical and radiographic parameters, early synovial hypervascularity associated with developing hyperplastic synovium gives way to a more obliterative hypovascular pattern associated with chronic erosions, periosteal reaction, and fibrous ankylosis. Microangiography offers an additional and helpful modality by which to investigate synovial microvascular morphology as well as the pathophysiology of joint destruction during erosive synovitis.

Angiography↗

Comparative microangiographic studies of glycerol- and mercuric chloride-induced acute renal failure in rats.

Microcirculatory abnormalities may be important in the genesis and/or maintenance of acute renal failure. This work describes the functional, microangiographic, and histopathologic alterations in two experimental models of acute renal failure. Glycerol and mercuric chloride (HgCl2) administration to dehydrated rats produced acute renal failure characterized by a similar degree of renal dysfunction at 24 hours and almost complete functional recovery at one week. Both toxins were associated with early (1/2-1 hour) microangiographically determined perfusion alterations, but in the rats given glycerol, a return to near normal appearance was noted at 2 to 6 hours. Subsequent studies did show mild to moderate residual changes at one week. In contrast, HgCl2 treatment was associated with progressive microcirculatory abnormalities that correlated in part with residual histopathologic alterations. These studies emphasize the discrepancy between functional, circulatory, and pathologic abnormalities in experimental acute renal failure and may improve our understanding of this complex disorder.

Acute Kidney Injury↗

The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging.

A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to 65% of the AL amount by measurement or time (6.5 hr). At 52 wk, food consumption and key pathology biomarkers correlated with 106-wk survival. The modified chow, 5002-9 fed AL, did not significantly improve survival. SD rats fed either diet AL consumed the greatest amount of feed and kcal/rat but consumed the same amount of feed per gram body weight as DR-fed rats. At 52 wk, AL rats fed either diet had the same brain weights as DR rats, but the AL-fed rats had greater body weight and body fat content and increased heart, lung, kidney, liver, adrenal, thyroid, and pituitary weights as well as an increased incidence and severity of degenerative and/or proliferative lesions in these organs. This study demonstrates that overfeeding best correlates with low 2-yr survival in SD rats and that simple DR by caloric restriction modifies key pathology biomarkers in the pituitary, mammary gland, kidney, and heart of SD rats at 52 wk that are predictive of 106-wk survival.

Aging↗

Diet, overfeeding, and moderate dietary restriction in control Sprague-Dawley rats: I. Effects on spontaneous neoplasms.

This study was designed to compare the effects of ad libitum (AL) overfeeding and moderate dietary restriction (DR) of two different diets on Sprague-Dawley (SD) rat 2-yr survival and the development of spontaneous neoplasms. SD rats were fed Purina Rodent Chow 5002 or a modified Rodent Chow 5002-9 containing lower protein, fat, metabolizable energy and increased fiber by AL or by DR at 65% of the AL amount by measurement or time (6.5 hr). At 106 wk, rats fed the 5002-9 diet AL did not have significantly improved survival over rats fed the 5002 diet AL. The 5002 diet fed DR by time (6.5 hr) improved survival for males but not females. Only DR by measurement of both diets resulted in lower mortality for both sexes. The most common cause of death in rats of both sexes fed either diet AL was pituitary tumors followed by mammary gland tumors in females and renal and cardiovascular disease in males. The overall tumor incidence by 106 wk was remarkably similar between AL and DR groups. However, compared to the 5002 AL group, a decrease in the age-adjusted (Peto analysis) incidence of pituitary adenoma was observed in all other male groups. This effect was noted in the female DR by measurement groups only. For males, compared to the 5002 AL group, a decrease in the age-adjusted incidence of pancreatic islet carcinoma was observed in the DR by measurement groups only. In females, compared to the 5002 AL group, the only other difference in tumor incidence was the mammary gland tumors, which showed a significant decrease in the age-adjusted tumor incidence or multiplicity in the 5002-9 AL, 5002-9 DR, and 5002 DR groups. Additional analyses of mammary gland tumors showed growth time (time from initial palpation until death), tumor doubling time, and tumor volume were generally not statistically significantly different between AL and DR groups, although AL females could sustain larger tumor volumes. Compared to the 5002 AL group, there were no other significant differences in the age-adjusted incidence of any other tumor site in animals fed a modified diet or subjected to moderate DR of either diet. The conclusion from this study is that moderate DR delays death due to fatal cardiovascular or renal degenerative disease and spontaneous tumors, particularly those of the pituitary and mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗

Diet, overfeeding, and moderate dietary restriction in control Sprague-Dawley rats: II. Effects on age-related proliferative and degenerative lesions.

This study compared the effects of ad libitum (AL) overfeeding and moderate dietary restriction (DR) of 2 different diets on Sprague-Dawley (SD) rat survival and spontaneous, age-related proliferative and degenerative lesions. SD rats were fed Purina Rodent Chow 5002 or a modified Rodent Chow 5002-9 containing lower protein, fat, metabolizable energy, and increased fiber by AL or by DR at 65% of the AL amount by measurement or time (6.5 hr). At 106 wk, rats fed the 5002-9 diet AL did not have significantly improved survival over rats fed the 5002 diet AL. The 5002 diet fed DR by time (6.5 hr) improved survival for males but not females. Only DR by measurement of both diets resulted in lower mortality for both sexes. By 106 wk rats fed either diet by AL had the same brain weights as DR fed rats, but AL fed rats had greater body weight, body fat content, and increased heart, lung, kidney, liver, adrenal, thyroid, and pituitary weights that correlated with an increased incidence and severity of degenerative and/or proliferative lesions in these organs. Moderate DR delayed the progression of chronic nephropathy by delaying the early development of glomerular hypertrophy that initiates the development of glomerular sclerosis and nephron loss in AL overfed rats. Moderate DR lowered the incidence, severity, and progression of cardiomyopathy and other degenerative, age-related lesions and appeared to delay the development of reproductive senescence in SD females. The conclusion from this study is that moderate DR delayed onset and progression of degenerative lesions, and death due to cardiovascular or renal disease, and thus potentially improves the bioassay to detect compound-specific chronic toxicity.

Aging↗

Pulmonary microangiography. A comparison of in vitro versus in vivo perfusion techniques in dogs.

Because of a need to correlate pulmonary microvascular changes with physiologic data during lung injury, in vitro and in vivo pulmonary capillary microangiography was performed on normal dogs and those subjected to oleic acid injury and glass bead microembolization. During these studies, no significant differences were found between microangiograms obtained after in vitro and in vivo perfusion techniques. This work therefore suggests that in vitro microangiography yields reliable morphologic information more conveniently than more expensive and difficult in vivo techniques. In vitro pulmonary capillary microangiography can provide reliable structural information which can be correlated with physiologic data.

Angiography↗