Determination of a new podophyllotoxin derivative, TOP-53, and its metabolite in rat plasma and urine by high-performance liquid chromatography with electrochemical detection

A high-performance liquid chromatographic method was developed for the determination of a new podophyllotoxin derivative, TOP-53 (I), and TOP-53 glucuronide (II) as its major metabolite in rat plasma and urine. For the analysis of I, the sample was chromatographed on a reversed-phase C18 column with electrochemical detection after consecutive two-step liquid-liquid extractions. Compound II was determined as I after enzymatic hydrolysis of II. This method was validated sufficiently with respect to specificity, accuracy, and precision. The limits of quantitation for both I and II were 2 ng/ml in plasma and 10 ng/ml in urine. The method is thus useful for the pharmacokinetic study of I.     

Relationship between the genomic organization and the overlapping embryonic expression patterns of the zebrafish dlx genes

To understand the relationship between the expression and the genomic organization of the zebrafish dlx genes, we have determined the genomic structure of the dlx2 and dlx4 loci. This led to the identification of the zebrafish dlx1 and dlx6 genes, which are closely linked to dlx2 and dlx4, respectively. Therefore, the inverted convergent configuration of Dlx genes is conserved among vertebrates. Analysis of the expression patterns of dlx1 and dlx6 showed striking similarities to those of dlx2 and dlx4, respectively, the genes to which they are linked. Furthermore, the expression patterns of dlx3 and dlx7, which likely constitute a third pair of convergently transcribed genes, are indistinguishable. Thus, the overlapping expression patterns of linked Dlx genes during embryonic development suggest that they share cis-acting sequences that control their spatiotemporal expression. The evolutionary conservation of the genomic organization and combinatorial expression of Dlx genes in distantly related vertebrates suggest tight control mechanisms that are essential for their function during development.     

Hypercoagulability and chronic atrial fibrillation: the role of markers of thrombin generation

BACKGROUND: We have studied 64 patients with congestive heart failure, half of them also with chronic nonvalvular atrial fibrillation (AF). Patients were also stratified according to a history of prior stroke. METHODS: The generation of thrombin was investigated by means of the molecular markers prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), because AF patients may have a hypercoagulable state. There was only a trend toward higher values of TAT and F1 + 2 for AF patients, while subjects with previous stroke (irrespective of AF) had increased levels of the markers of thrombin generation (TAT stroke+ 18.95 +/- 5.15 vs TAT stroke- 8.34 +/- 2.41; F1 + 2 stroke+ 2.22 +/- 0.29 vs F1 + 2 stroke- 1.32 +/- 0.12). The presence of spontaneous echo contrast (SEC) within left atrium was also investigated in 32 AF patients by transesophageal echocardiography. RESULTS: TAT were significantly higher in subjects (n = 11) with SEC (TAT sec+ 37.5 +/- 13.41 vs TAT sec- 8.7 +/- 2.51, p = 0.008). CONCLUSIONS: Finally, when we grouped into 1) those with both AF and stroke, 2) AF alone, 3) stroke alone and 4) sinus rhythm without stroke, levels of F1 + 2 were higher (and marginally higher TAT) in patients with AF and stroke than in those without stroke, revealing that there is a true clotting activation state in these subjects.     

Maternal nutrition and socio-economic status as determinants of birthweight in chronically malnourished African women

The birthweight is the most important determinant of mortality and morbidity in the neonatal period and may have an influence on health in adult life. The high rate of low birthweight in developing countries is therefore a major health problem. Maternal malnutrition is usually assumed to be a causal factor but other environmental factors are also involved. In this study we analysed maternal nutritional and socio-economic factors as determinants of birthweight in term infants from a rural African society characterised by a high rate of chronic malnutrition. Relations of maternal weight, gestational weight gain, parity, socio-economic status and infant sex with birthweight were analysed in 1,477 women and child pairs. The selected women were followed from early pregnancy and had an uncomplicated delivery at term of a living singleton child. The gestational weight gain was 5.6 (SD 6.0) kg and the mean birthweight 2.933 kg (SD 408). Maternal weight, representing the maternal long-term nutritional situation, was the most important independent determinant of birthweight, accounting for 13.0% of the variance in birthweight. The weight gain, representing the short-term nutritional situation, explained only 5.6% of the variance. Birthweight increased by 20 g (CI 18-23) for each kg maternal weight and by 15 g (CI 12-18) for each kg gestational weight gained. The socio-economic difference in birth-weight was 153 g (CI 109-196) 88 of which (CI 48-128) remained unexplained after adjustment for differences in maternal weight, parity and gender. Improved long-term nutritional situation and living conditions seems to be the most important prerequisites to counteract low birthweight in developing countries.     

