Treatment of type II gastric carcinoid tumors with somatostatin analogues.
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Adult↗
Biomedical subjects
M Migliori
Publications and source records attributed to M Migliori.
Influence of sex and age on blood pressure variability.
The aim of this study has been to identify changes of 24-h blood pressure variability, as related to age and sex in hypertensive subjects. As regards this point several international studies have shown the increase of morbidity and mortality caused by cardiovascular diseases in postmenopausal women produced by a lack of sex hormones, which had protected the women until this period. Each hypertensive subject was submitted to an ambulatory blood pressure monitoring (ABPM) and two variability indexes were obtained: S.D. and coefficient of variation (CV). The results have shown a strict correlation between blood pressure variability and age, without significant sex-related differences. A decrease of blood pressure variability and mean blood pressure (BP) values have also been found, in the night-time with respect to the day-time data; it was more pronounced in females than in males but this would not seem an age-related difference. Despite the fact that the correlation between blood pressure variability and age is very significant in every considered period in males, it has been found that women have statistical differences only in the day-time and in the nocturnal diastolic blood pressure (DBP) fluctuations. This might be caused by other independent factors, such as a postmenopausal lack of sex hormones.
Journal Article↗
Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR.
BACKGROUND: Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days. AIM: To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours. METHODS: A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months). RESULTS: In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed. CONCLUSIONS: Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.
Adult↗
The link of biocompatibility to cytokine production.
Recent studies suggest that chronic inflammation plays a role in the pathogenesis of cardiovascular disease. Cytokines released from jeopardized tissues stimulate the liver to synthesize acute phase proteins, including C-reactive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. More recently, it has been suggested that CRP is useful not only as a marker of the acute phase response, but is also involved in the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis. Several studies in uremic patients have implicated CRP as a marker of malnutrition, resistance to erythropoietin, and chronic stimulation in hemodialysis. An increased cytokine production secondary to blood interaction with bioincompatible dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and mainly IL-6 are the three proinflammatory cytokines involved in the pathogenesis of hemodialysis-related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysate and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminate dialysate. Therefore, CRP is implicated as a marker linking bioincompatibility associated with backfiltration and increased cytokine production with a clinical state of chronic inflammation.
Acute-Phase Reaction↗
Plasma C-reactive protein in hemodialysis patients: a cross-sectional, longitudinal clinical survey.
In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes <10 liters/session (10%), hemodiafiltration with infusion volumes <20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes <10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes <10 liters/session than in hemodiafiltration with infusion volumes >20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.
Acute-Phase Proteins↗
C-reactive protein as a marker of chronic inflammation in uremic patients.
Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. Several recently published papers have confirmed this strong association between CRP and the extent and severity of the atherosclerotic processes. In patients affected by predialytic renal failure, increased levels of CRP and interleukin (IL)-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation - even in the predialytic phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could at least in part be due to the dialytic technique. We provide evidence suggesting that the increase of CRP in stable dialytic patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants.
Arteriosclerosis↗
ANCA in dialysis patients: a role for bioincompatibility?
UNLABELLED: BACKGROUND. Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, pre-dialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. METHODS: A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. RESULTS: In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. CONCLUSIONS: No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation.
Adult↗
[Nutritional deficiency and Alzheimer's disease: how to identify and prevent].
Weight loss is a very common problem for patients with Alzheimer's Disease (AD), whether they live at home or in long-term care facilities. At any rate it depends on an imbalance between energy expenditure and intake. Though in the initial phases of the illness, the weight loss might be caused by socio-environmental and psychological factors and reduced autonomy, in the following stages it depends on Adversive Feeding Behaviours (AFBs). The AFBs invariably lead to protein, fat and sugar deficits as well as a vitamin deficit which presents a positive correlation with the cognitive performance level and negatively affects the course of the disease. Thus it is important to identify AFBs (Blandford Scale) as soon as possible, especially when they can be treated. Furthermore it is very important to recognise weight loss immediately and identify a possible malnutrition state, using investigative methods which allow for follow-up monitoring (Mini Nutritional Assessment). Pharmacological therapy of cognitive deficit and AFBs together with possible contemporary conditions (depression) and intervention on the nutrition, will be useful to avoid a deficiency state and the consequent negative repercussion on the disease.
Aged↗
Fecal elastase 1 determination in chronic pancreatitis.
