Partially Reversible Cortical Metabolic Dysfunction in Familial Hemiplegic Migraine With Prolonged Aura

We report a SPECT and PET voxel‐based analysis of cerebral blood flow and metabolic rate for glucose in a 23‐year‐old woman with familial hemiplegic migraine (FHM) caused by ATP1A2 gene mutation. In comparison with healthy subjects, a PET scan showed brain glucose hypometabolism, controlaterally to the hemiplegia, in the perisylvian area early in the attack (Day 1), without any SPECT perfusion abnormalities. Decrease in metabolic rate was only partially reversible at Day 78, concordant at this time with a remaining hemisensory loss. These findings provide further evidence for a primary cortical metabolic dysfunction in FHM.     

Outcomes of pregnancies with sonographically detected nuchal cords remote from delivery.

OBJECTIVE: To evaluate the outcomes of pregnancies with sonographically detected nuchal cords remote from delivery during the second and third trimesters of gestation. METHODS: A retrospective study of patients with and without nuchal cords detected by sonography during the second and third trimesters of gestation (17-36 weeks) was conducted. Variables included maternal age, parity, gestational age at sonography and at delivery, method of delivery, intrapartum fetal heart abnormalities, meconium-stained amniotic fluid, birth weight, 5-minute Apgar score, and neonatal intensive care unit admissions. RESULTS: A total of 233 patients were included in this study, of which 118 had sonographically detected nuchal cords identified in our department during the study period. There were no statistically significant differences between patients with sonographically detected nuchal cords and control patients with respect to maternal age, estimated gestational age at sonography, method of delivery, meconium-stained fluid, birth weight, intrapartum fetal heart abnormalities, 5-minute Apgar scores of less than 7, and neonatal intensive care unit admissions. Patients with nuchal cords detected by sonography were more likely to give birth before 37 weeks' gestation than control patients (21% versus 11%; P = .040). CONCLUSIONS: A sonographically detected nuchal cord is not associated with important perinatal complications.     

Seasonal variations and the contribution of cowpea (vigna unguiculata) and other legumes to nutrient intakes in Anambra state,Nigeria

A four‐day weighed food intake study was carried out in the wet and dry seasons in northern Anambra State, Nigeria, on pre‐school children and (during the wet season) on pregnant women. In both seasons the energy, calcium, riboflavin and niacin of the diet of the children were low while the diet of the pregnant women was deficient in most nutrients. No difference in energy intakes was observed in the two seasons; but in the wet season, protein, calcium and vitamin C intakes were lower (P<0.05) and fat and vitamin A intakes were higher (P < 0.01). The contribution to nutrient intakes by legumes was higher in the wet season, the period of food scarcity and increased prices. This difference was significant for energy and iron (P<0.05) and for protein and thiamine (P<0.01). The contribution was especially marked for protein, iron, thiamine and niacin (31%, 24%, 35% and 21% of pre‐school intakes respectively). Some local legume dishes were analysed and found to have a high nutritive value. This study confirms the importance of legumes in the diets of low income households.     

Biochemical characterization of fibrinogenolytic serine proteinases from Vipera lebetina snake venom.

Two glycosylated serine fibrinogenases isolated from Vipera lebetina venom have homologous N-terminal sequences and antigenic determinants but can be clearly differentiated according to substrate specificity, glycosylation levels, molecular mass and fibrinogen degradation. alpha-Fibrinogenase has no homolog among known serine proteinases. It has N-terminal similarity with snake venom arginine esterases but does not hydrolyze the esters of arginine, lysine and tyrosine. The enzyme has strong proteolytic activity and degrades alpha-chain of fibrinogen altering its clottability by thrombin. beta-Fibrinogenase is a typical arginine esterase which hydrolyzes esters and amides of arginine and attacks the beta-chain of fibrinogen.     

