Life-threatening chlorpromazine-induced acquired haemophilia A in a patient with a cavernous malformation involving the medulla oblongata.

INTRODUCTION: Chlorpromazine is a commonly used drug in several medical conditions associated with a wide range of side effects. Few cases of hemostatic disorder have been reported in the literature. CASE REPORT: A 39-year-old man had previously been diagnosed with a cavernous malformation of the medulla oblongata. Chlorpromazine was started to treat persistent hiccups. Twenty days later, the patient presented hepatitis and a pruritic rash. Haemostasis tests revealed a prolonged partial thromboplastin time associated with isolated decrease of factor VIII level and anti-factor VIII antibodies. Magnetic resonance imaging revealed recent asymptomatic bleeding. Introduction of eptacog alfa and prednisone allowed clinical and biological improvement as well as a prolonged remission after 12 months of follow-up.

[Myeloproliferative neoplasms related glomerulopathy]. / Glomérulopathies associées aux syndromes myéloprolifératifs.

Myeloproliferative neoplasms (MPNs, formerly called chronic myeloproliferative disorders) are clonal hematopoietic stem cell disorders characterized by the expansion of one or more of the myeloid lineages, including polymorphonuclear, erythroid, megakaryocytic, and mastocytic. The major complications of MPN are transformation into acute myeloid leukemia (occurring particularly in chronic myelogenous leukemia) and thrombotic and hemorrhagic events (most commonly observed in polycythemia vera and essential thrombocythemia). Renal involvement by MPN is infrequent. MPN-related glomerulopathy enlarges the spectrum of glomerular diseases associated with haematological neoplasms. MPN-related glomerulopathy is an under recognized late renal complication of MPN with poor prognosis. It is characterized clinically by heavy proteinuria and renal insufficiency. The histologic features of MPN-related glomerulopathy include variable degree of mesangial sclerosis and hypercellularity, segmental sclerosis, features of chronic thrombotic microangiopathy, and intracapillary hematopoietic cell infiltration. PDGF and TGFß likely have a crucial role in the pathogenesis of MPN-related glomerulopathy. Furthermore, aggregation of circulating hematopoietic cells within glomerular capillaries could potentially result in endothelial injury and morphologic changes resembling chronic thrombotic microangiopathy. Greater awareness of this entity is needed to define diagnosis and possible therapies.

[Characteristics of fractures of the distal part of the clavicle in children]. / Particularités des fractures des extrémités de la clavicule chez l'enfant.

Fractures of the clavicle are frequent in children and mostly affect the middle third. On the other hand, traumatic fractures of both medial and lateral thirds of the clavicle are rare. The lesions have special characteristics: difficulty in diagnosis for the medial third; risk of callus formation in the absence of surgical reduction of the lateral third. The authors report two observations of fractures of the medial and lateral thirds of the clavicle; they insist on the value of investigation by CT scan.

The certification of morphine and codeine in a human urine standard reference material.

The National Institute of Standards and Technology (NIST, formerly the National Bureau of Standards) has developed and certified a Standard Reference Material, SRM 2381, for use in testing for bias in determinations of morphine and codeine in human urine. Each unit of this SRM consists of three vials with different levels of morphine and codeine in lyophilized urine. Three different analytical methods, employing GC/MS, LC/MS, and MS/MS, were used to certify the concentrations of each analyte. Results from the three methods were in good agreement and, therefore, were statistically combined to yield certified values of 138, 293, and 578 ng/mL for morphine and 134, 283, and 591 for codeine. A round-robin study on this material among nine military laboratories demonstrated the suitability of the SRM for its intended purpose.

Frozen human serum reference material for standardization of sodium and potassium measurements in serum or plasma by ion-selective electrode analyzers.

