Search PubMed⌕ Search

Biomedical subjects

A Piccoli

Publications and source records attributed to A Piccoli.

At least 55 records · Page 3Linked to original sources

Effect of aprotinin on insulin sensitivity in non-insulin-dependent diabetes mellitus.

It has been suggested that kallikrein-kinin system may influence carbohydrate metabolism via a kinin-mediated increment of insulin-mediated glucose uptake. To evaluate the effect of acute inhibition of the kallikrein-kinin system on insulin sensitivity, a randomized, placebo-controlled, double-blind study was performed in 15 male non-insulin-dependent diabetic patients. After basal evaluation of insulin sensitivity with a 2-h euglycaemic hyperinsulinaemic clamp (40 mU m-2 min-1), patients were infused either with aprotinin (200,000 U.I.C. as intravenous bolus injection) or placebo (10 ml isotonic saline) in a cross-over fashion, at 1 week intervals. After both saline and aprotinin infusions, insulin sensitivity was reassessed by continuing the euglycaemic hyperinsulinaemic clamp for a further 1 h. Resulting data showed that aprotinin significantly improved total glucose uptake (from 16.2 +/- 2.9 mumol kg min-1 to 20.6 +/- 4.9 mumol kg min-1 p < 0.01), and decreased metabolic clearance rate of insulin (from 586 +/- 57 ml m-2 min-1 to 442 +/- 155 ml m-2 min-1, p < 0.05). Thus, in spite of the suggested positive effects of kinins on insulin-mediated glucose uptake, acute inhibition of the kallikrein-kinins system resulted in a paradoxical increment of insulin sensitivity, which was probably mediated by the reduced metabolic clearance rate of insulin.

Adult↗

Survival after resection for ductal adenocarcinoma of the pancreas.

A retrospective study was performed of 113 patients who underwent surgical resection of carcinoma of the pancreas from 1970 to 1992. The postoperative mortality rate was 15 per cent (5 per cent in the last 11 years). The actuarial 5-year survival rate was 12 per cent. Survival was significantly influenced by age (P = 0.03), vascular resection (P = 0.02), radicality of operation (P = 0.01), number of transfused blood units (P = 0.01), tumour differentiation (P = 0.002), lymph node status (P = 0.001), perineural invasion (P = 0.01), tumour size (P = 0.008), preoperative diabetes (P = 0.001) and stage (P = 0.0001). Multivariate analysis showed that stage, diabetes, age and grade were independent predictors of long-term survival. The type of pancreatic resection (Whipple, subtotal, total or distal pancreatectomy) did not influence prognosis. The 5-year survival rate was 14 per cent in the period 1970-1981 and 11 per cent in the period 1982-1992, with no statistical difference. These results suggest that patient characteristics and tumour findings rather than operative procedures affect long-term survival after resection for pancreatic carcinoma.

Adult↗

Trends in immunoglobulin G anticardiolipin antibodies in ten successful heparin-treated pregnancies.

The pregnancies of ten women, all with histories of at least two spontaneous abortions of unknown cause, were followed. All patients were positive for immunoglobulin (Ig) G anticardiolipin antibodies (aCL) and one also for IgM aCL, while none had lupus anticoagulant activity. During pregnancy, the patients were treated with calcium heparin in doses varying between 15,000 and 30,000 IU daily. IgG aCL were assayed on average at the 9th, 17th, 24th and 29th weeks of pregnancy and at the moment of delivery. Mean values of IgG aCL levels during the 10 pregnancies steadily fell as the pregnancies progressed, and this decrease was significant (r = 0.985, P = 0.002). All pregnancies terminated favourably, although delivery was brought forward in eight patients and six of the nine placentas examined showed signs of thrombotic events. We assume that a steady fall in IgG aCL levels during pregnancy may be considered as indicative of a favourable outcome.

Adult↗

Low molecular mass proteins and urinary enzymes in amniotic fluid of healthy pregnant women at progressive stages of gestation.

