Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

34 pituitary adenomas were examined by light and electron microscopical methods. Slices of tumor tissue fixed in formaldehyde or Bouin's solution, respectively, and embeded in paraffin were stained by hematoxylin-eosin, Goldner's method (including Orang G), periodic acid Schiff (PAS) reaction, and in some cases by Herlant's tetrachrom. The ultrastructure was studied using tumor tissue fixed in glutaraldehyde within 1 hour after removal. The adenomas were classified by their light microscopical characteristics as chromophilic or chromophobe tumors. Employing the PAS reaction and Goldner's staining method, 27 adenomas were found to give intense or weak staining reactions. By electron microscopical investigation , all the adenomas studied were seen to contain secretory granules more or less densely packed within the cytoplasm. The number of these granules was strongly correlated with the intensity of the tinctorial properties of the tumor tissue. Out of 11 acidophilic adenomas, 10 were observed consisting of typical STH cells. 4 acromegalic patients were found to possess heavily or poorly granulated STH cell adenomas (two patients in each of these groups). One patient with a clinical history of liver cirrhosis and gynecomastia was observed bearing an acidophilic (and erythrosinophilic) adenomatous hyperplasia of prolactin cells, 13 tumors consisted of cells exhibiting almost weak amphophilic staining properties and secretory granules of 100-250nm diameter, thus resembling cells which have been reported to produced ACTH. One of the patients suffering from these adenomas, showed the clinical signs of M. Cushing. By ultrastructural criterions, 3 adenomas with PAS-positive tumor cells were considered to be composed of gonadotropic cells. Only 7 adenomas were observed which did not give any chromophilic reaction. These tumors consisted of extreme poorly granulated cells which could not be significantly associated with one of the pituitary hormones by their morphological properties. In respect of the abundance of mitochondria, 4 out of the adenomas were designated as oncocytic tumors.
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PMID:[The ultrastructure of human pituitary adenomas (author's transl)]. 6 63

Cortisol and cortisone glucosiduronic acids were synthesised in a 14C-labelled from and utilised in a double-isotope derivative procedure for the analysis of cortisol glucosiduronate (FG) and cortisone glucosiduronate (EG) in human urine. Normal adults were found to excrete between 16 and 100 mug/24 h of FG (n = 14) and between 55 and 120 mug/24 h of EG (n = 15). Elevated values were observed in subjects with Cushing's syndrome and following ACTH stimulation. Abnormal excretion was noted in one patient with hepatic cirrhosis and in one case of cholestatic jaundice. The ratio FG/EG was markedly increased after ACTH stimulation and, in the normal group, was positively correlated to a highly significant degree (P less than 0.001) with FG excretion. These two observations suggest that EG excretion is less sensitive than FG excretion to variations in cortisol production.
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PMID:The urinary excretion of glucosiduronates of cortisol and cortisone. 17 71

To study the influence of the adrenal gland on plasma estrogen levels in male patients with hepatic cirrhosis, estrone and estradiol were measured under a variety of experimental conditions. Compared to controls, estradiol levels were moderately elevated by 26% (P is less than 0.05) in patients with hepatic cirrhosis (28.5 +/- 5.4 vs. 36.0 +/- 4.7 pg/ml plasma; n: 12), whereas estrone levels exhibited a two- to threefold increase under basal conditions (32.5 +/- 5.6 vs. 67.8 +/- 20.8 pg/ml; P is less than 0.01). ACTH application resulted in a striking increase in plasma estrone levels in both patients with hepatic cirrhosis and in normal subjects (61.8 +/- 27.5 vs. 27.3 +/- 7.8 pg/ml). During stimulation with ACTH, estradiol levels showed no significant changes. After suppression of the adrenal gland by dexamethasone administered for 5 days, plasma concentrations of estrone and estradiol were found to be reduced. The absolute decrease of estrone was significantly greater in patients with hepatic cirrhosis than in healthy male subjects (35.5 +/- 12.6 vs. 21.3 +/- 6.0 pg/ml; P is less than 0.05; n: 8). Estrogen values, however, were still high in patients with hepatic cirrhosis after 5 days of dexamethasone administration (37.1 +/- 17.6 pg estrone/ml and 23.9 +/- 3.6 pg estradiol/ml plasma). It is suggested that elevated plasma values of estrogens in this disorder may be derived predominantly from adrenal production. Peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels of estrogens in patients with hepatic cirrhosis.
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PMID:Estrone and estradiol in patients with cirrhosis of the liver: effects of ACTH and dexamethasone. 18 10

