[Recurrent nodular goiter. Characteristic features and surgical management]. / Nodozni retsidivni strumi. Osobenosti. Khirurgichno lechenie.

Purpose of the study was to investigate the frequency of the thyroid carcinoma in the recurrent nodular goiter, to analyse the applied operative methods, the observed complications and the obtained early and distant postoperative results. For the period 1985-1996 in the Clinic of Endocrine Surgery were performed 588 reoperations by 577 patients with nodular recurrent goiter, distributed as following: 539 females, aged 14-81 and 49 males, aged 11-69. In 431 cases (73%) was applied medial approach and in 157 cases (27%)--lateral operative approach by the mobilizing of the thyroid recurrence. In the early postoperative period were established the following complications: clinical hypoparathyroidism in 10 patients (1.7%) with calcium level from 1.44-2.01 mmol/l and recurrent nerve paralysis in 28 patients (4.76%), including: in 13 cases unilateral paralysis on the right side, in 9 cases unilateral--on the left side and in 6 cases--bilateral paralysis. The established in 28 patients (4.76%) thyroid carcinoma and the appeared in 59 cases (10%) new recurrence of the basic thyroid disease supported our tactic for radical operative treatment in all patients with nodular recurrent goiter.

[Surgical treatments in recurrent Graves' disease]. / Operativno lechenie na retsidivna bazedova bolest.

Seventy-six patients with clinical diagnosis Graves' disease, reoperated in the Clinic of Endocrine Surgery over the period 1985 through 1996, are analyzed. Distribution by gender and age: 3 men with mean age 55.33 y (range 49-60), and 73 women at mean age 39.67 years (range 19-69). The scope of secondary operation includes: thyroidectomy--3 cases, subtotal thyroid resection--55, lobectomy with contralateral subtotal resection--2, and unilateral predominantly subtotal resection--16 cases. It is the purpose of the study to assay the underlying causes of surgical relapse in Graves' disease, its relationship to the radicalism of the intervention, thyrostatic therapy duration, and early and late postoperative complications associated with its removal. In 16 cases (21.05%) secondary operative intervention is done against the background of enhanced production of thyroid hormones. A short 3 to 6-month thyrostatic course precedes the reoperation in eleven patients (14.47%). Unilateral thyroid resection is resorted to in 16 patients (21.05%). Postoperative hypothyroidism is observed in 6 cases (7.89%). A relapse of Graves' disease after reoperation is noted in 3 instances (3.94%). Six patients of the series reviewed (7.89%) develop postoperative hypoparathyroidism: transitory in four (5.26%) and permanent in two (2.63%). In the early postoperative period, paresis of n recurrents (n laryngeus inferior) develops in 2 patients (2.63%): left- and rightside, one each respectively. In terms of morphological patterns, the ensuing relapses after surgery in Graves' disease patients portray the initial pathological process: some cases show a tendency of nodular adenomatous hyperplasia development, sporadic cases form follicular adenomas, and in 14 cases (18.42%) lymphoid infiltrates predominate with a tendency to be converted into Hashimoto's thyroiditis. The presence of enhanced proliferative response induced by a variety of factors, therapeutic ones inclusive, is the basic morphological factor of the recurrent conditions described.

Ectopic ACTH-syndrome due to ovarian carcinoma.

The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome with fatal consequences is described. Both the clinical and the biochemical findings were consistent with ectopic ACTH production. A computed tomographic (CT) scan revealed intact pituitary and enlarged adrenal glands. Liver metastases were seen but the primary neoplasm was not found. Treatment with aminoglutethimide and other therapeutic measures were unsuccessful. A carcinoma of the right ovary was discovered on autopsy. The tumour cells showed immunoreactivity for neuron-specific enolase (NSE), ACTH and beta-endorphin with differing degree of intensity.

Neuroendocrine features of adrenal pheochromocytomas: histological and immunocytochemical evaluation.

Neuroendocrine features of 30 surgically removed adrenal pheochromocytomas were evaluated combining conventional histochemistry and immunocytology. The reactivity for neuron-specific enolase (NSE), S-100 protein, vasoactive intestinal peptide (VIP), calcitonin and ACTH was tested according to the peroxidase anti-peroxidase (PAP) method using polyclonal antibodies. The neuroendocrine marker NSE was found in all cases. S-100 protein was present in satellite cells in 11 (36.6%) tumors. Rare immunoreactive cells for somatostatin were found in 16 (53.3%), for VIP in 8 (26.6%), for calcitonin in 7 (23%), and for ACTH in 3 (10%) cases. Our results proved the histological and functional heterogeneity of pheochromocytomas. The multiple synthetic activity is their inherent feature as in other neuroendocrine tumors.

Streptozotocin-induced diabetes in rat. III. Antioxidant protection of vascular complications by flunarizine and aligeron.

In rats with streptozotocin-induced diabetes antioxidant protection of diabetic angiopathy was performed by flunarizine (10 mg/kg/day) and aligeron (10 mg/kg/day), applied intraperitoneally during 2.5 months of diabetes. Diabetic vascular complications were assessed by morphologic determination of PAS-positive mucopolysaccharides and measurement of vascular wall thickness in addition to quantitative estimation of lipid hydroperoxides, thromboxane A2/prostacyclin disbalance and plasma beta-thromboglobulin changes. Both drugs prevented development of diabetic angiopathy in rats by inhibition of lipid peroxidation, prostanoid synthesis and platelet activity, but the effect of flunarizine was more pronounced, which could be explained by its additional blocking effect of abnormal calcium flux into vascular cells. The free radical scavenging action of flunarizine and aligeron was investigated.

Streptozotocin-induced diabetes in rat. II. Lipid and lipid peroxide changes of lipoprotein fractions in diabetes complicated by hypertension and myocardial infarction.

