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Biomedical subjects

M Migliori

Publications and source records attributed to M Migliori.

At least 55 records · Page 3Linked to original sources

Cytokine production in haemodiafiltration: a multicentre study.

BACKGROUND: Bacterial contamination of dialysate may enhance cytokine production in haemodialysis. We tested the hypothesis that intracellular cytokines could be enhanced in a large group of patients exposed to backfiltration of dialysate over a long period of observation. METHODS: The intracellular cytokine (interleukin-1 receptor antagonist and interleukin-1beta) concentrations in chronic uraemic patients undergoing haemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared to those found in patients treated with a modified haemodiafiltration modality without backfiltration (Group I, 16 patients), in patients shifted from one modality to the other (Group III, 27 patients) and in 10 patients on haemodialysis (Group IV) in a 1-year multicentre study. Group V comprised 10 healthy volunteers. All dialysis monitors were equipped with dialysate ultrafiltration systems. Dialysate contamination was studied by the LAL and the peripheral mononuclear cell/interleukin-1beta assays in the presence or absence of polymyxin B. RESULTS: Intracellular interleukin-1 receptor antagonist and interleukin-1beta both increased significantly (P < 0.002) but slowly (after 8 months) in Groups II vs I, and during the 4-month period in haemodiafiltration with backfiltration in Group III. The incidence of post/predialysis concentration ratio (over 1.5) increased two- to threefold in patients treated with haemodiafiltration with backfiltration with respect to haemodiafiltration without backfiltration. Results on the assays for LAL (< 0.5 E/ml) and interleukin-1beta (range 80.1-90.2 pg/5 x 10(6) cells; 70.2-81.3 pg/5 x 10(6) cells with polymyxin B) showed a moderate-to-low degree of dialysate contamination. CONCLUSIONS: Backfiltration of dialysate with moderate-to-low degree of contamination may enhance cytokine synthesis in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality and/or at reducing backfiltration is highlighted.

Adult↗

Slow-release lanreotide treatment in endocrine gastrointestinal tumors.

OBJECTIVES: Lanreotide is a somatostatin analogue whose activity persists for 10-14 days. In this study, we treated a group of patients with gastrointestinal endocrine tumors with lanreotide to assess its therapeutic efficacy and tolerability. METHODS: Eighteen patients, 12 male and six female, mean age 58 yr (range, 25-80 yr) were studied. Ten had carcinoid tumors, five had nonfunctioning endocrine tumors, two had glucagonomas, and the remaining one had a gastrinoma. All patients had somatostatin receptors, demonstrated by octreoscan scintigraphy. Lanreotide was administered intramuscularly at a dose of 30 mg every 10 days, for a mean of 12 months (range, 5-18 months). Fifteen of the 18 patients had been previously treated with octreotide. RESULTS: In patients with carcinoid tumors, lanreotide markedly reduced daily bowel movements and flushing episodes. A reduction was also observed in urinary serotonin and urinary 5-hydroxyindoleacetic acid, although it was not statistically significant. A marked reduction in symptoms, and in plasma glucagon and serum gastrin levels, was also observed in patients with glucagonoma and gastrinoma. In the five patients with nonfunctioning endocrine tumors, as in all the other 13 patients, no significant effects were noted in the size of the tumor. The administration of lanreotide did not cause side effects, apart from transient abdominal pain and pain at the injection site in two patients. Only in the patient with gastrinoma was lanreotide suspended, because of the appearance of attacks of marked hypoglycemia. In the 15 patients previously treated with octreotide, no differences in the effects were noted with lanreotide. CONCLUSIONS: Lanreotide has a satisfactory therapeutic efficacy and tolerability in the treatment of gastrointestinal endocrine tumors; its effects are similar to those of octreotide. However, unlike octreotide, it can be administered once every 10-14 days, instead of 2 or 3 times daily and for this reason, it is preferable in clinical practice.

Adult↗

Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in patients with predialytic renal failure.

Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality. Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective. In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance 22.9 +/- 9.8 ml; range 8-32 ml/min) were treated in a cross-over randomized design with oral daily calcitriol 0.5 micrograms/die (Treatment A), three oral boluses of 2 micrograms of calcitriol a week (Treatment B) and a single oral bolus of 2 micrograms of calcitriol a week (Treatment C). All treatment periods lasted three months and were followed by a wash-out period of one month. Serum iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance were measured every two weeks. Serum iPTH was also determined in a control group of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21 +/-12 ml/min) observed for three months without calcitriol treatment. Daily oral intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270 +/- 169 pg/ml to 135 +/- 76 pg/ml (p < 0.01; B) and to 165 +/- 121 pg/ml (p < 0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n.s.). No significant differences in renal function were observed during the different study periods. Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure.

Administration, Oral↗

Biocompatibility evaluation of polyamide hemofiltration.

INTRODUCTION: Postdilution hemofiltration with a polyamide membrane is a renal replacement technique widely used, but very little information is available regarding the biocompatibility of this treatment. In this paper we report the results of an acute study of the biocompatibility of polyamide hemofiltration. PATIENTS AND METHODS: Complement activation such as C3a and C5a Des Arg (RIA), granulocyte degranulation like alpha 1 elastase intradialytic increase (ELISA) and the expression of high affinity membrane receptors for IL-2 (anti-TAC) were determined. Beta 2-microglobulin (RIA) intradialytic decrease, as well as its convective removal, was evaluated. The nature of protein layer adsorbed onto the polyamide membrane, at the end of the dialytic session was investigated with a new immunohistochemical technique. Cell-associated cytokine concentration (like IL-1 beta and IL-1Ra - ELISA) was determined on mononuclear cell lysates. RESULTS: A low degree of complement activation was detected with the polyamide membrane when data were adjusted for hemoconcentration and for 1 m2 of membrane surface area. An important convective removal not only of Beta 2-microglobulin (258+/-20 mg/session), but also of the activated anaphylatoxins (225+/-76 ng/ml for C3a and 22.5+/-4 ng/ml for C5a) was revealed. A marked deposition of all coagulation factors with no detectable amount of immunoglobulins and complement factors was revealed on the polyamide membrane at the end of the dialytic session. No intradialytic (for IL-1beta) (from 14. 1+/-3.0 to 13.5+/-2.9 pg/2.5 x 10(6) cell) and interdialytic (for IL-1Ra) (from 4572+/-1076 to 5408+/-615 pg/2.5 x 10(6) cell) cell-associated cytokine expression was induced by hemofiltration. DISCUSSION AND CONCLUSION: Polyamide hemofiltration is a highly biocompatible technique due to the use of a synthetic membrane with a sterile reinfusion fluid and the convective removal of the activated anaphylatoxins and Beta 2-microglobulin.

Adult↗

Clinical value of pancreatitis-associated protein in acute pancreatitis.

OBJECTIVES: Pancreatitis-associated protein (PAP) is a secretory protein that is overexpressed by the pancreas during acute pancreatitis. This study was carried out to assess the clinical value of PAP in acute pancreatitis, particularly its ability to indicate the severity of the disease. METHODS: Twenty-one healthy subjects, 58 patients with acute pancreatitis, and 20 patients with nonpancreatic acute abdomen were studied. In addition to serum PAP concentration, serum concentrations of amylase, lipase, and C-reactive protein (CRP) were measured at admission and, in patients with acute pancreatitis, during the following 5 days. RESULTS: On admission, serum PAP concentrations were abnormally high in 46 of the 58 patients with acute pancreatitis (79%); serum amylase, in 57 patients (98%); serum lipase, in all patients (100%); and serum CRP, in 40 patients (69%). During the subsequent days of the study, PAP and CRP tended to increase, whereas amylase and lipase decreased. No significant differences in PAP or amylase and lipase concentrations were found between patients with mild pancreatitis and those with severe pancreatitis during the entire study period, whereas from the third day to the sixth day, CRP concentrations were significantly higher in patients with severe pancreatitis than in those with mild pancreatitis. Among the 20 patients with nonpancreatic acute abdomen, PAP concentrations were abnormally high in 10 (50%), whereas amylase concentrations were abnormally high in five (25%), and lipase concentrations were high in two (10%). CONCLUSIONS: Our results indicate that the clinical value of PAP in acute pancreatitis is quite limited and, in particular, that PAP is not a useful marker for determining the severity of the disease.

Abdomen, Acute↗

Preexpanded radial forearm free flap to the scalp.

