Analysis of risk factors influencing imminent distress in growth-retarded fetuses undergoing oxygen test

We previously demonstrated a prognostic significance of maternal oxygen test in predicting imminent fetal distress. The purpose of this study was to investigate eventual other factors related to the length of the time interval elapsing between the Doppler diagnosis of brain sparing effect and abnormal fetal heart rate patterns. To this end we considered 101 growth-retarded fetuses free of structural and chromosomal abnormalities with a ratio between the pulsatility indices of umbilical and middle cerebral artery above the 95th centile in presence of a normal fetal heart rate pattern. The factors, other than the oxygen test, analyzed for a potential influence on this time interval were gestational age, presence of hypertension or preeclampsia, amniotic fluid index, severity of growth retardation (centile of the ultrasonographic estimated fetal weight) and 9 different Doppler indices calculated from extra- and intracardiac districts. Statistical actuarial methods were used to determine the effect of these prognostic factors on the duration of this time interval. The occurrence of abnormal fetal heart rate patterns (antepartum late heart rate decelerations) was used as censoring variable. The time interval between the entry in the study and delivery ranged from 1 to 39 days. Indications for delivery were fetal distress in 53 fetuses (52.4%) and different maternal or fetal complications in the remaining 48 fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)     

The choice of timing and methods in the surgical treatment of thoracic bone injuries in combined closed thoracic injuries during acute and early periods of traumatic disease]

Clinico-statistical analysis of the treatment results of 624 injured persons for the period from 1990 till 1995 year was conducted. In 509 (81.6%) of them the combined closed thoracic trauma was revealed, in 15 (18.4%)--the isolated closed affection of the skull, thorax, abdomen and extremities have occurred. The anatomic-functional model of the injury severity and prognosis outcome estimation was elaborated, an optimal timing and surgical treatment methods of the thoracic cage bones injury was substantiated, what have promoted to lower lethality from 50%--in injured persons, operated on without taking into account the trauma severity and prognosis outcome, to 31.6%--in operated on in the postponed order.     

Fetal plasma hypoxanthine level in growth-retarded fetuses before labor

Hypoxanthine is one of the purine nucleotides and is presumed to accumulate during hypoxia and acidemia. It remains uncertain, however, whether plasma hypoxanthine concentration is a useful indicator of fetal asphyxia; and its relationship to other markers of fetal physiologic state is not clearly defined. The aim of this study was to evaluate whether the level of fetal plasma hypoxanthine is correlated with fetal hypoxia and acidosis in growth-retarded fetuses before the onset of labor. Cordocentesis was performed in 34 growth-retarded fetuses at 31-35 weeks' gestation for the measurement of umbilical venous plasma concentrations of hypoxanthine, hemoglobin and lactate concentrations, blood gases, and base deficit. Umbilical venous plasma hypoxanthine concentration was found to be increased significantly, in parallel with the degree of acidosis (r = -0.74, P < 0.05) and base deficit (r = -0.41, P < 0.05), but not to bear a significant relationship to the degree of hypoxemia or other measured variables. We conclude that increases in the plasma concentration of hypoxanthine may reflect an impaired physiological state in growth-retarded fetuses before labor.     

Issues for covariance analysis of dichotomous and ordered categorical data from randomized clinical trials and non-parametric strategies for addressing them

Analysis of covariance is an effective method for addressing two considerations for randomized clinical trials. One is reduction of variance for estimates of treatment effects and thereby the production of narrower confidence intervals and more powerful statistical tests. The other is the clarification of the magnitude of treatment effects through adjustment of corresponding estimates for any random imbalances between the treatment groups with respect to the covariables. The statistical basis of covariance analysis can be either non-parametric, with reliance only on the randomization in the study design, or parametric through a statistical model for a postulated sampling process. For non-parametric methods, there are no formal assumptions for how a response variable is related to the covariables, but strong correlation between response and covariables is necessary for variance reduction. Computations for these methods are straightforward through the application of weighted least squares to fit linear models to the differences between treatment groups for the means of the response variable and the covariables jointly with a specification that has null values for the differences that correspond to the covariables. Moreover, such analysis is similarly applicable to dichotomous indicators, ranks or integers for ordered categories, and continuous measurements. Since non-parametric covariance analysis can have many forms, the ones which are planned for a clinical trial need careful specification in its protocol. A limitation of non-parametric analysis is that it does not directly address the magnitude of treatment effects within subgroups based on the covariables or the homogeneity of such effects. For this purpose, a statistical model is needed. When the response criterion is dichotomous or has ordered categories, such a model may have a non-linear nature which determines how covariance adjustment modifies results for treatment effects. Insight concerning such modifications can be gained through their evaluation relative to non-parametric counterparts. Such evaluation usually indicates that alternative ways to compare treatments for a response criterion with adjustment for a set of covariables mutually support the same conclusion about the strength of treatment effects. This robustness is noteworthy since the alternative methods for covariance analysis have substantially different rationales and assumptions. Since findings can differ in important ways across alternative choices for covariables (as opposed to methods for covariance adjustment), the critical consideration for studies with covariance analyses planned as the primary method for comparing treatments is the specification of the covariables in the protocol (or in an amendment or formal plan prior to any unmasking of the study.     

