Biomedical subjects
Publications and source records attributed to A Scotti.
The relation between young surgeons and transplantation has always been a "love and hate" one. Until a few years ago this branch of surgery was seen as pioneering, with extreme and and extensive training, and was reserved to few elected members. Nowadays things are different. In this article we try to understand the true reasons that young Italian surgeons avoid transplantation surgery.
BACKGROUND AND AIM: The aim of this trial was to evaluate the effect of doxazosin as add-on therapy in patients with hypertension not adequately controlled on current antihypertensive therapy, and impaired glucose metabolism. The effect of doxazosin administered as add-on therapy was to be considered significant both from clinical and statistical viewpoints if the proportion of patients with adequate control of blood pressure (BP<130/85 mmHg) would be at least 30% after 16 weeks of combined therapy. METHOD AND RESULTS: It was an open, multicenter phase IV study, lasting 19 weeks: 3-week qualifying/placebo run-in period+16-week dose titration/add on therapy period, involving 264 out-patients (158 m and 106 f; mean age+/-SD: 60.9+/-8.6 years; mean BMI+/-SD: basal 29.5+/-5.1, final 30.2+/-4.6) with blood pressure still >130/85 mmHg in spite of the antihypertensive treatment (ACE inhibitors 44%, AT II antagonists 21%, Ca antagonists 12%, other drugs 8%, polytherapy 15%) and affected by type 2 diabetes (n=219), impaired fasting glucose (IFG; n=16) or impaired glucose tolerance (IGT; n=29). Following a run-in, 3-week qualifying phase during which placebo was added to ongoing antihypertensive treatment, 16-week treatment with doxazosin was added at dosages from 1 up to 8 mg/day. Main outcome measures were: the percentage of patients with blood pressure <130/85 mmHg at the end of treatment; the effects of the combination therapy on glyco-lipidic metabolism: fasting plasma glucose, fasting insulin, glycated hemoglobin, insulin resistance (HOMA-R), plasma lipids; and the effect on the 10-year CHD risk (Framingham equation). RESULTS: 35% of patients were responsive (BP<130/85 mmHg) to add-on treatment with doxazosin (CI 90%: 30.3%-40.4%; P<0.05, stat. an. intention to treat). During the run-in phase with placebo, mean SBP/DBP (+/-SD) decreased from 155.6+/-13.2/91.8+/-6.8 mmHg (Week -3) to 151.9+/-12.9/90.1+/-7.2 mmHg (Week -1) and to 151.2+/-11.5/90.1+/-6.9 mmHg (Week 0). During add-on treatment with doxazosin, mean SBP/DBP (+/-SD) further decreased to 144.9+/-15.2/86.3+/-8.3 mmHg (Week 4), 139.7+/-15.3/83.4+/-7.9 mmHg (Week 8), 135.5+/-14.3/81.7+/-7.6 mmHg (Week 12) and 136.4+/-14.5/81.0+/-7.0 mmHg (Week 16). Overall, mean BP changes reached a plateau of about -15 mmHg (SBP) and -9 mmHg (DBP) after 16 weeks of treatment; at each visit the mean decreases from baseline were statistically significant. The following mean values of metabolic parameters were reduced during the study: fasting plasma glucose (-4.1mg/dl; -2.8%), fasting insulin (-2 microU/ml; -12.3%; P<0.05), glycated hemoglobin (-0.12%; -1.7%), HOMA-R (-1.03; -18.2%; P<0.05), total cholesterol (-1.85 mg/dl; -1.1%), LDL cholesterol (-1.35 mg/dl; -0.8%) and triglycerides (-5.64 mg/dl; -2.4%); mean HDL cholesterol increased (+1.79 mg/dl; +3.9%; P<0.01). At the end of study treatment, the percentage of patients with lab values returned within normal ranges, in comparison with basal values, was statistically significant (P<0.05) for the following parameters: fasting plasma glucose (6.3%), fasting insulin (7.5%), LDL cholesterol (6.0%). Ten-year CHD risk (+/-SD) decreased from 16.4+/-7.8% to 13.6+/-7.4% (final vs. basal: -2.87+/-3.9; -17%; P<0.01). Six patients (2.3%) reported 8 adverse drug reactions: dizziness (3), edema (2), headache (2), asthenia (1). In one out of these 6 patients, in whom doxazosin was associated to the ACE inhibitor quinapril, adverse reaction (peripheral edema) led to treatment withdrawal. CONCLUSION: In patients not responsive to antihypertensive treatment and concomitantly affected by impaired glucose metabolism, achievement of target BP was obtained in more than one third of cases after 16-week add-on treatment with doxazosin. Changes in glyco-lipidic parameters and reduction of 10-year CHD risk observed during the study, although of moderate extent, confirm the overall favourable effect of antihypertensive combinations including doxazosin.
