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.     

Space-based inhibition of return in children with spina bifida

Inhibition of return (IOR) refers to an increase in time to react to a target in a previously attended location. Children with spina bifida meningomyelocele (SBM) and hydrocephalus have congenital dysmorphology of the midbrain, a brain region associated with the control of covert orienting in general and with IOR in particular. The authors studied exogenously cued covert orienting in 8- to 19-year-old children and adolescents (84 with SBM and 37 age-matched, typically developing controls). The exogenous cue was a luminance change in a peripheral box that was 50% valid for the upcoming target location. Compared with controls, children with SBM showed attenuated IOR in the vertical plane, a deficit that was associated with midbrain dysmorphology in the form of tectal beaking but not with posterior brain volume loss. The data add to the emerging evidence for SBM deficits in attentional orienting to salient information.     

Eye position signals in human saccadic processing

Summary 1. We studied saccades to briefly flashed targets in 8 human subjects. The target flash occurred (i) during smooth pursuit (ramp-flash), (ii) just before a saccade to another target (step-flash), or (iii) during steady fixation (flash only). All lights were extinguished after the target flash so that smooth pursuit or saccadic eye movements occurred during the interval of complete darkness between the target flash and the saccade to it. We compared these saccades to those made without intervening eye movement (flash only), and quantified the extent to which the saccadic system compensated for the change in eye position that occurred during the dark interval. 2. Saccades to control flashes were reasonably accurate (mean gain 0.87) and consistent. Compensation for the intervening eye movement in the ramp-flash and step-flash paradigms was highly variable from trial to trial. On average, subjects compensated for 27% of the intervening pursuit eye movement on ramp-flash trials and for 58% of intervening saccadic movement on step-flash trials. 3. Multiple regression analysis showed that the variability did not depend on factors such as variations in underlying saccadic gain, response latency, timing of stimuli or size of the required response. We conclude that this variability is intrinsic to saccadic responses that require the use of an eye position signal. 4. These results show that an eye position signal is available to the saccadic system but that this signal has low fidelity. The high variability and low fidelity of the eye position signal suggest that the saccadic system does not normally operate in spatial coordinates, which require the use of an accurate eye position signal, but rather in retinal coordinates.     

Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte count among patients with HIV disease in Kampala, Uganda

Introduction

Total Lymphocyte Count (TLC) has been found to be an inexpensive and useful marker for staging disease, predicting progression to AIDS and death and monitoring response to ART. However, the correlation between TLC and CD4 has not been consistent. Access to HAART is expanding in Kampala, Uganda, yet there are no published data evaluating the utility of TLC as inexpensive surrogate marker of CD4 cell count to help guide therapeutic decisions.

Objective

To evaluate clinical illnesses and total lymphocyte count (TLC) as surrogate markers of the CD4 cell count in HIV infected persons being considered for ART.

Methods

A total of 131 patients were enrolled and evaluated by clinical assessment, TLC and CD4 count. Clinical illnesses and TLC dichotomized at various cut-point values were used to determine the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for the diagnosis of CD4 count <200 cells/mm³ among 100 participants fulfilling criteria for WHO clinical stage 2 and 3.

Results

A strong correlation was observed between TLC and CD4 (r = 0.73, p<0.0001). For all clinical syndromes, except pulmonary tuberculosis, the positive predictive values (PPV) for a CD4 count <200 cells/mm³ were high (>80%) but the negative predictive values (NPV) were low. Using the WHO recommended TLC cut-off of 1200 cells/mm³ to diagnose a CD4 less than 200 cells/mm³, the PPV was 100%, and the NPV was 32%.

Conclusion

Our data showed a good correlation between TLC and CD4 cell count. However, the WHO recommended TLC cutoff of 1200 did not identify the majority of WHO stage 2 and 3 patients with CD4 counts less than 200 cells/mm³. A more rational use of TLC counts is to treat all patients with WHO stage 2 and 3 who have a TLC <1200 and to limit CD4 counts to patients who are symptomatic but have TLC of >1200.