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Biomedical subjects

A Paci

Publications and source records attributed to A Paci.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty.

BACKGROUND AND OBJECTIVE: Oral morphine may be useful for postoperative pain relief, but few studies have tested its use after in-hospital surgery. METHODS: We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty. We recruited 60 patients who had total hip arthroplasty under general anaesthesia. The patients were randomized to receive placebo, 10 mg morphine sulphate or 20 mg morphine sulphate orally every 4 h for 24 h. The oral administration was started 3 h after the morphine-loading dose in the Post Anaesthesia Care Unit and then patients used intravenous morphine patient-controlled analgesia for 24 h. Pain score at rest (scored by patients on a visual analogue scale), sedation, nausea, vomiting and urinary retention were monitored. In 11 additional total hip arthroplasty patients, we determined the pharmacokinetics of morphine and its metabolites after oral administration of 20 mg morphine sulphate every 4 h for 16 h. RESULTS: The amount of morphine administered via patient-controlled analgesia over 24 h was reduced in the 20-mg group compared with that in the placebo group (19.0 +/- 2.7 mg vs. 33.0 +/- 5.5 mg; P = 0.03). No significant morphine-sparing effect was observed in the 10-mg group. Pain scores and side-effects were similar in all groups. The pharmacokinetic study revealed a limited and slow absorption of morphine. CONCLUSION: Despite a limited absorption of oral morphine postoperatively, high doses of oral morphine have a significant analgesic effect after total hip arthroplasty.

Administration, Oral↗
PubMed2006

Near infrared spectroscopy and process analytical technology to master the process of busulfan paediatric capsules in a university hospital.

The prescription of unlicensed oral medicines in paediatrics leads the hospital pharmacists to compound hard capsules, such as busulfan, an alkylating agent prescribed in preparative regimens for bone marrow transplantation. In this study, we have investigated how the general principle of process analytical technology (PAT) can be implemented at the small size of our hospital pharmacy manufacturing unit. Near infrared spectroscopy (NIRS) was calibrated for raw material identification, blend uniformity analysis and final content uniformity of busulfan hard capsules of 11 different strengths. Measurements were performed on capsules from 2 to 40 mg (n=440). After optimisation, accuracy and linearity of the NIRS quantitative method was demonstrated after comparison with a previously validated quantitative high performance thin layer chromatography (HPTLC) method. Such a comparison led to attractive NIRS precision: +/-0.7 to +/-1.0 mg for capsules from 2 to 40 mg, respectively. As NIRS is a rapid and non-destructive technique, the individual control of a whole batch of busulfan paediatric capsules intended to be administrated is possible. Actually, mastering the process of busulfan paediatric capsules with the NIRS integrated into the notion of PAT is a powerful analytical tool to assess the process quality and to perform content uniformity of at least 5mg busulfan-containing capsules.

Alkylating Agents↗
PubMed2005

[Ifosfamide induced encephalopathy: 15 observations].

INTRODUCTION: Ifosfamide is an alkylating agent used in the treatment of germ-cell tumors, sarcomas and lymphomas. One of its main side effects is the encephalopathy of which the incidence may reach 30% in the literature, in adults and children just as well. OBJECTIVES: Based on both our experience and a review of the literature, we propose some recommendations for the management of this complication. PATIENTS AND METHODS: We report 15 encephalopathy cases in non-brain tumor patients, which occurred between January 1987 and March 2002 in children from 2 to 17 years old, treated for solid tumors at the Institut Gustave Roussy. Ifosfamide was administered at a posology between 5.4 and 15 g/m(2)/course, associated with other antimitotics such as actinomycin D, etoposide or vincristine. RESULTS: Six patients experienced a grade III neurological toxicity according to the NCI classification, which developed as excess drowsiness lasting up to 36 hours. Six other patients developed grade IV neurotoxicity, including two comas resolving within 4 days and four short generalized convulsions. Three other children experienced grade II drowsiness. Brain MRIs were normal and EEG showed an aspecific encephalopathy tracing. This early central neurotoxicity appeared right from the first administration, and occurred immediately after the first injection or during the second or third day of treatment. It was most often reversible, usually 3 to 5 days after the last ifosfamide administration. Five patients were administered a treatment with Methylene Blue with a demonstrable efficacy in only one case. No death or neurological sequelae have been noted. Ifosfamide has been renewed after the neurological accident in 7 of those patients. Only 1 of those 7 patients developed grade IV neurotoxicity during the next course of treatment. In 2 of those 7 children, Methylene Blue was used in a prophylactic way. No neurological disorders have been noted during the next courses of treatment. DISCUSSION: In the literature, the following are described as risk factors for ifosfamide encephalopathy: advanced pelvic disease, previous cisplatyl treatment and renal failure. We have not found any of these predisposing factors in our series, but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments. CONCLUSION: Facing a clinical diagnosis of ifosfamide encephalopathy, it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptomatology recedes. The re-challenge of Ifosfamide is not contra-indicated and should be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours.

