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Biomedical subjects

G Gatti

Publications and source records attributed to G Gatti.

At least 55 records · Page 3Linked to original sources
PubMed1999

The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring.

OBJECTIVES: To assess whether the neurological or gastrointestinal adverse effects of ritonavir correlate with parameters of ritonavir systemic exposure. METHODS: Peak (Cmax) and trough (Cmin) ritonavir plasma levels were compared in 11 patients experiencing side-effects (group A) versus 10 patients without side-effects (group B). Ritonavir was administered with the following escalation dosing scheme: 300, 400, 500 mg twice a day for 3, 4, and 5 days, respectively, then the full dose of 600 mg twice a day. Blood sampling was done in group A within 24 h of the occurrence of side-effects and in group B after at least 3 days of the full dosage regimen. RESULTS: Both Cmax and Cmax were significantly higher (Mann-Whitney U test) in patients with side-effects. Cmax was [median (interquartile range)] 26.7 (22.7-33.3) mg/l versus 16.2 (13.4-17.0) mg/l (P = 0.001) and Cmin was 12.6 (9.1-13.9) versus 7.5 (4.9-8.6) mg/l (P = 0.002). CONCLUSION: Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.

Adult↗
PubMed1999

Specific high-performance liquid chromatography assay for determination of rifabutin plasma concentration following Extrelut column extraction.

A specific, precise and accurate assay for determination of rifabutin in human plasma using Extrelut column extraction was developed and validated. Rifabutin concentrations were calculated with a standard curve ranging from 5 to 800 ng ml(-1). using a split-curve approach. Chromatographic peaks were separated by means of a 5 microm Symmetry Shield RP8 using a KH2PO4 (0.05 M) buffer-acetonitrile mobile phase. Detection wavelength was set at 275 nm. Chromatography was carried out at room temperature (20-25 degrees C). The limit of quantification was 5 ng ml(-1). The recovery was over 71%. The intra-day precision of the assay was 5, 7, and 1% while the inter-day precision was 11.2, 8.1, and 5.8% at concentrations of 30, 150 and 500 ng ml(-1), respectively. The accuracy ranged from 99 to 108%. Forty of the drugs most commonly administered to HIV-positive patients were found not to interfere with the assay. The assay has been used in a comparative study of rifabutin pharmacokinetics in HIV-positive patients with or without wasting syndrome. reserved.

Antibiotics, Antitubercular↗
PubMed1999

Routine left atrial catheterization for the post-operative management of cardiac surgical patients: is the risk justified?

OBJECTIVE: To assess the risk/benefit ratio, including cost, associated with routine left atrial catheterization for the post-operative management of patients after cardiac surgery. METHODS: From November 1991 to June 1998, out of 6187 open heart procedures performed at our institution, 5815 patients (94%) receive a left atrial monitoring line inserted invasively by a unique and reproducible technique. Catheters were removed on the first or second postoperative day before chest tube removal. A subgroup of 385 patients (7%) were switched to a Swan-Ganz catheter postoperatively. RESULTS: A total of 14 patients suffered a complication related to the left monitoring line (0.24%). Bleeding necessitating transfusion occurred in 10 patients (0.17%), seven of whom required surgical reexploration (0.12%). Catheter retention occurred in four cases (0.07%), requiring a mediastinal reexploration in one and a minimally invasive procedures in three, for removal. No other complications related to the presence of a left atrial line emerged in this series. Apart from providing crucial hemodynamic information on a routine basis, in nine selected patients (0.15%) in a low cardiac output state with increased pulmonary vascular resistance and right ventricular failure, the left atrial line was used as a preferential route for catecholamine infusion, with significant hemodynamic improvement. CONCLUSIONS: Complications of left atrial monitoring catheters in cardiac surgery do occur but at a very low and acceptable rate. No mortality was correlated to their use in our series. Complication rate can be further lowered by a meticulous management of the device. The wealth of information and therapeutic options offered by this line appears to outweigh the associated risk.

Cardiac Catheterization↗
PubMed1999

Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects.