This study assessed the diagnostic accuracy of fecal elastase 1 in chronic pancreatitis. Fifty-three healthy subjects, 44 patients with chronic pancreatitis (22 severe, 13 moderate, and 9 mild), and 43 patients with nonpancreatic digestive disease were studied. Elastase 1 concentration was determined on a small sample of feces using a commercially available kit. Fecal chymotrypsin was also measured. With a cutoff level of 190 microg/g, all healthy controls except one (98.1%), and the majority of patients with nonpancreatic digestive diseases (40 of 43; 93.0%) had elastase values above this limit. Among the 44 patients with chronic pancreatitis, 34 (77.3%) had pathological values: all 22 (100%) with severe disease, 10 of 13 (76.9%) with moderate disease and 2 of 9 (22.2%) with mild disease. Chymotrypsin values were pathological in 25 of 44 (56.8%) patients with chronic pancreatitis: 17 of 22 (77.2%) with severe pancreatitis, 7 of 13 (53.8%) with moderate pancreatitis, and 1 of 9 (11.1%) with mild disease. The specificity was 95.8% for elastase 1 and 85.4% for chymotrypsin. The difference both in sensitivity and specificity of the two enzymes was statistically significant (P < 0.05). Fecal elastase 1 has a high sensitivity, superior to that of fecal chymotrypsin, in the diagnosis of chronic pancreatitis. For its simplicity and rapidity, it could represent the tubeless test of choice in chronic pancreatitis.
Adolescent↗
Plasma C-reactive protein in haemodialysis.
In recent years, acute phase reactants have been reevaluated as not merely biochemical markers of inflammation but also as active modulators of the inflammatory response. C-reactive protein - which is normally present in serum in only trace amounts, but whose concentration may rise markedly with inflammatory stimuli - was the first human acute phase protein discovered. It is now clear that cytokines are the major mediators of acute phase protein induction: interleukin-6 currently is felt to be the principal cytokine influencing C-reactive protein acute changes. Several studies have provided convincing evidence that among normal men, base-line serum levels of C-reactive protein are predictive of future myocardial infarction and ischemic stroke. The relevance of acute phase reactants in morbidity and mortality of haemodialysis patients has not been fully elucidated until now: in fact a few studies have implicated C-reactive protein in malnutrition, EPO-resistance, as a cardiovascular risk factor and as a marker of chronic stimulation in haemodialysis. The authors suggest the hypothesis of the occurrence of long-term complications in patients exposed to contaminated dialysate and suggest that back-filtration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminated dialysate.
C-Reactive Protein↗
Nitric oxide-dependent renal vasodilatation is not altered in rat with rHuEpo-induced hypertension.
BACKGROUND: Recombinant human erythropoietin (rHuEpo) is the treatment of choice in anemia associated with end-stage renal disease. Its major side effect is hypertension, which occurs in 8-30% of uremic patients. The exact mechanism of rHuEpo-induced hypertension has not been fully elucidated, and several possibilities have been proposed, such as a direct vascular effect of the drug with a shift in the balance of constrictor and relaxing endothelial factors (endothelins and nitric oxide (NO)). Recent papers suggested an enhanced rather than reduced activity of endogenous NO system in rats with normal renal function and rHuEpo-induced hypertension. Our study was designed to verify whether, in spite of enhanced activity of the renal NO system, rHuEpo may affect endothelium-dependent (acetylcholine-induced) and/or endothelium-independent (sodium nitroprusside-induced) vasorelaxation and to evaluate basal NO release by the infusion of NG-nitro-L-arginine methyl ester (L-NAME) in an isolated and perfused rat kidney model. METHODS: To investigate this hypothesis, we have determined systemic and renal NO activity in Wistar rats treated with a hypertensive dose of rHuEpo (150 IU/kg b.w. every other day for 2 weeks) by measuring stable NO metabolites (NO2+NO3) in the urine and have also evaluated variations in renal vascular resistance after the injection of Ach, SNP and the infusion of L-NAME. RESULTS: Hematocrit, hemoglobin concentration and arterial blood pressure were significantly increased in the treated group as compared with the controls. Urinary excretion of NO2+NO3 was significantly higher in treated than in the controls (438+/-66 vs. 294+/-36 nM/ml/min, p<0.01, respectively). There were no significant differences in the dose-response curves to Ach and SNP between the two groups. The renal vasoconstriction following the infusion of L-NAME was also similar in the two groups. CONCLUSIONS: The analysis of our results seems to indicate that the endogenous NO system activity was enhanced in rHuEpo-induced hypertension in rats with normal renal function and a resistance to NO was not developed in renal circulation. Further studies seem to be necessary to better clarify the exact mechanisms underlying the development of rHuEpo-induced hypertension.
Animals↗
Treatment of metastatic glucagonoma to the liver: case report and literature review.