IFN-alpha and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apoptosis

We hypothesized that IFN-alpha would enhance the apoptotic activity of bortezomib on melanoma cells. Combined treatment with bortezomib and IFN-alpha induced synergistic apoptosis in melanoma and other solid tumor cell lines. Apoptosis was associated with processing of procaspase-3, procaspase-7, procaspase-8, and procaspase-9 and with cleavage of Bid and poly(ADP-ribose) polymerase. Bortezomib plus IFN-alpha was effective at inducing apoptosis in melanoma cells that overexpressed Bcl-2 or Mcl-1, suggesting that this treatment combination can overcome mitochondrial pathways of cell survival and resistance to apoptosis. The proapoptotic effects of this treatment combination were abrogated by a caspase-8 inhibitor, led to increased association of Fas and FADD before the onset of cell death, and were significantly reduced in cells transfected with a dominant-negative FADD construct or small interfering RNA targeting Fas. These data suggest that bortezomib and IFN-alpha act through the extrinsic pathway of apoptosis via FADD-induced caspase-8 activation to initiate cell death. Finally, bortezomib and IFN-alpha displayed statistically significant antitumor activity compared with either agent alone in both the B16 murine model of melanoma and in athymic mice bearing human A375 xenografts. These data support the future clinical development of bortezomib and IFN-alpha for malignant melanoma.     

MDR-reversal activity of chalcones

The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in MDR reversal, causing a marked increase in drug accumulation from 0.4 to 40 microg/mL. In combination with epirubicin, compound 7 displayed synergistic properties while compound 3 exhibited an additive effect. The data presented here indicated that some calcone derivatives can be regarded as effective compounds for reversal of MDR.     

Hydatic cyst of the liver. Considerations on 337 cases

Hydatid disease of the liver is still endemic in certain parts of the world. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. The aim of the study is to analyze the results of the surgical treatment in hydatid disease of the liver in First Surgical Clinic, Ia?i. The study concerned a period of 12.5 years (1992 - 31.07.2004) and it included 337 cases. There were performed radical procedures (ideal cystectomy - 17 cases - 5.04%, hepatic segmentectomy - 8 cases - 1.48%, atypical hepatectomy - 10 cases - 2.96%) or conservative procedures (de-roofing - 37 cases - 10.97%, subtotal pericystectomy - 34 cases -10.80%, total pericystectomy - 19 cases - 5.63%, partial pericystectomy - 212 cases -62.90%). In 35 cases (10.38%) the operation was started laparoscopically and 12 cases needed conversion. Postoperative course was complicated in 112 cases (33.32%) (external biliary fistula, cavity suppuration, residual cavity hydatid relapse). Radical methods constituted operations that had excellent results, but they are feasible in few cases. Conservative procedures, relatively simple and still accepted, have a higher rate of morbidity. The laparoscopic approach is more and more used, with good results.     

Data Supplementation: A Pharmacokinetic/Pharmacodynamic Knowledge Creation Approach for Characterizing an Unexplored Region of the Response Surface

No HeadingPurpose. To develop a data supplementation [i.e., a pharmacokinetic/pharmacodynamics (PK/PD) knowledge creation] approach for generating supplemental data to be used in characterizing a targeted unexplored segment of the response surface.Methods. The procedure for data supplementation can be summarized as follows: 1) statement of the objective of data supplementation for PK/PD knowledge creation, 2) performance of PK knowledge discovery, 3) PK data synthesis for target dose group(s), 4) covariate data synthesis for virtual subjects in the target dose group(s), 5) discovery of hidden knowledge from real data set to which supplemental data will be added, 6) implementation of a data supplementation methodology, and 7) discovery and communication of the created knowledge. A nonparametric approximate Bayesian multiple supplementation and its modification, structure-based multiple supplementation, which is an adaptation of the approximate Bayesian bootstrap, is proposed as a method of data supplementation for PK/PD knowledge creation. The structured-based multiple supplementation methodology was applied to characterize the effect of a target dose of 100 mg that was unexplored in a previously concluded study that investigated the effect of 200- and 600-mg doses on biomarker response.Results. The target dose of 100 mg was found to produce a response comparable with that of the 200 mg and better than that obtained with the 600 mg.Conclusions. Implementation of the PK/PD knowledge creation process through data supplementation resulted in gaining knowledge about a targeted region of a response surface (i.e., the effect of a target dose) that was not previously studied in a completed study without expending resources in conducting a new study.