The revised International Headache Society classification (2004) represents a very good reference also for ear, nose and throat (ENT) specialists and can be largely shared. The authors follow the classification outline and comment on the chapters of ENT interest. The classification leaves unsolved problems and most of them are of ENT competence, such as mucosal contact point headache. It will be a task for ENT specialists to clarify the real role of very hypothetical primary forms frequently assigned to diagnosis without a correct rationale.
OBJECTIVE: At present, endonasal paraseptal splints are devices frequently employed in rhinosurgery. We evaluated the local tolerance of a newly shaped device, the Guastella/Mantovani splint (G/M-SVS), with respect to the physiological mechanism of mucociliary clearance. STUDY DESIGN AND SETTING: The study involved 20 patients who underwent septoplasty and/or turbinoplasty or other nasal surgical procedures. A sample of ciliated cells was obtained by nasal brushing and was examined ex vivo to determine the ciliary beat frequency (CBF) and morphology, before and 15 days after surgery. RESULTS: Before surgery the mean CBF was 10.87 Hz +/- 0.56 Hz and when splints were removed it was 10.25 Hz +/- 1.9 Hz. Morphological evaluation of the ciliary motion after surgery demonstrated a normal, coordinated beat. CONCLUSIONS: The G/M-SVS does not appear to interfere with the physiological mechanism of mucociliary clearance since CBF remain within a normal range. SIGNIFICANCE: This is the first study that demonstrates an optimal tolerability and safety of the septo-valvular splints on nasal mucosa.
Acute effects of oral calcium supplementation have been studied mainly in pre- and post-menopausal women, whereas very few data concerning men are available. We investigated the effects of 1.2 g of oral calcium administered for 4 days in 18 healthy young men. The day before the first calcium dosing (day -1) and the day of the last calcium dosing (day 4) total and ionized serum calcium and intact PTH were measured at multiple time-points up to 24 h; calcium, C-terminal telopeptide (CTX), pyridinoline (PYD) and deoxypyridinoline (DPD) were measured in urine collected every six h. On day 4, total and ionized serum calcium increased during the 6 h following oral calcium: the maximum increase over baseline was 5.04 and 7.4% respectively, occurring after 2.9 +/- 1.9 h (mean +/- SD) and 2.6 +/- 0.9 h. The AUC was significantly higher on day 4 than on day -1 for both total serum calcium (+4.6%, p<0.02) and ionized serum calcium (+9.2%, p<0.0001). Twenty-four h urinary excretion of total calcium increased significantly on day 4 (+15.1%, p<0.02), mainly as a consequence of increased excretion during the first 6 h. Serum PTH was suppressed by oral calcium, with a significant reduction of AUC on day 4 (-15.1%, p<0.05). Serum concentrations of intact PTH dropped from 26.4 +/- 9.8 pg/ml at time zero to a minimum mean value of 14.9 +/- 7.6 pg/ml at time +2 h. Bone resorption markers significantly decreased on day 4 (CTX -33.2%, p<0.001; PYD -28.5%, p<0.05; DPD -35.8%, p<0.02). Most of the effect was seen in the first 6 h after oral calcium load. These data support the concept that acute suppression of PTH and bone resorption induced by calcium administration is not gender specific and provide the rationale to further assess also in men the long-term effects of oral calcium in the prevention and treatment of osteoporosis.