The radial forearm flap is a versatile tool for the reconstructive surgeon because of its thinness, durable skin quality, aesthetic match, and relative ease of dissection. This flap is an ideal candidate for reconstruction of head and neck defects. One of the drawbacks is its relative small size, which may limit its use in certain applications. We describe the preexpansion of the radial forearm flap for its use in covering a large scalp defect. Preexpansion of the radial forearm free flap enables the reconstructive surgeon to increase the size of the flap markedly without altering its neurovascular anatomic relationships. Also described is the unexpected benefit of a periprosthetic capsule that covers the flexor tendons of the forearm and acts as an excellent bed for a skin graft.

Burns↗

Acute suppression of parathyroid activity during hemofiltration.

Hemofiltration (HF) induces a significant reduction in parathormone (PTH). This effect is related not only to the convective removal of PTH molecules but also to the biological suppression of parathyroid glands by plasma-ionized calcium (iCa) increase. The acute inhibitory effect on parathyroid gland activity, ionized calcium mass balance, phosphate kinetics and intact PTH (PTHi) dialytic removal during post-dilution polyamide HF were studied in 31 chronic uremic patients. HF ensures good phosphate removal (from 2.54 +/- 1.19 to 1.27 +/- 0.35 mEq/l; p < 0.01), a positive iCa mass balance (8 +/- 4 mmol/session) with a iCa plasma increase and negligible convective PTHi removal (9 +/- 2 pg/ml). Study of the PTHi profile during HF characterized two different parathyroid responses: 26/31 patients showed a physiological parathyroid gland response to the iCa increase (from 1.17 +/- 0.09 to 1.42 +/- 0.07 mmol/l; p = 0.002) with a significant PTHi decrease (from 123 +/- 111 to 35 +/- 28 pg/ml; p = 0.01) and a maximal PTH inhibition of 88%. In 5 patients, with more severe hyperparathyroidism, in spite of a comparable increase in iCa (from 1.28 +/- 0.12 to 1.46 +/- 0.08 mmol/l; p = 0.02), this physiological calcium-PTHi feedback was lost, revealing an autonomization of the gland (maximal inhibition of 45%). In our experience, study of the PTHi profile during a single HF session may represent a clinical test for the functional exploration of parathyroid glands, suggesting future (medical or surgical) clinical strategy.

Acute Disease↗

[The risk factors for pancreatic cancer].

This review summarises the current state of knowledge regarding the risk factors for pancreatic cancer. Of all the factors studied, only smoking is well established. Excessive dietary fat and protein may increase the risk, but this has not been proven conclusively. Fruits and vegetables, on the other hand, may offer a protective effect. The role of coffee remains controversial. There is no concrete evidence that alcohol, tea, occupational exposure, diabetes, gallstones, cholecystectomy or gastrectomy are significantly associated with this tumour. A possible predisposing role for chronic pancreatitis cannot be excluded.

Adult↗

[New etiopathogenic, clinical and therapeutic findings in multiple endocrine neoplasia type 1].

Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome comprises tumors or hyperplasia of different glands, including parathyroid, pituitary, adrenal cortex and the gastroenteropancreatic system. The vast majority of MEN 1 are found in familial clusters, although a few cases are sporadic. Hypercalcemia and/or nephrocalcinosis are the first and most common clinical manifestation in familial MEN 1 syndrome, followed by islet cell tumors (especially those secreting gastrin or insulin) and pituitary dysfunction due to either functioning or non-functioning microadenomas. Genetic studies indicate that familial MEN 1 syndrome is inherited through a dominant gene with incomplete penetrance and variable expression. The diagnosis of MEN 1 syndrome is mainly based on the careful assessment of the clinical history, symptoms physical evaluation along with the assay of serum electrolytes (i.e., calcium, phosphorus, etc.) and hormonal substances (i.e., gastrin, insulin, pancreatic polypeptide, prolactin, adrenocorticotropic hormone, etc.). In addition, several provocative tests have been used to identify endocrine tumors (particularly those of the gastroenteropancreatic system) and imaging techniques play a crucial role for the diagnostic approach in MEN 1 syndrome. Even though in the long term, the prognosis of MEN 1 syndrome is unfavourable. Recently, however, many therapeutic strategies, including both surgical and pharmacological options, have been developed to reduce the size of the neoplasm and control symptoms associated with hormone oversecretion.

Antineoplastic Agents, Hormonal↗

Antiplatelet activity of cis-resveratrol.

