Isolation and characterization of an abnormal alpha slow-moving high-density lipoprotein subfraction in serum from children with long-standing cholestasis

An abnormal high-density lipoprotein (HDL) subfraction, detected during periods of mild jaundice in the serum of seven children with chronic cholestasis from birth, was isolated and characterized. This fraction, identified by its slow alpha electrophoretic migration, is present in addition to normal HDL and differs from the abnormal HDL previously described in cholestatic syndromes. It is devoid of apolipoprotein B but is precipitated by phosphotungstate-MgCl2. These properties allowed its isolation by double selective precipitation. This subfraction is undetectable with this procedure in the serum of healthy subjects, is rich in cholesterol, and contains a large amount of apolipoprotein E, which may explain its precipitation by phosphotungstate-MgCl2. These apo E-containing HDL may play a major role in the lipid metabolism of patients with long-standing cholestasis during periods of mild jaundice.     

L’hypercalciurieHypercalciuria.

Hypercalciuria is a biological syndrome defined as excretion in the urine of more than 0.1 mmol/kg/24 hours of calcium in the absence of dietary restrictions. A number of endocrine, renal, and bone diseases can cause hypercalciuria. Urinary calcium excretion is substantially influenced by the intakes of calcium, sodium, protein, carbohydrates, alcohol, and potassium, so that a poorly balanced diet can result in hypercalciuria. Recently, there has been a burst of interest in molecular studies of rare lithiasis syndromes, all of which are due to mutations in the ClCN5 chlorine channel gene. Mutations affecting the calcium-sensitive receptor (CaSR) have been identified in other forms of hypercalciuria. Idiopathic hypercalciuria is defined as hypercalciuria that persists after correction of dietary imbalances and has no detectable cause. The classification suggested by Pak (class I, class II, class III, and “renal” hypercalciuria) is controversial and of little assistance in clinical practice. Three mechanisms can be incriminated in idiopathic hypercalciuria: increased intestinal absorption of calcium, defective reabsorption of calcium by the renal tubule, and increased bone resorption. Overexpression of the vitamin D receptor and a deficiency in renal tubule enzymes may be involved also. Bone mineral density is moderately decreased in idiopathic hypercalciuria, particularly of the renal type. The risk of vertebral fracture seems increased, however. Overproduction of calcitriol and of cytokines that stimulate bone resorption have been incriminated in the bone loss. Treatment of the cause is essential in secondary hypercalciuria (dietary advice, treatment of an underlying disease…). A diet low in sodium and meat and containing no more than 800 mg of calcium per day has been advocated in idiopathic hypercalciuria. Hydrochlorothiaide therapy is warranted in patients with osteopenia and an inadequate response to dietary therapy.     

Cerebrotendinous xanthomatosis: treatments with simvastatin, lovastatin, and chenodeoxycholic acid in 3 siblings

We report 3 sisters treated for cerebrotendinous xanthomatosis. We treated one, with a severe neurologic form of the illness, with chenodeoxycholic acid, then lovastatin and simvastatin. These drugs had different efficacy and tolerance, but induced no clinical improvement. Her sisters, without neurologic symptoms, received chenodeoxycholic acid, which normalized the cholestanol level. Optimal treatment of this illness must begin before there is significant clinical symptomatology.     

Analysis of ABO discrepancies occurring in 35 French hospitals

BACKGROUND: The risk of immunohemolytic reaction owing to ABO-mismatched mistransfusion is 100 to 1000 times higher than the risk of viral infection. Like analysis of incident reports, evaluation of near-miss events can provide useful insight into hazardous situations for mis-matched blood transfusion. The aim of this prospective study was to assess the incidence and root causes of all ABO discrepancies, detected by a central hematology laboratory, in blood samples referred from 35 district hospitals. STUDY DESIGN AND METHODS: ABO discrepancies were detected by comparing either two current blood specimens or a current and historical specimen collected over a 5-year study period. Discrepancies were investigated by retyping new samples, checking sample identification, and reviewing previous hospital records. RESULTS: A total of 118 ABO discrepancies were discovered in a series of 407,769 tests carried out during the study period. The incidence of ABO discrepancies was 1 per 3,400. This figure was 10 times higher than the incidence of ABO-mismatched transfusions. Most of these ABO discrepancies were due to phlebotomy errors, that is, collection from wrong patient. The second most common cause involved clerical errors during patient registration or identification. CONCLUSION: ABO discrepancies can result from errors made not only by the medical staff during phlebotomy but also to by the clerical staff during registration and identification. These findings emphasize the need to standardize data transmission between health care personnel.     