Adolescent↗
PubMed2005

[Shelf-lives of morphine and pethidine solutions stored in patient-controlled analgesia devices: physico-chemical and microbiological stability study].

Morphine and meperidine in Patient-Controlled Analgesic devices are commonly used to treat chronic pain patients. These devices deliver a programmed amount of drug and allow self-administration by the patient depending on the pain. In our department of pharmacy, 300 devices were manufactured in 2003. The aim of this study was to assess their shelf-life. The devices were filled aseptically and without preservatives with 1 and 40 mg/ml morphine solution and 5 and 20 mg/ml meperidine and stored over 30 days at room temperature and protected from light. Culture assay of the solutions showed that they remained sterile for 30 days. No turbidity of any solutions from samples collected twice a week was noticed. pH and osmolarity remained constant. Drug concentrations were determined using stability indicating HPLC method, as we showed that degradation products can be separated from the drugs. Little loss of meperidine occurred within 21 days (<5%) and morphine concentration, which increased, because of solvent evaporation, remained lower than 5% within 21 days but increased up to 10% after 30 days. No traces of degradation products (pseudomorphine or pethidic acid) were detected. The physicochemical and microbiological stability of morphine and meperidine hydrochlorides stored in such devices has been established for 21 days at room temperature and protected from light.

Analgesia, Patient-Controlled↗
PubMed2005

[Validation of a new methodology for characterizing ultrasound contrast agents (UCA)].

PURPOSE: Validation of an experimental ultrasound system on erythrocyte suspensions with variable levels of aggregation and application to the echogenicity quantification of UCA under quasi-physiologic flow conditions. MATERIALS AND METHODS. The system is constituted with a Couette cell with variable applied shear rates, an ultrasound emitter/receiver and a digital scope for radio-frequency signal acquisition. Ultrasound indices (UI) were defined for the two experimental established protocols based on the gold standard laser methodology. Washed red cells with or without variable Dextran 70 kD concentrations were used to simulate a wide particle size range. A preliminary application to UCA was conducted with Levovist for calibration of the system. RESULTS: For each protocol, applied ten times on identical whole blood samples, a student t-test revealed no significant variation for all UI. Results on washed red cells were in good agreement with Rayleigh's theory of ultrasound backscattering. Significant correlations were obtained between laser and UI for washed red cells with different Dextran concentrations. An elevation of 12.13 dB in backscattered intensity was obtained after addition of Levovist. CONCLUSION: The constituted Couette system allowed reproducible and accurate echogenicity quantification of small scatterers such as UCA in quasi-physiologic blood flow conditions.

Contrast Media↗
PubMed2005

Pure surgical treatment of 109 aneurysms.