OBJECTIVES: Amniotic fluid alpha1-microglobulin (alpha1-m) and beta2-microglobulin (beta2-m) levels, as well as N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities, were measured in the course of uncomplicated pregnancies to assess their variations as gestation progresses. DESIGN AND METHODS: Samples were obtained from 141 healthy pregnant women divided into three groups on the basis of gestational stage. Quantitative estimation of proteins was performed immunometrically and enzyme activities were determined spectrophotometrically. RESULTS: It was found that, during pregnancy, alpha1-m and beta2-m concentrations as well as AAP activity significantly decrease, although their reduction patterns vary. Controversial results were found for NAG activity: the normalization of values for amniotic fluid creatinine significantly changed the reduction pattern of this enzyme. No statistically significant differences were found between male and female fetuses for amniotic fluid values of the biochemical substances studied. CONCLUSIONS: The behavior observed for alpha1-m, beta2-m, and AAP might be linked to the progressive development and maturation of fetal renal tubular function. Amniotic fluid total NAG activity seems not to depend only on fetal urinary excretion.

Acetylglucosaminidase↗

Arthroscopic synovectomy in rheumatoid and psoriatic knee joint synovitis: long-term outcome.

A long-term prospective study was performed to evaluate the safety and long-term outcome of surgical arthroscopy (AS) for persistent rheumatoid (RA) and psoriatic (PsA) knee joint synovitis (KJS). Local signs of joint inflammation (tenderness, swelling, "ballottement') and range of motion (ROM) were scored and the sum, taken as a global outcome measure, was recorded in 17 RA and 18 PsA knees, both before and at follow-up periods of 2, 6, 12, 24 and 36 months after surgical AS (knee joint synovectomy; meniscal curettage, cartilage shaving or chondrectomy, according to the degree of cartilage damage). A survival analysis (Kaplan-Meier) of the long-term outcome of surgical AS treatment and of the predictive value of clinical parameters of knee joint involvement was also performed. No intra- or post-operative morbidity, pain worsening or loss of joint motion was observed and all patients were discharged within 48 h. Comparison of the parameters of knee joint evaluation showed a significant reduction of the signs of joint inflammation and a significant increase in the ROM in all follow-up periods. At 36 months, the survival curves showed a 61.2% cumulative probability of clinical remission and 72.8% of definite improvement. No significant differences in the prognostic importance of RA, compared to PsA diagnosis, were observed, although higher percentages of PsA compared to RA knees (86.3% and 45.7% respectively) reached the end point of clinical remission at 36 months. KJS duration, radiographic severity and cartilage damage were not predictors of poor long-term outcome of AS synovectomy. Surgical AS treatment for PsA knees with more advanced cartilage damage gave a better long-term outcome. A total of 50.7% of operated knees reached the end point of a KJS relapse at 36 months, the majority (82%) within the initial 18 months of follow-up. Our study indicates that AS synovectomy is a safe procedure requiring short hospitalization which, in combination with second-line medical treatment, can reduce local inflammation in RA and PsA KJS, and preserve knee joint ROM for up to 3 yr.

Adult↗

A new method for monitoring hydration at high altitude by bioimpedance analysis.

Our study evaluated the performance of a graphical method for monitoring the fluid variation at high altitude in seven adult Caucasian male subjects (average age 25 yr, average height 177 cm). The graphical approach is called the Resistance-Reactance (RXc) graph method and is based on standard bioimpedance analysis (tetrapolar, 50 kHz frequency). Measurements were taken at sea level before the expedition, at 5050 m after 1 wk and 3 wk, and again at sea level after descent. Plasma and urine electrolytes, osmolalities, and the free-water clearance were determined by standard methods. All climbers had baseline impedance vectors within the reference 95% tolerance ellipse for the Italian male population. The high altitude dehydration caused a significant lengthening of vectors, which after descent underwent a significant shortening and returned close to the baseline values. Average urine volume increased by 1.4 l.d-1 in the first week and average body weight decreased by 4.4 kg after 3 wk. The RXc graph method could be useful in the planning of the individual climber's appropriate dehydration and fluid intake at altitude since a feedback control of the hydration is allowed without any assumption of body composition.

Acclimatization↗

Photosensitivity in systemic lupus erythematosus: laboratory testing of ARA/ACR definition.

