A distribution study with (14)C-otilonium bromide in the rat: evidence for selective tropism for large intestine after oral administration.

The aim of this study was to determine the plasma levels and the tissue distribution of otilonium bromide, measured as total radioactivity, after oral administration of 2 mg/kg of (14)C-labeled drug to rats. Radioactivity levels were very low in the plasma (ranging from 2.7 ng Eq/ml at 1.5 h to 0.6 ng Eq/ml at 24 h) as compared with those found in the gastrointestinal (GI) tract, indicating negligible systemic otilonium bromide absorption. Results from both quantitative radioluminography of whole body tissue distribution and radioassay of dissected parts of the GI tract carried out with liquid scintillation counting clearly demonstrate the presence of radioactive compounds in the walls of the GI tract at all sacrifice times. In the other tissues and organs examined, radioactivity was only found in trace amounts in the liver. The presence of radioactivity in the GI walls reflected the transit kinetics of drug-enriched contents. The radioactivity in large intestine walls was measurable at otilonium bromide concentrations in the range of micromole equivalents/kg, from 4 to 8 h after drug administration. Total body radioactivity recovery was 95, 101, 24, and 9% at 1.5, 4, 8, and 24 h, respectively. In conclusion, orally administered (14)C-otilonium bromide is poorly absorbed systemically, as indicated by the very low plasma radioactivity levels, but it is able to effectively penetrate into the large intestine walls, a recognized target for drugs oriented toward irritable bowel syndrome therapy.

Skin distribution of fipronil by microautoradiography following topical administration to the beagle dog.

To investigate the localisation of fipronil in dog skin, [14C]-fipronil was topically applied to a male beagle dog (spot-on administration) at the therapeutic dose of 10 mg/kg. By means of autohistoradiography, the radioactivity was precisely detected in the skin and appendages at various intervals after application. Radioactivity was predominantly observed within the stratum corneum, the viable epidermis, and in the pilo-sebaceous units (mainly in the sebaceous glands and epithelial layers). [14C]-fipronil was significantly detected in these structures up to 56 days post-treatment, in the application zone (neck) but also in the lumbar zone, thus indicating the mechanical displacement of fipronil. No radioactivity was detected in either the dermal or the hypodermal layers, confirming the low percutaneous passage of fipronil.

Secretion in milk and transplacental transfer of two iodized oils, Lipiodol UF and Oriodol, in rabbits.

Many countries in the world are inhabited by populations suffering from iodine deficiency. These populations are affected by serious diseases directly related to iodine deficiency. Iodized oil (Lipiodol UF or Oriodol) is routinely used orally or intramuscularly to treat these populations, including pregnant women. The experiments of the present study in gravid or lactating rabbits show that there is transplacental transfer of iodine and secretion of iodine in milk after administration of iodized oil and consequently an accumulation of iodine in the thyroid glands of the mother, the fetus and the neonate. The advantages of treating pregnant women with iodized oil in the populations concerned is thus confirmed. The oral route can be substituted by the intramuscular route.

[Malaria epidemic during a military-humanitarian mission in Africa]. / Epidémie de paludisme au cours d'une intervention militaro-humanitaire en Afrique.

A malaria epidemic broke out among French servicemen during a humanitarian military mission carried out in Central Africa in 1996. The purpose of this study was to determine compliance with drug prophylaxis for malaria by measuring blood levels of antimalarial drugs (combination treatment using chloroquine-proguanil or treatment with doxycycline) as well as to assess the conditions of vector control. The incidence density rate of malaria over a 60-day period was 3.1 cases per month per 100 men. Only reinforcement troops were affected. The risk of developing malaria was 5 times higher among new arrivals than in servicemen who had been in the zone for several months (95% CI relative risk = [2.9-7.8]). Type of prophylactic treatment had no effect on the incidence density rate. Study data showed that 40.2% of those treated for malaria were not in compliance with prophylactic treatment at the time of the malarial attack and that those who were in compliance with prophylaxis, i.e. the remaining 59.8%, presented a strain of plasmodium that was resistant to the prophylactic drugs at doses used. Findings also indicated the epidemic occurred mainly because operating conditions prevented implementation of proper vectorial control. The risk of epidemic could probably have been reduced by improving compliance with prophylactic treatment and changing standard vectorial control techniques, e.g. by using insecticide-treated uniforms.

