Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment

The clinical significance of an interstitial duplication of (15)(q11-q13) remains unclear and controversial. The reported phenotypes vary widely and appear to be influenced by the parent of origin of the duplication. Aside from cases of dup(15) reported with autism, the behavioral phenotype of individuals with dup(15) has not been described. We present three families, two with intrachromosomal duplication (15)(q11-q13) ascertained because of developmental delay in a relative. Two families show clear evidence of multigenerational maternal inheritance. The individuals discussed in this paper have minor anomalies and developmental delays. In addition, we describe a behavioral phenotype which often includes attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder. Responses to medications used to manage these behaviors are also described, including a positive response to methylphenidate and a poor response to fluoxetine. The duplication in each presenting individual, and available family members, was investigated utilizing cytogenetic and molecular techniques including high resolution cytogenetics, fluorescence in situ hybridization (FISH), DNA methylation studies, and quantitative fluorescence PCR. High resolution cytogenetic techniques alone missed some cases, demonstrating the need to confirm results with other methods.     

Opsonin-independent phagocytosis of surface-adherent bacteria by human alveolar macrophages

Opsonin-independent mechanisms of phagocytosis may be important in host defense of certain body sites such as the lung. In this study, one such mechanism, "surface phagocytosis," was investigated by measuring the uptake of unopsonized [3H]-labeled Staphylococcus aureus and Pseudomonas aeruginosa adherent to a plastic surface by human alveolar macrophages (AM) and peripheral blood polymorphonuclear leukocytes (PMN). Efficient uptake of unopsonized bacteria by both cell types was observed. Electron microscopic studies suggested that the manner in which these cell types encounter adherent bacteria is different. While AM appear to gather in organisms at their periphery as they spread out upon the underlying substrate, PMN seem to sweep bacteria up as they move along the plastic surface. Bacterial killing determined by a fluorochrome microassay was decreased by AM compared to PMN. Although the precise mechanism whereby phagocytes recognize unopsonized bacteria adherent to a surface remains to be determined, this aspect of phagocytic cell function may prove to have clinical relevance.     

Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro

1,2,3,4-Tetrahydro-5-aminoacridine (THA; tacrine) reportedly improves cognitive deficits in certain individuals with Alzheimer's disease. The present study describes increased glucose oxidation and acetylcholine (ACh) synthesis by mouse brain slices after THA treatment. THA increased [U-14C]glucose decarboxylation and ACh formation in a concentration-dependent manner in hippocampal slices (50 nM less than 50 microM less than microM). In striatal and cortical slices, 50 microM THA effectively elevated the oxidation of glucose and its incorporation into ACh. Thus the efficacy of THA treatment on Alzheimer patients may be partially related to increased ACh synthesis and oxidative metabolism.     

Comparison of the radiosensitivity of interleukin-2 production between species, between tissues, and between young and old individuals

The radiosensitivity of interleukin-2 (IL-2) production was assessed of (a) peripheral blood mononuclear cells (PBMC) of young humans, dogs, and mice (C57BL/6); (b) PBMC and splenic cells of young mice; and (c) PBMC of young and old humans and the splenic cells of young and old mice. The results indicate that (a) large differences in radiosensitivity exist between the PBMC of humans, dogs, and mice (e.g., the radiation doses which resulted in 37% remaining IL-2 activity (D37) of human, dog, and mouse PBMC were 3771, greater than 10,000, and 1398 rads, respectively); (b) only a small difference exists between the PBMC and splenic cells of mice; and (c) no difference exists between the PBMC of young and old humans and between splenic cells of young and old mice. Topological abnormalities, as judged by scanning electron microscopic analysis, could not be detected in dog PBMC after their exposure to 1800 rads, but could be detected in mouse PBMC after their exposure to 400 rads.     