OBJECTIVE: The aim of our study was to evaluate the prevalence of photosensitivity in SLE as defined by either clinical or laboratory assessment, the concordance of findings obtained by two methods, and the relationship between photosensitivity and clinical and immunological parameters. METHODS: Forty-four SLE patients and 31 healthy subjects were included. Patients and controls underwent a standard questionnaire testing and the minimal erythemal dose (MED) measurement performed by Dermalight-Blue Point. The standard questionnaire was designed in order to meet, as near as possible, the definition of photosensitivity included in the ARA/ACR criteria for classification of SLE. RESULTS: The prevalence of photosensitivity was (patients vs controls): 57% vs 45% according to questionnaire; 79.5% vs 51.6% (P = 0.02) according to MED. The agreement between questionnaire and phototest was absent in SLE (kappa 0.01) and poor in controls (kappa 0.36). Discoid rash was significantly associated with questionnaire positive (P = 0.01) and renal involvement with questionnaire negative results (P = 0.02), serositis with MED abnormality (P = 0.03), malar rash and anti-Sm antibody with MED normal values (P = 0.03 and P = 0.01), respectively). Moreover, by multivariate analysis, malar rash and anti-Sm antibody significantly predicted MED-defined photosensitivity, with probability ranging from 42% (presence of both) to 92% (lack of both). CONCLUSIONS: Photosensitivity is frequently observed in SLE patients as well as in healthy subjects. Its prevalence is significantly higher in SLE than in controls only when it is detected using the laboratory method. However, due to the difficulty in objectively defining such manifestation, the disagreement between questionnaire and MED results was high and its clinical meaning appears ambiguous. Thus, the use of photosensitivity as a classification criterion for SLE remains questionable, at least when it is assessed according to the ARA/ACR definition.

Adolescent↗

The abnormal red-cell oxalate transport is a risk factor for idiopathic calcium nephrolithiasis: a prospective study.

An abnormal erythrocyte transmembrane oxalate flux was described in recurrent idiopathic calcium nephrolithiasis. To verify whether it might represent a risk marker of renal stone disease, two prospective studies were carried out. One hundred ninety patients with idiopathic calcium nephrolithiasis who were enrolled at their first episode of lithiasis during the period 1984 to 1986, form the basis of the first prospective study. The impact of erythrocyte oxalate transport anomaly, gender, familial occurrence of nephrolithiasis, hypercalciuria, hyperoxaluria, and hyperuricosuria on stone recurrence by both bivariate and multivariate analysis of frequencies was assessed. The predictive value of the erythrocyte anomaly for a patient's becoming a stone former was also assessed in five nephrolithiasis families. Recurrence occurred in 57.9% of patients; this was significantly associated with the erythrocyte anomaly, hyperoxaluria, and male gender. However, when using multivariate analysis, only gender and the erythrocyte anomaly were statistically significant and were independent predictors of recurrency. The probability of stone recurrency predicted by the logistic model ranged from 30.1% for women with normal erythrocyte oxalate transport, to 73.4% for men with the erythrocyte anomaly. The family follow-up showed that only subjects with the erythrocyte abnormality become renal stone-formers in the 8-yr survey. By showing the predictive value of the erythrocyte oxalate anomaly for recurrent calcium nephrolithiasis, our findings support the notion that this anomaly is a risk factor in renal stone disease.

Adolescent↗

Circulating catecholamines and metabolic effects of captopril in NIDDM patients.

