Sepsis of the hip due to pressure sore in spinal cord injured patients: advocacy for a one-stage surgical procedure.

STUDY DESIGN: Retrospective study reporting characteristics and management of septic arthritis of the hip due to pressure sores in spinal cord-injured patients. OBJECTIVES: To describe clinical and biological data of septic arthritis of the hip and its treating management. SETTING: The database of the regional SCI referral center, Nantes, France. METHODS: We retrospectively collected data from 33 cases of septic arthritis of the hip in the medical files of 26 patients. RESULTS: We analyzed 33 cases of septic arthritis of the hip treated in one French referent center for spinal cord-injured patients from January 1988 to December 2009. Most patients had a thoracic complete paraplegia and nearly two-third (17 out of 26) had no systematic follow-up. In 25 out of 33 cases, the septic arthritis of the hip was due to a trochanteric pressure sore. The causal pressure sore was most frequently associated with a persistent drainage. The standard radiological examination led to the diagnosis in 30 cases and, in 7 questionable cases, magnetic resonance imaging was more contributory. Surgery always consisted of a wide carcinological-like excision and of a subtrochanteric proximal femoral resection including both greater and lesser trochanters. A musculocutaneous flap was realized for all cases and the choice of the muscle depended on the localization of the causal pressure sore but also of the remaining choices, as most of the patients had already undergone a prior surgery. An antibiotic treatment was adapted to multiple samples during surgery. CONCLUSION: We do advocate for a one-stage procedure including a subtrochanteric proximal femoral resection and a musculocutaneous flap.

[Recommendations for pediatric oxygen therapy in acute and chronic settings: Needs assessment, implementation criteria, prescription practices and follow-up]. / Recommandations pour l'oxygénothérapie chez l'enfant en situations aiguës et chroniques : évaluation du besoin, critères de mise en route, modalités de prescriptions et de surveillance.

Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com.

[Recommendations for pediatric oxygen therapy in acute and chronic settings: needs assessment, implementation criteria, prescription practices and follow-up]. / Recommandations pour l'oxygénothérapie chez l'enfant en situations aiguës et chroniques : évaluation du besoin, critères de mise en route, modalités de prescription et de surveillance.

Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com.

[Severe skin reaction with mucous membrane inflammation during MINE chemotherapy]. / Réaction cutanée sévère avec mucite au cours d'une chimiothérapie de type MINE.

BACKGROUND: MINE chemotherapy is used to treat refractory Hodgkin's disease. Cutaneous adverse effects of MINE regimen are uncommon and chiefly consist of erythema and oedema of the extremities. More recently, a number of cases of panniculitis and subcutaneous inflammatory oedema have been described. OBSERVATION: We report the case of a 17-year-old girl developing acute and painful oedema of the limbs with panniculitis of the trunk. This incident was associated with inflammatory lesions of mucous membrane, in particularly in the genital area and on the tongue. These signs occurred 7 days after initiation of MINE chemotherapy, with no other drugs being introduced. A drug-induced reaction was suspected due to the absence of any other aetiology, particularly infectious disease. The condition gradually improved with symptomatic pain therapy. The patient's chemotherapy was subsequently modified. DISCUSSION: The chronology of the symptoms, spontaneous improvement after the end of treatment, and the absence of other potential causative factors resulted in a hypothesis of a cutaneous adverse reaction to the MINE regimen. The signs could be due to capillary leak syndrome resulting from the toxicity of vinorelbine on endothelial cells. Dermatologists should be aware of these cutaneous adverse effects and of the inflammatory lesions of mucous membrane newly described herein.

[Treatment of homozygous familial hypercholesterolemia with LDL-apheresis on a 4-year-old child]. / Traitement d'une hypercholestérolémie familiale homozygote par LDL-aphérèse chez un enfant de 4 ans.

Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease associated with increased atherosclerosis, resulting in premature death near the age of 20 years. Treatment requires the LDL-apheresis system. M, born from a consanguineous union, suffers from HFH (total-cholesterol=12.29 g/l, LDL-cholesterol=9.65 g/l). Diet and drug treatment was not associated with decreased LDL-cholesterol. At the age of 4.5 years (body weight: 16.7 kg), M began treatment with LDL-apheresis. Apheresis treatment was given every 2 weeks using the Direct Adsorption of LIpoprotein (DALI system, a process that involves total-blood filtration. During the first 26 sessions, the mean reduction in LDL-cholesterol was 67+/-12%, while HDL-cholesterol decreased by only 17+/-11%. Mean LDL-cholesterol concentration decreased from 6.54+/-0.93 g/l (before apheresis) to 2.21+/-0.95 g/l (after apheresis). Apart from iron deficiency anemia, no major side effects were observed. LDL-apheresis using the DALI system is associated with significant reductions in LDL-cholesterol (similar to reports from the literature) without major side effects, even in a child weighing less than 20 kg. A long term, multinational (European) study is needed to confirm these results.

