Respiratory distress syndrome in second-born versus first-born twins. A matched case-control analysis

The well-known increased risk of the respiratory distress syndrome in a twin born second as compared with the twin born first is usually attributed to the second twin's predisposition to depression at birth ("asphyxia"). We analyzed the etiologic roles of birth order, presentation, and depression at birth in the development of the respiratory distress syndrome in matched case-control populations drawn from 221 preterm twin pairs. Among the 39 twin pairs discordant for respiratory distress syndrome, the second twin was the affected member in 31 pairs. Second birth order was the only independent risk factor, but only in vaginal deliveries (matched odds ratio, 14.2; 95 percent confidence interval, 2.5 to 81.1). Second twins delivered abdominally did not have an increased risk relative to first twins (odds ratio, 0.9; confidence interval, 0 to 17.8). When depression at birth was evaluated as an outcome variable, malpresentation, rather than birth order, was the major risk factor (independent matched odds ratios of 2.7 [confidence interval, 1.0 to 7.5] and 1.3 [0.7 to 2.5], respectively). Thus, second twins' increased risk of respiratory distress syndrome cannot be explained by a predisposition to depression at birth; a more important factor may be that second twins do not benefit from the salutary effects of labor to the same extent as first twins.     

Using simulation to instruct emergency medicine residents in cognitive forcing strategies.

PURPOSE: Recent literature defines certain cognitive errors that emergency physicians will likely encounter. The authors have utilized simulation and debriefing to teach the concepts of metacognition and error avoidance. METHOD: The authors conducted a qualitative study of an educational intervention at Lehigh Valley Hospital during academic year 2002-03. Fifteen emergency medicine residents--eight from postgraduate year three (PGY3) and seven from postgraduate year two (PGY2)--experienced a difficult simulator lab scenario designed to lead them into a cognitive error trap. The debriefing was a PowerPoint with audio format CD-ROM with a didactic on succinylcholine (15 minutes) and cognitive forcing strategies (30 minutes). After debriefing, residents were interviewed by an ethnographer with an 11-question (15-minute) interview and completed an eight-question written survey. RESULTS: The residents ranked this experience second only to direct patient care for educational effectiveness. Survey results (Likert scale, 1 = disagree completely to 5 = agree completely) included "Improved my ability to use succinylcholine" (mean = 4.73), "Improved my ability to diagnose and treat hyperkalemia" (mean = 4.6), and "Cognitive forcing strategies is a useful educational effort" (mean = 4.33). The major interview themes that evolved were that the simulation lab was a positive experience; succinylcholine knowledge was gained; mistakes caused reflection/motivation; the lab was stressful; attending feedback was desired; the lab was realistic; and cognitive forcing strategies were discussed. When asked what they learned, more of the PGY3s commented on cognitive strategies or heuristic techniques (six out of eight), whereas the PGY2s commented on knowledge gained about succinylcholine (five out of seven) and only one PGY2 mentioned cognitive strategies. CONCLUSION: Pilot data suggest that metacognitive strategies can be taught to residents, though they may be better understood by upper-level residents.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.     

Inhibition of HIV-1 by modification of a host membrane protease

While it is clear that CD4 Is the receptor for the gp120 envelopeprotein of HIV-1, substantial evidence suggests that other hostcell proteins are required for successful membrane fusion. Studieswere initiated to examine the potential for a protein receptorwhich has an elastase-like character to participate in fusionof HIV-1 with permissive host cells. A synthetic elastase inhibitorwas shown to significantly reduce HIV-1 infectivity when presentduring, but not after, the initial contact between virus andcells. A human T cell elastase-like membrane component was purifiedand shown to be lipid-associated. By competitive Inhibition,the purified protein was shown to bind gp160 within the HIV-1fusion domain. The binding parameters of whole T cell membraneextract, with a hydrophobic pentapeptide representative of thefusion domain, suggested an elastase-like protein is the single,secondary T cell receptor for HIV-1 (K = 1x10³ M^–1). Thepentapeptide interacted with porcine and human (epithelial andpolymorphonuclear leukocyte), but not murine, elastase isoforms,suggesting its participation In the permissiveness of host cellsto infection.     