AIMS: This serendipitous study revealed an unexpected effect of Jufeng grape juice on the CYP1A2-mediated metabolism of phenacetin. Investigation of the inhibition of CYP1A2 by grapefruit juice was involved but a translation error led to the grape juice substitution. METHODS: Twelve healthy subjects took a single oral dose of phenacetin (900 mg) on two randomized occasions together with 200 ml water or grape juice. Plasma phenacetin and paracetamol concentrations were assessed by h.p.l.c. RESULTS: Ingestion of grape juice was associated with reduced plasma phenacetin concentrations, while paracetamol levels were unaffected. Paracetamol to phenacetin AUC ratios increased from 13.9+/-3.1 to 24.3+/-3.8 after ingestion of grape juice. CONCLUSIONS: These findings suggest enhanced first-pass metabolism of phenacetin, due to CYP1A2 activation by grape juice or to desaturation of CYP1A2 isoenzymes secondary to a slower rate of phenacetin absorption.

Acetaminophen↗
PubMed1999

Pharmacokinetics of rifabutin in HIV-infected patients with or without wasting syndrome.

AIMS: The purpose of the study was to compare the pharmacokinetic parameters of rifabutin obtained in a group of patients without wasting syndrome (NWS) with those obtained in a group with wasting syndrome (WS). METHODS: A single dose of 300 mg rifabutin was administered in the fasting state to the patients in both study groups and blood samples were scheduled to be collected at the following times: 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72 and 96 h following administration. Data were analysed using noncompartmental methods. The pharmacokinetic parameters of rifabutin in patients with and without wasting syndrome were compared using the Mann-Whitney U-test. RESULTS: Cmax was 0.34+/-0. 14 mg l-1 in NWS patients and 0.55+/-0.16 mg l-1 (P=0.01) in patients with WS. tmax was 4.2+/-1.5 and 3.3+/-2.3 h (P=0.17) in NWS and WS patients, respectively. The AUCs were similar in the two study groups. V/F was 2905+/-1646 l in NWS patients and 1701+/-492 l (P=0.07) for the WS group. These differences are less pronounced following normalization of V/F to patients body weight (43.7+/-20.1 vs 35.4+/-10.3 l kg-1 ). t1/2,lambdaz tended to be shorter in patients with WS (31.4+/-12.9 vs 46.0+/-23.5 h, P=0.12). CONCLUSIONS: Our study suggests that the pharmacokinetics of rifabutin in patients with wasting syndrome are not altered to a degree that is clinically important.

Adult↗
PubMed1999

Comparison of food composition tables and direct chemical analysis for the assessment of macronutrient intake in a military community.

Food composition tables (FCT) were validated against chemical analysis (CA) to assess energy, carbohydrate, lipid, protein and fibre content of the food consumed by Italian Army cadets. The absolute difference between FCT and CA in 2 separate weeks was < or = 0.7% for energy, < or = 4.1% for carbohydrates, < or = 2.9% for lipids, < or = 6.2% for proteins and < or = 31.6% for fibre. It is concluded that FCT can be used to assess energy, carbohydrate, lipid and protein but not fibre intake in this military community.

Adolescent↗
PubMed1999

Penile elongation and thickening--a myth? Is there a cosmetic or medical indication?

Penile lengthening and thickening techniques can be performed in different ways for treatment of congenital penile hypoplasia and dysmorphophobia in terms of aesthetics or function. Particularly for penile lengthening, a combination of surgery and stretcher device is suggested. Surgery for lengthening comprises three different stages: suture with plane alternating edges of the pubo-penile skin, infrapubic lipectomy, and section of the suspensory ligament. Our approach to penile thickening differs depending on whether dysmorphophobia is related to aesthetics or function. While pericavernosal apposition of autografts is suggested in the first case, a technique developed by the authors is performed in the latter, which comprises bilateral longitudinal incision of the corpora cavernosa and enlargement of the tunica albuginea by means of saphenous grafts. The endothelial lining, which constitutes the internal surface of the veins, is highly compatible with the endothelium of the corpora cavernosa; therefore, the incidence of postoperative subareolar fibrosis and occlusive vein pathology is lower than after surgery performed with techniques using grafts of other material. The described procedure did not cause postoperative complications in terms of infection, wound healing and cosmetic appearance. All subjects resumed regular sexual activity after 4 months without any disturbance or functional limitation. Diametrical measurements at the 9-month follow-up revealed an increase of 1.1-2.1 cm. The reliability and efficiency of these procedures are strongly influenced by factors other than technical problems; however, expert diagnosis and psychological consultation in the case of dysmorphophobia will confirm and specify the indications.

Humans↗
PubMed1999

Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women.

