Nancy A Staley

Radiation-induced renal disease: A clinicopathologic study

Radiation injury to the renal parenchyma is an unusual cause of renal insufficiency. Light, immunofluorescence and electron microscopic studies were performed on the renal tissue from two patients in whom renal insufficiency developed within a year after they received abdominal irradiation. The glomerular lesion in both patients was similar. Mild endothelial cell swelling and basement membrane splitting were noted consistently on light microscopy. The electron microscopic examination revealed marked subendothelial expansion with electron-lucent material associated with deposition of basement membrane-like material adjacent to the endothelial cells. In some capillary loops, the endothelial cell lining appeared to be completely lost. The pathogenesis of radiation-induced renal injury is still uncertain. It is speculated that local activation of the coagulation system with consequent thrombosis of the renal microvasculature may be extremely important.

Cardiac and skeletal muscle abnormalities in cardiomyopathy: Comparison of patients with ventricular tachycardia or congestive heart failure

Results of cardiac muscle and skeletal muscle biopsies were compared in 22 patients with cardiomyopathy; 11 patients presented with symptoms secondary to ventricular tachycardia (Group 1) and 11 had symptoms of severe congestive heart failure (Group 2). No patient had structural or ischemic cardiac disease. In Group 1 patients, hemodynamic abnormalities were subtle, but invasive study demonstrated dilated cardiomyopathy in two patients and restrictive cardiomyopathy in nine. In Group 2, eight patients had dilated cardiomyopathy and three had restrictive cardiomyopathy. Cardiac biopsy results were abnormal in all 22 patients and the abnormalities were similar for the two groups. Cardiac histologic study revealed a spectrum of abnormalities including fibrosis, dilated sarcoplasmic reticulum, increased numbers of intercalated discs and mitochondrial abnormalities. Histologic abnormalities of skeletal muscle were similar in each group, consisting of endomysial fibrosis and increased lipid deposits. Slightly more than half of the Group 1 and Group 2 patients also had a low concentration of skeletal muscle long chain acylcarnitine. These data demonstrate that abnormalities of both cardiac and skeletal muscle are common in patients with cardiomyopathy; abnormalities are similar whether initial symptoms are due to ventricular tachycardia or congestive heart failure. It is suggested that these patients with cardiomyopathy may have a generalized myopathy.

Radiation induced renal disease: a clinicopathologic study

Sixteen patients with membranoproliferative glomerulonephritis who required kidney transplantation because of renal failure were evaluated for evidence of recurrence of the original disease by serologic and morphologic studies. Of the 12 patients with transplant tissue available for study, seven showed membranoproliferative glomerulonephritis by light morphology. Four of these seven also had hypocomplementemia, and this hypocomplementemia was characterized by decreased serum CH50, C3 beta1A or C3-C9 but norma serum C1, C4 and C2 by hemolytic assay. Immunofluorescent microscopy demonstrated more intense glomerular deposition of C3 and properdin in the hypocomplementemic patients. Ultrastructural studies demonstrated intramembranous deposits typical of dense deposit disease in one patient who also had marked hypocomplementemia. One patient who had two transplant biopsies and persistent hypocomplementemia showed progression from predominantly mesangial glomerular changes to both capillary wall and mesangial abnormalities. This study has shown a high rate of recurrence of membranoproliferative glomerulonephritis in the transplanted kidneys. A high death rate was noted in persistently hypocomplementemic patients. The serum C profile in hypcomplementemic patients who received translants was similar to that seen before transplantation, but the signficance of this finding remains unknown.

