Meaningful word acquisition is associated with walking ability over 10 years in Rett syndrome.

PURPOSE: To investigate walking ability in Japanese patients with Rett syndrome (RTT). METHODS: Walking ability was assessed in 100 female Japanese patients with RTT using univariate and multivariate analysis in all age groups, and in patients over 10 years of age. We analyzed walking ability and confounding factors including prenatal-perinatal histories, developmental milestones, somatic and head growth, anthropometric data, body mass index, age of loss of purposeful hand use, age at onset of stereotypic hand movement, history of autistic behavior, age at regression, presence or absence of seizures, and the results of MECP2 genetic examination from the Japanese Rett syndrome database. RESULTS: Univariate analysis revealed that acquisition of walking in all age groups was significantly correlated with the acquisition of meaningful words, microcephaly, and crawling (P < 0.0001, P = 0.005, P < 0.0001, respectively). Univariate analysis revealed that walking ability over 10 years of age was significantly correlated with acquisition of meaningful words, microcephaly, and body mass index (P < 0,0001, P = 0.005, P = 0.0018, respectively). MECP2 mutations R306C, R133C, and R294X were significantly associated with different acquisition of crawling (P = 0.004) and walking (P = 0.01). Multivariate analysis revealed that only acquisition of meaningful words was significantly correlated with walking ability over 10 years of age. This trend excluded the genetic effects of R306C, R133C, and R294X. CONCLUSIONS: Meaningful word acquisition was robustly associated with walking ability over 10 years. Prognosis of walking ability may be predicted by the acquisition of meaningful words. This information is potentially useful for early intervention and the planning of comprehensive treatment for young children with RTT.

Serum immunoglobulins in patients with chronic hepatitis C: a surrogate marker of disease severity and treatment outcome.

BACKGROUND/AIMS: Moderate polyclonal hypergammaglobulinemia is a common finding in chronic viral liver disease; however, its clinical significance has not been completely elucidated. We attempted to determine whether serum immunoglobulin levels were correlated with the disease severity and the treatment outcome in patients with chronic hepatitis C. METHODOLOGY: In a total of 102 patients with chronic hepatitis C, we performed serum tests on immunoglobulins and determined the histology activity index (HAI) score by liver biopsy. In 97 patients, immunoglobulin levels were followed prior to and 6 months after interferon (IFN) therapy. RESULTS: Serum gamma (y)-globulin and immunoglobulin (IgG) were well correlated with HAI score (both; p < 0.0001), grading score (both; p < 0.01), and staging score (both; p < 0.0001). Among the 97 patients who received 6 months of IFN monotherapy, 31, 29, and 37 patients were complete, transient and non-responders, respectively. In the three subgroups, a significant difference was found in histological HAI, grading, and staging scores (p < 0.01, p < 0.05 and p < 0.0001, respectively), and in serum levels of gamma-globulin and IgG (both; p < 0.0001). Following IFN treatment, serum gamma-globulin and IgG were significantly decreased in the complete responders (both; p < 0.0001). Furthermore, serum levels of gamma-globulin and IgG of 1.5 g/dL were useful for predicting the treatment outcome of IFN monotherapy. CONCLUSIONS: The measurement of serum gamma-globulin and IgG is a valuable non-invasive tool for assessing the disease severity and treatment outcome in patients with chronic hepatitis C.

Development of hypoxemia in alcoholic liver disease.

The aim of this study was to investigate the arterial hypoxemia in Japanese patients with alcoholic liver disease (ALD) with regard to alcohol consumption and/or disease severity. Hypoxemia was observed in 78% patients with ALD and in all 46 patients with alcoholic liver cirrhosis (ALC) and 33 (56%) of 59 patients with noncirrhotic alcoholic liver disease (NCALD) (P < 0.0001). The partial pressure of oxygen (PaO2) was 71.1 +/- 5.2 mm Hg in ALC and 78.7 +/- 6.3 mm Hg in NCALD (P < 0.0001). The oxygen consumption in ALD was significantly higher than that in control subjects (P < 0.0001), and a high oxygen consumption was seen in 88% of the patients with ALD, in all 46 ALC patients, and in 46 (78%) of 59 NCALD patients (P < 0.01). Following abstinence from alcohol, the PaO2 and oxygen consumption significantly recovered after day 2 (P < 0.0001), whereas the prothrombin index did not change in either NCALD or ALC patients. Multivariate analysis showed that alcohol consumption and oxygen consumption were significant independent predictors of PaO2. In conclusion, the present findings suggest that increased oxygen consumption due to alcohol ingestion is principally responsible for the hypoxemia in ALD patients.