PURPOSE: To evaluate the effect of oxcarbazepine (OCBZ) on the pharmacokinetic profile of steroid oral contraceptives. METHODS: Twenty-two healthy women aged 18-44 years were recruited, and 16 of them completed the study. By using a randomized double-blind crossover design, each woman was studied in two different menstrual cycles, during which placebo or OCBZ (maintenance dosage, 1,200 mg/day) was given in randomized sequence for 26 consecutive days with a washout of at least one cycle in between. A steroid oral contraceptive containing 50 microg ethinylestradiol (EE) and 250 microg levonorgestrel (LN) was taken for the first 21 days of each cycle. Plasma concentrations of EE and LN were measured by gas chromatography-mass spectrometry in samples collected at regular intervals on days 21-23 of each cycle. RESULTS: Compared with placebo, areas under the plasma concentration curves (AUC(0-24h, geometric means) decreased by 47% for both EE (from 1,677 to 886 pg.h/ml; p < 0.01) and LN (from 137 to 73 ng.h/ml; p < 0.01), during OCBZ treatment. Peak plasma EE concentrations decreased from 180 pg/ml during the placebo cycle to 117 pg/ml during the OCBZ cycle (p < 0.01), whereas peak plasma LN concentrations decreased from 10.2 to 7.7 ng/ml (p < 0.01). The half-lives of EE and LN also decreased from 13.6 to 7.9 h (p < 0.01) and from 28.8 to 15.8 h, respectively (p < 0.01). CONCLUSIONS: OCBZ reduces plasma concentrations of the estrogen and progestagen components of steroid oral contraceptives, presumably by stimulating their CYP3A-mediated metabolism in the liver or gastrointestinal tract or both. Because this may lead to a decreased efficacy of the contraceptive pill, women treated with OCBZ should receive preferentially a high-dosage contraceptive and should be monitored for signs of reduced hormonal cover.

Adolescent↗
PubMed1999

Mid-term results after heart valve replacement with the CarboMedics bileaflet prosthesis: experience with 785 implants.

BACKGROUND: The aim of the study was to evaluate our clinical experience with the CarboMedics Heart Valve Prosthesis. METHODS: Between October 1991 and December 1997, six hundred seventy-two consecutive patients (361 men, 54%; 311 women, 46%; mean age 57 +/- 12 year, range 6-73 years) underwent mechanical valve implantation at the Division of Cardiac Surgery of the University of Verona. Preoperatively, 69% of the patients were in NYHA FC III or IV. Eighty-one patients (12%) had undergone a previous cardiac operation and 14.5% had an ejection fraction less than 35%. We performed an aortic valve replacement in 309 patients (78 valved-conduits for replacement of the entire aortic root), a mitral valve replacement in 250, and a double valve in 113. 52 patients (8%) underwent associated myocardial revascularization. RESULTS: Early mortality was 2.8% (5/309 aortic, 1.6%; 11/250 mitral, 4.4%; 3/113 double, 2.6%). Late mortality was 4.4%. Actuarial survival at 5 years was 89.3% (aortic, 91.1%, mitral 86.4%, double 90.5%). Thromboembolism occurred in 26 patients (3.9%) and major hemorrhagic events in 20 (3%). Nine patients (1.3%) required a reoperation, in 3 cases (0.4%) after endocarditis (Staphylococcus epidermidis). No structural deterioration occurred in our series. CONCLUSION: Our study appears to confirm the safety and reliability of the CarboMedics mechanical valve prosthesis, even in old age groups. This bileaflet prosthesis demonstrates no structural deterioration, a low incidence of complications, and good hemodynamic performance.

Adolescent↗
PubMed1999

Factors influencing outcome after emergency surgical repair of acute type A aortic dissection.

OBJECTIVE: We retrospectively reviewed our more recent experience with acute type A aortic dissection in order to identify possible risk factors influencing current surgical results. METHODS: Between January 1990 and January 1998, 122 patients (86 males and 36 females; mean age 60 +/- 12 years) underwent emergency repair of acute type A aortic dissection using a standard surgical approach. Seventy-four (61%) patients required isolated replacement of the dissected ascending aorta, 27 (22%) required additional replacement of the aortic arch and 21 (17%) required total aortic root replacement. Surgical outcome was evaluated in terms of operative mortality and morbidity. Results of patients presenting with preoperative complications (Group C) (i.e. cardiac tamponade, cerebral stroke, cardiogenic shock, acute myocardial infarction, anuria or visceral ischemia) were compared with those of uncomplications cases (Group U) and with a calculated risk of expected operative mortality (EOM-rate) based on an analysis of each patient set of preoperative risk factors. Sixteen preoperative and 18 perioperative variables were also analyzed to identify conditions influencing morbidity and mortality. RESULTS: Fifty-seven patients (47%) presented with preoperative complications (Group C) and 65 (53%) did not (Group U). Overall operative mortality was 22% (27 patients). Mortality within subgroups was 40 and 6% for complicated and uncomplications cases, respectively (p < 0.001). The 85% of the overall mortality occurred in Group C patients. During the experience, the operative mortality rate actually observed ranged from 0 to 38% and was similar to the calculated expected risk, thus proving a direct relationship with the amount of complicated cases operated on each year. Multivariate analysis revealed that older age and hemopericardium significantly increased the risk of operative death, while male gender, preoperative complications, postoperative bleeding, duration of circulatory arrest and aortic cross-clamp time significantly predicted morbidity (p = 0.02). CONCLUSIONS: Current results of emergency repair of acute type A aortic dissection are strictly dependent on the number of complicated cases referred for operation. Earlier diagnosis and prompt referral before development of preoperative complications appear essential to improve surgical results.

