A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

Distinctive Serial Magnetic Resonance Changes in a Young Woman with Rapidly Evolved Neurocysticercosis,with Positron Emission Tomography Results

A woman aged 21 years noticed numbness of the left hand, dysarthria, and right hemiparesis. Magnetic resonance imaging (MRI) showed homogeneously enhanced lesions in the bilateral cerebral white matter; these enlarged within 2 weeks, showing ringlike enhancement, and then spontaneously decreased in size and enhancement. Neurocysticercosis was confirmed by repeated, significantly positive serology results and the dramatic response to praziquantel. Subsequently, positron emission tomography (PET) revealed persisting regions of possibly decreased cerebral uptake of [18F]2–fluoro–2–deoxyglucose. This is the first documentation of such distinctive serial MRI changes and the results of PET in neurocysticercosis.     

Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.     

Simultaneous development of insulin dependent diabetes mellitus and alopecia areata universalis

Alopecia areata universalis developed gradually over nine months in a 25-year-old woman. When her scalp hairs were totally lost and other body hair began to fall out, the symptoms of insulin dependent diabetes mellitus, an organ-specific autoimmune disease, developed rapidly and progressed to diabetic coma. Alopecia did not regress after the metabolic state improved following insulin therapy. Biopsy of the scalp skin revealed significant reduction of the total number of hair bulbs and prominent lymphocyte infiltration into the remaining hair follicles. Insulin dependent diabetes mellitus and alopecia areata universalis are both thought to be related to the autoimmune mechanism and sometimes coexist. However, simultaneous development of these two disorders is extremely rare.     

Diagnosis of Kala-Azar by Nested PCR Based on Amplification of the Leishmania Mini-Exon Gene

To diagnose visceral leishmaniasis (kala-azar), we have developed a nested PCR method based on amplification of the mini-exon gene, which is unique and tandomly repeated in the Leishmania genome. Nested PCR was sufficiently sensitive for the detection of DNA in an amount equivalent to a single Leishmania parasite or less. We examined the usefulness of this PCR method using bone marrow aspirates and buffy coat cells collected from kala-azar patients who had or had not received chemotherapy in northwest China. We obtained PCR positivity for all of the parasitologically positive bone marrow samples from the patients. Some ambiguities with the primary PCR results were eliminated by the subsequent nested PCR. The buffy coat samples from 7 of 12 patients with splenomegaly were positive by the nested PCR, although only 2 of them were positive for parasites by culture. However, buffy coat samples from nine children, whose splenomegaly has been reduced and clinically cured by antimony treatment, were all negative. Thus, this nested PCR method represents a new tool for the diagnosis of kala-azar with patient blood samples instead of bone marrow or spleen aspirates obtained by more invasive procedures.     

The effect of sustained-release theophylline granules in the inhibition of exercise-induced asthma]

We studied the protective effect of sustained-release theophylline granules on early or late response in exercise-induced asthma (EIA) in 16 patients ranging in age from 7 to 18 years. A standardized exercise test was examined 2 hours after administration of theophylline granules on one day and after no medication on another day. On both days, the lung functions and the serum theophylline and cortisol concentrations of the patients were examined before exercise and over a period of 8 hours after exercise. On days without medication, early response was seen in 16 patients and late response in 6. On days with medication, the theophylline granules inhibited early response in 13 of the 16 patients and late response in 5 of the 6 patients. This suggests that theophylline preparation is a useful drug for inhibiting the dual responses of EIA.     

The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

Clinical significance of IgG4 antibody determination in children against egg white, milk, soybean and Dermatophagoides farinae]

The measurement of IgE and IgG4 antibodies against egg white, milk, soybean and Dermatophagoides farinae was performed by FAST (fluorescence allergosorbent test) using 21 serum samples obtained from non-allergic children and 160 serum samples from atopic children with bronchial asthma and/or atopic dermatitis. Their antibody levels were evaluated for any association with disease severity and for clinical significance in establishing diagnosis. It was found that children with bronchial asthma showed lower levels of IgE antibodies against egg white, milk and soybean and higher levels of IgE antibodies against Dermatophagoides farinae compared with those of children with atopic dermatitis, while both groups showed higher levels of egg white and milk-specific IgG4 antibodies compared with non-allergic children. These IgE and IgG4 antibody levels revealed a tendency to correlate with disease severity in patients with atopic dermatitis, while this was not observed in patients with bronchial asthma. The contribution percentages of IgG4 antibody determination, together with IgE antibody determination, in retrieving causal allergens were 71% for egg white, 70% for milk and 48% for soybean allergy, implying their diagnostic value in establishing clinical diagnosis.