[What do we expect from Radiopharmacy software?] / Qu'attendons-nous des logiciels en radiopharmacie ?

The Radiopharmaceutical Health Products circuit or RHP (radiopharmaceutical drugs, radiopharmaceutical preparation and radioactive implantable medical devices) is a complex process that nowadays requires computerization. This circuit must be in accordance with both the legislation on medicinal products and the legislation on artificial radioelements. It is acknowledged that computerization of the circuit; possibly different within each organization, provides assistance to stakeholders: pharmaceutical analysis of prescription, pharmaceutical preparation and preparation of doses to be dispensed and waste management for example. The software also allows real-time monitoring of the activity and traceability of the various pharmaceutical processes. In addition, they are generally interfaced with equipment used routinely: dose calibrator, dose dispensing equipment. In the absence of any legislation for these software products, which are not considered either as medical devices or as software to assist prescription or dispensation, a working group, under the aegis of the Société Française de Radiopharmacie (SoFRa), has written a minimum set of specifications for these radiopharmaceutical software products. The analyses of the risk maps of different hospital structures allowed a global analysis and synthesis of the different processes, settings, interfaces and requirements for the proper use of these software. The specifications include the very specific requirements of radiopharmacy (notion of radioactive decay, complex preparations with chemical synthesis, traceability.) and will allow software publishers to propose tools adapted to our practice and the RHP circuit.

Using bone marrow matrix to analyze meprobamate for forensic toxicological purposes.

Bone marrow (BM) analysis is of forensic interest for postmortem toxicological investigations where blood samples are unavailable or unusable. Due to the lack of studies, it remains difficult to interpret concentrations of xenobiotics measured in this matrix. Based on a statistical approach published previously to interpret meprobamate concentrations in bile and vitreous humor, we propose here a diagnostic test for interpretation of BM meprobamate concentrations from analysis of 99 sets of autopsy data. The mean age was 48 years (range 18-80 years, one unknown) for males and 50 years (range 19-80 years, one unknown) for females, with a male/female ratio at 0.768. A BM concentration threshold of 11.3 µg/g was found to be statistically equivalent to that of a blood meprobamate concentration threshold of 50 µg/ml in distinguishing overdose from therapeutic use. The intrinsic qualities of this diagnostic test were good with sensitivity of 0.82 and specificity of 0.92. Compared to previous tests published with the same objective on vitreous humor and bile, this study shows that BM is a useful alternative matrix to reveal meprobamate overdose when blood, vitreous humor, and bile are not available or unusable.

Gas chromatography-tandem mass spectrometry assay for the quantification of four benzodiazepines and citalopram in eleven postmortem rabbit fluids and tissues, with application to animal and human samples.

Pharmacokinetic studies and postmortem toxicological investigations require a validated analytical technique to quantify drugs on a large number of matrices. Three-step liquid/liquid extraction with online derivatization (silylation) ahead of analysis by gas chromatography-tandem mass spectrometry was developed and validated on rabbit specimens in order to quantify citalopram and 4 benzodiazepines (diazepam, nordazepam, oxazepam and temazepam) in 11 biological matrices (blood, urine, bile, vitreous humor, liver, kidney, skeletal muscle, brain, adipose tissue, bone marrow (BM) and lung). Since the 11 biological matrices came from the same animal species, full validation was performed on 1 matrix, bone marrow (considered the most complex), while the other 10 underwent partial validation. Due to non-negligible matrix effects, calibration curves were performed on each matrix. Within-day and between-day precision (less than 12.0% and 12.6%, respectively) and accuracy (from 88.9% to 106.4%) were acceptable on BM at both low and high concentrations. Assessment on the other matrices confirmed accuracy and within-day precision (less than 12%, and generally between 85.1% and 114.5%, respectively). The lower limit of quantification of the method was 1ng/g for nordazepam, 5ng/g for citalopram and 10ng/g for oxazepam, diazepam and temazepam. The combination of 3-step extraction and MS/MS detection provided good selectivity in all matrices, including the most lipid-rich. Application to real-case samples showed that the method was sensitive enough to describe distribution patterns in an animal experiment, and specific enough to detect molecules in highly putrefied samples from human postmortem cases.

Postmortem measurement of caffeine in bone marrow: influence of sample location and correlation with blood concentration.

