[Boutonneuse mediterranean fever. Epidemiology, etiology, diagnosis, treatment].
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Biomedical subjects
Publications and source records attributed to J Jourdan.
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The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography with fluorescence detection. As reported previously, a wide range of plasma levels were found among our patients. It appears that in addition to being quickly cleared from the plasma, both DOX and DOXol are excreted in detectable amounts in parotid saliva, a route of elimination that has been given little attention, if any. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to drug and may play a role in causing stomatitis in patients receiving DOX by the i.v. route. Since huge interindividual and pronounced intraindividual differences were found in S/P ratios that mostly were not systematically related to the plasma drug concentration, the concentration in parotid saliva was not useful in predicting the level of free DOX and DOXol in plasma. For the parent drug and its metabolite, the S/P ratios increased significantly with time during the 48-h period after dosing.
A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of doxorubicin (DOX), pirarubicin (PIRA) and their metabolite, doxorubicinol, in plasma. The detection was performed at 480 nm for excitation, and 590 nm for emission. The proposed technique is selective, reliable, and sensitive. The limit of quantification was 2 ng ml-1 for DOX and 5 ng ml-1 for PIRA. The reproducibility of the analytical method through statistical coefficients is approximately 5%. The accuracy of the method is good; the relative error is less than 5%.
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The authors report the case of an intrapericardial bronchogenic cyst in a 42 year old woman with no cardiac symptoms. Despite extensive investigation, the final diagnosis was made only at anatomopathological examination. A pericardial localisation of this embryological tumour is very rare and a number of features of the condition are described. In this case, the carbohydrate antigen (CA 19-9) was a veritable marker of this tumour. This association, described for the first time, between a simple biological marker and an intrapericardial bronchogenic cyst, could be a valuable diagnostic aid in a pathology in which surgery could reasonably be deferred should the diagnosis of bronchogenic cyst be certain.
Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.
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Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time.
A case of mitral and aortic valvular replacement combined with double coronary artery bypass grafting is reported in a 64-year-old woman who presented with a history of heparin-induced thrombocytopenia. The use of a conventional dose of heparin did not induce the formation of a plasma platelet-aggregation factor. The necessity of postoperative anticoagulation was ensured by the prescription of antivitamin K, started on the morning of the operative day.
Multiple myeloma (MM) is characterized by the presence of lytic bone lesion and frequent hypercalcaemia. These are due to an excessive osteoclastic resorption in association with a low bone formation, as demonstrated by bone histomorphometry. Conversely, B-cell malignancies other than MM are rarely associated with lytic bone lesion and/or hypercalcaemia. In this study we have analysed quantitative bone histology in 65 patients with B-cell malignancies other than MM at diagnosis: chronic lymphocytic leukaemia (CLL, n = 20), non-Hodgkin's lymphoma (NHL, n = 25), Waldenström's disease (WD, n = 14), hairy cell leukaemia (HCL, n = 6). Fifty patients presented no clinical evidence of increased bone resorption, including no lytic bone lesions radiologically detectable and/or no hypercalcaemia. 80% of these patients (40/50) had increased bone resorption parameter using quantitative bone histology, including 19/29 (65.5%) patients with CLL or WD and 21/21 (100%) patients with NHL or HCL (P less than 0.01). As a control group, seven patients lacking bone marrow involvement on bone sample presented no excessive bone resorption. However, eight patients presented lytic bone lesions and/or hypercalcaemia. All of these patients had increased resorption parameters with high numbers of osteoclasts per surface trabecular bone (mean = 35.3), as opposed to the patients lacking lytic bone lesions and/or hypercalcaemia (mean = 6.6, n = 28) and to normal individuals (mean +/- SD = 3.8 +/- 1.7 and 6.3 +/- 2.6, respectively before and after 60 years). In all the cases, excessive histologic bone resorption was mediated by mononuclear small osteoclasts (mean osteoclast length +/- SD = 27.3 +/- 4.1 as compared to normal range = 35.0 +/- 1.0, P less than 0.001). In different in vitro models, these small mononuclear osteoclasts are considered as progenitors. These data suggest an abnormal osteoclast differentiation in B-cell malignancies other than MM, probably due to differences in the production of local factors acting on bone remodelling.
Arteriovenous fistula is one of the main causes of high output cardiac failure. The authors report a case following lumbar disc surgery. There are a number of features which may suggest this complication both during surgery and in the immediate postoperative period which are important because the patient may only become symptomatic a long time after operation with a clinical presentation which leads to a cardiological rather than to a surgical referral.
