Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel.

OBJECTIVE: Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the "Associazione Italiana Narcolettici e Ipersonni" is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians. MATERIALS AND METHODS: A multidisciplinary panel, including patients, public institutions, and representatives of national scientific societies of specialties possibly involved in the diagnostic process of suspected narcolepsy, was convened. The project was accomplished in three phases. Phase 1: Sleep experts shaped clinical pictures of narcolepsy in pediatric and adult patients. On the basis of these pictures, Red Flags were drafted. Phase 2: Representatives of the scientific societies and patients filled in a form to identify barriers to the diagnosis of narcolepsy. Phase 3: The panel produced suggestions for the implementation of Red Flags. RESULTS: Red Flags were produced representing three clinical pictures of narcolepsy in pediatric patients ((1) usual sleep symptoms, (2) unusual sleep symptoms, (3) endocrinological signs) and two in adult patients ((1) usual sleep symptoms, (2) unusual sleep symptoms). Inadequate knowledge of symptoms at onset by medical doctors turned out to be the main reported barrier to diagnosis. CONCLUSIONS: This report will hopefully enhance knowledge and awareness of narcolepsy among non-specialists in sleep medicine in order to reduce the diagnostic delay that burdens patients in Italy. Similar initiatives could be promoted across Europe.

7-ketocholesterol inhibits Na,K-ATPase activity by decreasing expression of its α1-subunit and membrane fluidity in human endothelial cells.

As cholesterol, oxysterols, can insert the cell membrane and thereby modify the functions of membrane-bound proteins. The Na,K-ATPase is very sensitive to its lipid environment, seems to be involved in important endothelial functions as the regulation of nitric oxide (NO) release. The effects of 7-ketocholesterol , an oxysterol present in oxidized LDL, was investigated on Na,K-ATPase in isolated human endothelial cells. Cells were incubated 24h with lecithin-, cholesterol- or 7-ketocholesterol liposomes (6 µg/ml). K+-stimulated paranitrophenyl phosphatase activity, reflecting Na,K-ATPase activity, was evaluated as well as cell viability and lipoperoxidation. The expression of Na,K-ATPase subunits mRNAs and membrane fluidity were also investigated. As Na,K-ATPase and nitric oxide seem to be related, we determined the production of NO and the expression of endothelial NO synthase mRNAs. Na,K-ATPase activity was strongly decreased by 7-ketocholesterol. This decrease, not related to lipoperoxidation, was correlated with a decreased expression of the Na,K-ATPase α1-subunit messengers and with rigidity of plasma membranes. Cholesterol induced similar effects but was less potent than 7-ketocholesterol. Basal NO production and expression of endothelial NO synthase mRNAs were not modified by 7-ketocholesterol. Our new findings demonstrate that 7-ketocholesterol, used at non toxic doses, was very potent to disrupt the transport of ions by Na,K-ATPase and perturb membrane structure. These data demonstrate that 7-ketocholesterol induces endothelial dysfunction without cell death that may contribute to early events in atherosclerosis.

Neonatal adrenal hemorrhage presenting as contralateral scrotal ematoma.

Neonatal adrenal hemorrhage may rarely present as scrotal hematoma. This condition can simulate a torsion of the testis requiring an immediate surgical exploration of the scrotum. Ultrasonographic study of the abdomen can find out intraperitoneal or retroperitoneal bleeding in order to avoid unnecessary surgical intervention. The case of a newborn with right adrenal hemorrhage presenting as left scrotal hematoma is reported.

Peripheral diabetic neuropathy and polyunsaturated fatty acid supplementations: natural sources or biotechnological needs?