OBJECTIVE: To evaluate the effects of captopril on circulating catecholamine levels in NIDDM patients and the possible relationship between captopril-related changes in circulating catecholamine levels and insulin sensitivity. RESEARCH DESIGN AND METHODS: Fourteen nonobese normotensive NIDDM men (aged 44.5 +/- 5.1 years) underwent a 2-h euglycemic-hyperinsulinemic clamp (40 mU.m-2.min-1). Baseline evaluation of insulin sensitivity was followed by the random assignment of each patient to either captopril or placebo treatment, according to a crossover double-blind design. Euglycemic-hyperinsulinemic clamp studies were then repeated for all patients after both placebo and captopril treatments. Plasma norepinephrine (NE) and epinephrine (E) levels were assessed before, during, and after each clamp. RESULTS: Resulting data showed that plasma catecholamine levels increased during baseline euglycemic-hyperinsulinemic clamp (NE: +23.6% time 0 vs. time 120 min, P < 0.05; E: +24.8% time 0 vs. time 120 min, P < 0.05). Captopril treatment significantly increased total glucose uptake (from 19.0 +/- 9.0 to 26.8 +/- 10.1 mmol.kg-1.min-1, P < 0.05) and reduced baseline plasma NE (P < 0.001) and E (P < 0.05) levels. However, the magnitude of the NE (+25.7% time 0 vs. time 120 min, P < 0.001) and E (+27.2% time 0 vs. time 120 min, P < 0.05) increments during euglycemic hyperinsulinemia were not affected by the drug. Percentage changes in the ratio of total body glucose uptake to circulating insulin levels and corresponding decrements of baseline plasma E levels after captopril therapy were negatively correlated (r = -0.57, P < 0.05). CONCLUSIONS: The reduction of circulating catecholamines could contribute, at least in part, to the captopril-related amelioration of insulin sensitivity.

Adult↗

Body fluid overload and bioelectrical impedance analysis in renal patients.

Using a new bivariate vectorial approach to the standard bioimpedance analysis (tetrapolar, 50-kHz frequency), we evaluated the performance of a graphical method for the identification of patients with fluid overload. Two hundred and seventeen adult Caucasian subjects were divided into four classification groups: 86 healthy control subjects, 55 patients with mild-to-terminal chronic renal failure in conservative treatment (15% with apparent edema), 36 patients with idiopathic nephrotic proteinuria (58% with apparent edema), and 40 obese subjects. We found a bioimpedance threshold for apparent edema on the lower pole of the sex-specific 75% tolerance ellipse (bivariate tolerance interval) of the healthy population. This innovative graphical method allows identification, monitoring and therapy planning of patients with fluid overload using direct bioimpedance measurements without any assumption on body composition.

Adolescent↗

Thrombin-activated human platelets release two NAP-2 variants that stimulate polymorphonuclear leukocytes.

Thrombin-activated human platelets release substance(s) of a proteic nature which induce an increase in the intracellular calcium concentration in polymorphonuclear leukocytes (PMN). Aim of this study was to characterize the platelet released product(s) responsible for PMN stimulation. PMN-stimulating activity was isolated from platelet supernatant by FPLC and HPLC. The N-terminal sequence analysis revealed that the purified fractions consisted in 90% of a peptide of 73 amino acids and in 10% of a peptide of 74 amino acids; both are truncated forms of the connective tissue-activating peptide III (CTAP-III), a platelet alpha-granule product, and have 3 and 4 additional amino acids at the N-terminus compared with the neutrophil-activating peptide 2 (NAP-2): Asp-Leu-Tyr and Ser-Asp-Leu-Tyr, respectively. Treatment of platelet supernatant (previously depleted of PMN-activating nucleotides) with Affi-gel heparin resulted in the disappearance of PMN-stimulating effects, suggesting that NAP-2 variants, which are heparin-binding proteins, account for ATP-independent PMN-stimulating activity of the supernatant. Cross-desensitization between rNAP-2 and the platelet supernatant and inhibition by the anti-NAP-2 antibody are in agreement with this conclusion. Although NAP-2 and its variants are reportedly generated from the inactive precursors, CTAP-III and platelet basic protein, through a proteolytic cleavage, NAP-2 variants were not generated in our system by proteases deriving from platelets or contaminating leukocytes. Indeed, treatment of intact platelet suspensions with different protease inhibitors failed to modify the calcium stimulating activity of the resulting supernatants. In conclusion, thrombin-activated platelets release NAP-2 variants which are not generated outside the platelets by proteolytic processing but are released in an active form. This finding enhances our understanding of platelet-PMN interaction in thrombosis and inflammation.

Blood Coagulation Factors↗

Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo.

Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction could play a significant role in the development of atherosclerotic lesions in hyperinsulinemic conditions.

