Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies

This article describes how genetic components of disease susceptibility can be evaluated in case-control studies, where cases and controls are sampled independently from the population at large. Subjects are assumed unrelated, in contrast to studies of familial aggregation and linkage. The logistic model can be used to test collapsibility over phenotypes or genotypes, and to estimate interactions between environmental and genetic factors. Such interactions provide an example of a context where non-hierarchical models make sense biologically. Also, if the exposure and genetic categories occur independently and the disease is rare, then analyses based only on cases are valid, and offer better precision for estimating gene-environment interactions than those based on the full data.     

Performance of inattentive-overactive children on selected measures of prefrontal-type function

Several theorists have suggested that childhood inattention-overactivity ("attention deficit disorder," "hyperactivity") may arise from a deficit in the inhibitory mechanisms of the prefrontal cortex. Accordingly, it was hypothesized that inattentive-overactive children would exhibit prefrontal-type deficits on several relevant neuropsychological measures. Subjects were 21 elementary school pupils who had been referred for disruptive behavior problems and who had been rated as high in inattention-overactivity. Controls were 26 age-matched normal children from the same school. It was found that the Inattentive-Overactive group, relative to the Control group, performed in the direction of prefrontal-type deficit on three measures that have an empirical history of discriminating patients with prefrontal lesions from controls: Perseverative errors on the Wisconsin Card Sorting Test, errors on the sequential Matching Memory Task, and Necker Cube reversals. On three theoretical indices of prefrontal-type deficit--Trailmaking, the Stroop Color-Word Test, and a sequential memory task for children--the Inattentive-Overactive group also exhibited predicted deficits. There were no differences between groups on the WISC-R Vocabulary subtest. The results of the study are generally compatible with a prefrontal-deficit theory of inattention-overactivity. However, the presence of other deficits cannot be ruled out nor can an organic cause be inferred from these findings alone.     

Phenotypic pattern of B cells in the appendix: reduced intensity of CD19 expression

The lymphoid tissue of the appendix is considered as part of the gut-associated lymphoid tissue (GALT). In order to understand better the immunological significance of the appendix we analyzed the cellular composition of normal and inflamed human appendix tissue by flow cytometer with special attention to expression of the CD19 and CD5 markers on B cells. Cellular analysis was also performed on peripheral and appendical vein blood samples as well as on omentum and peritoneal fluid samples. The study population included seventeen patients aged 2-15 yr. (mean age - 11.5 yr.) undergoing appendectomy. Ten children were diagnosed with acute appendicitis while 7 had a normal appendix. RESULTS: Compared to the peripheral blood, the appendix contained a significantly higher percentage of CD19 cells (47.6% of total lymphocytes versus 15%, p<0.0001), and B1 cells (4.98% of total lymphocytes versus 2.42%, p=0.001). In addition, the intensity of CD19-staining was markedly decreased in the appendix (mean - 395.7), and also in the omentum (mean - 398.2) as compared to peripheral lymphocytes (mean - 497.7, p<0.0001 for both comparison). Comparison between the inflamed and the non-inflamed appendices revealed that the inflamed appendix contained a significantly higher proportion of B1 cells (5.64% of total lymphocytes versus 3.53%, p=0.032), and also a higher B1/b cell ratio (0.13 vs. 0.07, p=0.01). CONCLUSIONS: These results indicate that the appendix tissue contains higher number of B1 (and B) cells compared to the peripheral blood and that these cells play a role in the primary immune response to acute infection/inflammation in the appendix. Appendiceal B cell population is unique in term of CD19 intensity expression on their surface.     

A hypothesis concerning the role of endogenous colchicine-like factors in the etiology of Alzheimer''s disease

A hypothesis concerning the etiology of Alzheimer's disease is presented. It is argued that the formation of neurofibrillary tangles, paired helical filaments and senile plaques result from an increase in the activity of endogenous colchicine-like factors. The consequences of such an increase are 1) a blockade of axonal transport, 2) an accumulation of neurofilaments in the cytoplasm of neurons and 3) a redistribution of lysosomes from the cell bodies of neurons to the dendrites. In the absence of cytoplasmic lysosomal enzymes, the accumulated neurofilaments are cross-linked and metabolically stabilized by enzymes in the cell body. Neurons laden with neurofibrillary tangles and dendritic lysosomes would be prone to lysis and could participate in the formation of senile plaques.     

