Les onze propositions issues des 3es États généraux des malades du cancer et de leurs proches de la Ligue contre le cancer

Sans résumé     

Use of amniotic membrane transplantation in the treatment of venous leg ulcers

Amniotic membrane (AM), the most internal placental membrane, has unique properties including antiadhesive effects, bacteriostatic, wound protection and pain-reduction properties, as well as epithelialization initialization capacities. Furthermore, AM is widely available and less costly than other bioengineered skin substitutes. In a prospective pilot study, we evaluated the safety, feasibility, and the effects on healing of AM graft in 15 patients with chronic venous leg ulcers. AM grafts were prepared from placentas harvested during cesarean section. All grafted AM had adhered to the wound bed 7 days after being applied with a 100% engraftment rate. The percentage of granulation tissue increased significantly (from 17% on day 0 to 69% on day 14, p<0.0001), along with a significant decrease of fibrinous slough (from 36% at day 0 to 16% at day 14, p<0.001). A significant clinical response occurred in 12 patients (80%) including complete healing (20%) in three during the 3-month follow-up period. The ulcer surface area decreased significantly from a mean value (+/- standard deviation) of 4.59 +/- 2.49 cm(2) at baseline to 2.91+/-2.01 cm(2) on day 30 (p<0.001). All patients experienced a significant reduction of ulcer-related pain rapidly after AM transplantation. No adverse events were recorded. AM transplantation seems to function as a safe substrate, promoting proper epithelialization while suppressing excessive fibrosis. Further advantages of biotherapy with AM are its easy and low-cost production, and that it can be applied as an ambulatory treatment without immobilization. AM transplantation may thus be considered to be an alternative method for treating chronic leg ulcers.     

Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Dynamics of bacterial hand contamination during routine neonatal care.

OBJECTIVE: To evaluate the dynamics of bacterial contamination of healthcare workers' (HCWs) hands during neonatal care. SETTING: The 20-bed neonatal unit of a large acute care teaching hospital in Geneva, Switzerland. METHODS: Structured observation sessions were conducted. A sequence of care began when the HCW performed hand hygiene and ended when the activity changed or hand hygiene was performed again. Alcohol-based handrub was the standard procedure for hand hygiene. An imprint of the five fingertips of the dominant hand was obtained before and after hand hygiene and at the end of a sequence of care. Regression methods were used to model the final bacterial count according to the type and duration of care and the use of gloves. RESULTS: One hundred forty-nine sequences of care were observed. Commensal skin flora comprised 72.4% of all culture-positive specimens (n = 360). Other microorganisms identified were Enterobacteriaceae (n = 55, 13.8%); Staphylococcus aureus (n = 10, 2.5%); and fungi (n = 7, 1.8%). Skin contact, respiratory care, and diaper change were independently associated with an increased bacterial count; the use of gloves did not fully protect HCWs' hands from bacterial contamination. CONCLUSIONS: These data confirm that hands become progressively contaminated with commensal flora and potential pathogens during neonatal care, and identify activities at higher risk for hand contamination. They also reinforce the need for hand hygiene after a sequence of care, before starting a different task, and after glove removal.     

High resolution solid-state 29si nmr spectroscopy of silicone gels used to fill breast prostheses

We have used ²⁹Si solid-state nuclear magnetic resonance (NMR) spectroscopy to study the chemical structure of the silicone gels in virgin and explanted breast prostheses. Despite evidences of alteration in the morphological appearance of the silicone gel inside the breast prosthesis, our results do not reveal changes in the chemical nature and structure of the silicone gels after implantation. In addition to the main ²⁹Si resonance peak at ?22.26 ppm that corresponds to the resonance frequency of the D repeat unit of the polysiloxane chains, the high sensitivity of our NMR technique allows the detection of very low concentrations of silicone compounds. Within our experimental detection limit of 0.2%, no signal between ?90 ppm and ?150 ppm are observed. This indicates that no silica products are present inside the gel of the prostheses. Furthermore, our ²⁹Si NMR spectra indicate differences in the chemical compositions of the silicone gels from different manufacturers.     

Nerve agent poisoning in primates: antilethal, anti-epileptic and neuroprotective effects of GK-11

 Organophosphorus nerve agents are still in use today in warfare and as terrorism compounds. Classical emergency treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, recent experiments with primates have demonstrated that such treatment, even when administered immediately after organophosphate exposure, does not rapidly restore normal electroencephalographic (EEG) activity and fails to totally prevent neuronal brain damage. The objective of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an antiglutamatergic compound, as a complement to the available emergency therapy against organophosphate poisoning. GK-11 was injected at a dose of 0.1 mg/kg (i.v) after a 45-min latency period to heavily intoxicated (8 LD₅₀) primates. Just after intoxication, man-equivalent doses of one autoinjector containing atropine/pralidoxime/diazepam were administered. The effects of GK-11 were examined on survival, EEG activity, signs of toxicity, recovery after challenge and central nervous system histology. The present data demonstrate that treatment with GK-11 prevents the mortality observed after early administration of classical emergency medication alone. EEG recordings and clinical observations also revealed that GK-11 prevented soman-induced seizures and motor convulsions. EEG analysis within the classical frequency bands (beta, theta, alpha, delta) demonstrated that central activity was totally restored to normal after GK-11 treatment, but remained profoundly altered in animals receiving atropine/pralidoxime/diazepam alone. GK-11 also markedly accelerated clinical recovery of soman-challenged primates. Lastly, this drug totally prevented the neuropathology observed 3 weeks after soman exposure in animals treated with classical emergency treatment alone. GK-11 represents a promising adjuvant therapy to the currently available emergency polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in a human clinical trial for a different neuroprotective indication. Received: 16 June 1997 / Accepted: 23 September 1997     

Treatment of hepatitis B and C after liver transplantation. Part 2, hepatitis C

Abstract End-stage liver disease caused by the hepatitis C virus is a major indication for liver transplantation. However, recurrence of hepatitis in the graft is a major issue. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 60%–80% of patients, and 6%–28% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by antiviral drug side effects. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25% of patients, but indications, modality and duration of treatment should be assessed.     

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Biphasic insulin aspart given thrice daily is as efficacious as a basal-bolus insulin regimen with four daily injections: a randomised open-label parallel group four months comparison in patients with type 2 diabetes.

AIMS: To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp). METHODS: A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI< or =30 kg/m (2)) or BIAsp 50 (BMI>30 kg/m (2)) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated. RESULTS: Mean HbAlc (+/-SD) decreased from 9.1+/-0.7% to 7.8+/-1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups. CONCLUSIONS: A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.