Timing and intensity of early fevers and the development of allergies and asthma

BACKGROUND: Early childhood fevers appear to protect against later allergies and asthma. What is not known is the time in which fevers exert this effect and whether the degree of temperature increase is important. OBJECTIVE: We sought to examine the relationship between the time and degree of early fevers and later allergies and asthma. METHODS: Eight hundred thirty-five children from southeast Michigan were enrolled at birth. Clinic records from their first 2 years were abstracted for episodes of fever. At age 6 to 7 years, children underwent allergy testing. We examined fevers occurring within 6-month intervals in the first 2 years of life and outcomes at age 6 to 7 years. The primary outcome measures were allergic sensitization, asthma, asthma with allergic sensitization, and asthma without allergic sensitization. RESULTS: In the unadjusted analysis each episode of fever between 7 and 12 months of age was associated with a lower odds of allergic sensitization (odds ratio [OR], 0.71; 95% CI, 0.54-0.93) and asthma with allergic sensitization (OR, 0.43; 95% CI, 0.21-0.90) at age 6 to 7 years. Likewise, every 1 degrees C increase in the maximum temperature between 7 and 12 months was associated with a lower odds of allergic sensitization (OR, 0.77; 95% CI, 0.61-0.96) and asthma with allergic sensitization (OR, 0.62; 95% CI, 0.40-0.94). After adjusting for potential confounders, each episode of fever between 7 and 12 months was associated with a lower likelihood of asthma with allergic sensitization (adjusted OR, 0.33; 95% CI, 0.11-0.94) at age 6 to 7 years. CONCLUSIONS: Both the timing and intensity of childhood fevers appear to be important factors in the development of allergies and asthma.     

Eosinophil activation in allergic disease

The eosinophil granulocyte is a pro-inflammatory cell which in its granules contains an abundance of highly cytotoxic proteins such as eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil protein X and major basic protein. Upon stimulation of the cell, these proteins as well as a number of lipid mediators such as leukotriene C4, prostaglandin and platelet-activating factor are released to the exterior. The molecules which are produced during inflammatory reactions of the allergic type attract eosinophils to the target organ and stimulate them to liberate their products. The physiological meaning of this reaction is probably to combat invading parasites; however, in their absence accumulation and activation of eosinophils may cause disease, and one such disease may be chronic asthma.     

Transient atypical lymphocytosis in patients with emergency medical conditions

Lymphocytosis in older adults is unusual and frequently indicates chronic lymphocytic leukemia or other lymphoproliferative disorder. This report describes 73 patients, aged 43 to 93 years, who presented with emergency medical conditions and who had absolute lymphocytosis, with absolute lymphocyte counts ranging from 4.1 to 12.9 X 10(9)/L (4100 to 12,900/mm3). The lymphocytosis was characterized morphologically by atypical lymphocytes and was transient, followed, in most instances, by a neutrophilia. Most of the patients presented with serious cardiac conditions; the remaining presented with other critical disorders including status epilepticus and traumatic injuries. The mortality rate was high (50%). The lymphocytosis in some patients was probably secondary to the administration of epinephrine. The lymphocytosis in those not receiving epinephrine may have represented a physiologic reaction to severe stress.     

Tourniquet inflation after intra-articular morphine and bupivacaine administration following knee arthroscopy

We performed a randomized doubled-blind study to evaluate whether there was a benefit in delay in tourniquet deflation with intra-articular administration of morphine and bupivacaine following operative arthroscopic surgery. In 34 patients the tourniquet was deflated immediately and in 38 patients the tourniquet remained inflated for 10 min following injection. The analgesic efficacy was assessed using pain scores and the amount of supplementary analgesia required. The results demonstrate no benefit in delay in tourniquet deflation.     

Comparison of the Rodac imprint method to selective enrichment broth for recovery of vancomycin-resistant enterococci and drug-resistant Enterobacteriaceae from environmental surfaces

We compared the Rodac imprint technique to selective enrichment broth for detecting vancomycin-resistant enterococci (VRE) and multidrug-resistant Enterobacteriaceae (MDRE) on surfaces. Rodac plates contained tryptic soy agar with 5% sheep blood, vancomycin (6 microg/ml), ceftazidime (2 microg/ml), amphotericin B (2 microg/ml), and clindamycin (1 microg/ml). Two types of broth were used: brain heart infusion (BHI) and BHI plus vancomycin (6 microg/ml) and ceftazidime (2 microg/ml) (BHIVC). Of the 46 surfaces cultured for VRE, 12 (26%) were positive. Of the 12 VRE-positive surfaces, 11 (92%) grew from Rodac, 8 (67%) grew from BHIVC, and 7 (58%) grew from BHI. A larger study is needed for MDRE, as only 4 of 43 surfaces were MDRE positive. The Rodac imprint technique successfully recovered VRE from environmental surfaces.