Fatal metformin overdose: case report and postmortem biochemistry contribution.

Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process.

Níveis críticos de fósforo no solo e na planta para gramíneas forrageiras tropicais, em diferentes idades

Dois experimentos foram realizados simultaneamente, em casa de vegetação, para avaliar os efeitos da idade das plantas e de períodos de rebrotação sobre os valores dos níveis críticos de fósforo no solo e na planta para duas gramíneas forrageiras tropicais. Os tratamentos corresponderam aos arranjos fatoriais 2x5x5, no estudo de crescimento inicial, e 2x2x5, no estudo de rebrotação. Os fatoriais consistiram de duas espécies (Brachiaria decumbens cv. Basilisk e Panicum maximum cv. Mombaça); cinco idades (14, 28, 42, 56 e 70dias após a emergência), durante o crescimento inicial e em dois períodos do estudo da rebrotação (28 e 42dias) após um crescimento inicial de 42dias, e cinco doses de fósforo (0, 64, 128, 320 e 640mgdm-3). Os tratamentos, com três repetições, foram distribuídos em blocos ao acaso. Nos ensaios, utilizou-se amostra de Latossolo Vermelho-Amarelo. Para determinação dos teores de fósforo disponível no solo, foi utilizado o extrator Mehlich-1. Os níveis críticos (NíCrí) de fósforo no solo para B. decumbens foram maiores do que para P. maximum Os NíCrí no solo decresceram exponencialmente com a idade das plantas de 95,1 e 75,6mgdm-3, aos 14dias, para 38,1 e 28,4mgdm-3, aos 70dias, com relação a B. decumbens e P. maximum, respectivamente. Na fase de rebrotação, os NíCrí no solo foram semelhantes nos dois períodos, com valores próximos aos estimados para as plantas aos 70dias. Os NíCrí de fósforo na parte aérea das plantas decresceram exponencialmente de 0,57 e 0,60dagkg-1, aos 14dias, para 0,08 e 0,07dagkg-1, aos 70 dias, com relação a B. decumbens e P. maximum, respectivamente. B. decumbens apresentou maiores valores de NíCrí de fósforo na parte aérea das plantas, exceto na idade de 14dias. Na fase de rebrotação, os NíCrí na parte aérea foram maiores aos 28dias, diminuindo, aos 42dias, para valores similares aos estimados nas idades de 56 e 70dias, no crescimento inicial. Assim, para avaliação criteriosa do estado nutricional da planta em termos de fósforo e recomendação de fertilização, recomenda-se considerar a idade das plantas após o plantio da forrageira e a cada ciclo de crescimento.

Droit commercial

Chronique de jurisprudence et de législation pour l'année 2008

Weight-bearing bones are more sensitive to physical exercise in boys than in girls during pre- and early puberty: a cross-sectional study.

We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. BACKGROUND: Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. METHODS: We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. RESULTS: Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20-0.33, p < 0.01), but not in girls (r = 0.02-0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p < 0.05). CONCLUSIONS: Sex differences in BMC during pre- and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.

Kaschmir, jardin du bonheur : roman (Edition originale) / Renée Dunan

Collection : Oeuvre littéraire inédite. N° 1. Octobre 1925

High activity of Fosfomycin and Rifampin against methicillin-resistant staphylococcus aureus biofilm in vitro and in an experimental foreign-body infection model.

Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 μg/ml; daptomycin, 0.125 μg/ml; vancomycin, 1 μg/ml; rifampin, 0.04 μg/ml; and tigecycline, 0.125 μg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log10 CFU/ml at 128 × the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by <1 log10 CFU/ml with fosfomycin and tigecycline, 1.7 log10 with daptomycin, 2.2 log10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log10 with fosfomycin-daptomycin, and >6.0 log10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cage-associated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 μg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cage-associated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-associated infections, but it cannot replace rifampin as an antibiofilm agent.

Current developments in the radiotherapy approach to elderly and frail patients with glioblastoma multiforme.

The benefit of postoperative radiotherapy (RT) has been demonstrated in elderly patients aged 65 years or older with glioblastoma multiforme. Hypofractionated RT schedules can reduce the time and morbidity of treatment while maintaining comparable survival outcomes to lengthy conventional RT. Current international randomized clinical trials are studying the optimized hypofractionated RT regimens, hypofractionated RT in comparison with temozolomide chemotherapy and hypofractionated RT in comparison with the same RT plus temozolomide. Given the guarded prognosis of the elderly and frail patients, quality of life and side effects of treatment should be closely examined. As more than half of cancers in the world occur in developing countries, hypofractionated RT could be better utilized as a cost-effective treatment for this group of patients.