Hepatobiliary cystadenoma with mesenchymal stroma in a patient with chronic hepatitis C.

Hepatobiliary cystadenoma was suggested to be uncommon and it is often difficult to make a differential diagnosis. We report a case of a 65-year-old woman who presented with changes in the structure of a cyst that had been observed for the previous 10 years. Diagnostic imaging revealed a 7-cm-diameter cystic lesion with internal septations and papillary projections in her liver. All laboratory test results were normal; however, cystic fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were raised, at 160 ng/ml andover 200,000 U/ml, respectively. Owing to changes in the structure of the cyst and the difficulty of differential diagnosis from cystadenocarcinoma, a complete surgical excision was performed. The histological findings indicated that the tumor consisted of a multilocular cyst lined by glandular cells (with cuboidal or tall columnar cystoplasm), which were immunohistochemically positive for cytokeratin, CEA, epithelial membrane antigen, and CA 19-9. The underlying stroma was composed of proliferating primitive spindle cells which were immunoreactive for vimentin, alpha-smooth muscle actin, muscle-specific actin, and desmin, and resembled ovarian stroma. From these findings, this tumor was diagnosed as hepatobiliary cystadenoma with mesenchymal stroma. Even though the tumor was previously diagnosed as a simple liver cyst, it was necessary to pay special attention to the changes in the structure of the cyst, using ultra sonography and/or computed tomography, bearing in mind hepatobiliary cystadenoma with mesenchymal stroma. The malignant potential of this tumor is stressed, and complete surgical resection is the recommended therapy.

Propagermanium: a nonspecific immune modulator for chronic hepatitis B.

Although antiviral agents have been adopted for the management of chronic hepatitis B, they have only limited efficacy because of the underlying impaired immune status. Propagermanium, a hydrophilic polymer of 3-oxygermyl propionate, has been reported to have potent immune modulatory activity associated with antiinflammatory and antineoplastic properties. For example, propagermanium augments lymphocyte functions in CD4 and CD8 cells, and in natural killer (NK) cells, and induces the production of several cytokines. A controlled pilot study of 16-week treatment with propagermanium for chronic hepatitis B (of moderate and mild grades on hepatic histology) revealed a sustained clearance of hepatitis B e (HBe) antigen and a favorable biochemical response at week 16 of treatment and at week 48 post-treatment. An open study also supported the clearance of hepatitis B virus from the blood and the possible improvement of histologic grading in the liver. There were few adverse events. A postmarketing survey, however, revealed the occurrence of moderate to severe liver damage after the treatment in about 4% of patients. Despite the exact nature of the liver damage being unclear, a putative cause is the swift removal of virus-infected hepatocytes by an immune reaction through the treatment. A subtle balance between host and viral conditions is the factor which most determines hepatitis B virus persistence. The rationale for a nonspecific immune modulator for the treatment of chronic hepatitis B will be the restoration of cellular immune responsiveness to viral infection. Although the cellular immunity for hepatitis B virus prior to the treatment should be studied, adequate observation of hepatic functions and viral markers in the recipients is clinically useful to predict liver failure during the treatment. In summary, the propagermanium regimen offers a potent and safe approach that is cost-effective for appropriate chronic hepatitis B patients with reserve hepatic capacity, and will provide new perspectives for immune therapy in chronic hepatitis B.

Hyperendothelinemia and ICG clearance in alcoholic and nonalcoholic cirrhosis.

Plasma endothelin (ET) levels are generally increased in cirrhosis patients in line with the severity of disease; however, the pathophysiological significance remains to be clarified. We evaluated the plasma ET levels in 49 patients with alcoholic cirrhosis and in 53 patients with nonalcoholic cirrhosis of the same disease severity. The plasma ET level was significantly elevated in alcoholic patients (P < 0.0001) and slightly so in nonalcoholic patients (P < 0.01); the difference was significant between the groups (P < 0.0001). The plasma ET level was positively correlated with the Child-Pugh score (P < 0.0001) and negatively correlated with prothrombin index (P < 0.001) and indocyanine green (ICG) clearance (P < 0.0001). The plasma ET level decreased 32% in alcoholic patients after abstinence (P < 0.001), but remained correlated with ICG clearance (P < 0.001) and the Child-Pugh score (P < 0.01), but not with prothrombin index. Regression analysis revealed that the plasma ET level was correlated with estimated hepatic blood flow and alcohol abuse. These findings suggest that hyperendothelinemia in cirrhosis patients is related to alcohol abuse and disease severity, especially to impaired hepatic hemodynamics.