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Biomedical subjects

L Loutan

Publications and source records attributed to L Loutan.

63 records · Page 4Linked to original sources

[Metabolites of hypoglycemic sulfonylureas in kidney failure. Experience with glibenclamide].

Renal insufficiency is a factor which predisposes to hypoglycemic accidents in subjects treated with hypoglycemic sulfonylureas. Glibenclamide (glyburide) is eliminated from the body mainly by metabolism, with the result that renal insufficiency has little effect on its biotransformation. In order to determine to what extent the retention of the metabolities intervenes in such hypoglycemic accidents, rats with ligatured ureters received intraperitoneal injections of 1 mg/kg glibenclamide or hydroxy-glibenclamide (the main metabolite), or of saline. For each animal there was a control animal which had undergone a simulated operation. For six rats with renal insufficiency, glibenclamide caused hypoglycemia of the same intensity as in the control group but more prolonged. With hydroxy-glibenclamide the glycemia was signficantly lower than in the control group. Hydroxy-glibenclamide has an obvious hypoglycemic activity which represents 1/6 of that of the parent drug, but 50--100 times that of tolbutamide. Its retention contributed to the intensification and prolongation of the hypoglycemic effect of glibenclamide in rats with renal insufficiency.

Acute Kidney Injury↗

[Hypoglycemic sulfonylurea metabolites: clinical interest. Experiences with glibenclamide in the rat].

Glibenclamide, a hypoglycemic sulfonylurea, is extensively metabolized by the body and eliminated primarily in the form of its hydroxylated derivatives. The major metabolite, 4-trans-hydroxy-glibenclamide, is usually cleared rapidly from the bloodstream, but in certain pathological states (e.g. renal failure) blood levels of this product may increase. A protocol therefore was designed to test the hypoglycemic potency of this important metabolite in rats. Various quantities were injected intraperitoneally, and alterations in blood glucose concentrations were measured during a 5-hour period and compared to those in animals similarly treated with glibenclamide and in saline-injected controls. Using the dose capable of decreasing blood glucose levels by 30% (ED30) as a comparative index, it was observed that the metabolic has a marked hypoglycemic activity; though 6--7 times less potent than the parent drug, 4-trans-hydroxy-glibenclamide is nevertheless more potent than tolbutamide. Thus, while the glibenclamide metabolite probably has little influence on blood glucose when its clearance is normal, this product may exert marked effects if allowed to accumulate in the blood, as for example in renal failure. Finally, the role of such sulfonylurea metabolites should be taken into account when attempting to explain the occasional excessive and sustained hypoglycemia which occurs in some diabetic patients treated with these drugs.

Animals↗

Sodium stibogluconate cardiotoxicity and safety of generics.

Between April 9 and May 5 2000, an outbreak of fatal cardiotoxicity occurred in Nepal amongst visceral leishmaniasis patients treated with a recently introduced batch of generic sodium stibogluconate (SSG) from GL Pharmaceuticals, Calcutta, India. Eight (36%) of 23 patients treated with this batch died, and in 5 (23%) death was attributed to the cardiotoxicity of the drug. This contrasts with the low total death rate (3.2%) and death rate due to cardiotoxicity (0.8%) observed among 252 patients treated between August 1999 and December 2001 with generic SSG from Albert David Ltd, Calcutta, India. These data show that every batch of generic SSG should be subject to rigorous quality control prior to use.

Antimony Sodium Gluconate↗

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline.

Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P = 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.

Adult↗

Skin changes in chronic lymphatic filariasis.

Seventeen men and 31 women with unilateral lower limb lymphoedema attributed to chronic lymphatic filariasis were examined in the filarial out-patient clinic of the Government General Hospital, Madras, India. Skin changes such as skin fold thickening, hyperkeratosis, hypo- or hypertrichosis, pachydermia, pigmentary changes, chronic ulceration, epidermal and sub-epidermal nodules, and clinical intertrigo were observed and compared between the different lymphoedema grades. These lesions are not specific to chronic lymphatic filariasis, and have been described in other conditions displaying lymphostasis. They are thought to be favoured by secondary infections, which should be dealt with appropriately to prevent the progression of the disease and the onset of elephantiasis.

Adolescent↗

Medical evacuations and fatalities of United Nations High Commissioner for Refugees field employees.

BACKGROUND: Over the last 20 years, the number of conflicts and humanitarian interventions has steadily increased, as has the level of insecurity on operation sites. So far, little information is available concerning the morbidity and mortality of expatriates and local employees working in the field for humanitarian agencies. METHODS: A retrospective study was conducted in order to review the causes of medical evacuations and deaths of the United Nations High Commissioner for Refugees field employees. All medical records reported to the headquarter's medical services over 2 years (1994-1995) were collated and analyzed. RESULTS: A total of 199 cases (162 medical evacuations, 37 deaths) was reported over these 2 years for a monthly average of 4,151 field employees. Ninety-four men and 68 women were evacuated, 34 men and 3 women died. Expatriate employees represented two-thirds of the cases. Expatriates from Europe, North America, and Japan represented 58 in 122 evacuated expatriates and 2 in 9 deaths of expatriates. The major causes for evacuation were infectious diseases (17%), obstetric-gynecological conditions (15%), accidents (15%), ophthalmology/ear, nose, throat/dentistry (11%), gastrointestinal diseases (10%). The major causes of fatalities were infectious diseases (41%), cancer (24%), accidents (16%), cardiovascular diseases (11%). Firearms caused 4 fatalities and 2 medical evacuations. Fifty-nine percent of the cases occurred in Africa. CONCLUSIONS: Infectious diseases remain a leading cause of fatalities and medical evacuations, particularly AIDS-related diseases among local African employees. A large number of accidents and obstetric-gynecological conditions was also noted. Special emphasis should be put on preventive measures and access to health care for nationals. Systematic data collection and surveillance would help in designing properly adapted strategies to minimize risks for relief workers in the field.

Adult↗

Safety and immunogenicity of a new inactivated hepatitis A vaccine in concurrent administration with a typhoid fever vaccine or a typhoid fever + yellow fever vaccine.

Two clinical studies were conducted to evaluate the safety and immunogenicity of concomitant administration of a new inactivated hepatitis A (HA) vaccine and either a typhoid fever (Vi) vaccine or a combination of Vi and yellow fever (YF) vaccines. In study 1, 62 healthy adults received HA+Vi into the deltoid muscle on contralateral sides. In study 2, 59 healthy adults received HA and a combined Vi/YF vaccine into the contralateral deltoid muscles. Reactogenicity was evaluated for 14 days following vaccination. Blood samples (for antibody titration) were obtained prior to vaccination on days 0 and 28 in study 1 and prior to vaccination on day 0 and on days 14 and 28 in study 2. The overall rate of local reactions was 19% at the HA injection site and 75% at the Vi injection site in study 1; the rate of systemic reactions was 41%. In study 2, local reactions occurred at 27% and 78% of the HA and Vi/YF injection sites; the rate of systemic reactions was 42%. All reactions were transient. Twenty-eight days after vaccination, the seroconversion rate was 100% for HA antibodies and 90% for the Vi vaccine in study 1. Rates of seroconversion in study 2 were 100% for the HA vaccine, 92% for the Vi vaccine, and 100% for the YF vaccine. Although this study was not comparative, both tested combinations were safe and immunogenic, and their routine use for persons at risk, such as travelers, can be recommended.

Adolescent↗