The basal level of secretion of hypophyseal (ACTH, STH) and peripheral glucocorticoid (cortisol, corticosterone) hormones as related to the immune status (lymphocyte subpopulations, serum immunoglobulins, circulating immune complexes, macrophagal component) and specific marker profiles of viruses B and delta was measured in 142 children with different forms of chronic virus hepatitis B and delta (D). The patients with chronic persistent hepatitis was characterized by the "cortisol" type response of stressor adaptation hormones in parallel with the genetically determined weak immune response, demanding no correction. The patients with chronic active hepatitis B and D demonstrated the "central" type of hormonal response with a primary increase in the content of ACTH and CTH and a moderate rise of the cortisol level, which correlated with pronounced secondary immunodeficiency of the T cell and macrophagal components of immune response. In the patients with chronic virus hepatitis B and D, the hormonal profile, as liver cirrhosis develops, is characterized by an increase in corticosterone and blood somatotropin and by a relatively low cortisol content. This reflects depletion of the mechanisms of adaptation and correlates with deep insufficiency of all the three components of immune response. The use of human leukocytic interferon and T-activin exert a well-defined effect on hormonal adaptation of immune response, promotes completion of HB-virus infection replication and the onset of a stable remission.
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PMID:[Clinico-pathogenetic role of hormones of the pituitary-adrenal system and somatotropin in the development of immunosuppression in chronic hepatitis B and delta infection in children and the approach to its correction]. 166 32

The relationship between adrenocorticotropic hormone as well as renin and potassium activity and blood aldosterone secretion was examined in normal subjects and patients with chronic hepatic diseases. It is demonstrated that aldosterone stimulation is controlled by simultaneous renin-angiotensin (RA) and hypothalamo-adenopituitary effects in normal subjects and patients with chronic active hepatitis (CAH), the RA effects prevailing in normal subjects, and hypothalamo-adenopituitary ones, in CAH patients. Cirrhosis of the liver was associated with the greatest deviations in the stimulant-aldosterone relationship. Viral cirrhosis with ascites featured a considerable RA increase, affecting the adrenals, while the contribution of ACTH was reduced considerably. ACTH level was the highest in patients with alcoholic cirrhosis.
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PMID:[Hormonal changes in chronic diffuse diseases of the liver]. 255 Oct 48

Chronic liver disease may be accompanied by disturbed sodium and water homeostasis. There is usually sodium retention and ascites. However, spontaneous natriuresis has also been reported in humans and experimental animals with liver cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver disease, is known to induce the inhibition of the osmostimulation of vasopressin (AVP) release. We have therefore investigated the osmoregulation of AVP release in 11 dogs with chronic hypercortisolism associated with advanced liver dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary-adrenocortical activity was investigated by measuring the concentration in multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24-hr urine. Urine specific gravity was also measured. The feedback regulation of the system was investigated by measuring these hormones in plasma after an intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of the release of AVP was investigated by the intravenous infusion of a 20% NaCl solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the threshold osmolality at which it commenced and the sensitivity, which reflects the magnitude of the response. All dogs had highly increased urinary cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(-6)). The mean basal plasma concentrations of the three pituitary-adrenocortical hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally, 14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of the secretion of ACTH and cortisol in response to dexamethasone was unaffected. Urine specific gravity was significantly decreased. The regulation of AVP release was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic threshold at which the release of AVP was induced was abnormally high in seven of the dogs with liver disease and in the normal range in one. It could not be determined in three dogs. The sensitivity of AVP release in response to increasing plasma hypertonicity was normal in two dogs and decreased in nine. In three dogs, there was no increase in AVP release. None of the dogs had normal values for both the sensitivity and the threshold.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release in dogs with hepatic encephalopathy. 762 76

