Males on the life-course-persistent and adolescence-limited antisocial pathways: follow-up at age 26 years

This article reports a comparison on outcomes of 26-year-old males who were defined several years ago in the Dunedin longitudinal study as exhibiting childhood-onset versus adolescent-onset antisocial behavior and who were indistinguishable on delinquent offending in adolescence. Previous studies of these groups in childhood and adolescence showed that childhood-onset delinquents had inadequate parenting, neurocognitive problems, undercontrolled temperament, severe hyperactivity, psychopathic personality traits, and violent behavior. Adolescent-onset delinquents were not distinguished by these features. Here followed to age 26 years, the childhood-onset delinquents were the most elevated on psychopathic personality traits, mental-health problems, substance dependence, numbers of children, financial problems, work problems, and drug-related and violent crime, including violence against women and children. The adolescent-onset delinquents at 26 years were less extreme but elevated on impulsive personality traits, mental-health problems, substance dependence, financial problems, and property offenses. A third group of men who had been aggressive as children but not very delinquent as adolescents emerged as low-level chronic offenders who were anxious, depressed, socially isolated, and had financial and work problems. These findings support the theory of life-course-persistent and adolescence-limited antisocial behavior but also extend it. Findings recommend intervention with all aggressive children and with all delinquent adolescents, to prevent a variety of maladjustments in adult life.     

Redox ratio of mitochondria as an indicator for the response of photodynamic therapy

The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.     

A phase II trial of temozolomide and IFN-alpha in patients with advanced renal cell carcinoma.

The combination of temozolomide (TEM) and interferon-alpha (IFN-alpha) previously demonstrated a 30% response rate in metastatic melanoma. A single institution, phase II trial evaluating the efficacy of TEM/IFN in patients with advanced renal cell carcinoma (RCC) was conducted. Safety and tumor response were the main outcomes. Eligible patients received 200 mg/m(2)/day TEM orally on days 1-5 every 28 days, with IFN 2.5 million U/m(2)/day subcutaneously (s.c.) three alternate days/week for days 1-15 first cycle, then 5 million U/m(2)/day s.c. 3 alternate days/week throughout each 28-day cycle. Efficacy was evaluated every 8 weeks, and dose-limiting toxicities (DLTs) were treated with dose reductions of the culprit drug. Sixteen patients (ages 37-67) were initially enrolled. Of the 14 evaluable patients, there was one minor response. Best response was stable disease, with 7 patients remaining on study for > or =6 months. Five were alive for more than 2 years, and 2 remain alive at 45 and 50 months after enrollment. DLTs included TEM-induced myelosuppression and IFN-induced fever/chills. Other toxicities were mild to moderate (grades 1-3). The combination of TEM/IFN proved quite tolerable. This regimen appears inactive in terms of response in this population with poor prognosis, but the patients with stable disease > or =6 months remain of interest.     

The prevalence of Candida albicans-associated diarrhoea in Buea, South West Cameroon

A total of 362 stool specimens were collected from 184 and 178 patients presenting at the Buea district Hospital with and without diarrhoea, respectively. The samples were screened and cultured for Candida albicans using standard microbiological procedures. Of the 184 diarrhoeic stool cultures, 35.9% showed C. albicans overgrowth as indicated by count >or=10(4) CFL/mL. Of the 178 non diarrhoeic stool cultures, C. albicans was identified in 23.6% of samples and counts were all <10(4) CFU/mL. An association was observed for C. albicans overgrowth and diarrhoea (p<0.001). The majority of isolates (87.8%) from the 66 samples showing candida overgrowth were susceptible to Amphotericin B in anti-fungal drug sensitivity assays. Results of the study highly suggest that C. albicans is an important cause of diarrhoea in the study area. We recommend that this fungus should be routinely checked in individuals presenting with diarrhoea particularly children and patients on prolonged or frequent antibiotic therapy.     

Soluble and membrane-bound forms of brain acetylcholinesterase in Alzheimer''s disease

In order to determine the effect of Alzheimer's disease on the relative distribution of soluble and membrane-bound molecular forms of acetylcholinesterase (AChE) in the brain, postmortem samples (delay interval less than 12 h) were obtained from parietal cortex (Brodmann area 40) and hippocampus as well as the areas containing their respective projection nuclei, i.e., substantia innominata and septal nucleus, in 9 patients with Alzheimer's disease (AD) and 4 normal controls. The monomer (G₁), dimer (G₂), and tetramer (G₄) forms of AChE were examined. In AD compared to controls, significant changes occurred in area 40 and hippocampus but not in the areas containing projection nuclei, and included loss of mean total AChE activity, decrease in the relative percentage of membrane-bound G₄, and increase in the relative percentage of soluble G₁---G₂. Percent of soluble G₄ was unaffected in AD brain. In area 40 but not hippocampus a large increase in percent membrane-bound G₁-G₂ occurred. Thus, these results emphasize that the selective decrease in membrane-bound G₄ accounts for the decrease in total G₄ activity in AD brain.     

Direct detection of infectious HIV-1 in blood using a centrifugation-indicator cell assay

Plasma HIV RNA is a useful surrogate marker for predicting HIV-1 disease progression in infected individuals but provides no information regarding the infectious viral titer. Traditional assays of infectious HIV-1 are, however, time consuming, insensitive, use non-standardized reagents and are subject to selection bias introduced by prolonged cultivation. In this pilot study infectious HIV-1 was detected directly in patient plasma using the indicator line HeLa-CD4-CCR5-LTR/beta-gal in a centrifugation-culture method. Replication competent HIV-1 was identified within 2 days of tissue culture inoculation in six (26%) of 23 plasma specimens. The capability of a new cell line, MT4-CCR5-tat, to amplify plasma HIV-1 was also tested. HIV was cultivated from ten (71%) of 14 specimens using MT4-CCR5-tat cells before titering the virus with the indicator cell assay. Using these stable cell lines in refined versions of this assay it may be feasible to develop rapid, simple methods for titering infectious plasma HIV-1 and for testing the susceptibility of the virus to antiretroviral drugs.     