[Exercise alveolar hypoventilation in long-term survivors of bronchopulmonary dysplasia]. / Hypoventilation alvéolaire à l'exercice chez des enfants avec dysplasie bronchopulmonaire.

BACKGROUND: We aimed to confirm that children who have survived bronchopulmonary dysplasia (BPD) display lower ventilation during exercise than healthy children, and to determine whether alveolar hypoventilation associated with exercise-induced hypoxemia occurred in these children. METHODS: Twenty children with BPD (birth weight 1441+/-523 g [mean +/- SD], gestational age 31+2.3 weeks), aged 7 to 14 years, and 18 matched healthy children, born at term, performed resting pulmonary function and cardiopulmonary incremental exercise tests. Arterialized capillary blood gases were measured at rest and at maximal exercise in the BPD group. RESULTS: The BPD group showed moderate expiratory airflow limitation and hyperinflation. Maximal oxygen uptake and ventilatory threshold were similar in the two groups. The BPD group displayed ventilatory limitation on exercise, with greater use of the ventilatory reserve (p<0.01), lower maximal ventilation (p<0.01), tidal volume (p=0.01). Changes in ventilation (p<0.0001) and tidal volume (p=0.003) during exercise were significantly smaller in the BPD group than in controls, at similar submaximal workloads. At peak exercise, we observed hypoxemia in 12 BPD children (60%). In the subgroup with hypoxemia, a significant increase in PaCO2 (p=0.01) was measured at peak exercise, showing alveolar hypoventilation sustained by the lower tidal volume. CONCLUSIONS: Despite normal maximal aerobic performance, BPD children showed ventilatory limitation on exercise, frequently with hypoxemia and alveolar hypoventilation. Despite an improvement in their pulmonary condition, continued follow-up by cardiopulmonary exercise testing, is strongly recommended.

Human leukocyte elastase hydrolysis of peptides derived from human elastin exon 24.

In normal and pathological tissues, polymorphonuclear leukocyte proteases (elastase, cathepsin G and proteinase 3) may generate soluble peptides through limited proteolysis of elastin, the main component of mature elastic fibres. Elastin-derived peptides display diverse biological activities including cell migration, differentiation, proliferation, chemotaxis, tumor progression and up-regulation of metalloproteinases. To be biologically active, their structures must adopt a beta-turn conformation which accommodates to the cell surface-located elastin binding protein. In this study, we established that human elastin exon 24-derived peptides are hydrolysed by leukocyte elastase, when the active site is fully occupied (from S(5) to S'(3)). As shown by mass spectrometry analyses, a major cleavage site was demonstrated at a Val-Ala bond and a minor one at Gly-Val bond. For longer peptides, the hydrolysed fragments could themselves be re-hydrolysed. If the shortest fragments do not contain the GxxPG sequence known to stimulate cellular effects, some of the intermediates together with hydrolysis fragments generated by other proteases such as proteinase 3, may possess this motif.

Proteinase 3 hydrolysis of peptides derived from human elastin exon 24.

In normal and pathological tissues, elastin-derived peptides proceed of elastin degradation by polymorphonuclear leukocyte proteases: elastase, cathepsin G and proteinase 3. They were demonstrated to have a chemotactic activity, to promote cell proliferation and protease release, . . .. To be biologically active, their structures, which reflect elastase specificity, must adopt a beta-turn conformation which accommodate to the cell surface-located elastin binding protein. In this study, we establish that human elastin exon 24-derived peptides containing at least two repeated VGVAPG sequences are hydrolyzed by the proteinase 3 (Pr3). As shown by mass spectrometry analyses, the demonstrated cleavage sites are in agreement with previously reported Pr3 substrate specificity and its lengthy substrate binding site. The characterization of the Pr3-generated products indicate that they contain at least one GXXPG sequence known to stimulate cellular effects after binding to the elastin receptor.

Recent trends in protease-catalyzed peptide synthesis.