AIM: Target of this study was to investigate outcomes after pure surgical treatment of intracranial aneurysms. METHODS: Patients with intracranial supratentorial circle aneurysms were retrospectively reviewed between July 1994 and October 1998. Studied cases were admitted at the Department of Neurosurgery of S. Maria-Hospital, Terni, a Government supported General Hospital. One hundred and nine Hunt and Hess Grade 0 to III patients with supratentorial circle aneurysms was studied in order to determine whether advances in the surgical management of intracranial aneurysms have improved surgical outcomes and which factors may predict outcome. All patients were managed only with standard neurosurgical aneurysms clipping procedures. Outcomes evaluation was made at patients' discharge and classified on the base of the Glasgow Outcome Scale (GOS). Surgical timing, SAH grading, pre and post surgical symptomatic vasospasm, temporary clipping, and intraoperative aneurysm rupture were correlated with outcomes. RESULTS: Surgical results showed a 75% excellent outcome. Mortality rate was 3%. Hunt and Hess grade 0 highly influenced outcome. Differences in outcomes among grades I to III were not significant. No differences in outcomes related to temporary clipping were noted. A low rate of intraoperative aneurysm rupture is reported: 5 out of 109 cases. In all these cases outcome was good, with neither mortality or morbidity. CONCLUSIONS: Results indicate a progressive improvement in surgical outcomes, suggesting that there still exist margins for improvements in pure surgical management of intracranial aneurysms.

Adult↗
PubMed2003

Identification and quantitation of antineoplastic compounds in chemotherapeutic infusion bags by use of HPTLC: application to the vinca-alkaloids.

An instrumental quantitative high-performance thin-layer chromatographic (HPTLC) method has been developed for the determination of vinca-alkaloids (antineoplastic compounds) in chemotherapeutic infusion bags prepared in a hospital pharmacy. The method uses automated band application onto silica gel plates containing a fluorescent indicator and scanning densitometry of fluorescence-quenched zones of samples and standards. Samples were analyzed to check the content of the active substance against the label declaration of the preparation. The four compounds were separated using the following solvent system CH(2)Cl(2)-CH(3)OH (93:7, v/v). Vincristine (VCR) and vinorelbine (NVB) were assessed in the same run whilst vinblastine (VLB) and vindesine (VDS) were analyzed in a second run. HPTLC allows the identification and the quantitation of more than 20 samples in the same chromatographic run. The analysis of the samples requires 30 min compared with more than 2 h using a typical HPLC method. Moreover, there is no need for a conditioning step, as with HPLC, and each analysis by HPTLC is less expensive.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Dual-mode gradient HPLC procedure for the simultaneous determination of chloroquine and proguanil.

In order to assay the antipaludic capsule of the Service de Santé des Armées (SSA), that contains two antimalarial drugs, i.e. chloroquine sulfate (CQS, cp1) and proguanil hydrochloride (PGH, cp5), a HPLC procedure was developed. A reversed-phase ion-pair high-performance liquid chromatography (HPLC) method with an ultraviolet detection at 254 nm was set up and validated. Elution system includes programming of both organic concentration and flow-rate known as 'dual-mode gradient'. This method allows the simultaneous determination of both active compounds and separation of four process related substances. The method is simple, rapid, selective and accurate, and the precision is good with an inter- and intra-assay of <2%. The sensitivity is particularly suitable for pharmaceutical quality control.

Antimalarials↗
PubMed2002

Human pharmacokinetic study of heated intraperitoneal oxaliplatin in increasingly hypotonic solutions after complete resection of peritoneal carcinomatosis.