The two essential fatty acids linoleic and alpha-linolenic acids, precursors of the n-6 and n-3 PUFA family, respectively, are known to play a strong regulatory function on cells via their incorporation into membrane phospholipids, and also on microcirculation by the production of eicosanoids. Moreover, diabetes mellitus induces impairment in PUFA metabolism due to an inhibition of desaturases, the enzymes involved in their synthesis. The decrease in PUFA bioavailability will conduct to marked alterations in membranes as well as impairment of the microcirculation. Those metabolic perturbations are involved in part in the degenerative complications of diabetes such as neuropathy. Nutritional supplementations with PUFA have given very interesting results in experimental diabetic neuropathy but also in human diabetic neuropathy. The gamma linolenic and arachidonic acids, members of the n-6 family, prevent the physiological abnormalities associated to neuropathy. The results obtained with the n-3 family PUFA are more discordant, probably because of the simultaneous use of eicosapentaenoic and docosahexaenoic acids. Nevertheless, the use of docosahexaenoic acid-enriched phospholipids produced positive results in the treatment of experimental diabetic neuropathy. These PUFA are available from natural sources but a biotechnological demand exists to provide these PUFA in different structural forms.

Dose dependent accretion of docosahexaenoic acid (DHA) in cardiac membranes of rats fed egg yolk powder enriched in DHA.

We tested the hypothesis that enrichment of the diet with docosahexaenoic acid (DHA) enriched egg yolk powder could modify specifically the (n-3) fatty acids content of rat plasma, red blood cells and heart membranes. Dose-dependent effect of DHA was studied in rats supplemented during 4 weeks. Three groups of adult male rats, DHA10, DHA35 and DHA60 (n = 5 each), had their diet supplemented with 10 mg, 35 mg or 60 mg DHA/kg body weight/day, respectively. Fatty acid composition of membranes and plasma lipids were determined. A significant dose-dependent increase in DHA was observed in all three types of samples. Arachidonic acid (AA) levels did not change in heart and red blood cell membranes whereas it increased significantly in plasma with the DHA35 diet. These results contrast with that previously reported for fish oil supplementation where a decrease in AA levels was reported. Hence, DHA enriched egg yolk supplementation leads to a specific accretion of DHA without competition on AA status.

Docosahexaenoic acid-enriched egg phospholipids supplementation induces accretion of arachidonic acid in rat blood lipids.

Animal and humans studies have shown that supplementation with triacylglycerides containing omega3 fatty acids, mainly docosahexaenoic acid (DHA) and eicosapentaenoic acid, can induce a decrease in arachidonic acid (AA) in blood lipids. Interestingly, we observed in a previous work that a supplementation with DHA enriched eggs in a healthy elderly population induced an accretion of AA in their blood lipids. The present study investigates whether purified DHA enriched egg phospholipids could be responsible for this effect. Four groups of rats were supplemented daily, for eight weeks, with DHA phospholipids (10, 30 or 60 mg/kg) or with soybean phospholipids. Red blood cell membranes and plasma fatty acid levels were compared with that of rats without supplementation. Soybean phospholipids supplementation increased the level of AA in blood lipids but decreased that of DHA. The doses of DHA phospholipids, 30 and 60 mg/kg, induced greater amounts of AA without affecting significantly DHA levels. In contrast, DHA phospholipids supplementation, 10 mg/kg, in which there was the greatest amount of AA, induced only a slight increase in AA levels. Moreover, DHA levels were decreased by this supplementation. These results demonstrate that specific increases in AA levels are preferentially associated with DHA phospholipids levels in supplementation.

Secondary migration of a central venous catheter: a rare complication.

The Authors describe a case of spontaneous migration in the right jugular vein of a central venous catheter tip, properly positioned in the right atrium through the right subclavian vein two days before.

Acenocoumarol therapy in pediatric patients.

To determine guidelines for administering and monitoring acenocoumarol therapy in children, 93 patients (median 5.1 years, range: 0.2-18 years) were prospectively evaluated over a 33-month period. The loading doses used were: <1 year, 0.20 mg x kg-1; >1-5 years, 0.09 mg x kg-1; 6-10 years, 0.07 mg x kg-1; 11-18 years, 0.06 mg x kg-1. In this study, the loading dose and the dose to achieve and maintain target therapeutic range (TTR) for acenocoumarol are age-dependent, with infants having the highest and teenagers having the lowest requirements. The use of a different loading dose according to age has allowed most of the children (80%) in all the age groups to achieve TTR in less than 1 week. No patients had serious bleeding or thrombotic complications. We conclude that there is an age-dependent response to acenocoumarol in pediatric patients. The implementation of an age-adjusted loading dose regimen reduces the length of hospitalization required to achieve effective anticoagulant therapy.