Early alterations in the function of sarcoplasmic reticulum in a naturally occurring model of congestive cardiomyopathy

In a naturally occurring model of congestive cardiomyopathy-round heart disease of turkeys, Ca2+ transport of isolated cardiac sarcoplasmic reticulum was evaluated at 1, 10, 28, and 56 days of age. Ca2+ binding in round heart disease birds was reduced to between 55% and 75% of values measured in age-matched commercial control turkeys (P less than 0.05 to less than 0.01). Similarly, Ca2+ uptake in round heart disease birds was reduced to between 52% and 87% of values measured in age-matched commercial control turkeys (P less than 0.05 and less than 0.01). Ca2+-stimulated ATPase values were similar in 1-, 10-, and 28-day-old round heart disease and commercial control turkeys. However at 56 days of age, when all round heart disease birds showed moderate to marked left ventricular dilatation. Ca2+-stimulated ATPase was reduced to 75% of control values (P less than 0.05). Depression of Ca2+ binding and Ca2+ uptake preceded the appearance of cardiac dilatation and may contribute to the pathogenesis of round heart disease. Depression of Ca2+-stimulated ATPase, present only after cardiac dilatation developed, appears to be secondary to cardiac failure. Sarcoplasmic reticulum function in round heart disease birds immunosuppressed by cyclophosphamide treatment (40 mg . kg-1 . d-1 for the first 4 days of age) was evaluated at 10 days of age. This treatment increased Ca2+ binding by 73% (P less than 0.05), and Ca2+-uptake by 58% (P less than 0.01) over values measured in untreated round heart disease birds. Reversal of the altered Ca2+ transport in sarcoplasmic reticulum by early immunosuppression supports the hypothesis that the immune system plays an integral part in the development of the congestive cardiomyopathy of round heart disease.

Carnitine Alterations in Spontaneous and Drug- Induced Turkey Congestive Cardiomyopathy

ABSTRACT: Carnitine and acylcarnitines were measured in plasma and tissues of control turkeys, turkeys with an inbred spontaneous cardiomyopathy, and turkeys with furazolidone- induced cardiomyopathy. Heart failure was evident in both types of cardiomyopathy from decreased systemic blood pressure and cardiac dilatation compared to controls. Plasma free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine were significantly elevated by 76 to 614% (p < 0.01) in the two cardiomyopathy models compared to control. The highest carnitine levels were found in the most hypotensive turkeys. Liver free carnitine and short-chain acylcarnitine levels were also elevated by 45 to 537% (p < 0.05) in both types of cardiomyopathy. Free carnitine was elevated by 126% in left ventricle and by 54% in skeletal muscle of the furazolidone-treated turkeys (p < 0.05). We speculate that hepatic synthesis of carnitine may be increased in response to hypotension and progressive cardiac dysfunction in cardiomyopathic turkeys. Such an increase may be useful to promote β-oxidation of fatty acids as a cardiac energy source.

Perinodular hydropic degeneration of a uterine leiomyoma: A diagnostic challenge

Perinodular hydropic degeneration of a uterine leiomyoma is a rare form of the more common hydropic change observed in leiomyomas. With minimal discussion in the surgical pathology literature, appropriate evaluation may be challenging because the differential diagnosis includes other uncommon uterine disorders such as intravenous leiomyomatosis, diffuse leiomyomatosis, myxoid leiomyosarcoma, endometrial stromal sarcoma, angiofibroma, and angiomyxoma. We describe such a diagnostic challenge in a 42-year-old woman with a left adnexal mass discovered during an annual examination. With only three cases of perinodular hydropic degeneration previously reported, this case is the first with extrauterine extension and was initially concerning for a more aggressive process.

Role of the unstirred layer in protecting the murine gastric mucosa from bile salt