PURPOSE: We studied the pharmacokinetics of heated intraoperative intraperitoneal (i.p.) oxaliplatin (LOHP) solution and its safety profile in increasingly hypotonic solutions. This is the first clinical study of i.p. chemohyperthermia with hypotonic solutions. METHODS: Patients with peritoneal carcinomatosis (PC) underwent complete cytoreductive surgery followed by intraoperative i.p. chemohyperthermia (IPCH) with successive dextrose solutions of 300, 200, 150 and 100 mosm/l. LOHP (460 mg/m(2)) was administered in 2 liters of solution/m(2) at an i.p. temperature of 42-44 degrees C for 30 min. IPCH was performed using an open procedure (skin pulled upwards) with a continuous closed circuit. Patients received intravenous leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)) just before IPCH to maximize the effect of LOHP. i.p. plasma and tissue samples were analyzed by means of atomic absorption spectrophotometry. Sixteen consecutive patients with PC of either gastrointestinal or peritoneal origin were treated. The safety of the procedure was studied. RESULTS: Pharmacokinetics: The mean duration of the entire procedure was 7.7 +/- 2.6 h. Half the LOHP dose was absorbed within 30 min at all dose levels. Absorption was not higher with hypotonic solutions than with isotonic solutions. The area under the curve of LOHP in plasma did not increase with decreasing osmolarity of the i.p. solutions. Intratumoral LOHP penetration was high; it was similar to that at the peritoneal surface, and about 18 times higher than that in nonbathed tissues. LOHP penetration was not significantly increased by using hypotonic solutions. SAFETY: There was a very high incidence of unexplained postoperative peritoneal bleeding (50%) and unusually severe thrombocytopenia in the 150 and 100 mosm/l groups. CONCLUSION: Contrary to experimental studies, this clinical study showed no increase in tumoral or systemic penetration of LOHP with i.p. hypotonic solutions (200, 150 or 100 mosm/l) during IPCH. A high incidence of i.p. hemorrhage and thrombocytopenia was observed.

Antineoplastic Agents↗
PubMed2001

Separation methods for alkylating antineoplastic compounds.

The separating method for alkylating neoplastic compounds were reviewed based on the classification of the Merck Index (12th Edition). Each section, whenever available or relevant, was subdivided according to the following approach: stability studies, extraction methods, gas chromatography, high-performance liquid chromatography and capillary electrophoresis. At the end of each chapter a separate table summarizing the main characteristics of the separating method were established. In particular LODs and/or LOQs were expressed as quantity to facilitate comparison between methods. This review highlights the problems to measure trace levels of these compounds into biological fluids with respect to their instability, adsorption to glass and plastic or derivatization requirements. Over the last decades, HPLC seems to be more popular than GC for separating the alkylating agents. The development of narrow- or microbore LC coupled to MS is certainly the way to further improve both separation and sensitivity obtained in the different papers surveyed for this review.

Antineoplastic Agents, Alkylating↗
PubMed2001

Post-treatment diagnostic accuracy of a new enzyme immunoassay to detect Helicobacter pylori in stools.

BACKGROUND: Helicobacter pylori has attracted increasing attention among gastroenterologists because of its pathogenic potential, stimulating the search for non-invasive diagnostic tests. AIMS: In this study the efficacy of a new enzyme immunoassay designed to detect H. pylori antigens in stools (HpSA) was evaluated before and after eradication therapy. METHODS: HpSA was performed on stool samples collected from 268 patients whose H. pylori status was defined on the basis of concordant results for the (13)C-urea breath test, rapid urease test and histology. The H. pylori-positive patients were treated with a 1-week triple therapy to eradicate the infection. One (T30) and 3 months (T90) after the end of therapy, (13)C-urea breath test and HpSA were repeated in the treated patients. RESULTS: The overall diagnostic accuracy of HpSA at T30 (83%, 95% confidence interval (CI) 77--89%) was significantly lower in comparison to the values obtained at baseline (94%, 95% CI: 91--97%) and at T90 (97%, 95% CI: 94--99%). No significant difference was found between the diagnostic accuracy of HpSA at baseline and at T90 (P=0.253). CONCLUSIONS: The present data suggest that HpSA provides a low diagnostic accuracy when used shortly after treatment. It needs a longer period of follow-up (8--12 weeks) to reach a reliability comparable to the (13)C-urea breath test.

Adult↗
PubMed2000

Quantitative high-performance liquid chromatographic determination of acrolein in plasma after derivatization with Luminarin 3.

A rapid, sensitive and specific high-performance liquid chromatographic method for the quantification of acrolein (1), one of the toxic metabolites of oxazaphosphorine alkylating agents (cyclophosphamide and ifosfamide) was developed. Condensation of acrolein with Luminarin 3 afforded a fluorescent derivative that could be specifically detected and quantified. Chromatographic conditions involved a C18 RP column Uptisphere and a gradient elution system to optimize resolution and time analysis. The method showed high sensitivity with a limit of detection of 100 pmol/ml and a limit of quantification of 300 pmol/ml. This technique is particularly suitable for pharmacokinetic studies on plasma of oxazaphosphorine-receiving patients.