Enzymatic peptide syntheses may be either thermodynamically- or kinetically-controlled. The former may be catalyzed by any proteases; the latter is limited to serine and cysteine proteases. This methodology is quite stereospecific and avoids side chain protection but is suffering of some drawbacks. Thus, only two industrial processes are by now developed: the production of aspartame and the conversion of porcine into human insulin. However, recent improvements have been carried out in different directions: 1-Search for proteases with high and/or new P'1 and P1 specificities. 2-Protease engineering to promote synthesis towards hydrolysis and to enlarge specificity. 3-Development of mimetic or "inverse" substrates to limit further hydrolysis of synthesized peptide. 4-Change of the physical state of reactants. Three axes have mainly be explored: solid-solid conversion, use of cross-linked enzyme crystals (CLEC) and enzyme immobilization. 5-Modification of experimental conditions. The principal and recent developments deal with: heterogeneous catalysis, synthesis in low water-containing organic solvents, in ionic liquids or at subzero temperatures. This review will illustrate these new orientations with examples described in the recent literature.

[Obstetrical prognosis of labour induction with mifepristone after 41 weeks of gestation]. / Pronostic obstétrical du déclenchement artificiel du travail au-delà de 41 semaines d'aménorrhée en fonction de la réponse à la mifépristone.

OBJECTIVE: To compare the mode of delivery in two groups of patients selected by their response after induction of labour with mifepristone. PATIENTS AND METHODS: We studied retrospectively 89 cases of labour induction with viable children after 41 weeks of gestation. Bishop scores were less than 6. Patients were given 200 mg of mifepristone per day for 48 h. They were retrospectively divided into group 1 (spontaneous onset of labour or premature rupture of membranes before the third day) and group 2 (not in labour by that date). RESULTS: The mean Bishop score at inclusion was 3.1 +/- 1.3. Among the 51 patients (53.9%) in group 1, one required prostaglandins and we performed 10 cesarean sections. In group 2, the mean Bishop score at the 3rd day was 4.4 +/- 1.3 (P < 0.0001). Twenty-four patients required prostaglandins (P < 0.0001) and we performed 17 cesarean sections (P = 0.01). The number of cesarean sections increased with the dose of prostaglandins (P = 0.025). We observed no maternal or fetal complications. DISCUSSION AND CONCLUSIONS: Mifepristone was successful in inducing labour spontaneously in over 50% of pregnancies after 41 weeks of gestation. In the other group, the probability of vaginal delivery was reduced especially when high doses of prostaglandins were required. After the use of mifepristone, we suggest to shorten the duration of prostaglandin administration (two applications of 2 mg dinoprostone) before performing cesarean section.

Stability of fludrocortisone acetate solutions prepared from tablets and powder.

To assess the stability of fludrocortisone acetate oral solutions prepared from tablets and powder at three temperatures over a 60-days period. Solutions of fludrocortisone acetate 40 microg/ml were prepared from commercially available 0.05-mg tablets and powder in ethanol 17% v/v. They stored in an amber glass prescription bottles at +4, +23 and +40 degrees C shielded from light. The concentrations of fludrocortisone acetate were determined in duplicate by high-performance liquid chromatography at 0, 1, 7, 14, 30, 50 and 60 days. The initial and final pH of solutions were compared. The recovery of fludrocortisone acetate from tablets was determined. The times (t(90)) needed for fludrocortisone acetate to fall to 90% of it's initial concentration were calculated by a linear regression analysis to allow the determination of the expired dates. The recovery of fludrocortisone acetate from tablets was 78 +/- 3%. The t(90) expressed with 95% confidence limits were 2 +/- 1 and 22 +/- 3 days for the solutions prepared from tablets and stored at +23 and +4 degrees C, respectively, whereas t(90) were 11 +/- 2 days and at least 60 days for the solutions prepared with the powder and stored at +23 and +4 degrees C, respectively. No color or odour changes were observed during the study period. The initial pH of the solutions prepared from tablets and powder were 7.7 and 6.9, respectively. No change of pH values was observed at the end of the 60 days. Significant degradation of fludrocortisone acetate occurred in formulations stored at +23 degrees C. Fludrocortisone acetate 40 microg/ml solutions prepared from tablets and powder were stable 19 days and at least 60 days, respectively, when stored at +4 degrees C. The solution prepared from powder is the best in term of stability and final concentration which is independent on the fludrocortisone acetate recovery.

