State of art in 11C labelled radiotracers synthesis.

Positron Emission Tomography has become a powerful scientific and clinical tool probing biochemical processes in the human body. Their clinical applications have proven to be vital in the evaluation and diagnosis of diseases. This is due, in large part, to advances in instrumentation and synthetic chemistry. Carbon-11 is a valuable radionuclide in PET as it virtually permits the synthesis of radiolabelled versions of any compound of interest. The syntheses with carbon-11 present several features: limited number of labelled precursors, sub-micromolar amounts of the starting materials, and a need for the introduction of the radioisotope as late as possible in the synthesis. All of these reasons have restricted complex radiosyntheses. The short half-life of carbon-11 (20.4 min) requires the rapid preparation and purification of carbon-11 labelled molecules. Those have to be carried out immediately before use from cyclotron produced precursors ([11C]CO2, [11C]CO, [11C]CH4) or reagents rapidly prepared from them ([11C]CH3I, [11C]COCl2, [11C]HCN). As a consequence carbon-11 has been underused compared to fluorine-18. However, because of the increasing molecular complexity and diversity of biologically active compounds, there is a need for new methodologies giving access in short time and high yield to radioactive (11)C-probes. The aim of this review is to emphasize the methodologies used in this field and to give a comprehensive overview of the numerous advances, which occurred over the past decade. In addition, for each labelling technique or reaction reported, a special attention has been brought to classify the applications in function of the targeted medical domain.

[Unusual haemostasis disorder in a seriously burned patient]. / Trouble inhabituel de l'hémostase au cours d'une brûlure grave.

We report the case of a woman severely burned during a gas explosion with an unusual disorder of haemostasis. The prothrombin time was very elevated, essentially by a drop in factor II. This abnormality persisted for a long time after the correction of the dilutional and consumption coagulopathy which followed immediately the burn. Blood analysis found fluindione and benzodiazepine derivatives. Such a disorder during a potentially suicidal burn must evoke a toxic aetiology.

[Is training on basic skills and management of critical events responsible of ethical considerations in anaesthesia and intensive care?]. / L'apprentissage des gestes invasifs et de la gestion d'une situation critique pose-t-il des problèmes éthiques en anesthésie-réanimation?

OBJECTIVE: To provide information on morbidity and ethical questions associated with learning of invasive techniques (tracheal intubation, positioning of central venous or epidural catheters) and management of anaphylactic shock. STUDY DESIGN: Retrospective survey. METHODS: Written questionnaire to 54 anaesthesiologists and 55 residents. RESULTS: Training was primarily performed by residents having a 6 months-experience for general anaesthesia and by more experienced residents for epidural analgesia. Residents observed first two or three procedures performed by seniors, but did not have theoretical lectures in 30 to 50% of cases. Dead bodies or manikins were rarely used. Despite the presence of experienced anaesthesiologists during the first attempts, there was a high morbidity rate which was considered by 22 to 37% of the interviewed anaesthesiologists a loss of benefit for the patients. Despite a high level of coaching, a high morbidity rate was associated with the first attempts. However, only few residents explicitly stated to be concerned by ethical questions. Among anaesthesiologists, who had yet to manage anaphylactic shock, 21 and 35% of them reported that diagnostic and treatment could have been performed faster. Virtual learning was misunderstood but 46% of anaesthesiologist described numerous advantages in using simulator of anaesthesia. CONCLUSION: Despite an apparent morbidity with a loss of benefit, informed consent of the patients were rarely obtained.

Inhalation induction using sevoflurane in children: the single-breath vital capacity technique compared to the tidal volume technique*.

The single-breath vital capacity technique is suitable for inhalation induction of anaesthesia, using sevoflurane in children aged > 5 years. The purpose of this randomised trial was to compare the single breath vital capacity technique with the conventional tidal volume technique. Seventy- three ASA 1 or 2 children were instructed during the pre-operative visit in the vital capacity technique. The main criterion measured was time to loss of the eyelash reflex. Induction was performed using a circle-absorber breathing circuit primed with sevoflurane 7% in 50% nitrous oxide/oxygen with 6 l.min(-1) fresh gas flow. Time required for induction, haemodynamic changes, airway tolerance and side-effects were recorded. The children's opinion on the technique used was scored using a visual analogue scale (0-100) and a Smiley scale (0-10). The time to loss of the eyelash reflex was found to be reduced in the vital capacity group compared to the tidal volume group. The time to central myosis, to achieve bispectral index values 60 and 40, haemodynamic changes, respiratory events and side-effect incidences were similar in both groups. However, we found that the vital capacity technique was preferred by the children to the tidal volume technique.