Lipid peroxide levels and plasma lipids were studied in plasma lipoprotein fractions of streptozotocin diabetic rats, spontaneous hypertensive rats (SHR) + diabetes, and in myocardial infarction rats (MIR) + diabetes. The duration of diabetes in all experimental groups was 2.5 months. We found a tendency of elevation of cholesterol in VLDL and fall in HDL2 but the differences were not significant. Total plasma triglycerides were increased in the three diabetic groups, and the increase was due to LDL fraction but again the differences were not significant. The lipid peroxide (LP) level in total plasma showed a significant increase in the three diabetic groups: in Wistar diabetic rats LP increased 3 times, in MIR + diabetes 3.5 times, and in SHR + diabetes 5 times. The increase of LP in the three diabetic groups was due to LDL with good correlation (r = 0.60) between LP and triglycerides in LDL of the three diabetic groups. The results are in agreement with the concept of the importance of lipoprotein fraction changes: increased cholesterol, triglycerides and lipid peroxides in atherogenic (VLDL and LDL) fractions, and decreased levels in antiatherogenic (HDL, HDL2) fractions in diabetes mellitus.

Streptozotocin-induced diabetes in rat. I. Influence of hypertension and myocardial infarction on the development of vascular complications.

Streptozotocin diabetes in rats was complicated by spontaneous hypertension (SHR) and myocardial infarction (MIC), considered as "risk groups". Renal function was assessed on the basis of blood urea nitrogen (BUN) and albuminuria. BUN increased by 36% in Wistar diabetic group, by 100% in SHR + diabetes, and by 51% in MIR + diabetes. Morphologic changes were assessed by estimation of PAS-positive glycosaminoglycans and measurement of vascular wall thickness of glomerular arterioles. The risk groups showed exaggerated tendency for development of diabetic angiopathy. A significant imbalance between TXA2 and prostacyclin was found, which was reflected by TXB2/6-keto-PGF1 alpha (the stable metabolites of TXA2 and prostacyclin, respectively) ratio, which increased by 38% in Wistar diabetic rats, by 61% in SHR + diabetes, and by 133% in MIR + diabetes. These changes correlated very well with increased platelet aggregability (r = 0.70; p less than 0.05) and with increased lipid peroxide level (r = 0.60; p less than 0.05), but neither with total plasma cholesterol (r = 0.20), nor with plasma triglycerides (r = 0.34). Lipid peroxides increased 5-fold in Wistar diabetic rats, 6-fold in SHR + diabetes, and 5.5-fold in MIR + diabetes. A causative relationship between TXA2/PGI2 imbalance and lipid peroxide changes on one hand, and diabetic angiopathy, on the other, was suggested.

Pathogenesis of cardiovascular disorders in streptozotocin-induced diabetes in rat. I. Cardiovascular, renal and morphologic changes in different stages of diabetes.

Some cardiovascular (heart rate and mean arterial pressure), and renal (glomerular filtration rate-GFR; renal plasma flow-RPF; filtration fraction-FF; blood urea nitrogen-BUN and albuminuria) parameters, coupled with morphologic examination, was undertaken in early (2 months) and late (6 months) stage of streptozotocin-induced diabetes mellitus in rats. The results showed a temporally (early) bradycardia and gradually increase of blood pressure with morphologic changes typical for diabetic cardiopathy. The increased GFR (by 92%), associated with significantly decreased RPF (by 37%), increased FF (by 133%), increased kidney weight/body weight ratio (by 88%), increased BUN (by 52%) and distinct albuminuria (13.53 +/- 2.08 mg/24 h/100 g b. w.), together with typical morphologic changes, suggested the development of diabetic nephropathy which was progressive with the duration of the disease.

Opioid peptides in experimental myocardial infarction. I. The effect of naloxone.

The effect of intravenous administration of the opioid antagonist naloxone in rats with acute left coronary artery ligation was studied. The results demonstrated that naloxone in a dose 2 mg/kg b. w. affords its protection on infarcted animals by two mechanisms: Reduces by 22% the incidence of early arrhythmias that occur within 15-20 minutes of acute myocardial ischaemia, and are responsible for the early (up to the 30th minutes) postligation death; Reverses the hypotension that results from the development of cardiogenic shock after 30 minutes myocardial infarction. The total mortality after naloxone treatment was significantly reduced by 22%. Naloxone does not influence significantly the size of the infarcted area but the incidence of left ventricle wall perforations was decreased by 38%. Both effects of naloxone are attributed to the antagonism of opioid receptors either directly on the myocardium or through blocking the central action of beta-endorphin. A direct effect of naloxone on the cardiac muscle action potential cannot be excluded.

Discrepancy between aldosterone production and renin-angiotensin system activity in Brattleboro rats.

It was demonstrated before that in addition to their typical changes in water-sodium-potassium balance Brattleboro rats, homozygous for hypothalamic diabetes insipidus (DI), revealed a discrepancy between aldosterone level and plasma renin activity (PRA). In the present study PRA was significantly increased (79%), and concomitantly juxtaglomerular (JG) index was increased, reflecting an increased secretory activity of renin-producing JG cells. Plasma concentration of aldosterone was significantly lower (-36%) in DI rats than in their Long Evans (LE) controls. Adrenal blood flow rates were not significantly different in both groups of rats but aldosterone concentrations in the adrenal venous effluents were significantly lower (-66%) in DI rats than in LE rats, suggesting that in vivo production rate of aldosterone was reduced in DI rats. This assumption was confirmed by morphometric data of zona glomerulosa. Our results demonstrated a significant reduction (50%) of angiotensin II receptors in the adrenal glands of DI rats, referring to the number of binding sites and to Kd. This finding threw light on the dissociation between a decreased aldosterone production and stimulated renin-angiotensin system in DI rats.