PubMed Health⌕ Search

Biomedical subjects

G Mombelli

Publications and source records attributed to G Mombelli.

At least 19 recordsLinked to original sources
PubMed2004

Development of a model based on body composition to predict drug kinetics-1 evaluation in healthy volunteers.

A kinetic model for widely used drugs, based on body composition analysis, was developed and evaluated in young and elderly healthy individuals. Body composition was studied by body impedance analysis (BIA). Antipyrine, amlodipine, digoxin and tobramycin kinetics, liver microsomal activity enzyme (lidocaine/MEGX test), and appropriate clinical and laboratory tests were carried out. Major variables (V(d), AUC, t(1/2), C(max), Cl) for these drugs were calculated, and the possible relationships with the other clinical and biochemical data were analyzed by the Pearson's moment correlation, forecasting models being then obtained by a multiple linear regression method. Major kinetic parameters, particularly for the mixed elimination drugs (liver/renal), i.e. digoxin and amlodipine, proved to be well correlated to data collected during the study, in particular with body structure parameters. Results were less satisfactory in the case of the mainly renally handled tobramycin. Mathematical models to forecast the kinetic behaviors of the three chosen drugs, using readily accessible data, showed both in the young and the elder, as well as in the whole examined population, very satisfactory correlations in the case of digoxin (R(2) ranging from 0.89 to 0.85) and amlodipine (R(2) between 0.81 and 0.91), less satisfactory (with a wide range of R(2), from 0.65 to 0.94), in the case of tobramycin.

Adult↗
PubMed2004

Development of a model based on body composition to predict drug kinetics; II. Application of the model to the use of digoxin in elderlies.

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

Aged↗
PubMed2001

Homocysteine, vitamins and gene mutations in peripheral arterial disease.

A case-control study was undertaken involving 51 consecutive patients with peripheral artery obstructive disease (PAOD) scheduled for angioplasty. Blood samples of these patients were analysed for plasma homocysteine (tHcy) and levels of vitamin B12 and folate, and the MTHFR gene was assessed for mutation. Patients were compared with age- and sex-matched controls who did not present with cardiovascular risk factors. Mean tHcy did not differ between cases and controls (13.3 +/- 5.7 and 12.6 +/- 4.9 micromol/l, P = 0.49). More patients were above the 95th percentile as determined from the data in the control group with an odds ratio (OR) that almost reached statistical significance [OR, 2.8; 95% confidence interval (CI), 0.9-8.7], but on separate analyses only female patients showed higher tHcy than female controls (15.6 versus 12.0 micromol/l, P = 0.05), with an odds ratio for tHcy above the 95th percentile of 10.5 (95% CI, 1.1-96.6). The TT genotype of the MTHFR gene was found in 24% of the patients and in 12% of the controls (OR, 2.3; 95% CI, 0.8-6.7). Our findings point to a modest association between tHcy and PAOD, with a difference between cases and controls restricted to the highest percentile in female patients. A weak but not significant association was also found for the TT genotype of the MTHFR gene.

Adult↗
PubMed2000

[Endemic and imported severe leptospirosis (Weil's disease) in southern Switzerland].

We report on 4 cases of severe icteric leptospirosis. Three patients developed renal failure requiring haemodialysis and one required mechanic ventilation for 10 days. On entry all patients presented with severe myalgia, particularly in the calves, jaundice, oligo-anuria and severe thrombocytopenia. In one case an acute abdomen-like presentation led to exploratory laparotomy. We believe that the abdominal pain was mainly due to rhabdomyolysis of the abdominal wall. The outcome was favorable in all cases and recovery of renal function was observed after a few days to several weeks. Three out of 4 patients were infected in southern Switzerland. This observation underscores the importance of wild and domestic animals as a leptospira reservoir. Patients presenting with acute renal failure and jaundice, but only mild-to-moderate elevation of transaminases, are suspect for leptospirosis regardless of travel to a tropical or subtropical country.

Acute Kidney Injury↗
PubMed2000

[Bilateral adrenal hemorrhage with adrenal insufficiency in the framework of primary antiphospholipid antibody syndrome].

We report a case of acute adrenal insufficiency in a context of probable bilateral adrenal haemorrhage, as revealed by CT-scan in a 52-year-old woman with a history of spontaneous abortion and repeated ischaemic stroke without symptoms or signs of collagen vascular disease. The symptoms began after the patient had successfully been treated for pneumonia. She had persistently high titres of IgG anticardiolipin antibodies, antibodies against beta 2-glycoprotein I and a lupus anticoagulant. The diagnosis of primary antiphospholipid syndrome with adrenal insufficiency was postulated.

Adrenal Gland Diseases↗
PubMed1999

Sustained improvement of performance and haemodynamics with long-term aerosolised prostacyclin therapy in severe pulmonary hypertension.