Adult↗

A decision analysis comparing three dosage regimens of subcutaneous epoetin in continuous ambulatory peritoneal dialysis.

Epoetin (recombinant human erythropoietin; EPO) therapy adds a significant cost to the management of end-stage renal disease, the majority of the extra expense being attributable to its acquisition cost. In a Japanese multicentre, randomised, prospective study, a significant dose-dependent response was documented with epoetin given subcutaneously (SC) once a week or once every 2 weeks to patients receiving continuous ambulatory peritoneal dialysis. Three different dosages were studied over 5 months in patients with a haematocrit (Hct) of 0.28 or less, namely 6000U (107 U/kg), 9000U (167 U/kg) and 12,000U (211 U/kg). Epoetin was given weekly for the first 2 months until the target Hct value of 0.33 was reached. The rates of response were 81, 85 and 100% with the 6000U, 9000U and 12,000U regimens, respectively. Subsequently, responders were maintained at the target Hct for an additional 3 months, with the administration frequency eventually being reduced to fortnightly or 4-weekly. Patients in the epoetin 6000U and 9000U groups who did not respond after 2 months' treatment underwent induction and maintenance with the 12,000U regimen. During the maintenance phase, patients receiving the epoetin 6000U and 9000U dosages required weekly (54 and 64%, respectively) or fortnightly (46 and 36%, respectively) injections. Patients receiving the 12,000U regimen were found to require weekly (9%), fortnightly (73%) or 4-weekly (18%) injections. Using these data, we performed a decision analysis that quantitatively incorporated the probability of attaining and maintaining target Hct levels in all patients (i.e. the effectiveness of epoetin), and direct costs as a function of both cumulative doses and injections required in all 3 strategies over 5 months. Decision analysis indicated that the most cost-effective SC epoetin strategy in patients undergoing peritoneal dialysis is epoetin 6000U weekly for 2 months, followed by maintaining the target Hct with weekly or 2-weekly epoetin 6000U for the next 3 months. Nonresponders should restart epoetin therapy using the 12,000U strategy. The 9000U and 12,000U strategies were associated with similar costs, because the economic advantages associated with the lower administration frequency of the 9000U regimen compared with the 6000U regimen were offset by its higher cumulative acquisition cost. In other words, decision analysis indicated that the most cost-effective strategy was to use the lowest effective dose, reserving the highest dosage for patients who do not respond after 2 months. The superiority of this strategy was confirmed by a sensitivity analysis performed on the cost of drug administration, which was varied from zero to $US60 per dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Cost-Benefit Analysis↗

Radical resection for ampullary carcinoma: long-term results.

Of 36 patients with carcinoma of the ampulla of Vater who underwent surgery between 1971 and 1990, 31 had a radical operation. There was one operative death. The overall 5- and 10-year survival rates were 56 and 37 per cent respectively. Survival was significantly influenced by tumour stage (P = 0.0002), lymph node status (P = 0.006) and the degree of differentiation of the lesion (P = 0.01). Three patients developed local recurrence after local excision of the tumour. Local or hepatic recurrence was common, even 5 years after pancreatoduodenectomy (four of 18 patients who suffered relapse). Radical resection can be curative in selected patients with ampullary carcinoma but late recurrence suggests the need for careful lifelong follow-up.

Adult↗

Efficacy of dilatations for anastomotic colorectal stenoses: prognostic factors.

The authors report their experience of 30 patients with colorectal anastomotic stenosis treated by 62 dilatation sessions in order to evaluate which anastomotic characteristics could influence the success of dilatation therapy. Patients were subdivided into group A (dilatation successful) and group B (dilatation unsuccessful). Overall, dilatation was successful in 73.3% of cases, with only one important complication. The prognostic factors considered were anastomotic dehiscence, adjuvant radiotherapy, presence of colostomy at dilatation, site, morphology and length of the stenosis, presence of neoplastic recurrence, type of anastomosis and type of dilatation. Radiotherapy, local neoplastic recurrence and large anastomotic dehiscence were the more important independent prognostic factors. If present together, they were associated with an almost 100% probability of failure and, vice versa, if they were absent this probability was 5%.

Adult↗