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Biomedical subjects

M Peracchi

Publications and source records attributed to M Peracchi.

At least 37 records · Page 2Linked to original sources

Gallbladder emptying and somatostatin and cholecystokinin plasma levels in celiac disease.

OBJECTIVE: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls. METHODS: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis. RESULTS: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings. CONCLUSIONS: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.

Adult↗

Plasma pancreatic polypeptide response to secretin.

OBJECTIVE: Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial. Therefore, we aimed to evaluate the plasma PP pattern after secretin administration in healthy subjects and in patients with gastroduodenal diseases investigated for recurrent ulcer disease and/or hypergastrinemia. METHODS: Synthetic secretin was given as an intravenous bolus (2U/kg) in ten patients with Zollinger Ellison syndrome, ten with duodenal ulcer, ten with atropic gastritis and ten healthy volunteers. Blood samples were taken before and at regular intervals for 30min after secretin injection. Plasma PP and gastrin levels were measured by radioimmunoassay. RESULTS: Secretin promptly and significantly (P<0.01) increased PP plasma levels in all groups of subjects without any differences in peak values. There were no significant correlations between PP and gastrin plasma levels. CONCLUSIONS: Secretin at pharmacological doses is a powerful stimulus for PP release.

Adult↗

Plasma somatostatin-like immunoreactivity and somatostatin-28 levels in obese men.

Somatostatin (SS) impairs nutrient absorption. It has been suggested that hyposomatostatinaemia may be involved in the pathogenesis of obesity. However, data on postprandial SS-like immunoreactivity (SLI) levels in obese subjects are controversial and the levels of SS-28, the main molecular form of circulating SLI in healthy subjects, have not been determined. To characterise the fasting and postprandial plasma pattern of SLI and SS-28 in obese men, we studied eight obese men (age 24-32 yr, BMI 33-42 kg/m2), with normal glucose tolerance test and normal gastric emptying of solids, and eight healthy men (age 24-39 yr, BMI 21-24 kg/m2). Blood samples were taken at regular intervals in fasting conditions and for 2 h after a standard solid-liquid meal (2.3 MJ). Plasma SLI and SS-28 were measured by RIA. Our results showed that fasting and postprandial plasma SLI and SS-28 levels were not significantly different in healthy and obese subjects. In conclusion SS-28 is the predominant form of circulating SLI in obese subjects. The normal pattern of fasting and postprandial plasma SLI and SS-28 levels in such subjects suggests that somatostatin does not have a pathogenetic role in obesity.

Adult↗

Physical state of meal affects gastric emptying, cholecystokinin release and satiety.

To verify the influence of food consistency on satiety mechanisms we evaluated the effects of the same meal in solid-liquid (SM) and homogenized (HM) form on satiety sensation, gastric emptying rate and plasma cholecystokinin (CCK) concentration. Eight healthy men, aged 21-28 (mean 24.5) years were given two meals (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, total energy 2573 kJ, with water 300 ml) differing only in physical state: SM and HM. The subjects consumed the meals in randomized order on non-consecutive days. The sensations of fullness, satiety and desire to eat were evaluated by means of a questionnaire, gastric emptying was assessed by ultrasonographic measurement of antral area, and plasma CCK concentration was measured by radioimmunoassay. The vegetable-rich meal was significantly more satiating (P < 0.05) when in the HM form than when eaten in a SM state. Furthermore, the overall gastric emptying time was significantly slowed (255 (SEM 11) min after HM v. 214 (SEM 12) min after SM; P < 0.05) and CCK peak occurred later (94 (SEM 12) min after HM v. 62 (SEM 11) min after SM; NS) when the food was consumed in the HM form. Independently of the type of meal, antral area was significantly related to fullness sensations (r2 0.46, P = 0.004). These results demonstrate that meal consistency is an important physical food characteristic which influences both gastric emptying rate and satiety sensation. Moreover, the relationship observed between antral area and fullness sensation confirms that antral distension plays a part in the regulation of eating behaviour.

Adult↗

Late-onset idiopathic hypoparathyroidism as a cause of diarrhoea.

A 62-year-old man presented with a 20-month history of intermittent watery diarrhoea and hypocalcaemia. At age 43 he had undergone partial gastrectomy with Billroth II anastomosis for perforated peptic ulcer and at age 57 developed megaloblastic anaemia with low serum cobalamin and folate levels. Exhaustive gastrointestinal studies performed to ascertain the cause of the diarrhoea were all negative. Plasma parathyroid hormone levels were undetectable and late-onset idiopathic hypoparathyroidism was diagnosed. Normalization of hypocalcaemia promptly corrected the bowel habit. Idiopathic hypoparathyroidism is an unusual cause of diarrhoea that should, however, be considered in patients with hypocalcaemia and associated diarrhoea without evidence of primary intestinal disease.

Diarrhea↗

Pattern of plasma cyclic nucleotides and related hormones in liver cirrhosis and hepatocellular carcinoma.