Overly literal interpretations of speech in autism: understanding that messages arise from minds

Children with autism and children with Down's syndrome watched the following enactment. A protagonist put one item in location A and another in location B and then left the scene. Subsequently, the items were swapped the other way round. Finally, the protagonist (who remained ignorant of the swap) requested the item in A. The observing child participant was asked to judge (1) which item the protagonist wanted and (2) which item the protagonist put in A. Unlike children with Down's syndrome, those with autism made more errors in judging that the speaker wanted the item in B than in judging that the item the speaker put in A is now in B; children with autism wrongly tended to interpret utterances literally, and they did this significantly more frequently than children with Down's syndrome. We conclude that children with autism have a difficulty making nonliteral interpretations that cannot be explained as (1) a realist bias, (2) an inability to inhibit a prepotent response, and (3) a failure to keep track of the exchange of items.     

Prenatal diagnosis of a highly undifferentiated brain tumour--a case report and review of the literature

Intracranial tumours, often presenting with progressive hydrocephalus, are rare congenital diseases accounting for 0.5-1.5 per cent of all cases of brain tumours diagnosed during childhood. The differential diagnosis includes vascular malformations, infarctions, and haemorrhages. Sonographic signs suggestive of glioblastoma, teratoma, and astrocytoma do not establish the histological diagnosis, however. We report a case of an undifferentiated fetal glioma detected at 29 weeks' gestation. The diagnosis of an undifferentiated brain tumour was suspected by sonography because of the lack of normal brain structures in conjunction with a diffuse echogenic central lesion and an external hydrocephalus. Because of the very poor prognosis, we induced labour by intravaginal and intravenous administration of prostaglandin E2 and achieved the vaginal delivery of a stillborn child whose head circumference corresponded to 38 weeks of pregnancy. Histological and immunochemical features of this undifferentiated congenital glioma (glioblastoma) are presented.     

Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia

OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure.     

Replacement of the anterior cruciate ligament by cold preserved bone-cruciate ligament-bone allotransplants. An experimental study in the sheep

One ACL in each of 17 mature sheep was replaced with a deep-frozen bone-an ACL bone allograft. Allografts were obtained from skeletally mature sheep using a standard aseptic technique and stored deep frozen for at least 6 days (mean 21 days). Macroscopical, biomechanical, and histological changes were evaluated 12, 24, and 52 weeks following implantation. At autopsy all allograft ligaments were present and demonstrated no evidence of infection or immune reaction. We found slight arthrotic changes in 3 knees after 12 weeks, in 4 knees after 24 weeks, and in 3 knees after 52 weeks. Twelve weeks after the operation the maximum load of the allografts was 17.5% of the contralateral controls and increased to 20.9% after 24 weeks and to 32% of controls after 52 weeks. Ligament stiffness in the linear region also increased from 18.9% of control (12 weeks) to 32.5% after 52 weeks, whereas maximum load decreased from 112.2% of controls (12 weeks) to 98% of controls (52 weeks). Histologically, the allografts progressively matured with time, becoming nearly identical to normal ligaments at 52 weeks.     

A case of paraquat poisoning and subsequent fatality presenting to an emergency department

Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is an herbicide associated with both accidental and intentional ingestion, leading to severe and often fatal toxicity. Prognosis is largely dependent on the amount of paraquat absorbed. Rapid identification of the symptoms of paraquat toxicity (burns or ulceration at the site of ingestion or injection, acute respiratory distress, and renal failure) can facilitate early treatment intervention to limit absorption. We report a case of a 71-year-old man with a suicidal ingestion of paraquat 2 days prior to presentation. Serum paraquat levels, time elapsed since ingestion, and clinical symptoms all indicated poor prognosis. The patient developed severe respiratory distress and progressive renal failure, and died 6 days after admission to the hospital.