Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams.

The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable.

[Responsibility due to medication errors in France: a study based on SHAM insurance data]. / Responsabilité liée aux erreurs médicamenteuses : données SHAM.

PURPOSE: The safe medication practices at the hospital constitute a major public health problem. Drug supply chain is a complex process, potentially source of errors and damages for the patient. SHAM insurances are the biggest French provider of medical liability insurances and a relevant source of data on the health care complications. METHODS: The main objective of the study was to analyze the type and cause of medication errors declared to SHAM and having led to a conviction by a court. We did a retrospective study on insurance claims provided by SHAM insurances with a medication error and leading to a condemnation over a 6-year period (between 2005 and 2010). RESULTS: Thirty-one cases were analysed, 21 for scheduled activity and 10 for emergency activity. Consequences of claims were mostly serious (12 deaths, 14 serious complications, 5 simple complications). The types of medication errors were a drug monitoring error (11 cases), an administration error (5 cases), an overdose (6 cases), an allergy (4 cases), a contraindication (3 cases) and an omission (2 cases). Intravenous route of administration was involved in 19 of 31 cases (61%). The causes identified by the court expert were an error related to service organization (11), an error related to medical practice (11) or nursing practice (13). Only one claim was due to the hospital pharmacy. CONCLUSION: The claim related to drug supply chain is infrequent but potentially serious. These data should help strengthen quality approach in risk management.

Metabolic response to the stress of critical illness.

The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

[Management of glycemia: an audit in 66 ICUs]. / Gestion de la glycémie : un audit dans 66 réanimations.

INTRODUCTION: The interest of tight glucose control in ICU is still debated. In France, no data are available regarding this therapy and the implementation of its guidelines. STUDY DESIGN: Sub-study of a one-day audit performed between January and May 2009. PATIENTS AND METHODS: During a one-day audit performed in 66 ICUs, trained residents collected data regarding the presence of a formal glucose control protocol and its practical application. RESULTS: A formalized glucose control protocol was found in 88% of patients. During the day before the audit, 3645 glycemia measurements were performed accounting for six measurements [4-9] per patient with a median higher value of 1.6 [1.4-2.1]. Hypoglycemia (<0.8 g/L) and hyperglycemia (>1.4 g/L in non-diabetic and >1.8 g/L in diabetic patients) were found in 81 (15%) and 326 (58%) patients respectively. Two episodes (0.36%) of severe hypoglycemia (<0.4 g/L) were reported. Factors associated with glucose control protocol application were: a high SOFA score, cardioversion, mechanical ventilation, intracranial pressure monitoring, steroid use and nurse to patient ratio less than 1/2.5. Hepatic failure was the only factor associated with hypoglycemia. DISCUSSION: Glucose control protocols are available in more than 80% ICUs but their implementation is still imperfect. However, the median glycemia meets international current recommendations. Severe hypoglycemia is a very rare event in ICU.

[Activity and the available human resources working in 66 French Southern intensive care units]. / Quelle activité et quels personnels soignants dans 66 unités de réanimation du sud de la France?

BACKGROUND: The aim of the study was to determine the activity and the available human resources working in 66 intensive care unit (ICU). METHODS: One-day audit performed between January 2009 and May 2009 by trained residents. RESULTS: Among 710 beds, 695 (98%) beds were available for 626 patients (occupation rate=90%). The two most frequent causes of admission were shock and pneumonia. On admission, the median SAPS II was 46. More than 75% of patients had at least two organ dysfunctions within their ICU stay (respiratory failure=80%, circulatory failure=67%). At the moment of the audit, the median SOFA score was 3, and 549 (88%) patients had required a billing procedure with an admission SAPS II greater or equal to 15. Twenty seven percent of ICUs had a ratio patients/nurses or patients/aid nurse greater than 2.5 and 4, respectively whereas 58% ICUs had a ratio open beds/nurse greater than 2.5 or open beds/aid nurse greater than 4. CONCLUSION: In this study, more than 75% patients had at least two organ dysfunctions within their ICU stay and 88% required a billing procedure and had an admission SAPS II greater or equal to 15. Nevertheless, the staff resource remained below the 2002 decree in 27% ICUs.

