Low Level Of Statistical Significance Research Articles

Preclinical study of a controlled release oral morphine system in rats

The efficiency of a new controlled release oral system containing morphine hydrochloride elaborated by introducing the drug into the polymeric structure of Eudragit® L30D is evaluated. Its in vitro dissolution behaviour and its effectiveness using the tail flick test model of pain in rats are investigated. A significant reduction in the drug release rate from the morphine-Eudragit® L30D complex as well as a very high efficiency in the dissolution process have been found. The tested morphine complex has an analgesic effect in rats. This effect is very clear from 30 min to 8 h. At 12 h the effect remains clear but with a lower level of statistical significance. Furthermore, there are no significative differences between the different doses tested.

Left ventricular diastolic function in asymptomatic and symptomatic human immunodeficiency virus carriers: an echocardiographic study

Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction has been reported as the first echocardiographically detectable abnormality in several cardiovascular disorders. We tested the hypothesis that Human Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied early in the clinical course of the infection. Doppler echocardiographic and computerized time-motion parameters of LV diastolic function were obtained in 51 HIV patients and in 25 age- and sex-matched healthy controls. The HIV population consisted of 28 totally asymptomatic subjects and 23 patients with incipient AIDS. As compared to controls, the HIV group had similar heart rate, blood pressure level, LV dimensions and fractional shortening, but increased isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P < 0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05). Doppler-derived parameters of diastolic function were significantly altered in the asymptomatic HIV group vs controls. The LV diastolic indices were similar in symptomatic and asymptomatic HIV patients except for PWT, which was lower in the symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes between HIV patients and controls was also performed in two subgroups; these included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal contractile state. The two subgroups had abnormalities of diastolic function similar to those of the HIV group as a whole, but with somewhat lower levels of statistical significance. Our data strongly suggest that there is myocardial involvement at the early stage of HIV infection; however, its impact on the clinical course of the disease remains to be clarified.

Stimulus Timing Effects on Wada Memory Testing

To determine the effects of presenting Wada memory stimuli at different times after intracarotid amobarbital injection on Wada memory asymmetries. Wada memory asymmetries from three timing series were related to the laterality of eventual temporal lobectomy. Academic institution epilepsy surgery program. Forty-three patients with complex partial seizures who later underwent anterior temporal lobectomy (left temporal lobectomy, 24 patients; right temporal lobectomy, 19 patients). No patient included had abnormalities on magnetic resonance imaging scans to suggest a lesion other than gliosis. Memory performance for objects whose presentation began approximately 45 seconds after amobarbital administration differentiated laterality of seizure onset. Memory for items presented later and after partial return of language (on average 3 minutes 40 seconds postinjection) also differed as a function of ipsilateral vs contralateral injection, but at a lower level of statistical significance. Memory for items presented last during the procedure (on average 6 minutes postinjection) discriminated seizure groups at a still lower level of statistical significance. When used to predict lateralized temporal lobe impairment in individual patients, early object memory performance was significantly better than memory performance employing either middle (56%) or late (43%) stimulus presentation timings. The results of early object memory testing are superior to those obtained from stimulus presentation later in the procedure in documenting temporal lobe dysfunction associated with a lateralized seizure onset.

Relationship between molecular connectivity and carcinogenic activity: a confirmation with a new software program based on graph theory.

For a database of 826 chemicals tested for carcinogenicity, we fragmented the structural formula of the chemicals into all possible contiguous-atom fragments with size between two and eight (nonhydrogen) atoms. The fragmentation was obtained using a new software program based on graph theory. We used 80% of the chemicals as a training set and 20% as a test set. The two sets were obtained by random sorting. From the training sets, an average (8 computer runs with independently sorted chemicals) of 315 different fragments were significantly (p < 0.125) associated with carcinogenicity or lack thereof. Even using this relatively low level of statistical significance, 23% of the molecules of the test sets lacked significant fragments. For 77% of the molecules of the test sets, we used the presence of significant fragments to predict carcinogenicity. The average level of accuracy of the predictions in the test sets was 67.5%. Chemicals containing only positive fragments were predicted with an accuracy of 78.7%. The level of accuracy was around 60% for chemicals characterized by contradictory fragments or only negative fragments. In a parallel manner, we performed eight paired runs in which carcinogenicity was attributed randomly to the molecules of the training sets. The fragments generated by these pseudo-training sets were devoid of any predictivity in the corresponding test sets. Using an independent software program, we confirmed (for the complex biological endpoint of carcinogenicity) the validity of a structure-activity relationship approach of the type proposed by Klopman and Rosenkranz with their CASE program.