[Malaria in French Guiana: between tradition and modernism]. / Le paludisme dans le département francais de la Guyane: entre tradition et modernité.

Guyana is the only department of France in which malaria is a public health problem. The fact that 4,000 new cases including 80% due to Plasmodium falciparum and less than 5 deaths are reported each year shows that the disease is under control but has not been eradicated despite the quantity and quality of the resources that have been implemented. This region of 91,000 km2 with approximately 140,000 inhabitants can be roughly divided into 3 zones. Along the coastline where most of the population lives, malaria is uncommon. In the most remote scarcely populated areas of upper and middle Maroni and upper Oyapock, malaria is stable, perennial and well controlled. In low Maroni and low Oyapock, the impact of malaria is compounded by the high turnover of the population. There is a heavy and poorly controlled movement of migrant people on the two rivers that constitute the natural borders with Brazil and Surinam. Under these conditions strict measures cannot be implemented and malaria remains a problem in Guyana.

Whole body quantitative autoradiographic study of the biodistribution of iobitridol in rats.

RATIONALE AND OBJECTIVES: Iobitridol is a new nonionic low-osmolality contrast medium. During preclinical development of this agent, it was of interest to verify that it behaves like other urographic and angiographic contrast agents (i.e., as a tracer of extracellular fluid). METHODS: Male and female rats were imaged using a quantitative autoradiographic method after intravenous administration of iodine-125-labeled product at a dose of 300 mg iodine/kg. RESULTS: The radioactivity was rapidly distributed with substantial uptake in the thyroid, kidneys, and skin after 10 minutes. The central nervous system showed no uptake. The radioactivity was rapidly eliminated (i.e., after 24 and 48 hours, only traces were found) except in the thyroid (because of free radiolabeled iodides present in small quantities in the administered solution). The considerable renal uptake after administration can be attributed to urinary excretion of the radioactivity (86% of the administered dose after 24 hours). Total elimination was achieved after 48 hours. No sex-related effects were observed. CONCLUSION: The absence of a target organ, the abundant and rapid urinary elimination, and the absence of transfer across the blood-brain barrier suggest that iobitridol is a tracer of extracellular fluid.

[Assisted circulation by external heterotopic prosthesis as a bridge to heart transplantation]. / Assistance circulatoire en attente de transplantation cardiaque par prothèse hétérotopique externe.

Eleven patients aged 7 to 58 years were placed on assisted circulation with Pierce (2 cases) or Abiomed (9 cases) external prosthetic ventricles as a bridge to cardiac transplantation. The indications were terminal cardiac failure following cardiomyopathy (7 cases), decompensated ischemic heart disease (3 cases) and subacute post-transplantation rejection (1 case). The duration of the assisted circulation ranged from 24 hours to 11 days. All patients were transplanted but 3 died after transplantation (27%). The circulatory assistance was satisfactory in all patients as shown by the regression of clinical signs of low cardiac output and the normalisation of diuresis. The complications observed during assisted circulation and after cardiac transplantation were: haemorrhage (36%), infection (27%) and thromboembolism (9%). These preliminary results with a 72% post-transplantation survival rate, show that both systems are effective "bridges to cardiac transplantation". The Abiomen device is excellent value for money and relatively simple to install and represents a good compromise between the sophisticated techniques of circulatory assistance and the problems of the cost of health care.

Use of the Abiomed BVS System 5000 as a bridge to cardiac transplantation.