Calcium supplementation is widely used in deficiency status and as an adjuvant in the treatment of osteoporosis. As usual with endogenous substances, the calcium absorption, distribution and elimination processes are strictly controlled by homeostatic equilibria. Free calcium ion is the most representative active fraction of the circulating ion. Ion excretion is controlled by a saturable tubular reabsorption process which leads to a renal threshold. Cumulative urinary excretion of calcium is the end-point of absorption, distribution and elimination processes, and is thus a good indicator of bioavailability. In order to increase the oral bioavailability of calcium, the ion is administered in association with vitamin D, which is known to enhance intestinal calcium absorption. The aim of this study was to evaluate the absorption of calcium administered alone and in fixed combination with cholecalciferol (vitamin D3, CAS 67-97-0). In accordance with the study protocol, calcium carbonate (CAS 471-34-1; 1500 mg = 600 mg as calcium ion) was administered as such (reference) and associated with cholecalciferol (400 IU) (test) for four days (2 doses/day) to 18 healthy male volunteers in a sequential pattern, namely reference followed by test. Urinary excretion of total calcium, and serum concentration of free and total calcium, 25-OH-vitamin D3 and parathyroid hormone were carefully analysed the day before (baseline) and on the 4th day of dosing, with validated methods. The effect of cholecalciferol in promoting calcium absorption was clearly observed from urinary excretion of total calcium, which with the test treatment showed a 16.6% increase in excretion (p = 0.025) compared with the reference treatment. The mean excretion values on the 4th day, expressed in mg, were 238.85 and 204.83 with test and reference respectively. Moreover, the results demonstrated an increased serum concentration of both free and total calcium after dosing with test and reference by comparison with the baseline situation. The area under the serum concentration-time curve of total calcium increased from day -1 to day 4 from 550.98 to 575.90 mg l-1 h with test and from 543.03 to 568.16 mg l-1 h with reference. Similarly, ionised calcium increased on day 4 with both the treatments. Parathyroid hormone showed the expected typical decreasing behaviour after dosing with the test and reference drugs. The results of this study suggest that calcium carbonate is absorbed through the intestine when administered either alone or in association with cholecalciferol. Cholecalciferol, however, showed the typical expected activity in promoting calcium absorption, which was evident from the cumulative urinary excretion of the ion. To the authors' knowledge, this study is the first published paper demonstrating the absorption and pharmacodynamic effect of short-term administration of vitamin D associated with calcium at the doses recommended for supplementation in a fixed-combination pharmaceutical product.
RGS (regulators of G protein signaling) proteins negatively regulate the alpha subunit of G proteins by accelerating their intrinsic GTPase activity. In a previous work, we reported the cloning of a cDNA encoding for a new RGS protein, RET-RGS. We showed that it is specifically expressed in the retina, notably by photoreceptor cells and that it has an in vitro GAP activity on transducin. To understand the role of RET-RGS, and in particular to determine whether it regulates the phototransduction cascade in photoreceptor cells, RET-RGS was immunolocalized on rat retina sections. Whereas no labeling was detected in outer nor inner segments of photoreceptors cells, dense immunoreactive products were localized in the outer and inner plexiform layers which correspond to the regions of synaptic interplay between the different neurons of the retina including the photoreceptor cells. These results rule out a role of RET-RGS on the phototransduction cascade and suggest that it may participate in retina specific synaptic transductions.
PURPOSE: We performed a long-term, multicenter, randomized, double-blind trial to evaluate the efficacy and tolerability of low-dose, subcutaneous calcium-heparin (12,500 IU/day) in comparison with placebo in patients with stable peripheral arterial disease of the lower extremities. PATIENTS AND METHODS: At the end of a 2-week washout period, during which aspirin placebo was given, 201 patients were randomly assigned to receive either subcutaneous calcium-heparin or placebo for two 3-month treatment periods, each of which was followed by a 6-month period of observation. All of the patients were given low-dose aspirin (50 mg/day) throughout the 18-month study. The main efficacy variables were pain-free and maximum walking time (by standard treadmill test). Patients answered a questionnaire about pain and the limitation of daily activities. Results were analyzed by intention-to-treat. RESULTS: At the end of the study, the estimated increase in pain-free walking time was 39% in the heparin group and 23% in the placebo group (P = 0.09). The estimated increase in maximum walking time was 40% in the heparin group and 16% in the placebo group (P = 0.05). Patients treated with heparin also reported that they had to stop walking because of leg pain, or had daily activities limited by leg pain, less frequently than the placebo group (P <0.01). CONCLUSIONS: Treatment with low-dose subcutaneous calcium-heparin is safe and effective in improving walking performance and reducing physical disability in patients with stable peripheral arterial disease and claudication.
