Modeling of longitudinal academic achievement scores after pediatric traumatic brain injury

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.     

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.     

Inflammatory pseudotumor of lymph node and spleen: An entity biologically distinct from inflammatory myofibroblastic tumor

Inflammatory pseudotumors (IPTs) of the lymph node and spleen are an uncommon, benign cause of lymphadenopathy and/or splenomegaly that often bear striking clinicopathologic similarities to the inflammatory myofibroblastic tumors (IMTs) found in soft tissues. These tumors have classically been grouped together under the umbrella category of "inflammatory pseudotumor." Recent evidence shows that IMTs are in fact neoplastic processes that often harbor balanced chromosomal translocations involving the ALK kinase gene. These translocations result in expression of ALK kinase in IMTs as assessed by immunohistochemical studies. However, the relationship between IMT and IPT of the lymph node and spleen is uncertain. To determine if ALK tyrosine kinase expression is also present in IPT, 13 cases of IPT (9 involving lymph nodes, 4 splenic lesions) were examined for the presence of ALK tyrosine kinase by immunohistochemical staining on paraffin-embedded tissue. In addition, in situ hybridization studies for Epstein-Barr virus--encoded RNAs (EBER) and immunoperoxidase studies for human herpesvirus-8 (HHV8)--specific proteins were performed. All cases had clinical, morphologic, and immunophenotypic findings typical of IPT and had varying proportions of fibroblastic and inflammatory components. Age ranged from 11 to 75 (median, 40) years; 8 subjects were male, and 5 were female. None of the cases (0 of 13) had positive staining for ALK kinase or HHV8, and in 1 a lymph node (1 of 13) was focally positive for EBV (EBER) by in situ hybridization. The absence of ALK kinase as detected by immunohistochemical studies in IPT of the lymph node and spleen suggests that this entity is biologically distinct from the histologically similar IMT.     

Patients with adult respiratory distress syndrome (ARDS) demonstrate in vivo neutrophil activation associated with diminished binding of neutrophil-specific monoclonal antibody 31D8

Neutrophils (PMNs) from patients with adult respiratory distress syndrome (ARDS) were assessed for light scattering, membrane potential, and phagocytic responses using fluorescent probes and flow cytometry to evaluate individual cells. Qualitative and quantitative oxidant responses were measured by nitroblue tetrazolium (NBT) and cytochromec reduction assays, respectively. The results were correlated with the proportion of cells binding the PMN subset-specific monoclonal antibody 31D8. Despite an increased forward scatter signal (4.3±1.6 vs. 1.3±1.1 ARDS vs. control,P=0.041) and spontaneous NBT test (12.6±4.7% vs. 2.5 ±0.8% positive, ARDS vs. control,P=0.033) indicating in vivo priming of ARDS PMNs, there were no significant differences between ARDS and control PMNs in assays of stimulated membrane potential, NBT, and O·₂ ^– production or phagocytosis. However, positive correlations between the degree of prestimulus forward light scatter and subsequent O·₂ ^– production to FMLP (r=0.673,P=0.006) and between the percentage of bands and the O·₂ ^– response to PMA (r=0.660,P =0.003), suggest that the great variability of the ARDS PMN functional responses may relate to varying degrees of in vivo cell priming and/or deactivation. ARDS PMNs demonstrated a significantly lower percentage of 31D8 positive cells (73.4 ±7.5% vs. 94.5±1.6%,P=0.012) and a lower level of 31D8 staining when compared to normals (60.1±10.4% of control level,P=0.001). The lower 31D8 expression did not directly correlate with any functional parameter tested or with the proportion of immature cells. However, patients receiving an intravenous PGE₂1-infusion demonstrated a significant increase in 31D8 staining relative to controls and inhibition of PMA-stimulated O·₂ ^– production. The data suggest that the function of PMNs from ARDS patients varies widely and reflects great in vivo variation in cell priming. While the mechanism responsible for the lowered expression of the 31D8 antigen and its apparent modulation by PGE₁ is unknown, 31D8 may be an indirect marker for in vivo stress factors that regulate the preferential release of a structurally distinct PMN subset from the bone marrow.This work was supported in part by NIH grant P30-DK35747, a University of California, Davis, Dean's Research Grant, and The Upjohn Company.     