Acrolein↗
PubMed2000

Endogenous digitalislike factors in obstructive sleep apnea.

Recent studies have provided evidence that hypoxia may stimulate the release of endogenous digitalislike factors (EDLF). Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep and may be associated with sympathetic activation and a high risk of developing hypertension. This study was designed to measure EDLF in the plasma of patients with OSA diagnosed by polysomnography, with patients being classified by the number of apneic-hypopneic episodes/h sleep (apnea-hypopnea index, AHI). Plasma was obtained in the morning from 8 male normotensive OSA patients (OSA-N) (AHI 70+/-6), 2 untreated hypertensive OSA patients (OSA-HT), and 11 age-matched healthy male controls (C). EDLFs of different hydrophobicities were separated from the same plasma sample by solid-state C18-cartridges with 25% acetonitrile (ACN) (EDLF-1) followed by 40% ACN (EDLF-2). This procedure recovered ouabain in the first fraction and digoxin and digoxigenin in the second. EDLF was quantified in pM ouabain-equivalents by a human placenta radioreceptor assay. EDLF-1 levels were similar for OSA-N and C (231+/-55 vs. 258+/-58), whereas EDLF-2 levels were increased in OSA-N (244+/-51 vs. 110+/-25 in C, p=0.02). Norepinephrine was increased in apneics. The two OSA-HT had EDLF and norepinephrine levels similar to OSA-N. These preliminary results suggest that OSA is associated with an increase in the more hydrophobic EDLF levels in both normotensive and hypertensive states. No significant increase was found for the less hydrophobic ouabain-like EDLF.

Adult↗
PubMed1998

Encephalopathy, hearing loss and retinal occlusions (Susac's syndrome): a new case.

We describe a young woman with retinal arteriolar occlusions, encephalopathy, and hearing loss. At present this disorder is known as Susac's syndrome, a microangiopathy of the brain and retina whose pathogenesis is, however, unknown. The article reviews the clinical features of this rare, but not unusual, syndrome that can easily be misdiagnosed as multiple sclerosis.

Adult↗
PubMed1998

Endogenous digitalis-like factor and ouabain immunoreactivity in adrenalectomized patients and normal subjects after acute and prolonged salt loading.

The aim of our study was to evaluate whether adrenals are involved in the secretion of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain (EDLF-1), and whether acute plasma volume expansion is a physiological releasing stimulus for this factor(s) in humans. For this purpose, we measured the concentration of this substance(s) by a human placenta radioreceptor assay (RRA) and by the Du-Pont-NEN ouabain-EIA (immunoreactive ouabain, I-Oua) in plasma C18-extracts of eight normotensives and six patients with bilateral adrenalectomy before and after acute salt loading (2 lt 0.9% NaCl/2 h). The study was repeated after 2 weeks of increased sodium intake (200 mEq/day). Under basal conditions, EDLF-1 by RRA and I-Oua were similar in adrenalectomized patients and in controls and were not significantly modified by saline infusion. After 15 days of high sodium intake, basal plasma EDLF-1 and I-Oua were not significantly different from prediet levels, both in adrenalectomized patients and controls and were likewise unaffected by saline loading. Saline infusion, by contrast, significantly (P < or = .05) suppressed hematocrit and PRA and increased ANP both in controls and in patients, either before or after prolonged high dietary sodium. Plasma aldosterone (ALD) was similarly reduced (P < .001) in controls and, as expected, was undetectable in adrenalectomized patients. Our data indicate that in adrenalectomized patients circulating levels of EDLF-1 and I-Oua are similar to those of controls and that, in both groups, acute saline loading before and after sodium repletion does not influence circulating levels of these compounds. These findings suggest that, at least in humans, adrenals are not the main source of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain, and that plasma volume expansion may be not a sufficient stimulus for the release of this factor(s).

Adrenal Glands↗