We report a case of angiosarcoma of the pericardium in a 62-year-old man. Although the lack of myocardial adhesions allowed complete surgical exeresis, and despite chemotherapy, the patient died three months later because of early recurrence. Large, undifferentiated areas were found within the tumor, raising diagnostic problems with other malignant tumors of the heart. Histochemical, immunohistochemical, and ultrastructural studies confirmed the diagnosis of angiosarcoma.
The authors report the case of a myocardial abscess in an infectious endocarditis with a double localization, mitral and aortic. The way it is revealed, by severe and recurring ventricular arrhythmias, differs from the conduction disorders usually described. The diagnosis is suspected by non-invasive examinations, echocardiography and nuclear magnetic resonance. It is backed up by angiographic exploration. The intervention confirms the data obtained by cardiac imaging, and enables the ablation of the abscess which is cleaned out, and the cure of the valvular lesions. Taking into account the gravity of this complication, a close clinical, electrocardiographic and echocardiographic surveillance of all infectious endocarditis is necessary.
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The effect of the quinolone norfloxacin, a new antibacterial agent that is thought to induce convulsions in patients by inhibiting the binding of GABA, was tested on the two kinds of GABA A modulation of fTRH-induced TSH release from perifused rat pituitaries. Norfloxacin (50 mumol/l) was found to reverse the inhibitory effect of GABA (100 nmol/l) on the TSH release induced by TRH (10 nmol/l). The ratio of induced over spontaneous release was 0.79 +/- 0.05 in the presence of GABA, and 2.32 +/- 0.18 when norfloxacin was added 15 min before GABA vs 2.59 +/- 0.09 in the control response to TRH. Norfloxacin was also able to reverse the potentiating effect of GABA (10 nmol/l): the TSH response was 6.56 +/- 0.94 in the presence of GABA alone vs 2.92 +/- 0.35 with norfloxacin plus GABA. Norfloxacin was also able to reverse the potentiation induced by isoguvacine, a specific GABA A agonist (6.15 +/- 1.14 in the presence of isoguvacine vs 2.99 +/- 0.54 with norfloxacin plus isoguvacine). Our results suggest that norfloxacin may antagonize the effect of GABA via the two classes of GABA A receptor sites which differ in affinity and are responsible for the dual effect of GABA on the TRH-induced TSH secretion.
Coronary bypass was carried out in four patients who have received an intracoronary streptokinase infusion for acute myocardial infarction. Indications for emergency operation were a myocardial ischaemia time of less than 4 h and a slow flow in the reopened artery despite percutaneous transluminal coronary angioplasty. Two patients were in cardiogenic shock treated by inotropic drugs and intra-aortic balloon pump. In all cases, the level of fibrinogen was less than 1 g X l-1. During the operation, the fibrinolysis was stopped by the intravenous injection of aprotinine (3,000,000 U X 2) and tranexamic acid (15 mg X kg-1), the coagulation factors used by the fibrinolysis being replaced by fibrinogen (1 g per litre of blood volume) and fresh plasma (6 to 8 packs in function of the haemodynamic state). Patient heparinization was as usual (300 IU X kg-1). At the end of the cardiopulmonary bypass, after injection of protamine, clotting quality was good and the fibrinogen level was more than 1 g X l-1. In the postoperative period, blood loss was of little importance. Coagulation troubles due to therapeutic fibrinolysis were reversible. It was possible to return quickly the patient's coagulation state to normal, and so carry out emergency coronary arterial surgery in a defibrinated patient. The indications for surgery depended on cardiogenic factors only.
Twenty-two heterotopic heart transplantations were performed, in 19 of which the evolution of the recipient heart was estimated. Within the first postoperative hours the recipient heart was often more effective than the donor heart. The discrepant rhythm between the 2 hearts did not result in any pathological findings. The increased pressures in the recipient's right heart always decreased, sometimes within several weeks. The left atrial volume was found to be reduced while left ventricular contraction was sometimes unchanged, sometimes improved and in a few cases showed definite improvement with a mean decrease of the ultra-sound diastolic diameter of 20 mm on echocardiography. The technique of heterotopic systems seems to be a useful indication for end-stage cardiomyopathies with pulmonary hypertension (class IV) which is generally considered a contraindication for orthotopic heart transplantation.