The Abiomed BVS System 5000 (Abiomed Cardiovascular, Inc., Danvers, Mass.) is a gravity-filled, pneumatically driven external prosthetic ventricle that has been implanted as a circulatory support device in six patients 9 to 58 years of age, presenting with a refractory heart failure nonamenable to any type of corrective operation. Three (including a 9-year-old girl) had an end-stage nonobstructive myocardiopathy, and two (including one patient who had had a massive recent myocardial infarction) had an ischemic heart disease. When first seen, the 58-year-old patient had an acute rejection and graft failure occurring 2 months after a first transplantation. All patients showed evidence of a low-output state (cardiac index less than 1.5 L/min/m2), with renal failure (mean urinary output, less than 27 ml/min) and hypoxia (mean arterial oxygen pressure = 56 torr under 80% forced inspiratory oxygen), despite maximum pharmacologic support (dobutamine, 16 to 18 gamma/kg/min; dopamine, 3 to 18 gamma/kg/min; adrenaline, 0.2 to 0.7 gamma/kg/min; furosemide, 7 to 17 gamma/kg/min). The device was implanted through a midline sternotomy and under peripheral normothermic bypass. Five patients received a biventricular support, and one a single left prosthetic ventricle. The cannulation included a right-angled cannula in both the left and right atrium and a suture of the arterial Dacron tubes onto the ascending aorta and main pulmonary artery. After careful deairing of the tubing and ventricles, the console was activated and the bypass progressively discontinued. Heparin infusion was begun 3 hours after chest closure and was continued for the duration of assist pumping, which was 2 to 11 days (mean duration, 7.43 days). The system could provide a complete support of the circulation with both right and left ventricular index remaining stable at 2.4 to 3 L/min/m2. After a dramatic improvement at the time of the system activation, the urinary output remained adequate, thus allowing for a decreasing need for diuretic therapy. In two cases, including one of isolated left ventricular assist pumping, the circulation could be totally supported during 11 hours and 23 hours, respectively, of refractory ventricular tachycardia. Four of six patients were shortly weaned from inotropic agents. Hematologic studies showed a moderate decrease of the coagulation factors level during the first 6 hours of circulatory support, and this remained stable and within normal limits thereafter. There have been three cases of bleeding complications necessitating surgical revision on the sixth hour, the twelfth hour, and the sixth day, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Surgical treatment of aortic dissection. Value of echocardiography and MRI for long-term follow-up]. / Chirurgie des dissections de l'aorte. Intérêt particulier de l'analyse échocardiographique et de l'IRM pour le suivi à long terme.

Twenty-five patients aged 31 to 74 years (average 50 years) operated for type A aortic dissection (type I: 19 cases, type II: 6 cases) were included in this study. Surgical repair only concerned lesions of the ascending aorta. The hospital mortality was 20 per cent (5 cases), and usually secondary to extension of the dissection. With the exception of 2 late deaths, all patients were followed up for an average of 3.5 years. A late assessment including nuclear magnetic resonance imaging of the thoracic aorta was obtained in 17 of the 18 survivors. These investigations confirmed the good result of repair of the ascending aorta, the uselessness of systematic aortic valve replacement and the palliative nature of repair of type I dissection as 80 per cent of patients had a persistent patent false lumen in the distal aorta.

[Surgical treatment of complete atrioventricular canal. Value of the "composite double patch" technic]. / Traitement chirurgical des canaux atrio-ventriculaires complets. Intérêt de la technique de la "double pièce composite".

Between January 1, 1982 and January 1, 1988, 49 complete corrections of complete atrioventricular canal were performed in children aged from 4 months to 8 years. 41 were infants less than 2 years' old and 31 were less than one year old. In the last 35 patients the "composite double patch" technique was used, consisting of closure of the interventricular septal defect with a dacron patch, followed by closure of the ostium primum with a pericardial patch. The mitral cleft was left intact in the last 6 operations. The overall mortality rate was 35 p. 100 (17 patients). It was 23 p. 100 in infants under 1 year and 17 p. 100 in infants aged from 6 to 12 months at the time of surgery (p less than 0.01). Seven of the 35 children in whom the "composite double patch" technique was used died (20 p. 100). Only one early death was recorded among the last 15 children operated upon. Two reoperations were performed: one within one month of the first operation, the other 4 months later for residual mitral regurgitation with haemolysis. 32 children were followed up for periods of 2 months to 6 years, 10 of them for more than 3 years. Two late deaths occurred during the follow-up. Grade 2 or 3/4 residual regurgitation was found in 14 patients who have regular clinical and echocardiographic examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Technic for implanting biventricular external assistance devices. Pending cardiac transplantation]. / Technique d'implantation des procédés d'assistance biventriculaire externe. En attente de transplantation cardiaque.

The extensive development of orthotopic heart transplantation results in a relative shortage of grafts. When cardiac grafts are unavailable, some patients at the end-stage of decompensated heart failure may benefit from a biventricular external circulatory assistance device as a "bridge" to transplantation. We describe a reproducible technique for the implantation of such external devices, based on the systematic use of extracorporeal circulation. This technique was tested in 8 patients. Its main advantage is that it prevents thromboembolic complications which are a constant threat when the devices are used for a prolonged period.