Antithrombotic therapy is associated with better survival in patients with severe heart failure and left ventricular systolic dysfunction (EPICAL study).

BACKGROUND: In patients with congestive heart failure (CHF), clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality. Nevertheless so far, there is no published controlled study of long-term antithrombotic therapy in patients with CHF. The aim of this work was to identify the relationship between cardiovascular drug use, especially antithrombotic therapy, and survival of CHF patients in current clinical practice, using an observational, population-based database. METHODS: The EPICAL study (Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine) has identified prospectively all patients with severe CHF in the community of Lorraine. Inclusion criteria were age 20-80 years in 1994, at least one hospitalisation for cardiac decompensation, NYHA III/IV HF, ventricular ejection fraction < or =30% or cardiothoracic index > or =60% and arterial hypotension or peripheral and/or pulmonary oedema. A total of 417 consecutive patients surviving at hospital discharge were included in the database. The average follow-up period was 5 years. Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival. Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors. RESULTS: Duration of disease >1 year, renal failure, serum sodium > or =138 mmol/l, old age, serious comorbidity, previous decompensation, high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years. Oral anticoagulants, aspirin, lipid lowering drugs and beta-blockers use were associated with better survival. There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival. CONCLUSION: Antithrombotic therapy was associated with a better long-term survival in our study population of severe CHF. These results together with other previously published circumstantial evidence urge for a prospective, controlled and randomised trial specifically designed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure.

SR 142801, a tachykinin NK(3) receptor antagonist, prevents beta(2)-adrenoceptor agonist-induced hyperresponsiveness to neurokinin A in guinea-pig isolated trachea.

We investigated whether fenoterol was able to enhance contractile responsiveness to neurokinin A (NKA) on the guinea-pig isolated trachea. We then studied the effects of two inhibitors of nuclear factor kappa B (NFkappaB), gliotoxin and pyrrolidine dithiocarbamate, and of the tachykinin NK(1), NK(2) and NK(3) receptor antagonists, SR 140333, SR 48968 and SR 142801 and determined whether tachykinin receptor gene expression was up-regulated in the trachea after exposure to fenoterol. Fenoterol (0.1 microM, 15 h, 21 degrees C) induced an increased contractile response to NKA (mean of difference in maximal tension between control and fenoterol +/- S.E.M; +0.47 +/- 0.14 g, n = 26, P < 0.01). This hyperresponsiveness was strongly reduced by co-incubation with gliotoxin (0.1 microg/ml) or pyrrolidine dithiocarbamate (0.1 mM) and abolished by SR 140333 (0.1 microM) and SR 142801 (0.1 microM). SR 48968 (0.1 microM) diminished the tracheal contractility to NKA but failed to reduce the hyperreactivity induced by fenoterol. Tachykinin NK(1) receptor (NK(1)R), NK(2) receptor (NK(2)R) and NK(3) receptor (NK(3)R) gene expression was analyzed by semiquantitative RT-PCR. Compared to control tissues, NK(1)R and NK(2)R mRNA expression was increased by about 1.6-fold and 1.4-fold, respectively, in tissues treated with fenoterol. We were unable to detect the presence of NK(3)R mRNA in the guinea-pig trachea. In conclusion, fenoterol induces tracheal hyperresponsiveness to NKA and an up-regulation of NK(1)R and NK(2)R gene expression. The hyperresponsiveness implicates the NFkappaB pathway and is abolished by tachykinin NK(1) (SR 140333) and NK(3) (SR 142801) receptor antagonists.

[Drugs and drug abusers]. / Médicaments et abus toxicomaniaques.