Assay restriction profiles of three monoclonal antibodies recognizing the G3m(u) allotype. Development of an allotype specific assay

Three monoclonal antibodies raised against a purified human IgG3 paraprotein were found to exhibit a restriction profile for IgG3/G3m(u) and pan-IgG specificity which was dependent on the assay system. When adapted to an IgG3 subclass capture ELISA, all three McAbs discriminated between paraproteins expressing G3m(u) and antithetical markers G3m(st). One of the antibodies (PNF69C) was selected and conditions were optimised for Gm typing purposes. Using this system G3m(u) could be detected on captured IgG3 derived from human sera. This system may prove useful in the elucidation of Gm allotype profiles.     

Operative morbidity and reproductive outcome in secondary myomectomy: a prospective cohort study

BACKGROUND: This prospective study was designed to evaluate the operative morbidity and reproductive outcome in patients who had secondary myomectomy for recurrent symptomatic uterine fibroids. METHODS: A total of 58 women were subjected to a secondary myomectomy via the abdominal route. The operative morbidity such as blood loss, presence of adhesions and febrile index were estimated and the pregnancy outcome over a 2-4 year period of follow-up. RESULTS: The mean age and standard deviation (+/- SD) of the women was 35 (+/- 2.4) years. Nineteen patients (33%) had a postoperative temperature vertical line 100 degrees F and the estimated blood loss ranged from 159-2500 ml (median 700 ml). Seven patients (12%) required blood transfusion and one had a hysterectomy due to haemorrhage. Nine women (15.5%) became pregnant but only five (56%) had live births. Those with successful pregnancies tended to be younger with a mean age of 31.8 (+/- 2.6) years versus 35 (+/- 1.8) years, (P = 0.08, non-significant) and had fewer uterine leiomyomata; median with range values, 2 (1-6) versus 7 (6-15). The variables which best predicted the postoperative likelihood of pregnancy were; age, presence of tubal adhesions and the number of uterine fibroids. CONCLUSION: This prospective study showed a high operative morbidity and a poor fertility outcome after a repeat myomectomy. The factors affecting successful outcome in a logistic regression model were age, tubal adhesions and number of uterine fibroids.     

Molecular Insights into the Histogenesis and Pathogenesis of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) have long been problematic in terms of classification and determination of prognosis. Recent studies have suggested that GISTs differentiate toward a phenotype resembling the interstitial cells of Cajal. This has led to the important discovery that activating mutations in the KIT receptor tyrosine kinase play an important role in the pathogenesis of GISTs. These findings have helped clarify the distinction between GISTs and other mesenchymal neoplasms of the gastrointestinal tract and may translate into an improved ability to predict biologic behavior, as well as suggesting possible avenues for rational drug design for the treatment of GISTs. Int J Surg Pathol 8(1):5-10, 2000     

Effects of injections of 8-hydroxy-2-(di-n-propylamino)tetralin or muscimol in the median raphe nucleus on c-fos mRNA in the rat brain

Inhibition of the median raphe nucleus (MRN) by the local injection of 5-HT(1A) or GABA(A) receptor agonists produces strong activational effects on feeding, drinking and locomotor activity. Using an animal model of relapse, we have shown that intra-MRN injection of the 5-HT(1A) autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reinstates alcohol seeking in rats. The circuitry underlying the behavioral effects of intra-MRN injection of these drugs is not known. In order to identify the brain areas that may be involved, we measured levels of mRNA of the immediate early gene c-fos in discrete nuclei of the rat brain following intra-MRN infusions of these drugs. Male Wistar rats received intra-MRN infusions of 8-OH-DPAT (1 mug), muscimol (25 ng) or saline vehicle immediately prior to placement in locomotor activity chambers. Thirty minutes later, they were decapitated, and their brains processed for in situ hybridization of c-fos mRNA. In agreement with previous reports, injections of 8-OH-DPAT or muscimol into the MRN resulted in large increases in locomotor activity. Intra-MRN injections of these drugs increased c-fos in a number of brain nuclei previously shown to be involved in the rewarding effects of drugs of abuse in a regionally specific manner. Both drugs significantly increased the expression of c-fos mRNA in the medial frontal cortex, nucleus accumbens, lateral septum, dorsal bed nucleus of the stria terminalis and ventral tegmental area. In the ventral hippocampus, only 8-OH-DPAT increased c-fos, while in the basolateral nucleus of the amygdala and locus coeruleus, it was increased only by muscimol. These results are discussed in terms of the projections of the MRN and the pathways involved in relapse to alcohol and drug seeking.