[Pulmonary embolism and inferior vena cava agenesis: An unusual association]. / Embolie pulmonaire et agénésie de veine cave inférieure : une association inhabituelle.

INTRODUCTION: Inferior vena cava agenesis is a rare congenital anomaly, generally associated with thrombophilic conditions, and a predisposing factor for deep venous thrombosis (DVT), rarely complicated by pulmonary embolism, in a young population with atypical clinical features and frequent absence of risk factors. CASE REPORT: We report the case of a 30-year-old woman who developed a right iliac DVT, initially presenting as a low back pain and complicated by a pulmonary embolism, 8 months after a sleeve gastrectomy. Chest CT angiography revealed abnormalities that led to the diagnosis of inferior vena cava agenesis. Thrombophilic screening showed a heterozygous prothrombin gene mutation G20210A and hyperhomocysteinemia. The patient was treated with rivaroxaban with good results after 2 years of follow-up. CONCLUSIONS: In young patients without risk factors developing a deep venous thrombosis, an inferior vena cava anomaly should be considered. Although no therapeutic consensus has been currently established, inferior vena cava agenesis seems to be associated with a high prevalence of thrombophilic disorders. Screening could be useful, particularly in patients with a thrombotic family history.

[Cerebral sinovenous thrombosis and acquired antithrombin, protein C and S deficiency during chemotherapy in a young man: report of a case]. / Thrombose des sinus veineux endocrâniens et déficit acquis en antithrombine, protéines C et S au cours d'une chimiothérapie: observation clinique chez un jeune patient.

L-asparaginase is commonly used in the chemotherapy regimens for acute lymphoblastic leukaemia. Its use is associated with thrombotic complications in 1 to 14 % of the cases. The pathogenesis of this complication is still unclear. However, the decrease of antithrombin seems to play an important role. We report a case of a 17-year old man with a acute lymphoblastic leukaemia, who developed a cerebral sinovenous thrombosis due to an acquired deficiency of antithrombin and protein C and S following L-asparaginase chemotherapy. We discuss the use of prophylactic supplements of antithrombin and the value of screening of thrombophilia based on the recent medical literature.

Severe thrombophilic diathesis starting with hepatic vein thrombosis (BUDD-CHIARI syndrome) in a family with a new Protein S gene mutation.

We report the case of a 26-year-old man with a chronic Budd-Chiari syndrome with ascites, caused by a hereditary Protein S deficiency, in a Turkish family with consanguinity. In this family, the father, the two sisters and the young brother suffered from severe venous thrombosis of the limbs, with pulmonary embolism in two of them. Those thrombotic events are caused by a hitherto not reported mutation in the PROS 1 gene on chromosome 3, resulting in a severe familial Protein S deficiency. No other thrombophilic defect was detected in the family, despite extensive investigation. Furthermore, we observe hereditary twenty-nail dystrophy in this family, the two genes probably segregating independently. Prophylaxis is discussed.

[Acute portal thrombosis revealing hereditary hemochromatosis: report of a case]. / Thrombose portale aiguë révélant une hémochromatose héréditaire: à propos d'un cas.

The authors report the case of a 49-year old man in whom an inaugural portal vein thrombosis led to the diagnosis of hereditary hemochromatosis. In this case, the increase in ferritinemia and the T2-weighted MRI hepatic segmental hyposignal were considered as consequences of tissular necrosis while they did probe a real iron overload. Genetic testing, revealing C282Y/H63D compound heterozygoty, provided evidence for a diagnosis of hereditary hemochromatosis. Weekly venesections induced a calculated iron depletion of 3.5 g without occurrence of anemia, further supporting the diagnosis. We suggest that hemochromatosis should be considered in the differential diagnosis of idiopathic portal vein thrombosis when signs of abnormal iron accumulation exist.

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells.

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.

A Phase I Determination of Azithromycin in Plasma during a 6-Week Period in Normal Volunteers after a Standard Dose of 500mg Once Daily for 3 Days.