Are primed CD4+ T lymphocytes different from unprimed cells?

Primed and unprimed lymphocytes are usually classified as separate subsets of cells, based on phenotypic and functional distinctions. In the case of CD4⁺ T lymphocytes, primed cells are thought to proliferate more vigorously, quickly and easily, and to release a different profile of cytokines, than their naive equivalent. However, most of these data were obtained from studies in which populations of lymphocytes were compared before and after antigenic stimulation, and therefore did not distinguish between the effects resulting from the clonal expansion of specific precursor cells within such populations and those due to cell differentiation per se. We have investigated the contribution of precursor cell frequency to some of the functional changes observed in populations of CD4⁺ T cells following antigenic stimulation, using approaches in which antigen-specific precursor frequencies are high in both primary and secondary stimulations: mixed leukocyte reaction responses and cells from αβ T cell receptor transgenic mice. Our data suggest that when equivalent numbers of antigen-specific naive and previously primed CD4⁺ responder T cells are compared, there is no difference in their potency to proliferate but only the previously activated subset can generate cytokines such as interferon-γ.     

Using path analysis to understand executive function organization in preschool children

There continues to be no consensus definition of executive functions. One way to understand different executive function components is to study abilities at their emergence, that is, early in development, and use advanced statistical methods to understand the interrelations among executive processes. However, to fully determine the constructs of interest, these methods often require complete data on a large battery of tasks, which are difficult to obtain with young children. Path analysis is an alternative statistical technique that requires only a single measure of each construct, yet still allows researchers to investigate complex relations among measures, to compare nested models, and to compare model fit across groups. Therefore, 117 preschool children (ages 2 years 8 months to 6 years 0 months) completed several executive function tasks. Path analysis was used to determine the relations between complex problem solving and working memory, inhibition, and set shifting processes. The best-fitting model included paths from working memory and inhibition to problem solving, and a correlation between working memory and inhibition. Interestingly, in younger children, inhibition was the strongest predictor of problem solving, whereas working memory contributed more strongly in older children. Suggestions for useful statistical methods to investigate the relations among executive functions in children are discussed.     

Mycoplasma hyopneumoniae increases intracellular calcium release in porcine ciliated tracheal cells

We investigated the effects of intact pathogenic Mycoplasma hyopneumoniae, nonpathogenic M. hyopneumoniae, and Mycoplasma flocculare on intracellular free Ca2+ concentrations ([Ca2+]i) in porcine ciliated tracheal epithelial cells. The ciliated epithelial cells had basal [Ca2+]i of 103 +/- 3 nM (n = 217 cells). The [Ca2+]i increased by 250 +/- 19 nM (n = 47 cells) from the basal level within 100 s of the addition of pathogenic M. hyopneumoniae strain 91-3 (300 microg/ml), and this increase lasted approximately 60 s. In contrast, nonpathogenic M. hyopneumoniae and M. flocculare at concentrations of 300 microg/ml failed to increase [Ca2+]i. In Ca2+-free medium, pathogenic M. hyopneumoniae still increased [Ca2+]i in tracheal cells. Pretreatment with thapsigargin (1 microM for 30 min), which depleted the Ca2+ store in the endoplasmic reticulum, abolished the effect of M. hyoneumoniae. Pretreatment with pertussis toxin (100 ng/ml for 3 h) or U-73122 (2 microM for 100 s), an inhibitor of phospholipase C, also abolished the effect of M. hyopneumoniae. The administration of mastoparan 7, an activator of pertussis toxin-sensitive proteins G(i) and G(o), increased [Ca2+]i in ciliated tracheal cells. These results suggest that pathogenic M. hyopneumoniae activates receptors that are coupled to G(i) or G(o), which in turn activates a phospholipase C pathway, thereby releasing Ca2+ from the endoplasmic reticulum. Thus, an increase in Ca2+ may serve as a signal for the pathogenesis of M. hyopneumoniae.     

Evaluation of the Determine Rapid Syphilis TP assay using sera

The Abbott Determine Rapid Syphilis TP assay is a treponemal test that can be used in resource-poor settings that lack laboratory facilities. However, this test has not been extensively evaluated. We measured its sensitivity and specificity by using stored serum specimens (n = 567) from all persons who tested Treponema pallidum hemagglutination assay (TPHA) positive (n = 250) or TPHA indeterminate (n = 17) in the year 2001 and the first 300 patients in 2001 who tested TPHA negative at the Evandro Chagas Research Institute in Rio de Janeiro, Brazil. This rapid assay was independently interpreted by three different observers. With TPHA results as the reference, sensitivity ranged between readers from 95.6 to 98.4% and specificity ranged from 97.3 to 95.7%. There was little interreader variability in the interpretation of results, with approximately 98% agreement for all reader combinations. Of samples from persons with human immunodeficiency virus (HIV) infection (n = 198), sensitivity was 96.9 to 99.2% and it was 94.4 to 96.3% among HIV-negative persons (n = 127). Specificity was 92.4 to 95.5% among HIV-positive persons and 97.2 to 100% among HIV-negative persons. We found this test to have high sensitivity and specificity and little interreader variability, indicating that it may be easily used in resource-poor settings without laboratory facilities. Further studies are needed using this test on whole blood and under the clinical conditions for which it is intended.