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Biomedical subjects

A Secchi

Publications and source records attributed to A Secchi.

At least 73 records · Page 4Linked to original sources

Effect of low-dose dopamine on intestinal villus microcirculation during normotensive endotoxaemia in rats.

Hypoperfusion of the gut mucosa is thought to be a factor in the development of gut barrier failure during sepsis and septic shock. Dopamine stimulates DA-1 receptors which mediate regional vasodilatation in the gut. Therefore, we have investigated the effect of low-dose dopamine (3 micrograms kg-1 min-1) on the intestinal villus microcirculation during endotoxaemia in a rat model of normotensive endotoxaemia, using in vivo videomicroscopy. Blood flow in and the diameters of central villus arterioles were measured before, immediately after and 60 min after a 1-h continuous infusion of endotoxin 1.5 mg/kg body weight. After baseline measurements were obtained, rats received either an infusion of 0.9% saline (group A; n = 7) or a volume-equivalent infusion of dopamine 3 micrograms kg-1 min-1 (group B; n = 7) throughout the study. Control animals (group C; n = 7) received no endotoxin or dopamine. In group A, villus blood flow (mean baseline 8.4 (SEM 0.9) nl min-1) decreased by 29.7 (8.9)% to 5.9 (0.9) nl min-1 immediately after endotoxin challenge and by a total of 43.1 (7.3)% to 4.7 (0.7) nl min-1 after another 60 min. Simultaneously, villus arteriolar diameters decreased from 7.8 (0.2) to 6.9 (0.3) microns and to 6.5 (0.3) microns, respectively. In group B, villus blood flow (baseline 8.7 (0.4) nl min-1) was unchanged immediately after the 1-h infusion of endotoxin (8.3 (0.4) nl min-1). However, another 60 min later blood flow decreased by 28.8 (8.0)% to 6.1 (0.7) nl min-1. In contrast with group A, the diameters of the central villus arterioles were unchanged despite administration of endotoxin (7.9 (0.2) microns; 8.1 (0.4) microns; 8.2 (0.5) microns). In group C, there were no changes in villus blood flow or arteriolar diameters throughout the study. Our results indicated that low-dose dopamine did not prevent, but delayed and attenuated, the decrease in intestinal villus blood during normotensive endotoxaemia.

Animals↗

Dopexamine maintains intestinal villus blood flow during endotoxemia in rats.

OBJECTIVE: To determine the influence of dopexamine, a synthetic catecholamine ligand for dopaminergic and beta 2-adrenergic receptors, on alterations of the intestinal villus microcirculation in a model of normotensive endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar rats. INTERVENTIONS: Rats were treated with a continuous infusion of dopexamine (2.5 micrograms/kg/min; N = 7; group A) or 0.9% saline (n = 7; group B) during a study period of 120 mins. Both groups were given endotoxin (Escherichia coli lipopolysaccharide; 1.5 mg/kg Iv) over 60 mins. Animals in the control group (n = 7; group C) received a volume-equivalent infusion of 0.9% saline. Total volume substitution in all groups was 15 mL/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood flow in the intestinal villi of the distal ileum was determined using in vivo videomicroscopy at baseline, and 60 and 120 mins after the endotoxin challenge. These blood flow determinations were done by an observer who was unaware of the previous treatment of the animals. In addition, mean arterial pressure was monitored at baseline, and 15, 30, 45, 60, 75, 90, 105, and 120 mins later. The administration of 1.5 mg/kg endotoxin alone (group B) resulted in a reduction of the intestinal villus blood flow to 74.8 +/- 9.5% of baseline after 60 mins, and to 61.1 +/- 8.5% of baseline after 120 mins (baseline: 7.4 +/- 0.6 nL/min; 60 mins: 5.3 +/- 0.8 nL/min; 120 mins: 4.4 +/- 0.5 nL/min; p < .05). This reduction of blood flow was associated with a decrease in the arteriolar diameters by 13.8 +/- 2.5% after 60 mins, and by 17.1 +/- 4.3% after 120 mins (p < .05 vs. baseline). In contrast, villus blood flow in the dopexamine group (group A) did not show statistically significant changes during the entire study period, despite the administration of endotoxin (baseline: 8.2 +/- 0.6 nL/min; 60 mins: 7.3 +/- 0.8 nL/min; 120 mins: 7.8 +/- 0.5 nL/min). No vasoconstriction of the villus arterioles was noted in this group. In control animals (group C), the blood flow (baseline: 8.1 +/- 1.6 nL/min; 60 mins: 7.6 +/- 1.4 nL/min: 120 mins: 7.8 +/- 1.4 nL/min) and the arteriolar diameters remained unchanged throughout the observation period. Mean arterial pressure did not differ between groups: it remained unaltered in all groups during the entire study period. CONCLUSIONS: Dopexamine maintains intestinal villus arterial perfusion and prevents the vasoconstriction in villus arterioles during early normotensive endotoxemia. Therefore, further studies in critically ill patients will have to determine whether the early prophylactic use of dopexamine can limit ischemia and prevent the development of multiple organ failure.