[Secondary hyperkalaemic acute flaccid tetraplegia]. / Tétraplégie flasque aiguë secondaire à une hyperkaliémie.

A 57-year-old man with chronic renal failure and multiple vascular diseases presented an acute flaccid tetraplegia. Blood tests revealed renal failure with serum potassium of 9.69 mmol/l. The medullar and brain MRI were normal. The correction of the hyperkalaemia led to a fast and complete neurological recovery. This fact confirmed the diagnosis of secondary hyperkalaemic tetraplegia.

EFFECT OF PHALLOIDIN ON FILAMENTS POLYMERIZED FROM HEART MUSCLE ADP-ACTIN MONOMERS.

The effect of phalloidin on filaments polymerized from ADP-actin monomers of the heart muscle was investigated with differential scanning calorimetry. Heart muscle contains alpha-skeletal and alpha-cardiac actin isoforms. In the absence of phalloidin the melting temperature was 55 degrees C for the alpha-cardiac actin isoform and 58 degrees C for the alpha-skeletal one when the filaments were generated from ADP-actin monomers. After the binding of phalloidin the melting temperature was isoform independent (85.5 degrees C). We concluded that phalloidin stabilized the actin filaments of alpha-skeletal and alpha-cardiac actin isoforms to the same extent when they were polymerized from ADP-actin monomers.

Restenosis after balloon angioplasty for cerebral vasospasm.

Transluminal balloon dilatation for symptomatic vasospasm after subarachnoid hemorrhage is effective, and clinical studies have shown that it achieves long-lasting dilatation of spastic cerebral arteries. Delayed arterial renarrowing has not been reported. Here we report the case of a 58-year-old woman who presented asymptomatic and permanent restenosis after angioplasty for cerebral vasospasm.

[Hierarchical strategy for treating elevated intracranial pressure in severe traumatic brain injury]. / Hiérarchisation des traitements de l'hypertension intracrânienne chez le traumatisé crânien grave.

The objective of the treatment of intracranial hypertension is to decrease intracranial pressure (ICP) while maintaining cerebral blood flow (CBF). Despite numerous treatments, none of them associates total efficiency and security. Systemic secondary cerebral injuries, which are responsible for cerebral ischemia, lead us to administer non specific treatments in order to optimize CBF and cerebral oxygenation. Thus, the goals are: 1) to maintain cerebral perfusion pressure> or =70 mmHg; 2) to control metabolic status by preventing hyperglycaemia, anaemia and hyperthermia; 3) to maintain normoxia and normocapnia (hypercapnia increases ICP and hypocapnia decreases CBF). Beside the neurosurgical evacuation of extra- and intraparenchymatous haematomas, osmotherapy and cerebrospinal fluid (CSF) evacuation are the two specific treatments of intracranial hypertension. Osmotherapy consists in an administration of a hypertonic solution which induces a decrease in cerebral water and finally in ICP. Mannitol (20%), which is the reference, associates osmotic and rheologic effects, and decreases CSF production too. Recent data conduct us to administer larger doses, between 0.7 and 1 g/kg in 15 minutes. Hypertonic saline solution associates osmotic effects and plasma volume loading. Thus, this solution is particularly appropriate in severe head injury with arterial hypotension. CBF evacuation decreases rapidly ICP without any major side-effect. Until now, there is no proof of a superior efficiency of a treatment for intracranial hypertension compared to another. Considering their mechanism of action, all of them are efficient but potentially dangerous too. Indeed, the choice between treatments depends on data which are issued from the multimodal monitoring. General non specific treatments are always necessary. Specific treatments are indicated if ICP is above 20-25 mmHg. Maintaining cerebral perfusion pressure represents the first therapeutic goal. If intracranial hypertension persists, evacuation of CBF or osmotherapy may be advocated. In case of refractory intracranial hypertension, it may be useful to deepen neurosedation. Controlled hypocapnia and barbiturates remain a third line therapy providing to monitor and maintain an appropriate CBF and cerebral oxygenation. Controlled hypothermia and decompressive craniectomy must be individually discussed.

[Metformin-associated lactic acidosis]. / Acidose lactique et metformine.