Differential effect of omega3 PUFA supplementations on Na,K-ATPase and Mg-ATPase activities: possible role of the membrane omega6/omega3 ratio.

Several functional properties of Na,K-ATPase are strongly dependent on membrane fatty acid composition, but the underlying mechanism is still not well defined. We have studied the effects of two types of supplementations enriched in the w3 polyunsaturated fatty acids on the Na,K-ATPase and Mg-ATPase activities in sciatic nerve (SN) and red blood cells (RBC). Eight groups of rats, controls and diabetics, received a standard diet, supplemented or not with 30 or 60 mg/kg/day of docosahexaenoic acid (DHA) or with soybean for eight weeks. Diabetes induced significant decrease of Na,K-ATPase activity in SN (-23%) and RBC (-25%), without affecting Mg-ATPase activity. In RBC, soybean and DHA supplementations caused significant increases in Na,K-ATPase activity (in various range, +13% to +145%) in all groups, and in Mg-ATPase activity in control soybean (+65%), control and diabetic DHA high dose (+39%, +53%) and diabetic DHA low dose (+131%) groups. In SN, the soybean caused a significant decrease in Na,K-ATPase activity (-26%) and still more in the diabetic group (-53%). The DHA diet induced a slight decrease in activity in control groups, whilst during diabetes, at high dose, we noted an aggravation of this decrease (-36%). Mg-ATPase activity was not modified by supplementations except for the low dose of DHA where the activity was slightly decreased in the control group (-16%). The supplementations induced multiple tissue-specific modifications in the membrane fatty acid composition of RBC and of SN homogenates. Several specific correlations have been found between variations in fatty acids amounts and Na,K-ATPase activity in these tissues but only in RBC for Mg-ATPase activity. Indeed, we observed that the variations in Na,K-ATPase activity are positively and significantly correlated with changes in the omega6/omega3 ratio in SN as well as in RBC. These data clearly show, for the first time, that the diet could modulate the Na,K-ATPase activity via the omega6/omega3 ratio in the membranes. A similar correlation was observed with Mg-ATPase activity in RBC, suggesting also a dietary regulation of the enzyme; but for the SN, this activity might be regulated by a different omega6/omega3 ratio or by another pathway.

Gamma-linolenic acid restores renal medullary thick ascending limb Na(+),K(+)-ATPase activity in diabetic rats.

In diabetes, the activity of Delta-6 desaturase, which converts linoleic acid (LA) into gamma-linolenic acid (GLA), the first step of arachidonic acid (AA) synthesis, is decreased, leading to alterations in membrane phospholipid composition. On the other hand, 12 wk after the onset of diabetes, Na(+),K(+)-ATPase activity is reduced in many organs, including the kidney. The medullary thick ascending limb (MTAL) reduced Na(+),K(+)-ATPase activity, whereas the sodium load secondary to glomerular hyperfiltration was increased. The aim of our study was to examine whether the changes in membrane fatty acid composition resulting from the inhibition of Delta-6 desaturase may be involved in the decreased Na(+),K(+)-ATPase activity observed in the outer MTAL after 12 wk of diabetes. GLA is a fatty acid that by-passes the Delta-6 desaturase step. We measured the membrane fatty acid composition and the Na(+),K(+)-ATPase activity in the renal outer medulla of control and streptozotocin (STZ)-induced diabetic rats 12 wk after the induction of diabetes. Measurements were performed after supplementation of control rats with sunflower oil (SO) or GLA for 12 wk, and supplementation of 12 wk diabetic rats with SO for 12 wk or with GLA for 6 or 12 wk. Supplementation with GLA not only prevented the decrease in Na(+),K(+)-ATPase activity observed after 12 wk of diabetes but also time dependently stimulated Na(+),K(+)-ATPase activity in the outer medulla. The changes in Na(+),K(+)-ATPase activity were related to parallel changes in the amount of Na(+),K(+)-ATPase alpha(1) subunit protein. In addition, in diabetic rats only, Na(+),K(+)-ATPase activity was positively correlated with the amount of AA present in cell membranes (r = 0.92, P < 0.05). Our results indicate that nutritional GLA supplementation increases Na(+),K(+)-ATPase activity and expression in diabetic rats. In addition, the positive correlation between AA content and Na(+),K(+)-ATPase activity suggests that in diabetic rats, alterations in membrane fatty acid composition contribute to the decreased Na(+),K(+)-ATPase activity in outer medulla.