Adrenergic beta-Agonists↗

Lipoprotein profile after combined kidney-pancreas transplantation in insulin dependent diabetes mellitus.

In order to evaluate the effect of a combined kidney-pancreas (KP) transplantation in insulin-dependent diabetes mellitus (IDDM) patients on the lipid and lipoprotein profile, 15 KP patients were compared with 11 kidney (K)--transplanted IDDM patients, 19 IDDM patients on hemodialysis (HD), and 15 nondiabetic control subjects. Cholesterol, triglycerides, apo AI, and apo B were measured in total plasma and in VLDL, LDL, and HDL of all participants. VLDL cholesterol, VLDL-triglycerides, and VLDL-apo B were significantly lower in KP patients, but not in K patients, than in HD patients. In addition, patients in the K, but not in the KP, group showed high levels of apo B in LDL and an increased triglyceride/apo B ratio in VLDL, compared with patients in the HD group. The percentage of apo AI associated with HDL was significantly higher in both transplanted groups than in the HD group. However, compared with a nondiabetic control population, an increase in VLDL particles and in triglyceride content in LDL and HDL still persisted following combined KP transplantation. Insulin resistance (probably due to steroid therapy) associated with high peripheral and potentially low hepatic insulin levels (due to the systemic drainage of the transplanted pancreas) could be the main causes of the remaining lipoprotein abnormalities.

Adult↗

A sensitive and reliable method for assaying true human insulin without interaction with human proinsulin-like molecules.

In the present study our interests focused on the evaluation of a high capacity assay (MEIA) which allows true insulin determinations in the absence of cross-reactivity with proinsulin-like molecules. This method was compared to a commercially available radioimmunoassay (RIA) for insulin determination. As the latter gives insulin levels which represent a mixture of insulin and proinsulin-like molecules, the proinsulin-like molecules were quantitated by subtracting the true insulin levels measured using MEIA from the total insulin levels obtained using RIA. These methods were applied for the analysis of blood samples drawn in 63 normal subjects, 16 obese subjects, 3 patients submitted to islet transplantation and 4 patients with insulinoma. The MEIA was precise, fully automated and time-saving, making its application on a routine basis particularly attractive. MEIA and RIA were equally able to correctly quantify human insulin molecules. On the contrary, the antibody present in the true insulin assay did not interact with proinsulin-like molecules, which were recognized even in the presence of increasing insulin levels. In normal subjects, the true and total insulin levels in the fasting state and at the time peak after glucose- or arginine-induced endogenous insulin release were well correlated at r = 0.88 and 0.89, respectively. Interestingly, total insulin values were overestimated by 10%-16% as compared with true insulin levels, which represent proinsulin values superimposable on previously reported data. Proinsulin-like molecules made up 50% of the total insulin in obese and transplanted patients, and about 70% in patients with insulinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation.

The aim of the study was to evaluate whether the cephalic phase of insulin release is still present in patients submitted to simultaneous kidney and pancreas transplantation. Subjects were five kidney-pancreas-transplanted patients (group P) and five control (group C). The experimental protocol lasted 30 minutes, and blood samples were collected at 1-minute intervals. After a 20-minute period of steady-state fasting (premeal period), subjects received a palatable standard meal (pizza). Samples were collected over the subsequent 10 minutes (meal period). No evidence of an increase in serum free insulin, serum C-peptide, and plasma glucagon during food ingestion was observed in group P whereas the test was effective in eliciting cephalic-phase insulin and glucagon release in group C. Gastric inhibitory polypeptide and somatostatin did not show any variation during the test in both groups. In conclusion, the absence of cephalic-phase insulin and glucagon release in group P could be explained by denervation of the grafted pancreas. This early alteration could contribute to the impairment in glucose tolerance frequently observed in successfully pancreas-transplanted patients.