A freeze-fracture study of the influence of frost hardening treatments on the plasma membranes of Medicago sativa and Bromus inermis cell suspension cultures

Freeze-fractured suspension cultured cells of alfalfa (Medicago sativa L.) and bromegrass (Bromus inermis Leyss) were examined before and after frost hardening treatments for evidence of plasma membrane adaptation to frost. No chemical fixatives or cryoprotective agents were used and care was taken to ensure that there was no subjective bias in making counts of intramembrane particles. There were no patches of membrane free of intramembrane particles in any of the treatments, and only small differences in intramembrane particles frequencies were found. Cold hardening and abscisic acid hardening may have had different effects on intramembrane particles frequency, but because of the low level of statistical significance this was uncertain. Two arrays of membrane particles (strings and rosettes) were present in all treatments. It is concluded that the technique may be insufficiently sensitive to detect the subtle changes in membrane protein composition that probably accompany adaptation to frost. Key words: Medicago sativa, Bromus inermis, frost hardiness, membrane structure, freeze-fracture.

Ventriculoatrial or Ventriculoperitoneal Shunts in the Treatment of Hydrocephalus in Children?

The data on all 881 primary or revision shunt operations performed on 158 paediatric patients treated in Gothenburg, Sweden from 1967 to 1984 and 101 patients treated in Oulu, Finland from 1968 to 1983 were pooled for the purpose of comparative evaluation of the function of ventriculoatrial (VA) and ventriculoperitoneal (VP) shunts. Ventriculoperitoneal shunting was the method of choice in Gothenburg and ventriculoatrial shunting in Oulu. The results of the 723 operations (305 VA and 418 VP shunts) were evaluated as the other 158 operations were for ventriculostomas, shunt removals and other procedures. 80 children had exclusively VA shunts and 133 children had exclusively VP shunts. Irrespective of the method of analysis the VP shunts were more frequently infected. The estimated relative risk for obstruction of the shunt (Meyer-Kaplan method) was shown to be significantly higher in VA shunts, but only at a low level of statistical significance (p less than 0.1). All other shunt complications were distributed uniformly in both groups. There was, however, a trend towards a higher mortality among children with exclusively VA shunts. Therefore it was concluded that despite the higher risk for infection in VP shunts, these still should be considered a safer choice, as the complications of VA shunts present greater risks.

Stability in Waking-Sleep States in Neonates as a Predictor of Long-Term Neurologic Outcome

Thirty-three full-term neonates were ranked blindly on a scale ranging from the least to the highest "risk" for future neurologic complications on the basis of available perinatal biographies, tests, and examinations performed during the newborn period. Four prolonged polygraphic-behavioral recordings were obtained one week apart beginning at ten days after birth. Five waking and sleep states were scored in each session as percentages of total observation time, giving a total of 20 scores for each baby to be subjected to analysis of variance. These measures also provided individual profile consistency or variability in maintaining waking-sleep states over the selected period of postnatal time. The whole cohort, except three infants who could not be followed adequately, was then reexamined periodically over a period ranging from 3 to 4 years (+/- 6 months) for neurologic and developmental assessments. Except for two scores that produced a low level of statistical significance (P less than .05), the other 18 scores were found to be not associated with long-term outcomes. Even the first two scores were not satisfactory discriminators for the outcome of the individual babies. However, when coefficients of concordance (W) were computed from each individual baby profile, significant statistics (P less than .001) emerged to indicate good correlations between high or low W values in the newborn period and long-term outcomes. All 17 newborns who had W scores greater than 0.9 were found to be normal at follow-up regardless of the poor ranking given several of them during the newborn period. Among the 13 newborns who had W scores less than 0.9, 11 had a poor clinical outcome at follow-up, though several had been ranked initially as falling within the least "risk" group.

Circulating Immune Complexes of IgA Type in Dermatitis Herpetiformis

There is some evidence that dermatitis herpetiformis may be mediated by circulating immune complexes. This study attempts to define the antibody class of these complexes. All patients studied demonstrated granular deposition of IgA in the papillary dermis on direct immunofluorescence. Serum immune complexes were detected using the qualitative Raji cell immunofluorescent assay, as well as the quantitative immunoradiometric assay. A group of 25 dermatitis herpetiformis patients was found to have higher levels of IgA containing complexes compared to a group of normals (p < .01). Higher levels of IgG containing complexes were also noted in dermatitis herpetiformis patients at a low level of statistical significance (p < .1). The relationship of these complexes to the pathogenesis of dermatitis herpetiformis is yet to be determined.

An epidemiological study of sudden death in hard and soft water areas

Death certificates were obtained for men and women aged 30–59 yr in 6 towns with soft water and high CVD death rates and 6 towns with hard water and low CVD death rates. Further information was obtained from the certifying doctor in all deaths attributed to or associated with cardiovascular disease. The classification system used provided for three main groups of sudden death; definite, probable and possible and final coding was carried out “blind” by three independent observers. As anticipated, CVD death rates were higher in the soft water areas and differences in IHD death rates between soft and hard water towns were present in all age groups. Sudden death made up a greater proportion of male IHD deaths in the soft than in the hard water towns, but at a low level of statistical significance. With one exception, there was a fairly clear separation between hard and soft water towns in the proportion of IHD deaths which were sudden. Sudden death as a proportion of IHD death was consistently higher in the soft water towns when subjects were classified by age or social class and also during both winter and summer. The overall findings do not constitute firm evidence that the proportion of IHD deaths which are sudden is higher in soft water towns but they are sufficiently consistent to justify further investigation of sudden death in relation to the hardness of drinking water.