A 37-yr-old woman was admitted to our hospital for evaluation of diabetes mellitus, liver cirrhosis and primary amenorrhea. Serological and hematological examinations revealed that she suffered from hemochromatosis secondary to congenital dyserythropoietic anemia (CDA), characterized by ineffective hematopoiesis and erythropoietic dysplasia. Iron deposition was suggested by MRI on the pancreas, liver and pituitary gland. Endocrinological examinations demonstrated that she had isolated gonadotropin deficiency and ovarian failure, resulting in hypogonadotropic hypogonadism. In addition, despite normal responses of serum cortisol and plasma aldosterone to ACTH and furosemide-standing tests, respectively, serum dehydroepiandrosterone (DHEA) responded poorly to ACTH test, suggesting selective damage of zona reticularis in adrenocortical steroidogenesis in association with hemochromatosis.
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PMID:[Isolated gonadotropin deficiency and secretory discrepancy of cortisol and adrenal androgen by hemochromatosis secondary to congenital dyserythropoietic anemia]. 795 84

It is obvious that the most favorable therapeutic results can be obtained by hepatic lobectomy in the patients with intrahepatic calculi. However the number of patients in which hepatic lobectomy can be indicated is limited because of localization of lesions and some others. Endoscopic stone-extraction technique is the only therapeutic tool available in those patients. In this paper, technical know-how of postoperative cholangioscopy (POCS) and percutaneous transhepatic cholangioscopy (PTCS) was introduced and their clinical significance for management of intrahepatic calculi were discussed. POC was safely carried out 3 weeks after surgery if the extra-ductal limb of T-tube, lager than 14 Fr size, in the common bile duct, was brought out through the abdominal wall as straight as possible to obviate a tortuous sinus tract. PTCS was carried out through the sinus tract dilated up to over 14 Fr size after percutaneous transhepatic biliary drainage. Advantages of these modalities are; 1) they can be safely and repeatedly carried out if the sinus tract is maintained open. 2) stones visible are readily removable with the use of basket forceps or stone-integrator under endoscopic guidance and 3) preoperative application of PTCS provides us the important informations necessary to decide an adequate surgical procedure by delineation of intrahepatic anatomy. For the period started from 1975 when we introduced the first model of cholangiofiberscope to the end of 1995, 134 cases with intrahepatic calculi have been encountered and stone extraction was successful in 119 cases, success rate being 88.8%. The prognosis of the patients in which stone-extraction was successful was generally good. Main causes of failure in 15 cases were attributable to difficult location of lesion to perform choplangioscopy and concomitant liver cirrhosis or pururent cholangitis. The 6 cases with concomitant liver cirrhosis and pururent cholangitis were passed away before stone-extraction was completed. Therefore it can be said that complete stone-extraction was POCS or PTCS is very important to obtain a better long term prognosis in the cases with intrahepatic calculi. The authors believe that therapeutic results of inrahepatic calculi will be improved with the use of POCS or PTCS.
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PMID:[Non-surgical treatment of intrahepatic calculi]. 890 13