Adult↗

Eosinophil cationic protein in tears of normal subjects and patients affected by vernal keratoconjunctivitis.

The objectives of this study were to determine: 1) levels of tear eosinophil cationic protein (ECP) in patients with vernal keratoconjunctivitis (VKC); 2) the effect of pharmacologic therapy on ECP release; and 3) the correlation of this mediator with the severity of the disease. Tears were collected from 10 controls and 20 VKC patients before and after therapy for cytologic analysis and ECP measurement by radioimmunoassay. Ocular signs and symptoms were evaluated before tear collection. Mean ECP levels in controls were 7.5 +/- 0.4 microgram/l, and in VKC patients, 988.3 +/- 128 micrograms/l before therapy (P < 0.001) and 566.3 +/- 121 micrograms/l after therapy (P < 0.005). In dexamethasone (Dex) 0.1% or cyclosporin A (CsA) 2% patients (five per group), tear ECP decreased significantly after 7-14 days of treatment. Disodium cromoglycate (DSCG) 4% (five patients) for 14 days did not significantly affect ECP levels. ECP levels were significantly correlated with allergic signs (P < 0.001), symptoms (P < 0.001), and the number of eosinophils in tears (P < 0.005). The results of this study suggest that tear ECP levels accurately reflect the clinical status of VKC patients. The measurement of ECP may prove useful not only in the diagnosis and monitoring of allergic disease, but also as an objective parameter for the evaluation of new antiallergic therapies.

Adolescent↗

Effects of personality on metabolic control in IDDM patients.

OBJECTIVE: The aim of this study was to evaluate the relationship between poor metabolic control and maladaptive personality traits (according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised) in an adult-onset insulin-dependent diabetes mellitus sample group (n = 77). RESEARCH DESIGN AND METHODS: Metabolic control was evaluated through glycosylated hemoglobin (HbA1c). Personality traits were assessed with the Personality Diagnostic Questionnaire-Revised, a self-administered questionnaire. Residual pancreatic secretion (fasting serum C-peptide) was also evaluated. RESULTS: Principal components analysis revealed three personality profiles: "withdrawn-suspicious" (P1), "dramatic-dependent" (P2), and "aggressive-irresponsible" (P3). Multiple linear regression analysis showed that C-peptide levels and P2 personality profiles were significant and independent predictors of HbA1c plasma levels: P2 predicted high HbA1c values and C-peptide predicted low HbA1c levels. CONCLUSIONS: These data suggest that a P2 personality profile is a significant predictor of poor metabolic control.

Adult↗

Lacrimo-auricolo-dento-digital syndrome mimicking primary juvenile Sjögren's syndrome.

We describe a 24 year old female patient affected with symptoms of severe xerostomia and keratoconjunctivitis sicca since her childhood. She also had several malformations involving face and digits as well as cup shaped ears, enamel dysplasia and absence of lacrimal puncta. Hence, the diagnosis of Lacrimo-Auricolo-Dento-Digital (LADD) syndrome was made. The main differences between this rare, inherited disease and primary juvenile Sjögren's syndrome are pointed out.

Abnormalities, Multiple↗

Effect of anti-tumor necrosis factor alpha on leukocyte adhesion in the liver after hemorrhagic shock: an intravital microscopic study in the rat.

Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. At 1 and 5 h after resuscitation, intravital microscopy of the liver was performed after injection of acridine orange as marker of leukocytes in sham-control animals and in shock animals pretreated with anti-TNF monoclonal antibody (2 mg/kg b.w. TN3; Celltech, Slough, UK) or NaCl .9% 2 h prior to shock induction, respectively. At constant systemic hemodynamic conditions in all groups (e.g., normal MAP), sinusoidal diameters and sinusoidal blood flow were comparably decreased to approximately 75% of control values in all shock groups. Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S.E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Persistence of counter-regulatory abnormalities in insulin-dependent diabetes mellitus after pancreas transplantation.