To evaluate the pattern of plasma cyclic adenosine 3',5'-monophosphate, cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon levels in different stages of chronic liver diseases, we measured these variables in 20 normal subjects, 25 patients with genetic hemochromatosis, associated with liver cirrhosis in 19 cases and not in six, eight patients with compensated and 15 with decompensated alcoholic or posthepatitic cirrhosis, and 12 with hepatocellular carcinoma. All variables were within the normal range in non-cirrhotic hemochromatotic patients. Cyclic adenosine 3',5'-monophosphate levels were within the normal range (9.5-15.7 nmol/l) in hemochromatotic cirrhotics and elevated in other patients. Cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon were above the normal ranges (1.92-5.91 nmol/l, 8.8-62.7 ng/l, and 39-165 ng/l, respectively) in most patients with cirrhosis both with and without hemochromatosis and in most individuals with hepatocellular carcinoma. Cyclic guanosine 3',5'-monophosphate correlated with atrial natriuretic factor in the former groups but not in the latter. These findings indicate that glucagon and atrial natriuretic factor hypersecretion is an early event in cirrhosis, regardless of its etiology. In hepatocellular carcinoma, the underlying cirrhosis may account for most hormonal and metabolic changes although cyclic guanosine 3',5'-monophosphate increases could also be due to the neoplastic process per se.

Adult↗

Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types.

OBJECTIVE: We have investigated the prevalence of MEN 1 in patients with recognized pituitary adenomas. Since hyperparathyroidism is present in nearly 95-100% of patients with MEN 1 and frequently is the first condition to be identified, the study was limited to the identification of patients with hyperparathyroidism while the screening for gastroenteropancreatic (GEP) lesions was carried out in patients with both pituitary and parathyroid lesions. PATIENTS AND MEASUREMENTS: Serum total and ionized calcium, phosphate and intact PTH 1-84 (EASIA) were measured in 166 patients (68 with non-functioning pituitary adenoma, 42 with prolactinoma, 35 with GH-secreting adenoma, 17-with ACTH-screening adenoma, 1 with TSH-secreting adenoma, 1 with FSH-secreting adenoma and 2 with an only alpha-subunit secreting adenoma) referred to our clinic from 1990 to 1996. Plasma gastrin, somatostatin, pancreatic polypeptide and vasoactive intestinal peptide were measured by RIA in patients with hyperparathyroidism. RESULTS: Eight of 166 patients (4.8%) were found to have primary hyperparathyroidism and among these 2 also had a gastrinoma while there was no evidence of other GEP tumours. Considering the tumour type, 6 had prolactinoma (14.3%), 1 GH-secreting adenoma (2.8%) and 1 non-functioning adenoma (1.5%). In most patients the diagnosis of pituitary tumour was made several years before that of hyperparathyroidism (from 1 to 15 years) although 6 patients had previously suffered from urolithiasis and one had undergone gastric resections for recurrent peptic ulcers. One patient was identified as a MEN 1 gene carrier and 2 had relatives with signs and symptoms referable to parathyroid or GEP lesions. CONCLUSIONS: The study shows a prevalence of 4.8% of primary hyperparathyroidism in unselected patients with known pituitary tumours similar to that reported in a previous study. By contrast, the prevalence of MEN 1 in patients with prolactinoma was definitely high (14.3%). In most patients the diagnosis of pituitary tumours was made several years before that of hyperparathyroidism. Although the patients were believed to harbour a sporadic pituitary tumour, most of them had had signs and/or symptoms referable to one or both of the other organs involved in MEN 1, often concomitantly with those of pituitary tumours. These data indicate that the diagnosis of MEN 1 syndrome is missed in a substantial proportion of patients with prolactinomas and therefore the screening of these patients for the syndrome is strongly recommended.

Adenoma↗

Plasma somatostatin levels in patients with chronic idiopathic intestinal pseudo-obstruction.

OBJECTIVES: Somatostatin participates in the control of gut motility. Recently, somatostatin analogs have been proposed as therapeutic agents for chronic intestinal pseudo-obstruction, although the endogenous somatostatin pattern has never been assessed in this syndrome. We aimed to evaluate fasting and postprandial plasma somatostatin levels in patients with chronic idiopathic intestinal pseudo-obstruction (CIIP). METHODS: We studied eight patients with CIIP and 10 healthy volunteers. Blood samples were taken at regular intervals while patients and subjects fasted and during the 3 h after a standard solid/liquid meal (550 kcal) had been eaten. Somatostatin was measured by radioimmunoassay. RESULTS: Fasting somatostatin levels were normal, whereas postprandial peptide responses were markedly impaired or even absent in patients with CIIP. CONCLUSIONS: An impaired postprandial somatostatin response in patients with CIIP seems to be characteristic of this heterogenous disorder. Whether the lack of somatostatin response to a meal identifies patients with severe gut dysmotility for whom treatment with somatostatin analogs would be useful remains to be verified.

Adult↗

Duodenal mucosa and extracellular cyclic nucleotide pattern in coeliac disease.