Selective iron deposition in the zona glomerulosa of the adrenal cortex is observed in hemochromatosis. Hypoaldosteronism should be excluded before starting venesection, to avoid long-term volume depletion. We evaluated the aldosterone status in patients with hemochromatosis. As other endocrine organs can be affected by the disease as well, we simultaneously evaluated anterior pituitary, gonadal, thyroid and pancreatic beta-cell activity. Nine patients with hereditary or acquired hemochromatosis and highly increased plasma ferritin levels were investigated. In patients, liver cirrhosis had been confirmed histologically. Five patients complained of sexual dysfunction, and one had impaired glucose tolerance. Plasma aldosterone (PA) and renin activity (PRA) were measured after a period of normal (100 mmol/day) and low (10 mmol/day) sodium intake. A combined anterior pituitary function test and a glucagon stimulation test were undertaken to evaluate other endocrine functions. Both PA and PRA levels were decreased in one patient with liver cirrhosis, who also presented attenuated cortisol, prolactin and gonadotrophin secretion. No patients had signs of primary hypoaldosteronism with hyperreninemia. Hypogonadotropic hypogonadism was observed in 3 males and 1 female. Pituitary ACTH reserve was impaired in 2, GH and prolactin response in 1, and thyroid function in none of the patients. Glucagon-stimulated plasma C-peptide was impaired in one patient. In conclusion, primary aldosterone deficiency was not observed in patients with severe iron overload. Hyporeninemic hypoaldosteronism was found in one patient who also presented other endocrinopathies. Hypogonadotropic hypogonadism is the most frequent endocrine abnormality in hemochromatosis.
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PMID:Mineralocorticoid status and endocrine dysfunction in severe hemochromatosis. 1040 11

The involvement of vasopressin (AVP) in several pathological states has been reported recently and the selective blockade of the different AVP receptors could offer new clinical perspectives. During the past few years, various selective, orally active AVP V1a (OPC-21268, SR49059 (Relcovaptan)), V2 (OPC-31260, OPC-41061 (Tolvaptan), VPA-985 (Lixivaptan), SR121463, VP-343, FR-161282) and mixed V1a/V2 (YM-087 (Conivaptan), JTV-605, CL-385004) receptor antagonists have been intensively studied in various animal models and have reached, Phase IIb clinical trials for some of them. For many years now, our laboratory has focused on the identification of nonpeptide vasopressin antagonists with suitable oral bioavailability. Using random screening on small molecule libraries, followed by rational SAR and modelization, we identified a chemical series of 1-phenylsulfonylindolines which first yielded SR49059, a V1a receptor antagonist prototype. This compound displayed high affinity for animal and human V1a receptors and antagonized various V1a AVP-induced effects in vitro and in vivo (intracellular [Ca2+] increase, platelet aggregation, vascular smooth muscle cell proliferation, hypertension and coronary vasospasm). We and others have used this compound to study the role of AVP in various animal models. Recent findings from clinical trials show a potential interest for SR49059 in the treatment of dysmenorrhea and in Raynaud's disease. Structural modifications and simplifications performed in the SR49059 chemical series yielded highly specific V2 receptor antagonists (N-arylsulfonyl-oxindoles), amongst them SR121463 which possesses powerful oral aquaretic properties in various animal species and in man. SR121463 is well-tolerated and dose-dependently increases urine output and decreases urine osmolality. It induces free water-excretion without affecting electrolyte balance in contrast to classical diuretics (e.g. furosemide and hydrochlorothiazide). Notably, in cirrhotic rats with ascites and impaired renal function, a 10-day oral treatment with SR121463 (0.5 mg/kg) totally corrected hyponatremia and restored normal urine excretion. This compound also displayed interesting new properties in a rabbit model of ocular hypertension, decreasing intraocular pressure after single or repeated instillation. Thus, V2 receptor blockade could be of interest in several water-retaining diseases such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), liver cirrhosis and congestive heart failure and deserves to be widely explored. Finally, further chemical developments in the oxindole family have led to the first specific and orally active V1b receptor antagonists (with SSR149415 as a representative), an awaited class of drugs with expected therapeutic interest mainly in ACTH-secreting tumors and various emotional diseases such as stress-related disorders, anxiety and depression. However, from the recently described tissue localization for this receptor, we could also speculate on other unexpected uses. In conclusion, the development of AVP receptor antagonists is a field of intensive pharmacological and clinical investigation. Selective and orally active compounds are now available to give new insight into the pathophysiological role of AVP and to provide promising drugs.
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PMID:Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. 1243 36


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