Bile salts disrupt a functional gastric mucosal barrier which normally minimizes back-diffusion of H+ into mucosa. Our previous studies have shown that ionized bile salts disrupt the barrier to H+ by dissolving membrane lipids. The presence of an unstirred water layer on the surface of the gastric mucosa could protect against bile salt injury either by creating a concentration gradient of bile salt from lumen to mucosal surface or by slowing diffusion of lipid-laden mixed micelles away from the mucosal surface. In the present study we investigated this possibility in the anesthetized rat. Measurements of H+ back-diffusion and Na+ forward-diffusion across the gastric mucosa were made before and after exposure to a bile salt solution that was either unmixed or mixed by continuous withdrawal and injection. Using carbon monoxide diffusion, we observed this method of mixing to decrease the unstirred layer thickness from 880 to 448 micron (p less than 0.02). Mixing increased mean H+ back-diffusion induced by a 10 mM mixture of six conjugated bile salts from -2.58 to -4.11 microEq/min (p less than 0.01) and increased mean forward-diffusion of Na+ from 1.81 to 3.27 microEq/min (p less than 0.01). Mixing also increased efflux of mucosal phospholipid (32.7 to 52.2 nmol/min, p less than 0.05) and of cholesterol (4.89 to 8.87 nmol/min, p less than 0.05) into the bile salt solution. Addition of saturation amounts of lecithin and cholesterol to the bile salt solution completely prevented disruption of the barrier whether the solution was mixed or not. Mixing also increased mucosal uptake of bile salt from 74.6 to 221.3 nmol/min (p less than 0.01) when no lipids were added. In the presence of lecithin and cholesterol, mixing increased absorption of bile salt from 63.5 to 165.6 (p less than 0.02). These findings further support the hypothesis that bile salts disrupt the gastric mucosal barrier by dissolution of mucosal membrane lipids, and provide evidence that the unstirred water layer helps protect the gastric mucosa from bile salt injury.

Meibomian gland carcinoma: Report of a case with electron microscopic findings

Meibomian gland carcinomas compose about 1 per cent of the malignant tumors of the eyelids. They present in a characteristic fashion and are frequently mistaken for chalazia. Considerable time often elapses before a diagnosis is made. Early recognition and treatment are important because these tumors can behave in an aggressive manner. The following case report illustrates these features.

Accelerated idioventricular rhythm complicating atrioventricular junction ablation for automatic atrial tachycardia

A 13-year-old male with histologic evidence of cardiomyopathy, drug-refractory primary atrial tachycardias, and deteriorating left ventricular function underwent transcatheter His bundle ablation to control ventricular rate. Following an initial successful ablation at the level of the atrioventricular node, the patient exhibited an accelerated escape rhythm of apparent junctional origin (ventricular cycle length = 470 msec, HV = 100 msec) with complete heart block. A second ablation procedure was undertaken, following which an accelerated idioventricular rhythm (cycle length = 500 msec) became apparent and has persisted (follow-up 15 months). Thus, findings in this patient suggest that attempts to control refractory rapid ventricular responses in cardiomyopathy patients with primary atrial tachycardias may be complicated by the potential for junctional and idioventricular sites to exhibit similar abnormally accelerated subsidiary pacemaker function.

Arachidonic acid metabolism in thrombocytes and vascular tissues of turkeys.

Turkeys are hypertensive compared to mammals of similar size. In vitro synthesis of thrombocyte thromboxane B2 (TxB2), 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT), 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) and aortic prostaglandin (PG) production was studied in one to ten month old domestic white turkeys. Compared to normal human platelets, TxB2 production was increased (55.4 vs. 31.4%) and HETE production was markedly reduced (6.5 vs. 34.6%) in control thrombocytes. Similar to human platelets in which cyclooxygenase inhibition with aspirin results in an increase in HETE production, block of the thrombocyte enzyme with aspirin doubled the production of HETE. In vitro conversion of radiolabeled arachidonic acid (AA) showed that the primary PG produced by turkey aorta was PGE2. A 6-keto immunoreactive PG was present which comigrated with authentic 6-keto PGF1 alpha, but failure of the aortic supernatant to inhibit adenosine diphosphate or AA induced platelet aggregation suggested that PGI2 was not produced. The vasodepressor potency of PGE1, PGE2 and PGI2 was altered in awake turkeys with PGE1 and PGE2 having five times the hypotensive effect as PGI2. In addition, conversion of AA to PGE2 by aorta in one month turkeys was greater (17.3 vs. 9.2%) than in ten month old turkeys. Systemic arterial pressure was increased in the ten month old turkeys (188 mmHg) compared to one month old turkeys (143 mmHg). Thus, both vascular AA metabolism and the vasodepressor potencies of PGE2 and PGI2 are altered and the activity of the lipoxygenase pathway in thrombocytes is limited in the turkey.