[Post-acute long stay and extensive rehabilitation: study of the first year of work at a long stay university hospital unit]. / Lungodegenza post-acuzie e riabilitazione estensiva: studio sul primo anno di attività di un'Unità di Lungodegenza Ospedaliera-Universitaria.

Long stay is a new type of hospital admission geared to internal medicine patients requiring long-term stays in hospital and prolonged treatment for the purposes of stabilization or clinical rehabilitation. Given the lack of specific experience, we monitored the progress of a Long-Stay Unit with the aim to estimate the clinical and organizational impact. We studied 263 patients (59.3% females, 40.7% males; mean age 76.3 +/- 11.5 years, 42.2% all in their late eighties) coming from medical wards (75%) and from surgical wards (25%). The clinical complexity was prospectively estimated by a form divided into 3 sections: the first part was filled out at the time of transfer, the second part at set intervals throughout the period and the third at the end of the stay. Mean length of stay for medical patients was 33.2 days, for surgical patients 28.6 days (NS). Main transfer diagnosis: 50% of the patients fell into two diagnostic groups: malignant neoplasm (33.1%) and cerebral ictus (17.5%). Some data evidenced remarkable clinical complexity: 93.9% of the patients had one or more secondary diagnoses; when initially admitted 89.4% already presented with complications or serious outcomes; while in the Long-Stay Unit 83.3% required medical treatment and extensive nursing care; 87.1% had further major complications; 56.3% was totally dependent; 42.6% was totally bedridden and 35.4% died. In conclusion, the majority of long-stay patients in a medium-to-large polyclinic hospital present with several concomitant diseases, with extremely invalidating complaints, characterized over the short-to-mid term by serious clinical complications. They require a great deal of competent medical/nursing care as well as highly qualified internal medicine specialists.

Lipolytic activity of ricin from Ricinus sanguineus and Ricinus communis on neutral lipids.

The present study was carried out with a view of determining ricin lipolytic activity on neutral lipids in emulsion and in a membrane-like model. Using 2,3-dimercapto-1-propanol tributyrate (BAL-TC(4)) as substrate, the lipolytic activity of ricin was found to be proportional to ricin and substrate concentrations, with an apparent K(m) (K(m,app)) of 2.4 mM, a k(cat) of 200 min(-1) and a specific activity of 1.0 unit/mg of protein. This work was extended to p-nitrophenyl (pNP) fatty acid esters containing two to twelve carbon atoms. Maximum lipolytic activity was registered on pNP decanoate (pNPC(10)), with a K(m,app) of 3.5 mM, a k(cat) of 173 min(-1) and a specific activity of 3.5 units/mg of protein. Ricin lipolytic activity is pH and galactose dependent, with a maximum at pH 7.0 in the presence of 0.2 M galactose. Using the monolayer technique with dicaprin as substrate, ricin showed a lipolytic activity proportional to the ricin concentration at 20 mN/m, which is dependent on the surface pressure of the lipid monolayer and is detectable up to 30 mN/m, a surface pressure that is of the same order of magnitude as that of natural cell membranes. The methods based on pNPC(10) and BAL-TC(4) hydrolysis are simple and reproducible; thus they can be used for routine studies of ricin lipolytic activity. Ricin from Ricinus communis and R. sanguineus were treated with diethyl p-nitrophenylphosphate, an irreversible serine esterase inhibitor, and their lipolytic activities on BAL-TC(4) and pNPC(10), and cytotoxic activity, were concurrently recorded. A reduction in lipolytic activity was accompanied by a decrease in cytotoxicity on Caco2 cells. These data support the idea that the lipolytic activity associated with ricin is relevant to a lipase whose activity is pH and galactose dependent, sensitive to diethyl p-nitrophenylphosphate, and that a lipolytic step may be involved in the process of cell poisoning by ricin. Both colorimetric tests used in this study are sensitive enough to be helpful in the detection of possible lipolytic activities associated with other cytotoxins or lectins.