Recoverin is a 23 kDa myristoylated Ca2+-binding protein that inhibits rhodopsin kinase. We have used surface plasmon resonance to investigate the influences of Ca2+, myristoylation, and adenine nucleotides on the recoverin-rhodopsin kinase interaction. Our analyses confirmed that Ca2+ is required for recoverin to bind RK. Myristoylation had little effect on the affinity of recoverin for the kinase, but it raised the K0.5 for Ca2+ from 150 nM for nonacylated recoverin to 400 nM for myristoylated recoverin. Finally, our studies also revealed two separate and previously unreported effects of adenine nucleotides on the recoverin-rhodopsin kinase binding. The interaction is weakened by autophosphorylation of the kinase, and it is strengthened by the presence of ADP.
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BACKGROUND: Biliopancreatic diversion (BPD), by ad hoc stomach resection (AHS-BPD) has been accepted as an effective surgical treatment for morbid obesity. METHODS: Between 1.1.1992 and 31.7.1996, 59 patients (54 females, five males, mean age 40.3 years, range 23-61 years) underwent AHS-BPD. Mean preoperative body-weight was 121.2 kg (range 94-160), with a mean body mass index of 48.6 (range 35-64). Three of these patients were converted from a previous vertical banded gastroplasty to AHS-BPD (one patient with stomach preservation). After at least 36 months follow-up, seven patients underwent abdominal dermolipectomy (five with associated incisional hernia repair, one with thigh dermolipectomy). RESULTS: Mean post-operative hospital stay was 13 days (range 10-30 days). Follow-up is currently in progress in all patients. Excess body weight-loss was 78% in 33 patients with 24 months follow-up, with excellent long-term weight loss maintenance. Protein deficiency was the main specific complication, encountered in two patients (3.4%). Mortality was one patient (1.7%), due to pulmonary embolus. CONCLUSIONS: This clinical experience supports the effectiveness and safety of AHS-BPD, despite some criticism. This procedure appears to be suitable for patients with clinically severe obesity who will poorly tolerate food intake restriction but will accept long-term follow-up. Careful preoperative clinical assessment and selection of patients who will be reliable in long-term follow-up are the keys to success with AHS-BPD, both in terms of weight loss and reduction of specific metabolic complications.
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Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited inhibitory effects on prostaglandin synthesis. The renal effects of this drug were investigated by a double-blind cross-over study in 10 patients with cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg each) were given at midnight and 08:00 h and 80 mg of furosemide were injected intravenously at 09:00 h. The same procedure was followed on another day but a placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free water and electrolyte excretions) and urinary excretion of prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the first dose of the drug and for 2 h after furosemide injection. Platelet thromboxane production was also determined 9 h after the first administration of drug or placebo. Imidazole-salicylate did not affect renal function or inhibit kidney prostanoid production either under basal conditions or after the stimulating effect of furosemide. On the contrary, imidazole-salicylate significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/- 7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti-inflammatory drug that can be given to patients with decompensated cirrhosis without risk of inhibiting kidney prostaglandin synthesis or the renal response to furosemide.
Practical feasibility and clinical tolerability of low dose heparin given subcutaneously for the prevention of reinfarction were evaluated in this open, multicentric trial of post-marketing surveillance. 309 investigators participated. 2830 evaluable patients (2090 M, 709 F, mean age 63 years) who had in the previous 2 years a myocardial infarction were treated subcutaneously with calcium heparin (Calciparina Italfarmaco, 0.5 ml prefilled syringe) at the daily dosage of 12.500 U. The foreseen treatment length was of 1 year; after 6 months of daily injections, calcium heparin could be taken for cycles of 30 days, with 10 day intervals. The enrolled patients resulted to be representative of the population affected with ischemic cardiopathy. One year treatment with calcium heparin was completed by 2040 patients (72.1%); about 1/4 of the patients did not complete the protocol. Patient's subjective decision to withdraw accounted for 46.3% of withdrawals; poor tolerability accounted for 15% of withdrawals (3.8% of total patients). Overall, 237 patients (8.4%) suffered from adverse reactions (353 complaints). Local reactions at the injection site accounted for 60% of total adverse reactions, involving 7.5% of total cases. To follow, allergic reactions (2.5%) and other different types of adverse reaction (incidence less than 0.5%). By analyzing the reactions that provoked drug withdrawal, no organ or function (e.g.: haemostasis) were found to be at risk during the heparin treatment. 64 patients died during the trial. These deaths were in prevalence due to cardiovascular diseases: ventricular fibrillation, cardiac failure, arterial thromboembolism (cardiac reinfarction, stroke).(ABSTRACT TRUNCATED AT 250 WORDS)