Primary pulmonary hypertension and pulmonary hypertension associated with collagen vascular disease or HIV infection are rapidly progressive fatal diseases in spite of conventional medical therapy. Continuous intravenous infusion of prostacyclin has been shown to prolong life in severe primary pulmonary hypertension, and aerosolised prostacyclin has been used successfully on a short-term basis in patients with pulmonary hypertension. We investigated the effects of acute administration of aerosolised prostacyclin or its analogue iloprost in 5 patients with severe pulmonary hypertension; 4 of these patients were followed over a period of 7 months. On acute testing, mean pulmonary artery pressure decreased from 59 to 46 mm Hg (p = 0.01); echocardiographically estimated systolic pulmonary pressure further declined from 66 mm Hg after 2 days' treatment to 54 mm Hg after 7 months (p = 0.03). Symptom-limited walking distance significantly improved from 42 to 87 m after 2 days' treatment (p = 0.003); a further 2- to 8-fold increase was observed in single patients during follow-up. In severe pulmonary hypertension, aerosolised prostacyclin or iloprost improves exercise capacity and lowers pulmonary artery pressure beyond the level achieved on acute exposure.

Administration, Inhalation↗
PubMed1999

Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.

BACKGROUND: There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI). METHODS: In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin. RESULTS: There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens. CONCLUSIONS: In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.

Administration, Oral↗
PubMed1999

[Skin necroses, thrombocytopenia and deep venous thrombosis in subcutaneous thromboembolism prophylaxis with heparin: heparin-induced thrombocytopenia (HIT) type II].

We present a 52-year-old woman who developed a heparin-induced thrombocytopenia type II (HIT II) with deep vein thrombosis, thrombocytopenia and skin necrosis 7 days after initiating subcutaneous prophylaxis with 2 x 5000 U of unfractionated heparin. The platelet count fell from an initial value of 233 x 10(9)/L to 57 x 10(9)/L and normalized within 3 days after stopping heparin. Oral phenprocoumon was started, and her further course was uneventful. The pathogenesis and diagnosis of HIT II is illustrated, and the possible therapeutic options are discussed. To prevent this potentially lethal complication, it is important to begin oral anticoagulation on the first or second day of heparinization, and to stop heparin if the INR-value has been within a therapeutic range for 2 consecutive days. Platelet counts must be checked after 5 to 7 days of heparin therapy. In the case of suspected HIT II, a diagnostic test has to be performed, the heparin must be stopped, and an anticoagulation with either danaparoid or lepirudin is recommended.

Female↗
PubMed1999

Hemostatic activation under anticoagulant treatment: a comparison of unfractionated heparin vs. nadroparin in the treatment of proximal deep vein thrombosis.

BACKGROUND: Multiple clinical trials have been performed to compare standard heparin with low molecular weight heparin in the therapy of deep vein thrombosis, but little is known about the time course of the markers of hemostatic system during the treatment with these two heparin regimens. METHODS: Twenty patients with proximal deep vein thrombosis confirmed by duplex ultrasound and phlebography were randomly assigned to either unfractionated heparin (UH) given as an intravenous bolus of 80 U/kg followed by a constant infusion of 18 U/kg/h, or nadroparin 185 AXa IU/kg once daily subcutaneously. Oral anticoagulants were started at day 4. Markers of hemostatic activation (F1+2, FPA, TAT, D-dimer) were measured daily for 4 days. Primary endpoints were the time course of these markers; secondary endpoints consisted in the evaluation of thromboembolic and hemorrhagic complications by clinical outcome and Marder score. RESULTS: Treatment with UH resulted in a rapid achievement of therapeutic heparin levels. UH reduced markers of fibrin formation and fibrinolysis more rapidly than nadroparin (p < 0.05). Within the nadroparin group activation of prothrombotic markers four hours after the subcutaneous injection (peak level) was significantly lower when compared with the time prior to injection (trough level). Secondary endpoints showed no significant difference between the two groups. CONCLUSION: Continuous intravenous perfusion of UH administered on a basis of a weight-adjusted nomogram controlled markers of the hemostatic system more rapidly than once-daily subcutaneously administered weight-adjusted nadroparin.

Adult↗
PubMed1998

Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina.

BACKGROUND: In unstable angina, the clinical efficacy of heparin is limited in time, and recurrence of adverse events has been reported after discontinuation of the anticoagulant. METHODS: In 21 episodes of unstable angina, we used the plasma level of fibrinopeptide A (FPA) and of thrombin-antithrombin complex (TAT) to evaluate the pattern of thrombin inhibition by heparin and the effect of stopping heparin and initiating aspirin. RESULTS: At admission, the plasma level of FPA was increased: median value 3.7 ng/mL compared with 5.5 ng/mL in a control group of 20 patients with early myocardial infarction (not significant). The following findings were observed during a 4-day course of intravenous heparin infusion: (1) FPA decreased significantly 6 hours after the start of therapy; (2) FPA was lower when activated partial thromboplastic time (aPTT) was >1.5 times baseline; (3) there was a significant negative correlation between aPTT and FPA. Twenty-four hours after heparin was discontinued and aspirin initiated, a significant increase in TAT and FPA in plasma was observed. CONCLUSIONS: The results confirm ongoing fibrin formation in the active phase of unstable angina, indicate incomplete and variable inhibition of thrombin by heparin during continuous infusion, and suggest a risk of re-emergence of thrombosis (in spite of initiating aspirin) 24 hours after withdrawal of heparin. Data demonstrate a better control of thrombin activity when heparin is infused at rates that maintain aPTT at >1.5 times baseline, as currently recommended in unstable angina.

Aged↗