[Ocular ultrasonography in pediatrics: persistence of hyperplastic primary vitreous]. / Ecografia oculare in pediatria: persistenza del vitreo primitivo iperplastico.

AIM OF THE STUDY: To assess the diagnostic viability of ultrasound and color Doppler ultrasound in a particular segment of paediatric ophthalmology-persistent primary hyperplastic vitreous, in the presence of leucocoria, retrospectively evaluated in patients observed over the last two years. MATERIAL AND METHODS: We re-evaluated four patients (two new-born, one unweaned and one nine-years-old) who at ophthalmoscopic examination were suspected having persistent primitive hyperplastic vitreous. The follow-up included an ultrasound examination, basic color-Doppler ultrasound and re-evaluation during sedation both using an operative microscope and ultrasound. The examinations were performed with linear 7.5 Mhz probes and a Doppler frequency of 3.7 Mhz, while the sedation examination was performed with an anular 13 Mhz probe. The scans were sagittal and axial to correctly localize the lesion with respect to the lens, to ciliary bodies and to the optic nerve head. RESULTS: In the first patient ultrasound revealed a hyperechogenic inhomogeneous structure bilaterally in the vitreous structure; this extended from the posterior wall of the lens to the optic nerve head and retina, and was found to be highly vascolarized at the subsequent color-Doppler ultrasound. In the second patient there was an echogenic band extending from the posterior wall of the lens to the optic nerve head and to the retina, as the fourth patient showed a series of echogenic bands extending from the temporal ciliar of bodies to the temporal retina; in both cases no significant vascolarization was found by color Doppler ultrasound. In the third patient ultrasound showed a lesion involving nearly all of the vitreous body, with inhomogeneous structure with small calcifications and intense vascolarization. DISCUSSION AND CONCLUSIONS: Ultrasound supplies essential information for the diagnosis of persistent hyperplastic primary vitreous as it determines the presence of the lesion, its extension and retinal and optic nerve head involvement. As confirmed by operative microscopy the first patient had bilateral lesions involving the optic nerve head, as well as the retina, the latter which appeared raised. The second and fourth patients had typically posterior lesions; the lesion of the third patient was difficult to interpret even by operative microscopy. To conclude,Ultrasound proved to have an optimal sensitivity and specificity for precisely locating the site and extension of the lesion. By contrast, the difficulties and need for sedation with color Doppler ultrasound unlikely to be useful with paediatric patients.

Na,K-atpase alterations in diabetic rats: relationship with lipid metabolism and nerve physiological parameters.