A total of 502 children up to the age of 14 years were treated for iron deficiency or overt anemia. ITF 282 was prescribed to 256 children, and a commercially available ferrous polystyrene sulphonate preparation to 246, in a randomized double-blind, double-dummy, ten-center trial. One oral vial of ITF 282 (60 mg iron) was administered once a day to children weighing up to 40 kg; and twice a day to children with body weight equal or superior to 40 kg. In the reference group, oral vials of polystyrene sulphonate (52.5 mg iron) were administered once a day to children weighing up to 40 kg, and twice a day to children weighing 40 kg or more. Treatments lasted 60 days. The treatments' efficacy and tolerability were evaluated taking into consideration: special hematology, symptomatology, safety hematology and hematochemistry, urinalysis. At the end of treatment, the trend was detected to the normalization of the main hematologic parameters in both groups (hemoglobin, hematocrit, ferritin, blood iron, transferrin saturation, MCHC). Although in the first month the reference treatment appears to provide somewhat faster results, significantly greater values of blood iron are observed at the end of the observation in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was, although not significant, in favor of ITF 282, with a failure rate of 18.0 vs 24.0%. The general tolerance, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 13 patients complained of 13 events (1 heartburn, 6 constipation, 6 abdominal pain) vs 48 events reported by 43 patients with the reference medication (1 heartburn, 2 epigastric pain, 14 constipation, 14 abdominal pain, 3 skin rash, 14 vomiting). These observations confirm that, although the most modern preparations of ferrous ions exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease (with the use of more "physiologic" preparations in which the iron is reversibly bound to a protein carrier) the prevalence and, tendentially, duration and intensity of such events without prejudice for the clinical efficacy. Therefore, the good clinical tolerability of ITF 282 effectively removed one of the main obstacles to the correct compliance with iron treatments (necessarily to be taken long-term), as reduced the risks of undesired events in a particularly susceptible population subgroup, such as children.
A double-blind crossover study versus placebo of the renal effects of the nonsteroidal anti-inflammatory drug imidazole 2-hydroxybenzoate was conducted in 10 patients with compensated liver cirrhosis. The administration of the drug (750 mg, t.i.d., for three days) did not affect renal plasma flow, glomerular filtration rate, free water clearance nor the urinary excretion of sodium or potassium. Values of plasma renin activity also did not change after drug administration. Direct tubular damage from imidazole 2-hydroxybenzoate was also excluded by normal excretion of beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase. Urinary 6-keto-PGF1 alpha output were comparable during imidazole 2-hydroxybenzoate and placebo administration. These data indicate that this nonsteroidal antiinflammatory drug does not affect the renal function in patients with compensated liver cirrhosis.
The clinical efficacy and gastroduodenal tolerability of imidazole salicylate (imidazole 2-hydroxybenzoate, ITF 182), a new synthetic drug with an anti-inflammatory action, was evaluated endoscopically in comparison with those of piroxicam in elderly patients suffering from osteoarthrosis. Of the 41 patients entering the trial, only 38 completed the protocol (6 men and 32 women; mean age, 71; range, 65-80 years). After upper gastrointestinal endoscopy for the purpose of excluding gastric and duodenal mucosal lesions, the patients were allocated at random, according to a double-blind, double-dummy protocol, to treatment either with imidazole salicylate 750 mg three times daily or with piroxicam 20 mg once daily for a period of 4 weeks. Imidazole salicylate proved active in controlling a number of the pain symptoms caused by arthrosis, although its efficacy was inferior to that of piroxicam. Grade 2 gastric mucosal lesions were detected in 1 of 20 patients (5%) treated with imidazole salicylate; lesions corresponding to grades 2, 3, and 4 were found in 6 of 18 (33%) of those treated with piroxicam (P = .034). Painful dyspepsia was reported by 15% of the patients in the imidazole salicylate group and by 28% of those in the piroxicam group. On the basis of these results and under the experimental conditions adopted in this trial, the authors concluded that imidazole salicylate is characterized by good gastric tolerability and can thus be used in the treatment of rheumatic diseases in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
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