Three interlaboratory round-robin studies (RR1, RR2, and RR3) were conducted to identify a serum-based reference material that would aid in the standardization of direct ion-selective electrode (ISE) measurements of sodium and potassium. Ultrafiltered frozen serum reference materials requiring no reconstitution reduced between-laboratory variability (the largest source of imprecision) more than did other reference materials. ISE values for RR3 were normalized by the use of two points at the extremes of the clinical range for sodium (i.e., 120 and 160 mmol/L), with values assigned by the flame atomic emission spectrometry (FAES) Reference Method. This FAES normalization of ISE raw values remarkably improved all sources of variability and unified the results from seven different direct ISE analyzers to the FAES Reference Method value. Subsequently, a three-tiered, fresh-frozen human serum reference material was produced to the specifications developed in RR1-RR3, was assigned certified values for sodium and potassium by Definitive Methods at the National Institute of Standards and Technology (NIST), and was made available in 1990 to the clinical laboratory community as a Standard Reference Material (SRM); it is now identified as SRM 956. Albeit retrospectively, we show how applying an FAES normalization step identical to that used in RR4/5 to the ISE data for SRM 956 after the NIST Definitive Method values were known, consistently moved the ISE results for RR3 closer to the true value for Na+ and K+.

The certification of cocaine and benzoylecgonine in a human urine standard reference material.

The concentrations of cocaine and benzoylecgonine (BE) in Standard Reference Material (SRM) 1508, cocaine and metabolites in freeze-dried human urine, were determined at the National Institute of Standards and Technology (NIST, formerly NBS) by two independent methods. For cocaine, one method was based on gas chromatography/mass spectrometry (GC/MS); the other was based on high-performance liquid chromatography (HPLC). For BE, one method was based on GC/MS; the other was based on flow injection analysis/thermospray mass spectrometry (FIA/MS). The results for each pair of methods were statistically evaluated. Concentrations were determined in the SRM for three levels of cocaine and three levels of benzoylecgonine. Methylecgonine, although present in the material, was not determined. For cocaine, the concentrations were 90, 263, and 429 ng/mL of human urine. For BE, the concentrations were 103, 259, and 510 ng/mL of human urine.

Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry.

In response to the scheduled destruction of U.S. military stockpiles of the hallucinogenic agent 3-quinuclidinyl benzilate (QNB), a specific confirmatory test for human exposure to QNB was developed. The amount of the parent compound in the urine as well as the two major metabolites, 3-quinuclidinol (Q) and benzilic acid (BA), was determined because the relationship between QNB dose and levels of QNB and its metabolites in human urine is not known. QNB was determined in urine samples spiked at a target level of 0.5 ng/mL, and the metabolites BA and Q were determined at a target level of 5 ng/mL. The method uses solid-phase extraction to isolate each analyte from the urine and isotope dilution gas chromatography/mass spectrometry for quantitation. Each analyte is converted to its trimethylsilyl derivative for analysis. The analytical method was tested on eight different urine samples spiked with known amounts of the analytes near the target levels, at 10 times the target levels, and blank (unspiked) urine samples. The variabilities in the method are for the most part evenly distributed between three imprecision categories: GC/MS measurement, sample preparation, and the urine samples. The total imprecision (1 standard deviation) of a single measurement is about 15% of the value for each analyte.

Ascorbic and dehydroascorbic acids measured in plasma preserved with dithiothreitol or metaphosphoric acid.

We describe a rapid method for accurately and precisely measuring ascorbic acid and dehydroascorbic acid in plasma. Total analysis time is less than 10 min, replicate analyses of a single pool provide precision less than or equal to 2%, and values measured in supplemented samples agree with known concentrations of 4.68 and 11.83 mg/L. The stability and homogeneity of lyophilized plasma samples supplemented with ascorbic acid and dithiothreitol are documented. We also describe a procedure in which metaphosphoric acid (50 g/L) is used to prepare a reference material for the measurement of ascorbic acid and dehydroascorbic acid. The procedure for both acids consists of first measuring the native ascorbic acid, then reducing the dehydroascorbic acid, at neutral pH, with dithiothreitol, and finally measuring the total ascorbic acid; dehydroascorbic acid is then determined by difference. The metaphosphoric-acid-treated samples were stable at -70 degrees C, but stability decreased with temperature over the range examined, 4-50 degrees C.

Molar absorptivities of bilirubin (NIST SRM 916a) and its neutral and alkaline azopigments.