Type 1 diabetes induces several metabolic and biochemical disturbances which result in the alteration ofNa,K-ATPase, an enzyme implicated in the physiopathology of neuropathy Several fatty acid supplementations lessen this alteration. The aims of this study were to determine the possible relationships between Na,K-ATPase activity in nerves and red blood cells (RBCs) and, on one hand, the fatty acid alterations induced by diabetes in these tissues and plasma and on the other, on nerve physiological parameters. Two groups of rats, control and diabetic (n = 15), were sacrified 8 weeks after induction of diabetes with streptozotocin. Nerve conduction velocity (NCV), nerve blood flow (NBF), Na,K-ATPase activity and membrane fatty acid composition of sciatic nerves, red blood cells (RBCs) and plasma were measured. NCV, NBF and Na,K-ATPase activity in RBCs and in sciatic nerves were significantly decreased in diabetic rats. We revealed a positive correlation between Na,K-ATPase activity in sciatic nerves and both NBF and NCV and between Na,K-ATPase activity in RBCs and NBF and the same activity in sciatic nerve. Diabetes induced major changes in plasma fatty acids and RBC membranes and less important changes in sciatic nerve membranes. Na,K-ATPase activity correlated negatively with C20: 4 (n-6) and C22: 4 (n-6) levels in nerves and with C18: 2 (n-6) levels in RBCs. During diabetes, changes in the membrane fatty acid composition suggest the existence of a tissue-specific regulation, and the decrease in Na,K-ATPase activity correlates with the alteration in the level of specific fatty acids in RBCs and sciatic nerves. Modifications in the lipidic environment of Na,K-ATPase would be involved in the alteration of its activity. Na,K-ATPase activity seems to be implicated in the decrease of both NCV and NBF during diabetes.

Omegacoeur, a Mediterranean nutritional complement, stimulates Na,K-ATPase activity in human endothelial cells.

Fatty acids are known as modulators of the vasoactive properties of the vessel wall and can influence the physical and functional properties of cell membrane. The membrane-bound enzyme Na,K-ATPase plays a central role in endothelial function such as vasoconstriction. In a previous study, we have shown that omega3 fatty acids inhibited Na,K-ATPase activity in human endothelial cells. As Mediterranean diet is known to protect from cardiovascular diseases, we have investigated the effects of Omegacoeur, a Mediterranean nutritional complement consisting of omega3, omega6, omega9 fatty acids, garlic and basil, on Na,K-ATPase activity in human endothelial cells (HUVECs). Cells were incubated for 18 hr with pure lecithin liposomes or Omegacoeur-enriched emulsions (4 mg lecithin/ml). Na,K-ATPase and 5'-nucleotidase activities were determined using coupled assay methods on microsomal fractions obtained from HUVECs. Cell fatty acid composition was evaluated by gas chromatography after extraction of lipids and fatty acids methylation. The results showed that Omegacoeur (0.1 mM) increased Na,K-ATPase activity by 40% without changes in 5'-nucleotidase activity. Cells incubated with Omegacoeur preferentially incorporated linoleic acid. Therefore, linoleic acid or others constituents of Omegacoeur could be responsible of the stimulation of the Na,K-ATPase activity that might be related to changes in endothelial membrane fluidity.

Altered erythrocyte n-3 fatty acids in Mediterranean patients with coronary artery disease.

A low frequency of ischaemic heart diseases in Eskimos has been related to polyunsaturated fatty acids. We therefore studied fatty acid patterns associated with coronary artery disease (CAD) for a possible relationship between fatty acid profile and CAD diagnosis in Mediterranean patients. The gas chromatography method was used to analyze the membranes of patients' erythrocytes. The patients without coronary stenosis were used as controls. Patients with CAD showed increased percentages of saturated fatty acids (35.8 vs. 34.2%, P<0.001) and monounsaturated fatty acids (14.6 vs. 13.6%, P<0.01), as well as reduced percentages of polyunsaturated fatty acids (38.5 vs. 41.3%, P<0.001). The decrease in polyunsaturated fatty acids percentages was due to the series of n-3 fatty acids (9.2 vs. 11.4%, P<0.001), mainly at the expense of docosahexaenoic acid [C22:6 (n-3)] (4.9+/-0.25% vs. 6.4+/-0.23%, P<0.001) and docosapentaenoic acid [C22:5 (n-3)] (3.0+/-0.19% vs. 3.9+/-0.12%, P<0.001). The study shows altered n-3 fatty acids in Mediterranean patients with CAD. Our data suggest that the percentage of docosahexaenoic and docosapentaenoic acids in erythrocytes could be used as indicators of an independent risk factor for coronary artery disease.

Effect of a water-soluble fiber (galactomannans)-enriched formula on gastric emptying time of regurgitating infants evaluated using an ultrasound technique.