Glucagonoma, a rare neuroendocrine pancreatic tumour, is frequently malignant and often accompanied by hepatic metastases. Our aim was to consider the different treatments of metastatic glucagonoma to the liver and their results. A case of glucagonoma with metachronous, small, multiple and bilobar liver metastases is reported. Combined treatment with octreotide and hepatic arterial chemoembolization was applied with good results in terms of symptom relief, plasma glucagon levels and regression of hepatic metastases. Survival rates were also improved. Based on our experience, glucagonoma with metachronous, multiple, diffuse and bilobar hepatic metastases should be treated with octreotide plus hepatic arterial chemoembolization with improved outcome and prognosis.
Antineoplastic Agents, Hormonal↗
L-propionyl carnitine reduces toxicity correlated to cyclosporine-induced intracellular ATP concentrations.
In previous trials we proved how propionyl carnitine, an acyl carnitine characterized by its intense mitochondrial metabolic, and cardio and vasoprotective activity, could prevent the cyclosporine-induced nephrotoxicity. Subsequently we also noted how propionyl carnitine could prevent the increase in renal intracellular calcium, which is the base of many cyclosporine-induced toxic phenomena. In our trials, we used the isolated and perfused rat kidney technique to examine if with the variations of the concentration of intracellular calcium, the adenosine 5'-triphosphate concentrations also varied, and if this decrease could be corrected by administrating propionyl carnitine. The results we obtained in these experiments indicated that when propionyl carnitine was administered preventively, the concentrations of renal intracellular adenosine 5'-triphosphate which were decreased by the cyclosporine returned to their normal values and, at the same time, a decrease in the increased vascular resistance of the kidney was noted. Therefore, propionyl carnitine corrected one of the biochemical alterations which explained the pathogenesis of the renal damage induced by cyclosporine.
Adenosine Triphosphate↗
Cyclosporine-induced lipid peroxidation and propionyl carnitine protective effect.
Cell and tissue lipoperoxidation of the kidney induced by cyclosporine through the release of reactive oxygen species has recently been pointed out to be one of the factors responsible for the toxic phenomena related to the administration of cyclosporine. Our previous research on propionyl carnitine had shown an antilipoperoxidative effect of this substance on isolated cells such as erythrocytes and leukocytes, and also on the endothelial, vasal and cardiac tissues. In the experiments presented herein we also examined if propionyl carnitine could carry out its already well-known antilipoperoxidative effect in the renal tissue, and if this mechanism could be taken into consideration in order to explain the protective effect of propionyl carnitine against cyclosporine induced toxicity. Trials were carried out on isolated and perfused rat kidneys, and we were able to observe that propionyl carnitine exerted a protective action on toxic lipid peroxidation phenomena induced by cyclosporine. The results we obtained, together with other mechanisms which we had already proved regarding the intense protective activity of propionyl carnitine on cyclosporine-induced nephrotoxicity, complete the complex picture that describes the protective activity of propionyl carnitine against cyclosporine toxicity.
Animals↗
Acute CYA-induced ATP depletion is prevented by pretreatment with L-propionylcarnitine in isolated and perfused rat kidney.
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Adenosine Triphosphate↗
Verapamil prevents cyclosporine-induced hypertension by modulating endothelin A receptor expression in rat kidney membranes.
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Animals↗
Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium.
Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.
Adult↗
Hyperinsulinaemia, regional adipose tissue distribution and left ventricular mass in normotensive, elderly, obese subjects.
Obesity is a metabolic condition, related to abnormalities of the glyco-insulinaemic metabolism, and plays a substantial role in the development of cardiovascular disease. The aim of this study was to establish a correlation among left ventricular mass, evaluated echocardiographically according to Penn Convention criteria, blood pressure, evaluated by ambulatory blood pressure monitoring, anthropometric indices for evaluation of body mass index and waist to hip ratio circumference, regional adipose tissue distribution, evaluated by ultrasound measurements of visceral adipose tissue, and insulin resistance, evaluated by hyperinsulinaemia by oral glucose tolerance test. We selected two groups of elderly male subjects well matched for age (68.5 +/- 6.4 years): 29 obese and 20 lean, with a body mass index, respectively, of 34.6 +/- 2.9 and 23.4 +/- 2.3. Statistical analysis was carried out by Student's t-test and linear regression analysis. In spite of the fact that statistical analysis showed a higher, though not statistically significant, systolic and diastolic mean blood pressure in the lean subjects, we found an increased left ventricular mass in obese subjects (P < 0.0001). The area under the insulin curve was higher in obese than in lean subjects (P < 0.0001) while the area under the glucose curve was not significantly different in the two groups. Furthermore, linear regression analysis showed that in obese subjects left ventricular mass was strictly correlated with visceral adipose tissue (r = 0.607; P < 0.0001) and hyperinsulinaemia (r = 0.615; P < 0.0001). In conclusion, our data suggest that centripetal adipose tissue distribution and hyperinsulinaemia, independent of blood pressure values, are closely correlated with left ventricular mass.
Adipose Tissue↗