Conventional insulin therapy does not correct the counter-regulatory abnormalities of insulin-dependent diabetes mellitus. Pancreas transplantation is an alternative therapy that restores the endogenous insulin secretion in diabetes. In this study, the effects of segmental pancreas transplantation on counter-regulation to mild hypoglycaemia were evaluated. Glucose kinetics and the counter-regulatory hormonal responses were assessed in eight insulin-dependent diabetics with end-stage renal failure who had received pancreas and kidney transplantation 1 year previously, seven diabetic uraemic subjects (candidates for combined transplantation), five patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients and 10 normal subjects. Insulin (0.3 mU kg-1 min-1) was infused for 2 h to induce mild hypoglycaemia (plasma glucose 3.2-3.5 mmol l-1) and exogenous glucose was infused as required to prevent any glucose decrease below 3.1 mmol l-1. After transplantation, two of eight recipients had hypoglycaemic episodes reported in their medical records. During the study, hepatic glucose production was rapidly suppressed in the controls and in the patients on immunosuppression (-80 +/- 7 and -54 +/- 7%, P < 0.001 vs. basal), and rebounded to the baseline values within 1 h (-3 +/- 1 and -6 +/- 2%, P = NS vs. basal). The transplant recipients had similar suppression in the first hour (-88 +/- 8%, P < 0.001 vs. basal), but the suppression persisted in the second hour (-69 +/- 11%, P < 0.001 vs. basal) indicating a lack of glucose counter-regulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Combined pancreas and kidney transplantation normalizes protein metabolism in insulin-dependent diabetic-uremic patients.

In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8 +/- 2.8 vs. 6.8 +/- 1.1 microU/ml, P < 0.01) (107 +/- 17 vs. 41 +/- 7 pM); (b) reduced plasma leucine (92 +/- 9 vs. 124 +/- 2 microM, P < 0.05), branched chain amino acids (BCAA) (297 +/- 34 vs. 416 +/- 10 microM, P < 0.05), endogenous leucine flux (ELF) (28.7 +/- 0.8 vs. 39.5 +/- 0.7 mumol.m-2.min-1, P < 0.01) and nonoxidative leucine disposal (NOLD) (20.7 +/- 0.2 vs. 32.0 +/- 0.7 mumol.m-2. min-1, P < 0.01); (c) similar leucine oxidation (LO) (8.0 +/- 0.1 vs. 7.5 +/- 0.1 mumol.m-2.min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116 +/- 5 and 107 +/- 9 microM), ELF (38.1 +/- 0.1 and 38.5 +/- 0.9 mumol.m-2.min-1), and NOLD (28.3 +/- 0.6 and 31.0 +/- 1.3 mumol.m-2.min-1) (P = NS vs, CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P < 0.05), BCAA (38% vs. 47%, P < 0.05), ELF (28% vs. 33%, P < 0.05), and LO (0% vs. 32%, P < 0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P < 0.05 vs. CON) by insulin. Combined kidney and pancreas transplanation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9 +/- 0.7 vs. 36.1 +/- 0.8 mumol.m-2.min-1, P < 0.01 compared to CON), which was normalized by transplantation (44.3 +/- 0.8 mumol.m-2.min-1).

Adult↗

Simultaneous kidney and pancreas transplantation at the San Raffaele Scientific Institute: clinical experience and results.

Pancreas and kidney transplantation is performed in uremic IDDM patients to cure end-stage renal failure and diabetes. Seventy-two simultaneous kidney-pancreas transplantations were performed at our Institution between July 1985 and November 1994. All transplants were performed using heart-beating cadaver donors. The first 25 patients received 26 segmental pancreas according to Dubernard (KPS), whereas the last 46 patients received a whole, bladder-drained pancrea according to Sollinger (KPW). Mean pancreas cold and warm ischemia times were 294 +/- 14 and 44 +/- 2 minutes, respectively, in the KPS group and 660 +/- 37 and 40 +/- 8 minutes, respectively, in the KPW group. Twelve (48%) KPS patients and 19 (41%) KPW patients had postoperative pancreas surgical complications: vascular thrombosis led to graft failure in 5 KPS patients (20%) and 2 KPW patients (4%) (p = 0.01). Pancreatic fistula, hemorrhagic complications, and duodenum-bladder leakage were the surgical complications observed more frequently. Six KPS patients (24%) and 8 KPW patients (17%) underwent reintervention as a consequence of surgical complications. Fifteen KPS patients (60%) and 30 KPW patients (65%) experienced an acute kidney rejection episode, which was steroid-resistant in 14 KPW and 2 KPS patients. The actuarial survival rates for simultaneous kidney-pancreas recipients at one and 4 years were 92% and 84%, respectively, for KPS recipients, and 95% and 88%, respectively, for KPW patients. Kidney actuarial survival rates at one and 4 years were 96% and 76% respectively, for group KPS, and 93% and 89%, respectively, for KPW patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