BACKGROUND: Milk formulas enriched with water-soluble fibers are a first-line measure for infants with gastroesophageal reflux. However, it has been reported that these compounds could affect gastric emptying. The aim of this study was to evaluate the effects of these thickeners on gastric emptying time in infants with frequent regurgitation or vomiting. METHODS: Forty-seven infants, aged 1 to 12 months, with uncomplicated gastroesophageal reflux underwent two ultrasound evaluations of gastric emptying time after receiving either a standard formula or a formula enriched with 0.4 g galactomannan per 100 ml diluted milk. Gastric emptying time was calculated by measuring the antrum area at baseline and at defined intervals over the next 3 hours. RESULTS: The gastric emptying time (mean +/- SD) for the standard and the thickened formula was 136 +/- 33 and 133 +/- 34 minutes, respectively. There was no significant difference in the gastric emptying patterns of the two formulas. Gastric emptying time was longer after the standard formula in 15 of the 47 subjects, shorter in 15 of the 47, and the same in 17 of the 47. CONCLUSIONS: The ingestion of a water-soluble fiber-enriched formula does not have any significant influence on the gastric emptying time of infants with frequent regurgitation or vomiting.

Prothrombotic abnormalities in children with venous thromboembolism.

PURPOSE: The aim of this study was to determine the frequency of acquired or inherited prothrombotic disorders in a pediatric population with venous thromboembolism (VTE). PATIENTS AND METHODS: From May 1992 to April 1998, 56 consecutive children with VTE were prospectively studied at a single center. RESULTS: The median age was 8.4 years (range, 0.1-18 years). There was a male predominance. Fifty (89%) children had thrombosis in the lower venous system. Risk factors were detected in 54 (96%) children. Twenty-one (38%) thrombotic episodes were related to central venous lines. Family history of thrombosis was positive in 13 (23%) patients. In 26 (46%) patients, a prothrombotic disorder was detected. Nine of them had inherited disorders (protein C deficiency, 5 patients; protein S deficiency, 3 patients; Factor V Leiden mutation, 1 patient), and 13 children had acquired disorders (antiphospholipid antibodies, 5 patients; antithrombin deficiency, 8 patients). The remaining four showed combined abnormalities (Factor V Leiden mutation associated with inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 2 patients and inherited antithrombin deficiency, 1 patient). CONCLUSIONS: In the series, a high percentage of prothrombotic disorders was detected; thus, a complete hemostatic evaluation should be performed in all of the children with VTE whether the patients have one or more risk factors.

Effect of streptozotocin-induced diabetes on rat liver Na+/K+-ATPase.

Na+/K+-ATPase during diabetes may be regulated by synthesis of its alpha and beta subunits and by changes in membrane fluidity and lipid composition. As these mechanisms were unknown in liver, we studied in rats the effect of streptozotocin-induced diabetes on liver Na+/K+-ATPase. We then evaluated whether fish oil treatment prevented the diabetes-induced changes. Diabetes mellitus induced an increased Na+/K+-ATPase activity and an enhanced expression of the beta1 subunit; there was no change in the amount of the alpha1 and beta3 isoenzymes. Biphasic ouabain inhibition curves were obtained for diabetic groups indicating the presence of low and high affinity sites. No alpha2 and alpha3 isoenzymes could be detected. Diabetes mellitus led to a decrease in membrane fluidity and a change in membrane lipid composition. The diabetes-induced changes are not prevented by fish oil treatment. The results suggest that the increase of Na+/K+-ATPase activity can be associated with the enhanced expression of the beta1 subunit in the diabetic state, but cannot be attributed to changes in membrane fluidity as typically this enzyme will increase in response to an enhancement of membrane fluidity. The presence of a high-affinity site for ouabain (IC50 = 10-7 M) could be explained by the presence of (alphabeta)2 diprotomeric structure of Na+/K+-ATPase or an as yet unknown alpha subunit isoform that may exist in diabetes mellitus. These stimulations might be related, in part, to the modification of fatty acid content during diabetes.