Magnetic resonance imaging of human orthotopic heart transplantation: correlation with endomyocardial biopsy.

The ability of magnetic resonance imaging (MRI) to detect allograft rejection was studied concomitantly in two centers. In 29 patients MR images performed on a 0.5 T imager were compared with pathologic findings obtained by transvenous right ventricular endomyocardial biopsies. Eight patients had grade 1 or 2 acute rejection, and their myocardium thickness was increased significantly compared with values obtained in normal volunteers, in normal heart allograft patients, and in patients during the resolving phase of an acute rejection episode, whereas no abnormal signal intensity was found in the myocardium of heart allograft patients with acute rejection. This finding is quite in opposition to what was found in experimental models. This could be the result of the immunosuppressive regimen of those patients including cyclosporine, whereas few experimental studies included cyclosporine treatment. For chronic rejection or fibrosis, MRI did not allow the diagnosis because the MRI appearance was close to normal. Finally, MRI appears as a complementary technique to B-mode ultrasound in detecting nonimmunologic complications such as pericardial effusions and endocavitary processes. These data suggest that MRI could be used in the future to monitor rejection, to guide the timing of endomyocardial biopsy, and to assess the response after immunosuppressive treatment.

[Systematic detection of anti-HIV antibodies in donors before keratoplasty: justification and practical modalities]. / Dépistage systématique des anticorps anti-HIV chez le donneur avant kératoplastie: justification et modalités pratiques.

We recall the medical obligation to perform an HIV serology on corneal donors before keratoplasty. The ways to take samples of blood from a deceased person and the techniques which detect HIV antibodies are discussed. We emphasize on the contribution of preservation mediums in order to complete the investigations on the etiology of the death in non urgent keratoplasty. We also insist on the contribution of ELISA techniques to rapidly obtain the HIV serology in non urgent corneal grafts. The real risks of transmitting HIV virus during keratoplasty are discussed.

[Results of coronary surgery in patients over 70 years of age]. / Résultats de la chirurgie coronaire après 70 ans.

Among the 628 consecutive patients who underwent coronary bypasses performed by the same surgical group between January 1, 1982 and December 31, 1987, 71 (11 p. 100) were aged 70 years or more (mean: 72.5 years; range: 70-83 years). 99 p. 100 of the patients had a history of severe, disabling exertional angina (46 p. 100) or unstable angina (52 p. 100) of 55 months' duration on average; 35 patients (49 p. 100) had already experienced myocardial infarction. Coronary angiography showed a one-vessel disease in 1 case, a two-vessel disease in 1 case, a two-vessel disease in 31 cases and a three-vessel disease in 39 cases; 11 patients (15 p. 100) had stenosis of the left main coronary artery. The ventricular function was considered unaltered in 59 cases (83 p. 100). Altogether, 155 bypasses, including 25 internal mammary grafts, were performed, i.e. an average of 2.2 bypasses per patient. There was only one early (21st day) post-operative death. The post-operative period was uneventful in 57 patients (60 p. 100); 9 developed peri-operative necrosis. Seventy patients have been followed up for a mean period of 24 months: there were 3 late deaths of non-cardiac origin; 60 patients (84.5 p. 100) are now asymptomatic and 3 (4.5 p. 100) are suffering from residual angina. Early mortality excluded, the cumulative probability of survival at 5 years is 94 p. 100.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgery of the thoracic aorta. Value of tissucol]. / Chirurgie de l'aorte thoracique. Intérêt du tissucol.

The techniques for sealing with the Tissucol fibrin glue, used in repair of aortic dissections and aneurysms, are described. We applied this method to 24 patients operated upon for acute (9 cases) or chronic (15 cases) lesions of the thoracic aorta. No patients died of haemorrhage, and post-operative bleeding was only 500 ml on average. Provided strict precautions are taken, this adjuvant haemostatic method considerably improves the immediate prognosis of acquired aortic lesions. Other operations of cardiac surgery may benefit from these sealing techniques the cost of which must be weighed against the blood transfusion units that are saved.

[Aortic valve replacement using the Björk-Shiley valve. Long-term results (268 patients)]. / Remplacement valvulaire aortique par prothèse de Bjork-Shiley. Résultats à long terme (268 patients).

