Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

Immunohistological detection of Legionella pneumophila in lung sections.

Immunohistology was used for the detection of Legionella pneumophila serogroup I in necropsy tissue. Study of pneumonic lung from the recent Stafford outbreak has shown that this technique has a high sensitivity. A retrospective postmortem examination showed that L pneumophila serogroup 1 was an unusual cause of pneumonia in Oxfordshire during the study period. L pneumophila serogroup 1 can be successfully subgrouped, using a panel of monoclonal antibodies on formalin fixed paraffin embedded sections. Immunohistological methods have a potentially useful role in the diagnosis of Legionellosis at postmortem examination and in the epidemiological investigation of individual cases and outbreaks.     

Demographic and Clinical Factors Associated With Nonsurgical Osteoarthritis Treatment Among Patients in Outpatient Clinics

Objective

To identify patient demographic and clinical characteristics associated with osteoarthritis (OA) treatment use.

Methods

This was a secondary data analysis of 3 clinical trials among patients with hip or knee OA conducted in Duke Primary Care practices, the Durham Veterans Affairs (VA) Health Care System, and the University of North Carolina–Chapel Hill (UNC). At baseline, participants reported sociodemographic characteristics, OA‐related pain and function, and OA treatment use, including oral analgesics, topical creams, joint injections, and physical therapy. Separate, multivariable logistic models (adjusted for clustering of clinics and providers for the Duke and VA cohorts) were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between participant characteristics and each type of OA treatment.

Results

Oral analgesic use was reported by 70–82% of participants across the 3 cohorts. Physical therapy, knee injections, and topical creams were used by 39–52%, 55–60%, and 25–39% of Duke, VA, and UNC participants, respectively. In multivariable models, worse pain, stiffness, and function, per 5‐unit increase, were associated with greater odds of using any oral analgesic for the cohorts from Duke (OR 1.18 [95% CI 1.08–1.28]) and UNC (OR 1.14 [95% CI 1.05–1.24]), but not for the VA cohort (OR 1.04 [95% CI 0.95–1.14]). For all 3 cohorts, nonwhites had higher odds of using topical creams compared to whites.

Conclusion

Results suggest potential underutilization of therapies other than oral analgesics. Patient characteristics may affect OA treatment use, and understanding the relationship between these factors and OA treatment preferences may improve adherence to OA treatment guidelines.     

Old and new synthetic cannabinoids: lessons from animal models

Abstract

Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as ‘marijuana-like’ products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences. Animal models of drug addiction are frequently used in preclinical research to assess the abuse potential of new compounds, evaluate drug positive reinforcing effects and analyze drug-induced behaviors. Some of these protocols have been used recently to study the newly synthesized cannabinoid agonists and have started elucidating their pharmacology and actions in the brain. The aim of this review is to summarize the major findings reported by animal studies that tested synthetic cannabinoids of first, second, and third generation by using self-administration and reinstatement models, drug discrimination and conditioned place preference procedures. Altogether, behavioral studies clearly indicate that synthetic cannabinoids possess abuse liability, are likely to activate the brain reward circuit and induce positive subjective and reinforcing effects.     

Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.     

Validation of a microtiter plate ELISA for screening of postmortem blood for opiates and benzodiazepines

The object of this study was to evaluate the suitability of the Neogen Corp. microtiter plate enzyme-linked immunoassays (ELISA) for opiates and benzodiazepines for screening of postmortem blood. Ninety postmortem whole blood specimens were obtained from drug-involved deaths which had been screened and confirmed positive for opiates and/or benzodiazepines. Forty negative specimens were obtained from non-opiate-involved deaths. Specimens were tested using the Neogen Opiates Group and Neogen Benzodiazepines Group microtiter plate ELISA assays. No matrix effects were found for whole blood in these assays and a dilution of 1:5 was chosen to facilitate pipetting and to bring the IC50 of the microtiter plate ELISA assay within the range of opiates and benzodiazepines encountered in medical examiner specimens. True positive, true negatives, false positives, and false negatives were determined and graphed for the ELISA results against gas chromatography-mass spectrometry (GC-MS), gas chromatography-nitrogen-phosphorus detection and case histories. From these graphs and the ROC curves, the optimal cut-off for the Neogen Opiates Group ELISA was found to be between 20 and 50 ng/mL morphine equivalents and the optimum cut-off for the Neogen Benzodiazepines Group ELISA was between 20 and 50 ng/mL temazepam equivalents. The Neogen Opiates Group ELISA had a sensitivity of 95.2% +/- 2.7% and a specificity of 92.2% +/- 3.4% versus GC-MS at a cut-off of 20-ng/mL cut-off and a sensitivity of 88.8% +/- 3.9% and specificity of 96.8% +/- 2.1% versus GC-MS at a 50-ng/mL morphine equivalents cut-off. The Neogen Benzodizepines Group ELISA had a sensitivity of 100% +/- 1.3% and a specificity of 94.6% +/- 2.9% versus GC-MS (20-ng/mL temazepam equivalents cut-off) and a sensitivity of 95.8% +/- 2.5% and specificity of 98.2% +/- 1.8% versus GC-MS at a 50-ng/mL cut-off.     