Psychoneurodendocrine correlates of lymphocyte subsets during healthy ageing

Ageing has been associated with increased cortisol levels and absolute counts of T lymphocytes with memory phenotype. Although the mechanisms underlying these changes are still unknown, it has been speculated that this could be related to a dysfunction in FAS/CD95 expression in naive or memory cells. In this study, we investigated the role of psychoneuroendocrine variables in regulating CD95 expression on lymphocyte subsets. Forty-six elderly subjects (65-91 years) and 33 young adults (20-40 years) were recruited accordingly the SENIEUR protocol. The psychological status was measured by structured clinical interviews, salivary cortisol was assessed along the day (9, 12 and 22h) and peripheral blood lymphocytes were immunophenotyped. The elderly were more stressed, depressed and anxious than the young subjects. Cortisol levels were increased in the elderly, indicating an activation of the hypothalamic-pituitary-adrenal (HPA) axis. We observed reduced counts of CD45RA+CD95+ cells in the elderly compared to young adults. The elderly subjects also showed a reduced expression of CD3 and CD62L in contrast to increased CD95 expression in CD45RA+ cells. The emotional state was positively correlated with the lymphocyte markers. Our data suggest the healthy ageing is associated with psychoneuroendocrine alterations that may be implicated in the regulation of CD95 expression on peripheral T cells.     

Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil – A time series analysis

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11–1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82–0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.     

Clomipramine, a better reference drug for panic/agoraphobia. II. Psychomotor and cognitive effects

The present reference drugs for the treatment of panic disorder and agoraphobia are imipramine and alprazolam. The latter decreases performance and cognitive functioning. No study of such functions in panic/agoraphobia is available. Fifty four out-patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia (PAG), taking part in a parallel groups controlled trial of imipramine (mean dose ±SEM 114±9 mg), clomipramine (50±4 mg) and propanteline (active placebo) over 8 weeks, were studied. A test battery of psychomotor and memory tests was administered at baseline, and after 1, 4 and 8 weeks of treatment. Their results were compared (at baseline and at the end of the trial) with those of a control group of 57 normal untreated subjects. There was no difference between treatments, and no drug effect on any test at any time. No consistent difference between patients and controls was detected. Given its apparently higher potency, and the absence of deleterious effects on cognitive measures known to be affected by benzodiazepines, we conclude that clomipramine is better than imipramine or alprazolam as a reference drug for panic/agoraphobia.     

Serum levels of clomipramine and desmethylclomipramine and clinical improvement in panic disorder

Several placebo-controlled trials have shown the efficacy of clomipramine (CMI) in panic disorder. However, none has investigated the relationship between CMI, and desmethylclomipramine (DCMI) plasma levels, and outcome. In this trial, 41 patients meeting the DSM-III-R criteria for panic disorder with/without agoraphobia received 50-200 mg of CMI daily in a single-blind, flexible dose regimen for 14 weeks. At the end of treatment, 97% of the patients were free of panic attacks. Patients were classified into two groups of improvement according to the panic symptom items of the 'Patient-Rated Anxiety Scale'. A repeated-measures analysis of variance suggested a significant association between outcome and serum DCMI level/daily dose ratio as well as total serum level/daily dose. Patients with intense improvement showed DCMI and total serum levels lower than those with moderate improvement. The results indicate the importance of monitoring clomipramine and desmethylclomipramine serum levels in this disorder.     

Residual and acute effects of flurazepam and triazolam in normal subjects

Residual and acute effects of flurazepam and triazolam were studied in two double-blind, crossover, placebo controlled, single-dose experiments. Psychological and physiological effects were determined 10 h after night administration (flurazepam 30 mg and triazolam 0.5 mg), and for 6 h after morning ingestion (flurazepam 15 mg and triazolam 0.25 mg). Both drugs produced similar "hangover" effects, impairing motor performance and increasing sleepiness on the following morning. After morning administration pronounced sedative effects were found with triazolam, while flurazepam effects were mild and hard to distinguish from placebo. The clinical relevance of these findings is discussed, suggesting that these drugs may be conceived as belonging to two different types of hypnotic agents.     

An evaluation of the treatment of parapsoriasis with phototherapy

Whether parapsoriasis represents an early stage of T-cell cutaneous lymphoma is still the subject of controversy. We evaluated the efficacy of phototherapy in the treatment of parapsoriasis and its relation with TCCL. Patients diagnosed with parapsoriasis and treated with phototherapy PUVA or UVB-NB were selected. Between 1 to 8 years following treatment the evolution of their disease was evaluated. In 62 patients the cure rate was 79.3% and 17.2% showed improvement of the lesions. Only two patients developed full blown T-cell cutaneous lymphoma. Phototherapy is an excellent treatment for parapsoriasis, with high cure rates, regardless of the type of phototherapy employed. Of the 62 patients under study, parapsoriasis showed no general tendency to progress to T-cell cutaneous lymphoma.