Cloning and high-level expression of alpha-galactosidase cDNA from Penicillium purpurogenum

The cDNA coding for Penicillium purpurogenum alpha-galactosidase (alphaGal) was cloned and sequenced. The deduced amino acid sequence of the alpha-Gal cDNA showed that the mature enzyme consisted of 419 amino acid residues with a molecular mass of 46,334 Da. The derived amino acid sequence of the enzyme showed similarity to eukaryotic alphaGals from plants, animals, yeasts, and filamentous fungi. The highest similarity observed (57% identity) was to Trichoderma reesei AGLI. The cDNA was expressed in Saccharomyces cerevisiae under the control of the yeast GAL10 promoter. Almost all of the enzyme produced was secreted into the culture medium, and the expression level reached was approximately 0.2 g/liter. The recombinant enzyme purified to homogeneity was highly glycosylated, showed slightly higher specific activity, and exhibited properties almost identical to those of the native enzyme from P. purpurogenum in terms of the N-terminal amino acid sequence, thermoactivity, pH profile, and mode of action on galacto-oligosaccharides.     

Identification of a novel human RAD51 homolog, RAD51B

OBJECTIVE: To assess the relation between morbidity from acute diarrhea and the form of day care. STUDY DESIGN: The design was a retrospective cohort study. The setting was the city of Espoo, an urban-suburban municipality in southern Finland with a population of 170,000. The study population comprised 2568 randomly selected children aged 1 to 7 years. The main outcome measure was the occurrence of diarrhea. RESULTS: Children in day-care centers (DCCs) had an increased risk for acute diarrhea compared with children in home care. In the whole group of children in DCCs, the relative risk was 1.20 (95% confidence interval [CI], 1.08 to 1.34). The risk was greatest in 1- and 2-year-old children, for whom the estimated relative risks were 1.76 (95% CI, 1.28 to 2.43) and 1.56 (95% CI, 1.16 to 2.09), respectively. The proportion of diarrhea episodes attributable to DCC care in 1-year-old children was 49% (95% CI, 18% to 91%), in 2-year-old children 37% (95% CI, 11% to 73%), and in the whole group 17% (95% CI, 7% to 29%). The infection risk did not differ between children in home and family care. CONCLUSIONS: The results provide quantitative evidence that the care in DCCs is a major determinant of acute diarrhea in children, whereas family day care does not increase the infection risk.     

Mannitol at clinical concentrations activates multiple signaling pathways and induces apoptosis in endothelial cells

To examine the characteristics of Ha?ssaguerre's slow potential (SP) specific to effective catheter ablation of the slow pathway in AV nodal reentrant tachycardia, the properties of SP and its recording site were analyzed in 52 patients who underwent successful SP-guided ablation. The properties of SP included the ratio of the amplitude of SP to that of atrial potential (A)(SP/A), the SP duration, the interval between His-bundle potential (HP) and SP (HP-SP), the interval between A and SP (A-SP), the interval between SP and ventricular potential (V) (SP-V), and the ratio of A-SP to the interval between A and the V (A-SP/A-V). The SP recording site was determined by the ratio of the amplitude of A to that of V (A/V) and by the relative position of the ablation catheter on X ray (right anterior oblique projection), expressed as the ratio of the distance between the coronary sinus ostium and SP site to that between the coronary sinus ostium and HP recording site (relative SP position). Twenty-eight slow pathways were ablated with a single energy application, while the other 24 required applications > or = 2. In all successful applications, SP/A, SP duration, HP-SP, A-SP, SP-V, A-SP/A-V, A/V, and relative SP position were 51% +/- 25%, 28 +/- 5 ms, -11 +/- 9 ms, 57 +/- 25 ms, 68 +/- 13 ms, 46% +/- 9%, 15% +/- 13%, and 51% +/- 13%, respectively. A significant correlation was observed between the relative SP position and A-SP, and between the relative SP position and A-SP/A-V (r = 0.60 and 0.37, respectively), while it was not between the relative SP position and HP-SP, nor between the relative SP position and SP-V. When the characteristics of SP were comparatively analyzed between the effective and ineffective applications in 24 patients in whom applications > or = 2 were required, there was no difference observed in HP-SP, A-SP, SP-V, A-SP/A-V, and A/V. However, SP/A, SP duration, and the relative SP position in the effective applications were all greater than those in the ineffective ones (56% +/- 20% vs 35% +/- 18%, P < 0.001; 29 +/- 4 vs 26 +/- 5 ms, P < 0.01; and 52% +/- 15% vs 33% +/- 11%, P < 0.001, respectively). These results indicate that SP with an amplitude over a half of A amplitude and recorded at the mid-septum of the tricuspid annulus can be a marker for successful slow pathway ablation. Although the local atrial electrogram appears late as the SP recording site shifts to the lower position, the timing of SP relative to HP and V remained unchanged, suggesting that SP is independent of the local atrial activation.     

Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages

Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.