From 1974 till November, 1986, 268 adult patients aged from 15 to 84 years (11 p. cent over 70) underwent isolated aortic valve replacement by Björk-Shiley prosthesis. 81 p. cent of the prosthetic valves implanted were size 21 or over. The initial lesion was aortic stenosis (AS) in 40 p. cent, aortic regurgitation (AR) in 35 p. cent and aortic disease (AD) in 25 p. cent of the cases. The aortic valve lesions were degenerative (46 p. cent), rheumatismal (18 p. cent), congenital (12 p. cent), infective (19 p. cent including acute infective endocarditis) or dystrophic (7 p. cent) in origin. Pre-operatively, 54 p. cent of the patients were in NYHA functional class III and 14 p. cent in NYHA functional class IV. 7 p. cent presented with permanent atrial fibrillation. Mean pre-operative cardiac index was 2.49 1/mn/m2. Peri-operative mortality (up to 30 days) was 7.09 p. cent in both the 1974-79 period and the 1980-86 period; it was 3.4 p. cent in AS, 7.4 p. cent in AD and 10.7 p. cent in AR. The 249 survivors were followed up for a mean period of 5.3 years, or 1313 patient-years. 30 patients (11 p. cent) died subsequently (11 of prosthesis-related cause), giving an actuarial survival rate of 81.7 p. cent at 5 years and 71.4 p. cent at 10 years. 12 patients were reoperated upon, including 2 for prosthesis-related reasons (2.4 p. cent patient-years).(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical treatment of coarctation of the aorta in the infant less than a year old]. / Traitement chirurgical des coarctations de l'aorte chez le nourrisson de moins de un an.

Between 1972 and 1984, 141 infants of less than 12 months of age were operated upon for coarctation of the aorta. The abnormality was isolated in 41 cases (29 p. 100) and associated with ventricular septal defect (VSD) in 58 cases (41 p. 100), with transposition of the great vessels with or without VSD in 16 cases (11.3 p. 100), with cardiac valve disease with or without VSD in 11 cases (7.8 p. 100) or with miscellaneous intracardiac lesions in 15 cases (10.6 p. 100). Resection-anastomosis (Crafoord) was performed in 89 cases (63 p. 100), subclavian flap aortoplasty (Waldhausen) in 36 cases (26 p. 100) and dacron aortoplasty in 16 cases (11 p. 100). Cerclage of the pulmonary artery was combined with one or another of these operations in 65 cases (46 p. 100). Twenty-five patients (17.5 p. 100) died within 30 days of the operation, and 28 patients (24.7 p. 100 of those who survived surgery) died at a later stage. Three infants were lost sight of. Follow-ups ranged from 1 to 13 years (mean: 4.01 years). Fifteen infants (13.3 p. 100 of those who survived surgery) were reoperated upon for recurrence of the coarctation. Four infants (3.5 p. 100) now present with clinical signs of recoarctation and are awaiting treatment.

[Valvular replacement for isolated aortic stenosis. Predictive value of the preoperative cardiac index in survival]. / Remplacement valvulaire pour sténose aortique isolée. Valeur prédictive de l'index cardiaque pré-opératoire dans la survie.

The immediate and long-term results of aortic valve replacement for pure or predominant aortic valve stenosis were evaluated in 186 patients operated upon since 1975 and followed for up to 10 years. This population fell into two groups depending on whether the pre-operative cardiac index was superior (group I, n = 111) or inferior (group II, n = 75) to 2.3 l/min/m2. There was no significant difference between the two groups as regards the immediate (i.e. within 30 days) post-operative mortality rate (6.6% vs 8.1% respectively). In contrast, the cardiac index proved to be a significant post-operative prognostic factor in aortic stenosis, since the probability of survival at 5 years was 96.4% in group I and only 71.7% in group II (p less than 0.001). This high rate of mortality in group II was exclusively due to myocardial dysfunction (sudden deaths included) in these patients with low cardiac index. When late mortality was analyzed according to age (over or below 60 years) and to pre-operative cardiothoracic ratio (over or below 50), these two criteria also proved to be significant prognostic factors. However, considering the poor prognosis of unoperated aortic stenosis, these long-term results in group II should encourage surgical treatment in many cases, even those with advanced cardiopathy.