OBJECTIVES: The pharmacokinetics of azithromycin were evaluated in 12 healthy volunteers. METHODS: This was an open study in 12 healthy male subjects. Participants received a single dose of 2 x 250mg azithromycin (two azithromycin capsules) administered orally in the fasting state with 240ml water on three consecutive days. RESULTS: After oral intake of two capsules of 250mg azithromycin over three consecutive days (the normal treatment regimen in adults), azithromycin was present in measurable levels in plasma (>5 microg/L) for 7 to 17 days after the beginning of treatment. The apparent elimination half-life was very long (observed range: 49 to 108 hours, i.e. about 2 to 4.5 days). From the results in plasma, one can extrapolate that the azithromycin concentration would remain above 1 microg/L (corresponding to concentrations in tissues above 0.1 mg/L) for up to 15 to 30 days following treatment. The elimination half-life of azithromycin (average of 76 hours) was in agreement with values of depletion rates in tissues corresponding to a half-life of 60 to 72 hours. CONCLUSION: In conclusion, the utility of the long exposure of patients with benign respiratory infections to azithromycin and to subinhibitory concentrations of azithromycin should be questioned.

[Factor V Leiden and activated protein C resistance]. / Facteur V Leiden et résistance à la protéine C activée.

Factor V Leiden is characterised by a point mutation which prevents the physiologic inhibition of activated factor V by activated protein C (Activated Protein C Resistance). This mutation is now considered as the most frequent inherited thrombophilic disorder. It is found in about 20% of patients with venous thrombotic disease, far before ATIII, Protein C and S deficiency. Its prevalence (4% in the general belgian population, 1 to 15% in Europa) allows frequent associations with other thrombophilic disorders, inherited or acquired, such as contraceptive pill. Biological testing are now ready for screening, but the opportunity of a systematic evaluation in front of a risk situation remains a matter to discussion.

Comparative study of antiphospholipid antibody detection in eleven Belgian laboratories.

Twenty-six plasma samples have been sent to 11 different Belgian laboratories in order to detect the presence of antiphospholipid antibodies, either by immunological methods and/or by coagulation tests. A good concordance between laboratories was observed for coagulation tests. Laboratories using detection tests and performing mixing procedures and neutralisation procedures displayed the highest sensitivity as compared with laboratories which did not perform one of these two latter procedures. The concordance between laboratories for the immunological methods was much worse as compared with coagulation tests. This may be attributable either to an intrinsic problem of the immunological tests or to a selection bias due the fact that the plasmas used in this study were selected in coagulation laboratories only where the chance to find a lupus anticoagulant positive/ELISA antiphospholipid negative sample is high.

[Pulmonary embolism and pregnancy: report of a case; review of the literature]. / Embolie pulmonaire et grossesse: à propos d'une observation; revue de la littérature.

Pulmonary embolism occurring during pregnancy is a rare accident but that still brings about a high mother mortality; it seems to be five to six times more frequent during the pregnancy and the post-partum than for non-parturient women who don't take any estro-progestogens, pulmonary embolism would involve complications for 0.5/1000 pregnancies before delivery. As it presents a lot of diagnostic problems, it is under-estimated. The vascular radiological examinations expose the foetus or embryo to considerable radiation and to a risk of foetal hypothyroidism leading to backwardness. The lung perfusion scanning has the advantage of not injecting iodine but is not specific. Fortunately, some medical examinations such as plethysmography or Doppler echography are safe and can also guide the clinician. As far as therapy is concerned, intravenous heparin is the first intention treatment, it can be replaced subsequently by subcutaneous heparin (low molecular weight heparin). In case of heavy pulmonary embolism endangering the vital prognosis of the patient, in case of clinical or biological resistance to the medical treatment, it could be necessary to perform a pulmonary embolectomy with, if necessary, vena cava interruption with insertion of a mechanical filter.

Co-expression of CD2 or CD8 antigens in B-cell chronic lymphocytic leukaemia. A flow cytometry analysis of 3 cases.

