Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology

Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3⁺HLADR⁺ subset in three cases and the CD³⁻CD56⁺ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber- or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remissions, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.     

Age-related profile of neuroblastoma: A comparison of tumors detected by mass-screening with those detected clinically

Infants with neuroblastoma are known to have a favorable prognosis compared to those over 1 year of age. However, there is little biological information about the age-related heterogeneity of neuroblastoma. We evaluated the biological profile comparing cases detected by mass screening with those detected clinically. A total of 238 patients with neuroblastoma were classified into four groups according to their age at diagnosis. Patients in group A were 0–5 months of age (n = 31). Patients in group B were detected clinically and were 6–11 months of age (n = 25). Patients in group C were 6–11 months of age and were detected by mass-screening (n = 97). Patients in group D were more than 12 months of age (n = 85). The age-related heterogeneity was evaluated by Kaplan-Meier survival analysis, several clinical markers (neuron specific enolase, ferritin, vanillylmandelic acid and homovanillic acid) at diagnosis, tumor Ha-ras p21 expression and tumor N-myc amplification. Infant neuroblastoma had unique features in comparison to neuroblastoma diagnosed over 12 months of age. Clinical outcome of the patients in groups A and C was quite favorable. Even patients with stage III or IV disease in group A had a favorable prognosis. However, stage IVs disease in group A was not necessarily associated with a good prognosis and the early death after diagnosis was also characteristic. The biological profile of tumors in group C was similar to that in group A but different from the profile in groups B and D. Tumors in group B had a biological profile intermediate between groups A and D. Cases detected by mass screening (group C) provided a new clinical entity with a good prognosis. The difference in biological profiles might affect their clinical outcome of respective age group. These analyses confirm the significance of prognostic markers and may help to direct an appropriate modality of treatment for the individual patient.     

Biochemical and histological features of hepatitis G virus infection

To assess the biochemical and histological characteristics of hepatitis G virus (HGV) infection, we examined four patients who were infected with HGV only (HGV group), and compared them with 16 patients infected with both HGV and hepatitis C virus (HCV; HGV + HCV group) and 18 patients infected with HCV only (HCV group). Biochemical examination showed a significantly low level of serum alanine aminotransferase (ALT) in the HGV group, and that the gamma-glutamyl transpeptidase (γ-GTP)/ALT ratio in the same group was significantly higher than in the other two groups. Although all three patient groups had a similar degree of liver fibrosis, both the degree of periportal inflammation and total histological activity index were significantly lower in the HGV group than in the other two groups. Fibrous enlargement of the portal tract without lymphoid infiltration and thin fibrous septa was characteristically observed in the HGV group. No significant difference was found between the HGV + HCV group and HCV group. Our results suggest that biochemical and histological changes in HGV infection are very mild and quite different from those of HCV infection.     

Assessment of autonomic nervous activity during gastrointestinal endoscopy: Analysis of blood pressure variability by tonometry

We continuously measured blood pressure by tonometry in 30 patients during endoscopy to determine the influence of upper gastrointestinal endoscopy on cardiac events. Patients were divided into two groups: one group treated with scopolamine butylbromide as premedication (SB group) and another group without premedication (C group). Time- and frequency domain analyses of beat-to-beat systolic blood pressure variability were performed for 128 consecutive beats. For time-domain analysis, we calculated the coefficient of variation of systolic blood pressure (CV_BP). For the frequency domain analysis, we determined the low-frequency (LF_BP; 0.04–0.15 Hz) and high-frequency (HF_BP; 0.15–0.40 Hz) powers of the variation in systolic blood pressure and the ratio of LF_BP to HF_BP (LF_BP/HF_BP) during endoscopy. The CV_BP and HF_BP, indicators of parasympathetic tone, increased in the early phase of endoscopy but decreased significantly in the middle and late phases compared with the pre-endoscopy value. The ratio of LF_BP/HF_BP, an indicator of indirect sympathetic tone, increased throughout the endoscopic procedure. Moreover, premedication with scopolamine butylbromide prevents the excessive parasympathetic nervous reflex when an endoscope passes through the upper digestive tract and also brings both decreased parasympathetic tone and increased sympathetic tone at the late phase of endoscopic procedure. Our results indicate that gastrointestinal endoscopy induced an autonomic nervous abnormality, which may contribute to the occurrence of cardiac events during endoscopic procedures.     

Effect of Activated Charcoal and Atropine on Absorption and/or Exsorption of Organophosphorus Compounds in Rats

Effects of activated charcoal and atropine for the removal of organophosphorus compounds, which remain in the gastrointestinal tract or have already been absorbed into the systemic circulation, were investigated in rats. Activated charcoal extensively adsorbed the organophosphates fenitrothion, tolclofos methyl, piperophos and salithion, and its immediate administration after oral ingestion of fenitrothion remarkably reduced serum fenitrothion levels, but had no effect on the serum levels of the compound which had been absorbed from the gastrointestinal tract. Thus, all of the organophosphorus compounds were poorly exsorbed (0.002-0.39% of the dose in 120 min) from the blood into the intestinal lumen probably due to their extensive protein binding and large distribution volumes. Atropine inhibited absorption of fenitrothion in the perfusion in-situ and also delayed the absorption of the compound in-vivo, but had no significant effect on exsorption of fenitrothion. The serum fenitrothion levels on treatment with both atropine and charcoal significantly decreased compared with those of the control. We conclude that, oral activated charcoal will not be able to enhance the elimination of organophosphorus compounds which have already been absorbed into the systemic circulation, but constitute a useful method for the removal of the compounds remaining in the gastrointestinal tract because of its excellent adsorptive capacity.     

Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats

Abstract The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.     

MALIGNANT HEMANGIOENDOTHELIOMA

Background. The administration of interleukin-2 (il-2 ) has recently been reported to be favorable for treating malignant hemangioendothelioma (mhe ). Methods. Two patients with mhe responded well to intra-lesional injections of recombinant il-2 (ril-2 ) without major side effects. The purpose of this study was to characterize cells infiltrating the regressing tumor following ril-2 treatment. Immunohistochemical studies were performed on biopsy specimens taken from ril-2 -injected lesional skin. Results. It was shown that CD8⁺ lymphocytes and CD56⁺ natural killer (nk ) cells infiltrated at the ril-2 -injection sites, suggesting that these cells contributed to the tumor regression. In addition, MHE cells bore intercellular adhesion mole-cule-1 (icam -1) whose expression was augmented by rn-2 injections. Conclusions. These findings suggested, that ril-2 not only induces lymphokine-activated killer (lak ) cells and nk cells, but also facilitates these cytotoxic cells to adhere to MHE cells by enhancing icam -1 expression of tumor cells.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.