OBJECTIVE: The aims of this review are to precise the pathophysiological mechanisms leading to biguanide-associated lactic acidosis, to give elements of diagnosis, and to underline the precautionary conditions for prescribing these drugs by an improvement in physicians and patient's education. DATA SOURCES: A PubMed database research in English and French language reports published until December 2005. The keywords were: lactic acidosis, metformin, biguanide, diabetes mellitus. DATA EXTRACTION: Data in selected articles were reviewed, clinical and basic science research relevant informations were extracted. DATA SYNTHESIS: Metformin, which is an oral antidiabetic agent, is the only one biguanide available in France. It acts by enhancing the sensitivity to insulin by a decrease in the hepatic glucose production and an increase in its peripheral use. In term of glycemic control, it has the same efficiency than the other hypoglycemic agents. It represents the treatment of choice for overweight type 2 diabetic patients because of its beneficial effects on the weight loss and on the cardiovascular complications. The incidence of metformin-associated lactic acidosis is very low when contra-indications and appropriate rules for prescribing this drug are respected. The relationship between metformin and lactic acidosis remains largely controversial. In practical, we can distinguish three situations which have different prognosis. In the first case, metformin seems to be responsible for lactic acidosis because of self-poisoning or accidental overdose, and prognosis is good. In the second case, the association between metformin and lactic acidosis is coincidental rather than causal, and may be induced by an underlying organ failure. In the last case there is a cause of lactic acidosis which is worsened by a precipitating factor leading to metformin accumulation. The 2 latter situations are very severe as mortality rate is about 50%. Symptomatic treatments and renal replacement therapy which allows metformin removal are the curative treatment. Prevention is essential. It requires the respect of metformin contraindications and a better education of physicians and patients for a safe prescription. CONCLUSION: Due to its beneficial effects, metformin is the gold standard treatment for overweight type 2 diabetic patients. The essential precautionary conditions for prescribing metformin as well as the respect of its contra-indications permit largely to prevent lactic acidosis. This complication is serious when it is associated with intercurrent illnesses and metformin accumulation. The curative treatment is based on renal replacement therapy. Prevention only rests on the respect of the contra-indications. Education of physicians and patients concerning the rules of prescription remains essential.

Effects of acetylcysteine and ischaemic preconditioning on muscular function and postoperative pain after orthopaedic surgery using a pneumatic tourniquet.

BACKGROUND AND OBJECTIVE: The use of a pneumatic tourniquet can induce muscular and neurological complications in the operated limb. The genesis of these injuries could involve an ischaemia/reperfusion phenomenon and a compression under the cuff. We evaluated effects of an antioxidant, acetylcysteine and ischaemic preconditioning on the rhabdomyolysis and postoperative pain following a knee ligamentoplasty using a pneumatic tourniquet. METHODS: We included 31 patients scheduled for a knee ligamentoplasty randomly assigned in three groups (control, acetylcysteine 1200 mg the day before and 600 mg at the operative day, ischaemic preconditioning). RESULTS: There was a moderate rise in myoglobin and creatinine phosphokinase with no significant difference between the three groups. The muscular functional parameters were similar in all the groups. However, the morphine consumption within the first 48 h was smaller in the treatment groups (0.22 +/- 0.31 mg kg-1 and 0.22 +/- 0.23 mg kg-1 in the preconditioning and antioxidant groups, respectively) than in the control group (0.47 +/- 0.33 mg kg-1, P <0.05). CONCLUSIONS: Acetylcysteine and ischaemic preconditioning do not decrease the extent of rhabdomyolysis related to the use of a pneumatic tourniquet and do not improve the postoperative muscle recovery. On the other hand, they allow a significant reduction in the postoperative morphine consumption.

[Septic shock: blood glucose regulation]. / Sepsis sévère: le contrôle glycémique.