Smaller corpus callosum subregions containing motor fibers in schizophrenia

Neuropsychological and neurophysiological studies provide evidence for abnormal interhemispheric communication in schizophrenia. These abnormalities may have a substrate in structural irregularities of the corpus callosum. This study investigated schizophrenia patients (n=27) and healthy comparison subjects (n=31). Global and regional measurements of the corpus callosum were acquired from one midsagittal SPGR slice. Eight subregions were approximately matched to fiber pathways from cortical regions. Overall effects of diagnosis [Wilks' Lambda F(8,46)=2.45, p=0.03] and diagnosis by age interaction [Wilks' Lambda F(8,46)=2.58, p=0.02] were found in a MANCOVA of the eight functionally specific subregions. Specifically, chronic schizophrenia was associated with a smaller rostral body [lower by 6.9%, F(1,53)=9.70, p=0.003] and anterior midbody [lower by 9.7%, F(1,53)=4.89, p=0.03] subregions. The rostral body and anterior midbody subregions of the corpus callosum primarily have premotor, supplementary motor, and motor cortical fibers transversing through them. Functional abnormalities of the associated cortical regions are reported in schizophrenia. These novel findings suggest that structural abnormalities of the corpus callosum exist in schizophrenia, with perhaps the motor-specific subregions affected more than others. Structural differences in the corpus callosum may be a substrate for interhemispheric functional dysconnectivity in schizophrenia.     

Relationship between neuropsychological test performance and productivity at 1-year following traumatic brain injury

While there has been strong evidence for the ability of neuropsychological performance at resolution of posttraumatic amnesia to predict later productivity, there has been less conclusive evidence for the relationship of neuropsychological test scores to concurrent productivity status. The purpose of the current study was to evaluate the relationship of neuropsychological test performance at 1 year post-injury to productivity assessed at the same time point. Participants were 518 persons with medically documented TBI who were enrolled in the TBI Model Systems Research and Demonstration Project. Stepwise logistic regression was utilized to determine the contributions of neuropsychological test scores to productivity after accounting for demographic characteristics, injury severity, and pre-injury productivity. Missing neuropsychological test scores were accounted for in the model. Variables that remained in the model and accounted for a significant proportion of the variance included age, duration of impaired consciousness, pre-injury productivity, and scores on measures of GOAT, Logical Memory II, and Trail Making Test, part B. The results indicate that neuropsychological test performance provides important information regarding the ability of persons with injury to return to productive activities. The results also indicate that inability to complete neuropsychological tests at 1 year post-injury is associated with non-productive activity.     

Population of the HLA ligand database

We have established an HLA ligand database to provide scientists and clinicians with access to Major Histocompatibility Complex (MHC) class I and II motif and ligand data. The HLA Ligand Database is available on the world wide web at http://hlaligand.ouhsc.edu and contains ligands that have been published in peer-reviewed journals. HLA peptide datasets prove useful in several areas: ligands are important as targets for various immune responses while algorithms built upon ligand datasets allow identification of new peptides without time-consuming experimental procedures. A review of the HLA class I ligands in the database identifies strengths and deficiencies in the database and, therefore, the utility of the dataset for identifying new peptides. For instance, 212 HLA-A phenotypes exist of which 23 have a motif determined and 43 have peptides characterized. In terms of number of ligands, HLA-A*0201 has 258 characterized ligands, A*1101 has 25 peptides, while the remaining two-thirds of the HLA-A phenotypes have less than 10 associated peptide sequences. Characterization of ligands and motifs remains roughly the same at the HLA-B locus while the peptides of the HLA-C locus tend to be less characterized. These data show that 74% of HLA class I molecules do not have ligands represented in the database and thus algorithms based on the dataset could not predict ligands for a majority of the US population. Building upon this dataset and knowledge of HLA allelic frequencies, it is possible to plan a systematic expansion of the HLA class I ligand database to better identify ligands useful throughout the population.