Calf vein compliance increases following bed rest after aortocoronary bypass surgery

Early post-operative ambulation (<3 days) is expected to decrease the risk of venous thrombosis, whereas late ambulation (>7 days) increases the risk of orthostatic hypotension. The effect of post-operative bed rest on calf vein compliance was studied before (D ? 1) and 7 days (D + 7) after aortocoronary bypass surgery in 50 patients (41 men and nine women, 65 ± SD 10 years). Calf vein compliance was measured by strain gauge plethysmography and stepwise increases in thigh congestive pressure from 20 to 60 mmHg. Calf compliance [median (25 percentile–75 percentile)] increased significantly by 48% from D ? 1 to D + 7 [0·044 (0·039–0·051) vs. 0·065 (0·048–0·083) ml (100 ml mmHg)^?1, P<0·001]. This increase was reflected as increased calf volume for the 50 mmHg [D ? 1 2·10 (1·75–2·65) vs. D + 7 2·60 (1·70–3·00) ml 100 ml^?1, P<0·01] and 60 mmHg [D ? 1 2·50 (2·10–2·95) vs. D + 7 3·20 (2·30–4·00) ml 100 ml^?1, P<0·001] occlusion pressure levels. The associated pathologies (diabetes and arterial hypertension) and NYHA grades had no significant influence on the increase in compliance. Among the vasoactive therapeutic regimens, calcium channel blockers contributed significantly to the increased calf compliance, but only on D ? 1. The increase in venous compliance following aortocoronary bypass surgery is multifactorial but should be considered for prophylactic management of these patients.     

Activation of PAF receptor by oxidised LDL in human monocytes stimulates chemokine releases but not urokinase-type plasminogen activator expression

BACKGROUND: We investigated whether the increase of urokinase-type plasminogen activator (uPA) monocyte expression and chemokine releases induced by oxidised low density lipoproteins (LDL), which participate to vascular tissue remodeling and to atherosclerotic plaque rupture, involved proinflammatory phospholipid products having platelet-activating factor (PAF)-like activity via the PAF-receptor pathway. METHODS: uPA monocyte expression was stimulated by either copper ions-oxidised or O2*-/HO* free radical-oxidised LDL. The effects of PAF and oxidised LDL on the production of monocyte chemoattractant protein-1 and interleukin-8 were also examined. RESULTS: Synthetic PAF significantly enhanced chemokine releases (P<0.001) without modifying uPA expression. Copper-oxidised LDL, which exhibit a higher content in lysophosphatidylcholines than free radical-oxidised LDL, induced a significantly higher enhancement in uPA expression (P<0.05). By contrast, free radical-oxidised LDL were more efficient than copper-oxidised LDL to increase chemokine releases (P<0.01). Oxidised LDL-enhanced uPA expressions were not altered by the PAF-receptor antagonist SR27417, whereas increases in chemokine releases induced by oxidised LDL and by PAF were abolished. PAF-acetylhydrolase activity was rapidly and largely inhibited in free radical-oxidised LDL when compared to copper-oxidised LDL, suggesting that free radical-oxidised LDL would contain a higher content in PAF-like products than copper-oxidised LDL. CONCLUSION: Our results indicated that PAF-like oxidation products are responsible for the monocyte chemokine releases, but did not contribute to the enhanced monocyte uPA expression by oxidised LDL.     

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.     

Les 10es Entretiens de nutrition, institut Pasteur de Lille, France L’obésité, une maladie nutritionnelle ?

The continued increase in the prevalence of obesity is put down to the difference between our calorific needs and our calorie consumption. But aside from these quantitative causes, there may well also be qualitative explanations, connected with the different types of fatty acids to be found in our diet. The polyunsaturated fatty acids in the omega-3 and omega-6 groups have different and sometimes opposing roles in the synthesis, transport and storage of adipose tissue lipids. The omega-6 to omega-3 ratio has more than tripled over the past 40 years. There are now large quantities of mechanistic, epidemiological and clinical data supporting the hypothesis that an omega-3 deficit has a role in the genesis of obesity.