Blood glucose regulation is controlled by several hormones, neurological mechanisms and the hepatic autoregulation. Glucose uptake necessitates glucose transporters which are called GLUT. In physiological situation, 80% of glucose uptake of the whole body is produced by the non-insulin dependant tissues, via the GLUT 1 to 3 transporters. Glucose uptake by insulin dependant tissues is mediated by insuline, which activates GLUT-4 transporters. Because of the production of pro-inflammatory mediators (TNF-alpha), sepsis induces hyperglycemia, which results essentially from an hepatic insulinoresistance. This phenomenon leads to an acute load and uptake of glucose by the non-insulin dependant tissues. Hyperglycemia modifies inflammatory and immune reactions and enhances the production of reactive oxygen species. Thus, sepsis has an impact on blood glucose control and conversely. Blood glucose control has been found to decrease mortality and morbidity in critically ill patients. The exact mechanism, by which these beneficial effects are produced, remains controversial, due to euglycemia or to insulin infusion. Probably both mechanisms are implicated. In all cases the beneficial effects seem to be multifactorial: a decrease in oxydative stress, a protective effect in front of the burst suppression, multiple anti-inflammatory effects. The optimum level of blood glucose is still discussed and must be evaluated in further studies. In all cases, blood glucose level must be under or equal to 1,4 g/l. Even no clinical study evaluates precisely the impact of hyperglycemia during sepsis, a lot of arguments supports that blood glucose level must be a therapeutic goal in these situations.

[Pasteurella multocida meningo-encephalitis with aphasia in a young adult]. / Méningoencéphalite à Pasteurella multocida avec aphasie chez une adulte jeune.

We report the first case of Pasteurella multocida meningo-encephalitis with aphasia in a 28 year-old-patient. The investigations confirmed the diagnosis of bacterial meningitis. But the delay in identification of the organism involved iterative changes of antibiotherapy. The evolution was finally favourable with appropriate antibiotic treatment. The epidemiologic investigation highlighted the responsibility of a patient's cat carrying the same bacterial strain. Finally we discuss the epidemiologic, clinical and therapeutic features of this unusual meningitis.

Validation of dual-energy X-ray absorptiometry in live White Leghorns.

Dual energy x-ray absorptiometry (DEXA) was evaluated for use as a noninvasive tool to monitor skeletal integrity in live laying hens. The objectives of the current study were 1) to validate the use of DEXA in evaluating bone integrity in live birds as compared with excised bones under a normal nutritional regimen as well as in hens fed varying levels of dietary Ca and 2) to correlate densitometric scans with other bone strength criteria and egg traits. Densitometric scans were conducted on the tibia and humerus of live hens at 10-wk intervals from 17 to 67 wk of age. After each scan, bones were excised from euthanized hens to measure breaking strength characteristics and bone ash (experiment 1). Similar measurements were collected at 38, 48, and 58 wk of age from hens fed hypercalcemic (5.4%), control (3.6%), and hypocalcemic (1.8%) diets from 32 to 58 wk of age (experiment 2). The bone mineral density (BMD) and bone mineral content (BMC) between live and excised bone scans were highly correlated (r = 0.85 and 0.92, respectively, P < 0.0001, experiment 1). Densitometric scans of live birds were positively correlated with bone breaking force and bone ash (r = 0.68 and 0.73, respectively, P < 0.001) with little to no correlation with shell traits. In experiment 2, the excised tibial scan had lower BMD and BMC than the live bird (P < 0.01), whereas no difference was detected in densitometric scans of the humerus. The live and excised BMD and BMC of the tibia (r = 0.87 and 0.82, respectively, P < 0.001) and humerus (r = 0.94 and 0.93, respectively, P < 0.001) were highly correlated. Due to the high correlations between live and excised bone scans and the significant correlations of live scans to more traditional invasive bone measurement tests such as bone breaking force and bone ash, we concluded that DEXA is a useful noninvasive tool for evaluating skeletal integrity in live birds.