DRUG ABUSERS: Drugs are widely used by toxicomaniacs to reproduce drug effects. Drug abusers generally start with psychotrops, but other abuse drug classes. Toxicomanic behavior leads to addictive practices that are difficult to control. BARBITURATES: Both the oral and intravenous routes are used. The expected result is a state of ecstasy with a feeling of comfort. Intoxication may cause respiratory depression. Barbiturates induce physical and psychic dependence. Abuse is not widespread with this class of drugs. BENZODIAZEPINES: Drug abuses widely use benzodiazepines orally or intravenously. They search for a flash effect, with sedation and a feeling of comfort. All benzodiazepines induce physical and psychic dependence. Death may result from combinations leading to respiratory depression. Flunitrazepam is the most widely abused benzodiazepine in France. It induces serious neuropsychic disorders. ANTIDEPRESSANTS: Few are used, mostly at high doses. OPIATES: Administration gives the same effect as heroine injection. Opiates induce physical and psychic dependence. The adverse effects are similar to those of morphine with a higher risk of respiratory depression. AMPHETAMINES: Few are used, either orally or intravenously. They induce a flash with excitation, euphoria, and a period of invincibility. This is followed by a period of depression with risk of suicide. Psychic dependence is high. ANTICHOLINERGIC ANTIPARKINSONIANS: These drugs are well known to abusers for their hallucinatory effect. They induce atropinic adverse effects and physical and psychic dependence. GAMMA-HYDROXYBUTYRATE: This anesthetic is used for its euphoria and sedation effects. It may induce falling sickness or coma, with a risk of respiratory depression. KETAMINE: Administered via the intranasal route, ketamine induces a state of indifference. Death has been observed. ANABOLIC AND ANDROGENIC STEROIDS: These drugs are used for their physical and psychic stimulating effect. They induce potentially dangerous adverse effects such as cardiovascular, hepatic, neurological and psychiatric disorders. Clinical signs of addiction and weaning are observed. OTHERS: Several other drug classes are used by abusers, including analgics, beta-adrenergic agents, nasal vasoconstrictors and corticosteroids.

Hydrolysis of glycine-containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in vulnerable hosts. It may produce various virulence factors including proteases. Among them, LasA possesses both elastolytic and staphylolytic (hydrolysis of pentaglycine cross-links in the cell wall peptidoglycan) activities. To understand if its elastolytic activity results from a preference for glycine-rich substrates, we studied its ability to hydrolyse the 65 pentapeptides of human tropoelastin containing at least three glycines. As demonstrated by capillary electrophoresis (CE), 22 of these peptides were hydrolysed by LasA, generally at a single peptide bond and the catalytic ratio kcat/KM was determined for most of them. The highest value was obtained for LGGGA, 59 +/- 9 min(-1) x mmol(-1) x L. The specificity of hydrolysis was elucidated by CE, liquid secondary ion mass spectrometry and, in some cases, collision activated dissociation-mass analysis of ion kinetic energy. The preferred cleavage sites are GG and GA peptide bonds, the sequence GG(cleavage site)A being especially sensitive to hydrolysis. Both positions P2 and P'2 must be occupied for hydrolysis and the presence of an amino acid in P3 (but not in P'3) significantly increases the catalytic ratio. Considering these results, about 30 GGX sequences (X: G, A or Y) of human tropoelastin could be susceptible to LasA elastolysis.

[Staghorn lithiasis in an infant related to mineral water high in calcium]. / Calcul coralliforme du nourrisson lié à la prise exclusive d'eau minérale riche en calcium.

UNLABELLED: Staghorn lithiases in the infant are rare. We report a staghorn lithiasis related to high calcium intake due to the exclusive use of the mineral water Hépar. CASE REPORT: In an eight-month-old infant, an abdominal film performed for repeated urinary symptoms showed a right-sided staghorn lithiasis. Past history revealed that his diet had contained as high as four times the recommended daily intake for calcium (1,750 mg) related to the exclusive use of Hépar mineral water. The latter had been discontinued one month prior to admission. Excessive doses of vitamin D (1,480 U/day) were given at this time. Blood tests were normal. Treatment combined surgical removal of the stone by right pyelolithotomy, and three extracorporeal lithotrity courses. A postoperative infection had a simple course after antibiotics. CONCLUSION: This staghorn lithiasis is the second case report to complications associated with long-term exclusive intake of Hépar mineral water in an infant. It has been likely favored by excessive doses of vitamin D. It emphasizes the danger of the exclusive use of high-calcium mineral water.

Optical remote sensing inside an inhomogeneous axisymmetric medium: the absorption field measurement.

It is shown that the absorption field inside an inhomogeneous, rotationally symmetric medium with a spatially variable refractive index can be reconstructed by means of a tomographic technique. The classic Abel transform is extended to non-Euclidean optical media. The optical behavior of such a medium is described and, provided that the product of the refractive index with the radial distance is a monotonic function, an exact inverse formula is found. Both a numerical and an analytical test on a phantom function is carried out to prove the exactness of this formula. In contrast, when the assumption of a monotonic function is not true, it is shown that the reconstruction problem becomes subdeterminate because of the presence of annular regions, known as blind areas, inside of which no curved path reaches an extremum. The spatial localization and the size of these regions are related to the extrema of the index of refraction times the radial distance.