The anti-aggregating effect of cis-resveratrol (cis-3,4,5- trihydroxystilbene) has been evaluated in vitro in different concentrations on platelet-rich plasma from health volunteers. Cis-resveratrol at the concentration of 1 x 10(-5) and 1 x 10(-6) M was able to decrease collagen-induced platelet aggregation by 43.5 +/-11.4% and 26.8 +/- 14.6%, while trans-resveratrol at the same concentration showed a slightly lower activity. In view of the behaviour of these two isomers in biological fluids, the evaluation of resveratrol activity in animals and humans take into account the total amount of the two isomers.

Collagen↗

Antiplatelet activity of synthetic and natural resveratrol in red wine.

The antiaggregating effect of the phytoalexin resveratrol (3,4,5-trihydroxystilbene), alone or associated with red wine, and polyphenol have been evaluated in vitro at different concentrations on platelet-rich plasma from healthy volunteers. Resveratrol at the concentration of 3.56 micrograms/l was able to lower platelet aggregation by 50.3% +/- 1.83. Red wine containing 1.2 mg/l of natural trans-resveratrol and 3.6 milligrams of polyphenols diluted 1000-fold (final resveratrol concentration: 1.2 micrograms/l) inhibited platelet aggregation by 41.9% +/- 2.11. By adding resveratrol to the wine up to a concentration of 1.2 micrograms/l, inhibition was raised to 78.5% +/- 4.70. These results suggest that the antiaggregating activity of resveratrol is related to its concentration in wine.

Humans↗

Acute effects of calcitonin gene related peptide on renal haemodynamics and renin and angiotensin II secretion in patients with renal disease.

The renal haemodynamic effects and renin-angiotensin II response to calcitonin gene-related peptide (CGRP) infusion were assessed in 16 patients with moderate hypertension and renal insufficiency. CGRP lowered the systemic mean blood pressure by 13% and increased the heart rate by 25%; the glomerular filtration rate rose from 56 +/- 11 ml/min to 71 +/- 8 ml/min (p < 0.005), the renal plasma flow decreased from 369 +/- 19 ml/min to 342 +/- 25 ml/min (p < 0.002) and the filtration fraction increased from 15 +/- 0.2% to 20 +/- 0.2%. Plasma renin activity rose stepwise during the CGRP infusion from 1.28 +/- 0.5 ng/ml/h to 1.66 +/- 0.4 and 1.89 +/- 0.4 ng/ml/h (p < 0.001). Angiotensin II showed a marked increase after 10 min of infusion (91.6 +/- 47.00 pg/ml) (control value 6.01 +/- 3.09 pg/ml) and at the end (28.63 +/- 16.00 pg/ml) (p < 0.001). CGRP exerts an apparently favourable effect on renal function of patients with renal insufficiency, but the observed increase of glomerular filtration rate is obtained by an increase of intraglomerular pressure secondary to angiotensin II production.

Adult↗

Protein layer on hemodialysis membranes: a new immunohistochemistry technique.

In order to investigate the nature of the protein layer deposited on hemodialysis membranes we developed a direct immunohistochemical technique using fluoresceinated antibodies to plasma membranes. Fifteen patients on regular dialytic treatment were dialyzed with CU, HE, PAN, PS and PMMA and the dialyzers analyzed at the end of a standard dialytic session. Snap frozen sections of hollow fiber devices were treated with flourescein-isothiocyante conjugated antibodies for IgG, IgA, IgM C3c, fibrinogen, factor VIII, factor XIIIa-s, antithrombin III, fibrinogen degradation products (PDF) and plasminogen. Protein deposits were evaluated by a quantitative criteria, which evaluates the intensity of fluorescence and the area of the capillary wall occupied by this fluorescence by using an image analysis software. The coagulation cascade is activated by all membranes and similar deposits of these proteins were revealed, whereas important differences in C3c deposition were found.

Adsorption↗

Eliminant effects of calcitonin gene related peptide on the tubular epithelial cells in an isolated and perfused rat kidney.