Effects of ovulatory and egg laying cycle on bone mineral density and content of live White Leghorns as assessed by dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry has been validated in our laboratory as a noninvasive tool to assess skeletal integrity in live birds. The first objective of the current study was to determine if there were detectable changes in bone mineral density (BMD) and bone mineral content (BMC) while an egg was being formed in the oviduct. Implications from this experiment would define the time of day scans should be conducted for future experiments. Densitometric scans were conducted on the tibia and humerus of live hens undergoing active egg formation when hens were 0, 5, 15, and 20 h postoviposition at 24, 30, and 40 wk of age. No detectable changes in either the BMD or BMC of the tibia and humerus were observed as the egg was being formed in the reproductive tract at any age measured. These results suggest that densitometric scans may be conducted on bones in live birds at any time during the day, irrespective of the stage of egg formation. The second objective was to monitor the change and degree of variation in skeletal integrity of live birds during the first cycle of egg laying. The humerus and tibia of White Leghorns were scanned repeatedly at 10-wk intervals from 15 to 65 wk of age. The BMD of the humerus increased from 15 to 65 wk of age, whereas the BMD and BMC of the tibia increased from 15 to 55 wk of age, resulting in a bone-by-age interaction (P < 0.001). The BMC of the humerus did not change from 15 to 55 wk of age but increased at 65 wk of age. Age-related increases in BMD and BMC may be due to the inability of dual energy X-ray absorptiometry to distinguish medullary from structural bone. The CV for BMD and BMC of egg-type chickens was greater than 10% after 25 wk of age, which suggested that bone densitometry could be used as an indicator tool in genetic selection with a potential for improving skeletal integrity of birds.

Assessing bone mineral density in vivo: dual energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry can be used as a noninvasive tool to monitor the skeletal integrity of live birds. A pDexa X-ray bone densitometer was used to determine bone mineral densities (BMD) of the left tibia together with the fibula and the humerus of live, unanesthetized birds. Densitometry effectively detected changes in bone integrity of live birds fed varying levels of dietary calcium. Hens consuming 1.8, 3.6, or 5.4% dietary calcium had BMD of 0.147, 0.157, and 0.176 g/cm2 (SEM = 0.005), respectively (linear effect, P < 0.001). Likewise, bone ash weight, breaking force, stress, modulus of elasticity, and eggshell traits also increased linearly in response to increased calcium in the diet (P < 0.05). Densitometric live scans for BMD were positively correlated (P < 0.001) with bone breaking force (r = 0.65) and bone ash (r = 0.77). We also monitored BMD in live Leghorn and broiler females during their life cycle. The tibial BMD of White Leghorns and broilers increased from 15 to 65 wk of age with the BMD of the broiler tibia increasing at a greater rate than that of the Leghorn tibia (line x age interaction, P < 0.0001). A precipitous drop in BMD occurred during an induced molt of Leghorns subjected to 10 d of feed withdrawal. Our long-term goal is to improve skeletal integrity in egg-type chickens by genetic selection for improved BMD. By crossing a broiler with an egg-laying line, an F2 resource population of birds has been developed to identify quantitative trait loci influencing BMD in chickens.

The use of densitometry to detect differences in bone mineral density and content of live White Leghorns fed varying levels of dietary calcium.

Densitometry was investigated as a noninvasive tool to monitor skeletal integrity in live White Leghorns as an indicator for osteoporosis, a noninfectious disease resulting in mineral loss from the bone. The objectives of the experiment were 1) to assess the ability of densitometry to detect differences in bone integrity in live White Leghorns fed varying concentrations of dietary calcium and 2) to correlate densitometric scans with other bone test methods and production parameters that are sensitive to calcium concentrations in the diet. Hens were fed hypercalcemic (5.4%), control (3.6%), or hypocalcemic (1.8%) diets from 32 to 58 wk of age. A Norland densitometer was used to assess bone mineral density (BMD) and bone mineral content (BMC) of the left tibia and humerus in restrained, unanesthetized hens at 36, 46, and 56 wk of age (experiment 1) and at 38, 48, and 58 wk of age (experiment 2). Bones were excised from hens at 38, 48, and 58 wk of age for breaking strength measurements. Results from the densitometric scans showed that BMD and BMC of the humerus and tibia of live hens decreased linearly when hens consumed diets with decreasing concentrations of calcium (experiment 2). Similar trends in BMD and BMC were detected in experiment 1 at 36 wk of age using BW as a covariate. The results from the densitometric scans were comparable to those obtained from other bone tests commonly used. For example, bone breaking force, stress, and modulus of elasticity decreased linearly as hens consumed decreasing concentrations of calcium. Bone breaking force was correlated with BMD (r=0.65, P<0.001). We concluded that densitometry accurately measures differences in BMD and BMC in live birds fed varying concentrations of dietary calcium.

[Metformin-associated lactic acidosis remains a serious complication of metformin therapy]. / L'acidose lactique reste une complication grave du traitement par metformine.

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin.