Logistic regression in case-control studies: The effect of using independent as dependent variables

In case-control studies, cases are sampled separately from controls. In such studies the primary analysis concerns the estimation of the effect of covariables on being a case or a control. To explore causal pathways, further secondary analysis could concern the relationships among the covariables. In this paper the validity of such secondary analysis is addressed. In particular, the use of multiple logistic regression in case-control studies where the dependent variable is not the case/control indicator is explored. It is shown that only under very restrictive conditions will sample regression coefficients correctly estimate their true value. In many situations, it may be valid to regress one covariable on others in the control group, but not in the case group or the combined sample. This principle is illustrated by a study of sexually transmitted disease in Kenya.     

Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study.

A 1975 report stated that a schizophrenic genotype may be manifested in infants by a neurointegrative defect called pandysmaturation. Recent evidence supports this: (1) 12 studies found delayed development in schizophrenics' infants and in preschizophrenics; (2) "blind" psychometric evaluations favored an adult schizotypal disorder in four to six of seven high-risk subjects with pandysmaturation in the New York study; and (3) finally, in a partial replication of this method using the Jerusalem data, blind diagnoses of "probable" and "possible" pandysmaturation were significantly related to a parental diagnosis of schizophrenia and to cognitive and motor neurointegrative deficits at 10 years. Obstetrical complications were unrelated to diagnosis, pandysmaturation, or outcome in the overall sample. However, we found a small subgroup of schizophrenic offspring in whom the most severe motor deficits at follow-up were related to obstetrical complications, pandysmaturation, and low birth weight.     

Analysis of human T-cell receptor α-chain cDNAs isolated from peripheral blood mononuclear cells

T-cell receptor α-chain cDNA were generated from unstimulated peripheral blood mononuclear cells of a DR2,3,52a individual using a modified anchor PCR method. Fifty-six cDNA clones were identified representing 47 distinct T-cell receptor clonotypes and 26 VA loci. This analysis identified a new VA gene family VA30, and aew member of the VA6 gene family.     

Effect of experimental parameters on the formation of alginate-chitosan nanoparticles and evaluation of their potential application as DNA carrier

This study introduces a new procedure to prepare alginate-chitosan nanoparticles and examines several experimental parameters in relation to their formation and characteristics. Using DLS and TEM analysis, nanoparticle formation was shown to be predominantly affected by the ratio of alginate to chitosan, the molecular weight of the biopolymers and the solution pH. We report a method that results in spherical particles with mean diameters ranging from 323 nm to 1.6 microm, depending on the preparation conditions. The smallest particles were formed using lower molecular weight polymers with pH between 5.0 and 5.6 and having an alginate/chitosan weight ratio of 1:1.5. We have shown that DNA can be loaded with 60% association efficiency. Our system demonstrates suitable size, loading and release characteristics for application in drug- and gene-delivery systems.     

Attachment in infancy and preschool in low socioeconomic status rural Appalachian children: stability and change and relations to preschool and kindergarten competence

Attachment classifications were obtained from the Strange Situation at 15 months and at 4 years for a sample of 82 low socioeconomic status rural Appalachian children. The rate of secure attachment in infancy was 50.5%, and the majority of insecure infants were disorganized. At 4 years of age 61.2% of children were secure; early secure relationships were likely to be maintained, and about half of the insecure infants changed to a secure classification by 4 years. Overall, there was low but significant stability in attachment at the level of secure/insecure. Comparisons of (a) children who changed from insecure to secure with those who were stable insecure and (b) stable secure children with those who changed from secure to insecure identified contextual, child, and maternal interaction factors associated with attaining secure attachment. Assessments of cognitive and socioemotional competence at 4 years and kindergarten age suggested a protective effect of secure infant attachment but little benefit from secure preschool attachment.     

Recurrent Bacteremia Caused by a “Flexispira”-Like Organism in a Patient with X-Linked (Bruton’s) Agammaglobulinemia

Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin.     

An evaluation of commercial radioisotope methods for the determination of folate and vitamin B12.

Five commercial kits for the determination of folate and six kits for the determination of vitamin B12 were investigated. Their performance has been compared with microbiological methods for the two vitamins and with a non-commercial radioisotopic method for B12. The results show the importance of the determination of the reference range for an individual laboratory for each method. The precision of the kits varied appreciably, as did their performance using specimens from patients with different haematological disorders. In particular, certain kits failed to detect all patients with pernicious anaemia. The relative accuracy of the kits was assessed. Various factors which should be taken into account in the final selection of a satisfactory kit are discussed.     

Immunity reduces reservoir host competence of Peromyscus leucopus for Ehrlichia phagocytophila

Infection with Ehrlichia phagocytophila in white-footed mice is transient and followed by a strong immune response. We investigated whether the presence of acquired immunity against E. phagocytophila precludes white-footed mice from further maintenance of this agent in nature. Mice were infected with E. phagocytophila via tick bite and challenged either 12 or 16 weeks later by Ixodes scapularis nymphs infected with the same agent. Xenodiagnostic larvae fed upon each mouse simultaneously with challenging nymphs and 1 week thereafter. Ticks were tested for the agent by PCR, and the prevalence of infection was compared to that in ticks that fed upon nonimmune control mice. Only 30% of immunized mice sustained cofeeding transmission of E. phagocytophila between simultaneously feeding infected and uninfected ticks, compared to 100% of control mice. An average of 6.3% of xenodiagnostic ticks acquired Ehrlichia from previously immunized mice when fed 1 week after the challenge, compared to 82.5% infection in the control group. Although an immune response to a single infection with E. phagocytophila in white-footed mice provided only partial protection against reinfection with the same agent, the majority of mice were rendered reservoir incompetent for at least 12 to 16 weeks. Immunity acquired by mice during I. scapularis nymphal activity in early summer may exclude a large proportion of the mouse population from maintaining E. phagocytophila during the period of larval activity later in the season.     

Effect of IL-5, glucocorticoid, and Fas ligation on Bcl-2 homologue expression and caspase activation in circulating human eosinophils

IL-5 is a potent eosinophil viability-enhancing factor that has been strongly implicated in the pathogenesis of IgE-mediated inflammation in vivo. Recently published data have suggested that IL-5 (and related cytokines) may act by altering the expression of the anti-apoptotic regulator Bcl-2 or its homologues, but this is controversial. The behaviour of the recently described pro-apoptotic cysteine proteases (caspases) in eosinophils after IL-5 treatment has not been explored. We examined the effect of IL-5 on the expression of four major Bcl-2 homologues, as well as on the expression/activation of key members of the caspase cell death cascade in cultured circulating human eosinophils. The effect of relevant inducers of eosinophil apoptosis (glucocorticoid and Fas ligation) on these regulatory proteins was also examined. We observed baseline expression of the anti-apoptotic Mcl-1 and pro-apoptotic Bax proteins in immunoblots of eosinophil lysates, but not Bcl-x, Bcl-2. IL-5 treatment had the effect of maintaining this basal level of expression over time without altering the balance of Bcl-2 homologues. The (upstream) caspase 8 and (downstream) caspase 3 proenzymes were detected in eosinophils at baseline, and were processed during spontaneous and stimulated eosinophil death. IL-5 completely blocked caspase processing in spontaneous and dexamethasone-induced cell death, and significantly slowed processing during Fas ligation. Our data do not support the theory that IL-5 acts by altering the balance of anti-apoptotic and pro-apoptotic Bcl-2 homologues, but suggest that it may act by regulating activation of the caspase cell death cascade.