Adult↗
PubMed1999

Diagnosis and early surgical management of traumatic thoracic aortic disruption.

OBJECTIVE: Traumatic rupture of the thoracic aorta is a major cause of death. Survival greatly depends on early diagnosis, degree of injuries to other districts and timing of repair. To address the controversial aspects of this condition, we retrospectively reviewed our experience. METHODS: Between April 1984 and December 1998, 39 patients (31 males, 79%), with a mean age of 33 +/- 7 (range, 17 to 59 years), underwent surgical repair at our institution. Final diagnosis of aortic disruption was achieved in 33 patients (85%) by aortogram, and in 6 (15%) by transesophageal echocardiography (TEE) alone. Four patients (8%) had a false negative chest X-ray on admission. Twenty-four patients (61.5%) had additional major injuries to other districts (n = 4, cranial trauma; n = 13, cranial trauma + pelvic fracture; n = 5, lesions to abdominal viscera; n = 2, lesions to abdominal viscera + pelvic fracture). Surgical techniques included simple aortic cross-clamping in 7 patients (18%), partial femoral-femoral bypass in 17 (44%), and partial left heart bypass in 15 (38%). Two patients underwent direct aortic suture (5%), whereas 37 (95%) had interposition of a vascular graft. RESULTS: Three patients (8%) died after major hemorrhaging during the early phases of our experience. Paraplegia occurred in 1 patient (2.5%) in the single aortic cross-clamping group. There was no morbidity directly attributable to the administration of heparin for cardiopulmonary bypass. CONCLUSION: Although aortography is still the gold standard to achieve diagnosis, the use of TEE as a method of detecting traumatic injury to the thoracic aorta appears feasible in critical patients, advantageously saving time. With a meticulous surgical approach and the use of an effective method for distal aortic perfusion during repair, it is possible to achieve good outcomes.

Adolescent↗
PubMed1998

Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey.

A collaborative survey was performed to compare prescribing strategies for the treatment of epilepsy in Mediterranean countries, based on analysis of 500 questionnaires compiled by physicians in 14 different countries. For partial seizures, carbamazepine was the drug of choice in most countries, whereas the second choice of drug differed widely. For primarily generalized tonic-clonic seizures, valproic acid was usually preferred, but other drugs used widely in some countries included phenobarbital, phenytoin and carbamazepine. Lamotrigine was the most popular second-line drug for primarily generalized tonic-clonic seizures in the European countries. In patients where the initial drug failed, switching to an alternative monotherapy was usually the preferred strategy, but advocates of early use of combination therapy exceeded 30% in the respondents of seven countries. Most respondents, in all countries except Turkey, did not prescribe drugs to prevent recurrence of febrile seizures; however, intermittent prophylaxis with a benzodiazepine was advocated by a considerable number of physicians, and continuous prophylaxis was prescribed by a significant minority of respondents in France, Syria and Tunisia. New drugs were rarely used as first-line treatment due to high cost and inadequate experience. Overall, this survey indicates that there is a wide variability in therapeutic practices between and within countries. This information may be useful for the implementation of national educational activities and for the design of pragmatic trials aimed at comparing different therapeutic strategies.

Adult↗
PubMed1998

Effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition in Chinese subjects.

The effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition was evaluated in a controlled study of 36 healthy Chinese subjects. Each subject was administered a single oral dose of phenacetin (900 mg), and frequent blood samples were taken for up to 12 hours for simultaneous high-pressure liquid chromatography determinations of plasma concentrations of phenacetin and metabolically derived paracetamol. Compared with values observed in controls not exposed to cigarette smoking, subjects who smoked 7 to 40 (median, 20) cigarettes per day exhibited a 2.5-fold higher phenacetin apparent oral clearance (7.2, 4.3-12.0 L x h(-1) x kg(-1) vs 2.9, 1.8-4.6 L x h(-1) x kg(-1) [geometric means, 95% confidence intervals]; n = 12, p < 0.05). In subjects exposed to passive smoking, phenacetin's apparent oral clearance (3.6, 2.0-46.6 L x h(-1) x kg(-1), n = 12) was intermediate between the values observed in the two other groups. Plasma paracetamol levels were moderately lower in active smokers than in passive smokers and controls. These results demonstrated that, in contrast to results found in previous studies, Chinese subjects were fully susceptible to the inducing effect of cigarette smoke on CYP1A2 activity.

Adult↗
PubMed1998

Effects of home-based food preparation practices on the micronutrient content of foods.

We studied the effects of cooking on the vitamin and mineral content of vegetables (vegetable soup, cauliflower), meat (beefsteak) and fish (sole) and those of cutting (fruit salad) and squeezing (orange juice) on the vitamin content of fruits. In cooked dishes, vitamin retention ranged between 0 (folic acid, all dishes) and 94% (retinol, sole) and mineral retention between 63 (copper, cauliflower) and 96% (iron, vegetable soup). In orange juice, ascorbic acid appeared to be protected from oxidation for at least 12 h as compared with fruit salad. Our study shows that preparation of foods with techniques available at home may be responsible for losses of vitamins and minerals. Further studies are needed to ascertain the effects of these losses on nutritional status.

Cooking↗
PubMed1998

Penetration of clindamycin and its metabolite N-demethylclindamycin into cerebrospinal fluid following intravenous infusion of clindamycin phosphate in patients with AIDS.

Clindamycin, which is usually used in combination with pyrimethamine, has been proven effective in the treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients. However, it is not known if clindamycin achieves inhibitory concentrations at the site of infection. Also, it has been hypothesized that the activity of clindamycin against Toxoplasma gondii may be due, at least in part, to a metabolite. We evaluated the penetration of clindamycin and its major metabolite, N-demethylclindamycin (NDC), into cerebrospinal fluid (CSF) of AIDS patients undergoing lumbar puncture for diagnostic purposes. A single, 1,200-mg dose of clindamycin was administered as a 45-min intravenous infusion beginning at 1.5 or 2.5 h before CSF sampling. The concentrations of clindamycin in CSF ranged from 0.091 to 0.429 mg/liter at 1.5 h and from 0.120 to 0.283 mg/liter at 2.5 h following the beginning of the infusion. The concentrations of clindamycin in CSF were well above the 50% inhibitory concentration of 0.001 mg/liter and the parasiticidal concentration of 0.006 mg/liter. NDC was undetectable both in plasma and in CSF. Our study provides a pharmacokinetic rationale for the clinical efficacy of clindamycin in the treatment of cerebral toxoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients.

Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacokinetic model. Parameter estimates were the absorption rate constant (0. 201/h), clearance/bioavailability (CL/F; 60.9 liters/h), volume of the central compartment/bioavailability (231 liters), intercompartmental clearance (60.3 liters/h), and volume of the peripheral compartment/bioavailability (Vp/F; 1,050 liters). The distribution and elimination half-lives were 1.24 and 25.4 h, respectively. The covariates tested for influence on CL/F and Vp/F were sex, age, weight, height, body surface area, tobacco smoking, drug addiction, alanine aminotransferase levels, creatinine clearance, total protein, bilirubin, numbers of CD4(+) cells, presence of diarrhea, cachexia index, rifabutin use (prophylaxis versus therapy), rifabutin dose, study site, and the concomitant administration of clarithromycin, fluconazole, phenobarbital, ciprofloxacin, azithromycin, or benzodiazepines. The only statistically significant effects on rifabutin pharmacokinetic parameters were a 27% decrease in Vp/F due to the concomitant administration of azithromycin and a 39% increase in Vp/F due to tobacco smoking. Such effects may be considered clinically unimportant. Our results confirm the lack of a correlation of rifabutin pharmacokinetic parameters with parameters of disease progression and gastrointestinal function. Also, the lack of a correlation with covariates which were previously found to be significant, such as concomitant fluconazole and clarithromycin use, may suggest that the effect of such covariates may be less important in the real clinical setting, in which several concomitant factors may influence pharmacokinetic parameters, with an overall effect of no apparent correlation.

Adult↗