[Butyrylcholinesterase deficiency: how to analyse the cholinesterase activity in small children?]. / Déficit génétique de la butyrylcholinestérase: comment interpréter l'activité cholinestérasique chez le jeune enfant ?

We report the case of a prolonged neuromuscular blockade in an 18-month-old age girl following administration of a usual dose of succinylcholine. The diagnosis was highly suggested by the clinical history while cholinesterase activity was included in adult normal values but below values of a personal series of 41 small children. The familial analysis of dibucaine and fluoride number confirmed the hypothesis of an atypical variant (AA phenotype). The cholinesterase activity is higher in small children than in adult and has to be analysed according to the age.

[Anaesthesia and prostate surgery]. / Anesthésie et chirurgie de la prostate.

OBJECTIVES: To review the current data about anaesthetic management in prostate surgery with special regards on analysis and prevention of specific risks, appropriate anaesthetic procedure keeping with surgery and patient, recognition and treatment of adverse events. DATA SOURCES AND EXTRACTION: The Pubmed database was searched for articles (1990-2004) combined with references analysis of major articles on the field. DATA SYNTHESIS: It is strongly recommended to settle germfree urine in the preoperative period. The thromboembolic risk of radical retropubic prostatectomy for cancer parallels lower abdomen oncologic surgery and is prolonged. Preoperative evaluation of cardiovascular, respiratory, neurological and metabolic comorbidity is a source of prognostic information and an essential tool in the management of elderly patients with prostate disease. Extreme patient positioning applied in prostate surgery induces haemodynamic and respiratory changes and are associated with severe muscular and nervous injuries. The laparoscopic access for radical prostatectomy is a growing alternative to the open surgical procedure. Acute normovolaemic haemodilution is a consistent and cost-effective blood conservation strategy in reducing allogenic blood transfusion for radical retropubic prostatectomy. Whether open transvesical or transurethral prostatectomy for treatment of benign hypertrophy depends on the size of the gland: transurethral resection is safe up to 80 g. Intrathecal anaesthesia with a T9 cephalad spread of sensory block, produces adequate conditions for transurethral prostatectomy and allows a rapid diagnosis of irrigating fluid absorption syndrome. In spite of recommended preoperative antibiotic prophylaxis, bacteriemias are frequent during transurethral prostate resection.

Sedation caused by clonidine in patients with spinal cord injury.

BACKGROUND: In patients with spinal cord injury, cephalad spread of intrathecal (i.t.) medication could be delayed. METHODS: We used bispectral index and an observer scale to assess sedation after two different doses of i.t. clonidine in patients with or without spinal cord injury. Twelve patients with neurological deficit caused by trauma (Spinal Cord Injury, SCI) were compared with patients without neurological disease. They received 10 mg of i.t. bupivacaine with clonidine, with either 50 microg (low dose, n=6) or 150 microg (high dose, n=6) at L(2)-L(3). A further 12 patients, six with spinal trauma lesion and six healthy, received i.t. bupivacaine and 150 micro g of i.m. clonidine. RESULTS: Sedation and a decrease in BIS occurred only in patients receiving 150 microg of clonidine. Onset of sedation and the decrease in BIS was delayed in most spinal cord injured patients whatever the route of administration (P<0.001). Duration of sedation was not different between the groups. Delayed sedation and decrease of BIS after i.t. clonidine in patients with spinal cord injury are similar than those observed after i.m. clonidine. CONCLUSION: A systemic effect is likely to be the main reason for sedation.

Fluoride excretion in children after sevoflurane anaesthesia.