The effect of the infusion of calcitonin gene related peptide (CGRP) on the renal structure and enzyme release from tubular epithelial cells was studied. This study was performed in the model of an isolated perfused kidney to avoid the systemic effects and complex hormonal and neuromediated interaction following the CGRP infusion in the intact experimental animal. After infusion of CGRP, the perfused kidney, studied by semiquantitative histology and electron microscopy, did not show any alteration at the glomerular level; however, important histological lesions were apparent at the proximal tubular level: the brush border was destroyed and the epithelial cells were markedly flattened. This structural damage to epithelial cells was confirmed by electron microscopy. The alanine amino peptidase (AAP) and N-acetyl-glucosaminidase (NAG) were significantly increased in the effluent of the perfusion system, in confirmation of the histological damage. The direct toxic effect of CGRP on the tubular epithelial cells may be related to the reabsorption and tubular transport of this substance.

Acetylglucosaminidase↗

Protective effect of L-propionylcarnitine on cyclosporine-induced nephrotoxicity.

Nephrotoxicity has represented the major limitation in the use of cyclosporine A (CyA). The structural abnormalities at the level of the proximal tubular cells are necrosis, vacuolisation and lipid droplets, as well as CyA-induced glomerular afferent arteriole constriction and granular juxtaglomerular cell hyperplasia. The mode of action of vasoconstriction is not well known, but there appears to be substantial impairment of endothelial cell function leading to enhanced release of vasoconstrictors such as endothelin and thromboxane. L-propionylcarnitine (PC), one of the most potent analogues of carnitine, is able to correct and to prevent alterations in endothelial membrane permeability and it has been identified in the kidney of various animal species. To investigate a possible reduction of CyA-induced nephrotoxocity, we examined the effects of a pretreatment with PC before administering several doses of CyA in an isolated and perfused rat kidney. The histological findings showed that the perfusion with PC reduces the vasoconstrictive effect of CyA on the glomerular capillaries and preserves the tubular epithelium. The ratio of the diameter between the glomerular capillary tuft and Bowman's capsule was higher, while at the tubular level the ratio internal-diameter/diameter evaluated at the level of the basal membrane was lower in PC + CyA perfused kidneys than in only CyA perfused ones. The final value of perfusion pressure was lower in PC + CyA perfused kidneys than in only CyA perfused ones, confirming the histological findings. The release induced by CyA of alanine aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG), markers of tubular damage, was significantly reduced by pretreatment with PC. These data suggest that the pretreatment with PC reduces the CyA-induced nephrotoxicity in an isolated and perfused rat kidney.

Analysis of Variance↗

Bronchoalveolar lavage and its role in diagnosing cobalt lung disease.

The bronchoalveolar lavage (BAL) of two groups of hard metal workers (11 subjects) were examined and compared with BALs of 14 unexposed individuals as controls. The first group of workers included five asymptomatic subjects (2 females and 3 males) with normal lung function tests and chest X-rays. All the workers had been exposed daily to hard metal dust for 5 years before fiberoptic bronchoscopy. The second group of workers included six individuals (1 female and 5 males) with cobalt lung disease at biopsy. The BAL's cytology at the deep lung level is in agreement with a possible immunologic pathogenesis of the lung disease, similar to hypersensitivity pneumonitis (lymphocytosis with helper-suppressor ratio reduction). In order to identify diagnostic key-parameters, the data presented here are compared with data reported in literature for workers with a history of hard metal or cobalt (alone) exposure. Although the BAL can be useful, for a better definition of the reaction at the deep lung level, it seems insufficient per se for the diagnosis of hard metal lung disease.

Adult↗

Cardiac function study in hard metal workers.

The induction of cardiac effects in hard metal workers is uncertain. This study investigates cardiac function of a group of 31 hard metal workers with or without pulmonary disease. The average duration of exposure to cobalt containing dusts was 10.4 years (range 1-30), while the environmental levels of cobalt exposure ranged from 0.09 to 13.6 mg/m3 Co. Cardiac function has been studied by: ECG (electrocardiogram), exercise test (ET), ECG 24 h according to Holter (ECGH), echocardiogram (ECHO) and radionuclide angiocardiography with 99Tc (RNA). The aims of this work were (i) to show the existence of cobalt myocardiopathy in the workers analyzed and, (ii) to find an early indicator of cardiac dysfunction which could be used in the clinical examination of hard metal workers. Within the group of patients with hard metal lung disease, cases of myocardiopathy of doubtful aetiology have been found. The cardiac indexes obtained through RNA show ventricular dysfunction in healthy hard metal workers which could be a manifestation of initial pulmonary artery hypertension or of an early occult cor pulmonale due to an unknown fibrotic lung disease.

Adult↗