Bone marrow (BM) analysis is of forensic interest in postmortem toxicological investigation in case of limited, unavailable or unusable blood samples. However, it remains difficult to determine whether a drug BM concentration is therapeutic or represents overdose, due to the lack of studies on this alternative matrix. Given the variations in BM composition in the body, sample location was suggested to be a relevant factor in assessing BM concentration. The aim of the present study was to compare postmortem caffeine concentrations in various BM sample locations and secondly to consider the correlation between BM and blood concentrations. Six BM samples (right and left side: proximal and medial femur and 5th rib) and a blood sample were collected from 21 forensic autopsies. Gas chromatography coupled to tandem mass spectrometry was performed. Blood caffeine concentrations ranged from 60 to 7591ng/mL. Femoral and rib BM concentrations ranged from 51 to 6171ng/g and 66 to 7280ng/g, respectively. Blood concentrations were always higher than BM concentrations. As a good correlation was demonstrated between blood and rib BM and between blood and the average of the four femoral BM concentrations, blood caffeine concentrations could be correctly extrapolated from BM concentrations. BM caffeine concentration was found to depend on sample location. Rib BM caffeine concentrations appeared to be systematically greater than averaged femur values and concentrations were much more variable between the 4 femur BM samples than between the 2 ribs. From a practical point of view, for caffeine analysis, rib BM appeared more relevant than femoral BM, which requires multisampling to overcome the concentration variability problem.

Kienböck's disease and cerebral palsy case report.

INTRODUCTION: Pain is the main problem in patients suffering from cerebral palsy, particularly in adults. The upper limbs are affected in 25% of cases. Here, we report the case of a patient with Kienböck's disease. METHOD: Clinical case and literature review. A 28-year-old man suffering from dystonic quadriplegia consulted for progressively worsening pain in the right wrist. Kienböck's disease was diagnosed and conservative treatment with botulinum toxin in the flexor carpi radialis recommended. A good result was obtained with a decrease in pain. This result was still present two years later. DISCUSSION: Although few references are made to it in literature, Kienböck's disease in cerebral palsy is probably underestimated. Maintenance of the wrist in a permanent flexed position and muscular hypertonia may be risk factors. Knowledge of this particular clinical picture will enable it to be detected promptly and thus enable conservative treatment to be organised with a maximum chance of therapeutic success, preventing the need for surgery.

Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in bile.

Investigating toxicological causes of death may require alternative matrices when the usual ones are lacking. Whereas forensic toxicology uses bile almost only for xenobiotic screening, a diagnostic test interpreting postmortem bile concentrations of meprobamate is reported. Based on 128 sets of autopsy data, its intrinsic qualities were good, with 0.95 sensitivity and 0.93 specificity. In a French forensic population, the positive and negative predictive factors were 0.90 and 0.97, respectively. It is a useful means of revealing overdoses where blood samples are not available or of confirming blood tests when postmortem redistribution is suspected.

[Evaluation of Optium Xceed (Abbott) and One Touch Ultra (Lifescan) glucose meters]. / Evaluation des lecteurs de glycémie Optium Xceed (Abbott) et One Touch Ultra (Lifescan).

In order to build a continuous quality improvement approach for control of glucose meters in clinical divisions at Necker-Enfants Malades hospital, the analytical performances (precision and accuracy) of 2 glucose meters have been evaluated in our laboratory according to SFBC recommendations. Fifty-six heparinized whole blood specimens from patients and thirty-nine from healthy volunteers were analyzed on each of the two meters and compared to plasma glucose measurement on the Roche Hitachi 917 system. The correlation coefficient was 0.938 for Optium Xceed and 0.911 for One Touch Ultra. However, 14.7% and 18.9% of the results (n = 95) for respectively Optium Xceed and One Touch Ultra were discordant, i.e. higher than a 20% difference compared to reference blood glucose concentrations. Inaccuracy was more important for low glucose concentrations (< 5 mmol/L; 12/14 discrepant samples for Optium Xceed and 16/19 for One Touch Ultra). This data suggests a lack of accuracy, particularly for low glucose concentrations. Capillary blood glucose concentrations must therefore be interpreted with caution concerning the diagnosis of hypoglycemia and treatment of unstable patients. Moreover, quality control of glucose meters (blood glucose determinations concurrently at bedside and in the laboratory) is difficult to perform. It also raises questions about the responsibility of "point-of-care testing", an area still subject to discussion.