BACKGROUND: Defluorination of sevoflurane is catalysed by the hepatic enzyme cytochrome P450 2E1 (CYP2E1). Data about the ontogenesis (developmental variations in activity) of this enzyme suggest a low metabolism of sevoflurane during the first months of life. METHODS: To test this hypothesis, 45 children less than 48 months of age undergoing sevoflurane anaesthesia were enrolled in a prospective open clinical trial. The 24 h urine fluoride excretion was measured in five groups of children (A, <4 months; B, 4 to <8 months; C, 8-12 months; D, >12-24 months; and E, >24-48 months old). An index of sevoflurane metabolism (ISM) was calculated as the ratio of fluoride excretion, cumulative expiratory sevoflurane concentrations measured every minute during anaesthesia, and body surface area. ISM values were median (IQ 25-75%). RESULTS: ISM was lower in group A (n=9, 18.9 (11.2-29.5) than group C (n=11, 44.2 (37.5-53.5), P<0.05), group D (n=7, 52.6 (45.8-68.4), P<0.01) and group E (n=9, 53.6 (50.7-85), P<0.001). Median ISM expressed as a function of median age, exponentially increased with a rapid increase during the first months of life, followed by a slower increase after 10 months of age. CONCLUSION: These results suggest that, in children less than 48 months, sevoflurane metabolism parallels postnatal development of CYP2E1.

[Anesthesia for cesarean section in a patient with McArdle disease and hereditary dilated cardiomyopathy]. / Anesthésie pour césarienne chez une patiente atteinte d'une maladie de McArdle et d'une cardiomyopathie dilatée familiale.

A caesarean section was indicated in a 29-year-old parturient affected by a muscular deficit in myophosphorylase responsible for a type V glycogen storage disease (McArdle disease). This metabolic myopathy had been diagnosed two years previously, whereas the patient already suffered from a hereditary form of dilated cardiomyopathy. The muscular disease was invalidating on the functional level with exercise intolerance. The cardiopathy was little symptomatic but the dysfunction of the left ventricle worsened during the pregnancy with an ejection fraction calculated to 43%. In this case, we report the realization of a general anaesthesia in a patient who had epidural anaesthesia for a previous caesarean section.

[Evaluation of the cardiac risks in non-cardiac surgery in patients with heart failure]. / Evaluation du risque cardiaque en chirurgie non cardiaque chez l'insuffisant cardiaque.

Cardiac insufficiency represents a major risk factor in patients about to undergo non-cardiac surgery. The post-operative mortality is linked to the severity of the pre-operative functional impairment: rising from 4% in NYHA class 1 to 67% in class IV. The operative risk is greater when the cardiac insufficiency is more disabling, the patient is older (> 70 years) and if there is a history of acute pulmonary oedema and a gallop bruit on auscultation. The use of metabolic equivalents (Duke Activity Status Index) is recommended: the functional capacity is defined as excellent if > 7 MET, moderate between 4 and 7, or poor if < 4. A non-invasive evaluation of left ventricular function is necessary in each patient with obvious congestive cardiac insufficiency or poor control under the American consensus, but it is rare that the patient has not already been seen by a cardiologist. The degree of per-operative haemodynamic constraint is linked to the surgical technique and is stratified according to the type of surgical intervention and whether or not it is performed as an emergency. An intervention duration > 5 hours is associated with an increased peri-operative risk of congestive cardiac insufficiency and non-cardiac death. Deaths from a cardiac cause are thus twice as frequent after intra-abdominal, non-cardiac thoracic or aortic surgery and the post-operative cardiac complications are six times more frequent. Numerous studies have attempted to document the impact of different anaesthetic techniques on the prognosis for the population at increased risk of post-operative cardiovascular complications. It is advisable to opt for peripheral nerve blocks. The cardiovascular morbidity and overall mortality do not differ between general anaesthetic, epidural anaesthetic or spinal nerve block. The ASA (American Society of Anesthesiologists) classification is widely used to determine the overall risk. The ASA class and the age are however too coarse as methods of evaluation for the individual risk and for giving judicious pre-operative advice. Multifactorial cardiac risk indexes such as that of Goldman allow overall evaluation (taking the patient and the intervention into account) of the peri-operative cardiovascular risk in non-cardiac surgery as a function of predictive clinical elements. Nine variables concerning the patient's history, the physical examination and several simple supplementary examinations are identified for which the relative weight is recorded under a points system. The average risk score for a given procedure is converted into an average risk for a given patient using a nomogram such as Detsky's. Surgical acts which do not impose major constraints on the cardiocirculatory apparatus (ophthalmic surgery for example) do not require supplementary examinations. The risk of post-operative cardiac complications is low in the absence of the 9 risk factors defined by Goldman, as is an ischaemic syndrome (angina on light physical activity, unstable angina, myocardial infarction). Certain risk factors (jugular congestion, gallop bruit, recent myocardial infarction, non-sinus rhythm, extrasystoles, aortic stenosis) obviously require appropriate treatment beforehand. The sometimes difficult process demands a dialogue between the cardiologist and the surgeon, the recognition of the risk of surgery in a given centre, and the opinion of the patient duly informed of the terms of the discussion about him.