This study measured the values of cyclic nucleotides and adenylate and guanylate cyclase activities in duodenal mucosa homogenates to verify if they played a part in coeliac disease. Nine controls, 13 patients who did not receive treatment and nine patients who received treatment were studied. Cyclase activity assays were performed under basal conditions and in the presence of gliadin derived peptides. Duodenal mucosa cyclic nucleotide values and adenylate cyclase activity were significantly higher in patients who did not receive treatment than in those who did and in controls, whereas guanylate cyclase activity was similar in all groups. Gliadin derived peptides did not affect guanylate cyclase activity, but significantly increased adenylate cyclase activity in homogenates from patients who did not receive treatment. As extracellular cyclic nucleotide concentrations could reflect changes in their intracellular metabolism, plasma and urine cyclic nucleotide values were also measured in 25 controls and in 55 patients studied at different stages of their disease. Extracellular cyclic nucleotides were considerably high in patients who were not healed and became normal after about one year of treatment. These data suggest that cyclic nucleotides may participate in the pathophysiological processes of coeliac disease.

Adenylyl Cyclases↗

Abnormal growth hormone responsiveness to stimuli in women with active celiac sprue.

Baseline somatomedin C (Sm-C) and responses of growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) to TSH-releasing hormone (TRH) and to L-dopa were evaluated in 10 untreated and nine treated women with celiac sprue, and in 10 normal women. Mean basal Sm-C, GH, PRL, and TSH levels were similar in all groups of subjects. In all subjects, L-dopa decreased PRL levels, without affecting TSH, and TRH increased PRL and TSH levels. In both controls and treated patients, TRH did not influence GH secretion, whereas L-dopa significantly increased GH levels. In untreated patients, GH levels paradoxically increased after TRH (8/10) but were unaffected by L-dopa (7/10). Because L-dopa would stimulate hypothalamic GH-releasing hormone (GHRH) secretion, four untreated patients, unresponsive to L-dopa, received GHRH, and GH levels rose markedly. These data suggest that, in untreated celiac sprue patients, hypothalamic control of GH secretion is reversibly impaired.

Adolescent↗

Plasma cyclic nucleotide levels in patients with refractory anaemia with excess of blasts.

To verify the clinical usefulness of extracellular cyclic nucleotide determinations as tumour markers in preneoplastic syndromes, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were monitored in 47 patients with refractory anaemia with excess of blasts (35 RAEB and 12 RAEBt), 20 of whom progressed to acute leukaemia during the observation period. The control group consisted of 45 healthy subjects matched for age and sex. In all groups of patients plasma cAMP levels were within the normal range, whereas plasma cGMP levels were significantly higher than those of normal subjects in both RAEB and RAEBt patients, and increased further when progression to acute leukaemia occurred. These data suggest that serial determinations of plasma cGMP may be useful to monitor the progression of the disease, though there is no evidence that cGMP values at diagnosis may have a prognostic significance.

Adult↗

Effect of high doses of somatostatin on adenylate cyclase activity in peripheral mononuclear leukocytes from normal subjects and from acute leukemia patients.

In normal lymphocytes somatostatin non-competitively inhibited basal (ID50 5 x 10(-4) M) and isoproterenol- and forskolin-stimulated adenylate cyclase activity (Ac). In acute leukemia blasts, non-responsive to isoproterenol, forskolin, which activates the catalytic subunit, stimulated and somatostatin inhibited Ac, thus indicating the leukemic enzyme, though defective, retains the inhibitory pathway and catalyst function.

Acute Disease↗

A search for new anti-herpes virus compounds.

This study reports on the synthesis and the activity of a series of new compounds of nucleoside-type structure. They are characterized for being differently substituted in the aromatic ring of the base (deazoadenosine derivatives) or by bearing a dansyl group in the sugar moiety (dansylthymidine). One molecule belonging to this latter class of compounds (the 3'-0-dansylthymidine) is showing an anti-herpesvirus potential while being active in inhibiting the virus-encoded enzyme thymidine kinase. This finding may represent an important step for the synthesis of new enzyme inhibitors and it is discussed in terms of future developments of more active congeners.

Adenosine↗

Plasma cyclic nucleotide levels in acute leukemia patients.

To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.

Acute Disease↗

Defective granulocyte chemotaxis and natural killer activity in a patient with recurrent infections.

A 25-year-old male with a history of recurrent infections presented with fever, severe aplastic anaemia, splenomegaly and retroperitoneal node enlargement. Lympho-histiocytic granulomas were found in spleen, liver and lymph nodes. Granulocyte studies revealed normal morphology, severely impaired random migration and complete absence of directed locomotion. Whereas phagocytosis was slightly reduced, candidacidal activity and nitroblue tetrazolium reduction were normal. Basal granulocyte cyclic GMP levels were within the normal range while a 5-fold increase of cyclic AMP levels was observed. Numerous abnormalities were also found in the patient's lymphocytes: lack of delayed hypersensitivity, reduced response to mitogens, low OKT4/OKT8 ratio, absence of natural killer (NK) activity with normal number of cells recognized by NK-specific monoclonal antibodies. These observations describe a distinct clinico-pathologic entity and suggest the possibility of a common defect in granulocytes and in NK cells.

Adult↗