Three cases of biphenotypic CD2 or CD8 positive chronic lymphocytic B-cell leukaemias are reported. This represents an incidence of 15% in the authors' series, a frequency never mentioned previously. CD2 expression could be an example of asynchronous expression of an early pre-B antigen. CD8 expression might probe a true mixed lineage phenotype. These aberrant phenotypes were not associated with any peculiar clinical presentation.

Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control.

Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances.

Dissociation between uric acid and urea clearances in the syndrome of inappropriate secretion of antidiuretic hormone related to salt excretion.

1. Our purpose was to determine why hypouricaemia is more frequently observed than hypouraemia in the syndrome of inappropriate secretion of antidiuretic hormone. We have retrospectively analysed the scores of 35 patients with a chronic form of hyponatraemia related to the syndrome of inappropriate secretion of antidiuretic hormone and studied prospectively six patients. 2. The patients with high fractional excretion of filtered urea (greater than 55%) presented lower blood urea and lower salt excretion than the patients with normal fractional excretion of filtered urea, despite similar levels of hyponatraemia and of osmotic and uric acid clearances. In six hyponatraemic patients, an increase in salt intake was accompanied by a decrease in fractional excretion of filtered urea. In the syndrome of inappropriate secretion of antidiuretic hormone, the fractional excretion of filtered urea was inversely correlated to the fractional excretion of filtered sodium (r = -0.66; P less than 0.001), whereas the fractional excretion of filtered uric acid was not dependent on sodium excretion. 3. Hypouraemia with high fractional excretion of filtered urea in patients with the syndrome of inappropriate secretion of antidiuretic hormone is related to low urinary sodium excretion and thus reflects low sodium intake.

[Comparative study of 2 common tests for lupus anticoagulant determination: critical analysis of the results observed in 21 patients]. / Etude comparative de deux tests usuels de dépistage de l'anticoagulant du lupus: analyse critique des résultats observés chez 21 malades.

The Schleider and/or the Exner test have been found positive in twenty-one patients; five of these patients suffered of systemic lupus erythematosus (SLE). The Quick time and the activated partial thromboplastin time are normal in 52% of the cases. 40% have a minor haemorrhagic diathesis, without other significant clotting defect and 30% have thrombo-embolic complications. The Schleider index is more often strongly positive (greater than 2) in these two groups. 58% have an anemia, 25% a mild thrombocytopenia not deep enough to explain an haemorrhagic tendency (from 90.000 to 140.000/mm3). Several auto-immune tests are frequently positive even without SLE. The Schleider test is positive in 86% of the cases and appears a little more useful for the diagnosis than the Exner test, which has a 71% positivity.

Treatment of atrial fibrillation associated with hyperthyroidism by amiodarone and methimazole.

We treated a 78-year-old patient with hyperthyroidism and atrial fibrillation with amiodarone 1200 mg/day for 3 days and methimazole 60 mg/day. Sinus rhythm was restored within 3 days and serum levels of triiodothyroxine returned to normal within 4 days. A transient increase in serum rT3 concentrations was observed. Amiodarone associated with methimazole was useful in the management of atrial fibrillation and hyperthyroidism in our patient.

Potassium homeostasis in liver cirrhosis.

Extrarenal mechanisms are important in the defense against hyperkalemia. During a potassium load, cellular uptake is essential to avoid severe hyperkalemia. Liver and muscles represent the major buffering system, partially mediated by insulin, in the distribution of potassium between intracellular and extracellular fluids. To study the potential role of the liver, we administered an oral load of potassium (0.75 mEq/kg) to nine male patients with compensated cirrhosis and ten normal subjects of similar age, sex, and weight. Despite identical renal excretion, cirrhotic patients had higher potassium levels two and three hours after oral administration. Moreover, only cirrhotic patients presented a clear-cut increase in serum C-peptide concentration after the potassium load without any change in glucose level. It is likely that, in cirrhosis, liver failure contributes to the decrease in hepatic cellular potassium uptake despite insulin hypersecretion.