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands.

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring with different frequencies in patients compared to controls. Two segments were of most interest when the results of the association tests were combined with the probabilities of identity by descent of single haplotypes. For bipolar patients, the strongest evidence for a candidate region harboring a risk gene was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P=0.0075). Patients were tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161--D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands.

Does sevoflurane inhibit serum cholinesterase in children?

Serum cholinesterase activity was measured at induction, and following anaesthesia in 41 children aged between 4 and 30 months. The median exposure to sevoflurane was 273%.min. The results did not demonstrate any significant difference in cholinesterase activity, when expressed by gram of serum proteins following inhalation anaesthesia using sevoflurane or intravenous anaesthesia using propofol. The values (SD) obtained were 175 (42) UI.g(-1) before anaesthesia and 177 (43) UI.g(-1) following anaesthesia. The only change in cholinesterase activity detected was related to heamodilution. We conclude that plasma fluoride concentration following sevoflurane administration [13.8 (4.2) microm x l(-1)] is too low to exert an inhibiting effect on in vivo cholinesterase activity and that the previously reported decrease in mivacurium requirements during sevoflurane anaesthesia is unlikely to be due to inhibition by fluoride ions.

[Discitis after spinal anesthesia for transurethral resection of the prostate]. / Spondylodiscite après rachianesthésie pour résection transurétrale de prostate.

We described a case of discitis and meningitis following spinal anaesthesia for transurethral resection of the prostate. The patient received antibiotics for a month before surgery, because of Klebsiella prostatitis. Spinal anaesthesia was performed in L3-L4 interspace by using 22G Quincke needle. Bacteriaemia occurred during the first postoperative hours. Ten days after spinal anaesthesia, patient suffered from lumbar pain, exacerbated by vertebral percussion, and motor weakness within lower limb, which was marked on right side. MRI examination showed L3-L4 discitis with psoas abcess in regard, and epiduritis marked around L3 right spinal root. CSF examination confirmed meningitis but no bacteria was found. Antibiotics were administered over a 6 weeks period, and then patient discharged from hospital without neurological sequellae. Infectious discitis related to disk puncture during spinal anaesthesia and postoperative bacteriaemia was likely in our patient.

Amniocentesis and amnioinfusion during pregnancy. Report of four complicated cases.

We report two foetal complications after amnioinfusion with dye injection for evaluation of severe oligohydramnios in pregnancy. In the first case, an underskin colouring was to disappear within a few days. In the second case, an irreversible skin after-effect with muscular atrophy and lesion of the underskin tissues developed progressively, although the trained practitioner did not notice any particular resistance during the injection of the dye and the ultrasonographer did not point out that the foetus had been stuck by the needle. Both later reported cases concern two life threatening maternal complications due to amniocentesis for foetal karyotyping indicated by maternal age, a septic shock occurred 24h after entering the amniotic cavity, leading to a long stay in intensive care units. In one of those cases, the patient recovered from a cardiac arrest. We come to the conclusion that the essential continuous ultrasonographic monitoring cannot avoid all complications, some of which may lead to severe adverse foetal effects and others may need an intensive medical care for the mother, mainly after iatrogenic chorioamnionitis. Experience of the perinatologist remains an important factor to limit the complications without avoiding them completely. The indications must be carefully evaluated, the information given to the patients must be clear and in the future, intraamniotic injections of dyes will have to be avoided and replaced by non-invasive tests for diagnosis of preterm premature rupture of membranes, such as diamine-oxidase, foetal fibronectin or PROM-tests. The rules of a good practice will have to be defined and widely spread.