Adenovirus type 12 tumor antigen. II. Immunoprecipitation of protein kinase from infected and transformed cells by antisera to T antigen and some normal rat sera.

Protein kinase was found to be precipitated from adenovirus type 12 (Ad12)-infected KB cells and Ad12-transformed hamster cells by sera of tumor-bearing hamsters and rats: Immunoprecipitates obtained with T antigen reactive sera catalyzed transfer of ³²P from [γ-³²P]ATP to the γ-chain of IgG. Analogous products of control cells were without significant activity. Control hamster sera precipitated no protein kinase from infected and transformed cells. Some control rat sera (syngeneic with immune sera), however, were found to precipitate protein kinase from infected and transformed cells; particularly active in this respect were sera of female breeder rats. When partially purified, highly immunoreactive T antigen preparations from transformed cells were used as a source of enzymatic activity, protein kinase was detected only in precipitates obtained with immune sera.     

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.     

The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata andCercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines.     

Does feeding regime affect physiologic and thermal responses during exposure to 8, 20, and 27° C?

Summary When the loss of body heat is accelerated by exposure to low environmental temperatures, additional substrates must be oxidized to provide energy to sustain temperature homeostasis. Therefore, the present investigation examined the relation between feeding regime [pre-experimental carbohydrate feeding (FED) vs a fast (FAST)], during 120 min of exposure to 8, 20, and 27° C in well-nourished men. The following were examined: tissue insulation (I; °C · m² · W^–1), rectal temperature (T _re; °C), and oxygen consumption ( O₂; ml · kg^–1 · min^–1). O₂, T _re, and I revealed no significant differences between treatments (FED vs FAST) at any temperature. At 27° C, I was less (P < 0.05) than at 20 and 8° C, and decreased (P < 0.05) as exposure time increased. At 8° C, O₂was higher (P < 0.5) than at 20 or 27°C, and O₂increased as time increased (P < 0.05). T _re decreased (P < 0.05) as time increased for all conditions. Respiratory exchange ratio (R) differed (P < 0.05) between treatments (FED vs FAST), temperature (8 vs 20° C), and across time. Values for R suggests that carbohydrate accounted for 56% and 33% of caloric utilization during the FED vs FAST conditions, respectively. At 8 vs 20° C, R represented 54% vs 30% of cabohydrate utilization. Across time, R demonstrated that in both conditions (FED vs FAST) there was a decreased reliance on carbohydrate utilization for energy provision. From these data it appears that while substrate utilization differed between dietary treatment and across time this did not differentially affect O₂or T _re during protracted exposure to 8, 20, and 27° C. The higher R in the 8° C condition for both dietary treatments demonstrates that carbohydrate utilization is increased in shivering cold-exposed humans. However, the reduction in R across time suggests that fat oxidation is also involved in metabolic heat production and core temperature maintenance during shivering in the cold.     

Longitudinally orientated smooth muscle cells in rabbit arteries

Intima formation in vessels, spontaneous or experimentally induced, is generally characterized by the presence of longitudinally orientated smooth muscle cells (LSMC). During an experiment of neo-intima induction in carotid arteries in rabbits, by application of a nonconstrictive silastic cuff, a study was performed to investigate the presence of LSMC in the systemic and pulmonary circulations, in both elastic and muscular arteries. Three patterns could be distinguished: intimai cushions in muscular arteries, single or small groups of LSMC in the intima in elastic and larger muscular arteries, and intra-medially located layers or columns of LSMC in the aorta, the pulmonary artery, at the bifurcation of the aorta and around orifices of branches. In order to understand this peculiar orientation a biomechanical approach was used: this showed that near the lumen the circumferential stress is 4.5 times higher than the longitudinal. Because the cell surface of the smooth muscle cells exposed to this stress per unit vessel length is much less in the longitudinal than in the circular direction we conclude that the LSMC align in the direction which allows them to cope most effectively with the mechanical stresses.