Three laboratories in the U.S. and two in the Netherlands determined molar absorptivities (epsilon) of Standard Reference Material (SRM) 916a Bilirubin from the National Institute of Standards and Technology. In caffeine reagent the average epsilon values were 50,060 and 48, 980 L.mol-1.cm-1 at 432 and 457 nm, respectively. The epsilon value of the blue azopigment, obtained with the Reference Method for total serum bilirubin, was 76,490 L.mol-1.cm-1 at 598 nm. When the addition of alkaline tartrate was omitted, the molar absorptivity of the red azopigment was 56,600 L.mol-1.cm-1 at 530 nm.

Comparison of two isotope dilution/mass spectrometric methods for determination of total serum cholesterol.

Isotope dilution/mass spectrometric methods for total serum cholesterol, developed separately at the Karolinska Institutet (KI) and the National Bureau of Standards (NBS), were compared by applying them to a common set of serum pools. A search for the cause of a systematic difference of a few percent in results from the two methods revealed that the KI cholesterol standard contained lathosterol, which interfered with the calibration of the method. With NBS Standard Reference Material cholesterol used for new analyses at the KI, the average difference in mean values dropped to 0.2%. The NBS results are more precise. This is attributed to the protocols NBS used for sample preparation and mass spectrometry. However, these protocols make the NBS method more complex and time-consuming. A recent critical article on the use of this technique for total cholesterol is also examined.

A multilaboratory-evaluated reference method for the determination of serum sodium.

We carried out a statistically designed, multilaboratory study to evaluate a flame atomic emission spectroscopic (FAES) method for serum sodium as a Reference Method. definitive values for the serum pools for the study, with sodium in the 110-160 mmol/L range, were determined at the National Bureau of Standards by an ion-exchange/gravimetry method. The multilaboratory FAES results were judged against the preselected performance criteria for the Reference Method: maximum imprecision 1.5 mmol/L, maximum bias 2.0 mmol/L. The standard error of a single laboratory's performance of the method varied with concentration from 0.46 to 0.86 mmol/L with a maximum bias of 1.0 mmol/L; thus, the criteria were satisfied. The cooperating laboratories performed the method with either manual or semi-automated pipetting. Although both modes of pipetting satisfied our acceptability criteria, only the method with semi-automated pipetting is described here as the Reference Method. The statistical results indicate that the precision criterion can be fulfilled with fewer than four replicate analyses.

Total serum cholesterol by isotope dilution/mass spectrometry: a candidate definitive method.

We describe a highly accurate and precise method for determination of total cholesterol in serum by isotope dilution/mass spectrometry. The method was developed for a Study Group of the Committee on Standards of the American Association for Clinical Chemistry, for use in establishing the accuracy of a candidate reference method for total cholesterol, and fulfills their criteria for a definitive method. Cholesterol-d7 is added to serum, with the weight ratio of cholesterol-d7 to total serum cholesterol kept near to 1:1. The esters are hydrolyzed and the cholesterol is separated and converted into the trimethylsilyl ether derivative for measurement by combined gas chromatography/mass spectrometry. The intensity ratio of the molecular ions at m/z 465 and 458 is measured for each sample and for two calibration mixtures, according to a prescribed bracketing protocol. A weight ratio for the sample is obtained by linear interpolation of the ion-intensity ratios, and the total cholesterol is then calculated. The method was applied four times over several weeks to each of five serum pools. Statistical analysis involving consideration of both replication error and variability between weeks gave a coefficient of variation for a single measurement of 0.36%. The absence of interferences in the method was demonstrated by measurements at several other masses.

Statistical evaluation of CAP survey results for calcium, potassium, and blood urea nitrogen.

Throug the use of the statistical technic known as the linear model, a complete analysis has been made of data obtained in the Colleg of American Pathologists Survey of 1975 for calcium, potassium, and blood urea nitrogen (BUN). The analysis allows a separation of laboratories into core and non-core categories. It also allows for determination of the reproducibility of each analytic technic involved in this survey. For Ca and K, the results obtained by each analytic method were compared with the results obtained by the National Bureau of Standards through use of the definitive method. For BUN, the comparison was made with the average of values for all laboratories and all methods.