Background factors correlated with the psychological features of 254 outpatients with Type 2 diabetes mellitus in Japan.

UNLABELLED: For the purpose of identifying the features of psychological troubles and their significance in Type 2 diabetes mellitus outpatients, we analyzed how psychological troubles were affected by various background factors. SUBJECTS AND METHODS The subjects all consisted of outpatients > or = 40 years of age at the Fukuoka Red Cross Hospital in December 1996. We used the State-Trait Anxiety Inventory (STAI) to determine anxiety, the Self rating Depression Scale to determine depression. We divided the patients into the ones who demonstrated each specific psychological trouble and the ones who did not, and then analyzed the psychological trouble between the two groups with correlation to various background factors which may have led the patients to develop their respective psychological features. RESULTS: In a stepwise multiple logistic regression analysis, the presence of itching and polyuria, age (40-49 years old) and females were correlated with anxiety in this study. Depression was also correlated with the absence of photo-coagulation therapy and the absence of leisure time activities. CONCLUSION: Our results identified some of the features of psychological troubles and their significance in diabetic outpatients, It is therefore important to carefully consider these factors during medical consultations.

Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

PURPOSE: We sought to identify the clinical variables most critical to successful treatment of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH). PATIENTS AND METHODS: Among the factors tested were age at diagnosis (< 2 years or > or = 2 years), time from diagnosis to initiation of treatment with or without etoposide-containing regimens, timing of cyclosporin A (CSA) administration during induction therapy, and the presence or absence of etoposide. RESULTS: By Kaplan-Meier analysis, the overall survival rate for the entire cohort of 47 patients, most of whom had moderately severe to severe disease, was 78.3% +/- 6.7% (SE) at 4 years. The probability of long-term survival was significantly higher when etoposide treatment was begun less than 4 weeks from diagnosis (90.2% +/- 6.9% v 56.5% +/- 12.6% for patients receiving this agent later or not at all; P <.01, log-rank test). Multivariate analysis with the Cox proportional hazards model demonstrated the independent prognostic significance of a short interval from EBV-HLH diagnosis to etoposide administration (relative risk of death for patients lacking this feature, 14.1; 95% confidence interval, 1.16 to 166.7; P =.04). None of the competing variables analyzed had significant predictive strength in the Cox model. However, concomitant use of CSA with etoposide in a subset of patients appears to have prevented serious complications from neutropenia during the first year of treatment. CONCLUSION: We conclude that early administration of etoposide, preferably with CSA, is the treatment of choice for patients with EBV-HLH.

Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis.

Severe neutropenia (absolute neutrophil count <500/gl) is probably due to the combined effects of dysregulated cytokine production and chemotherapeutic agents, and is one of the risk factors in the initial treatment of patients with Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). We report here 9 cases of neutropenic HLH, of which 8 were treated with cyclosporin (CSA, 2-6 mg/kg/day; continuous infusion, or 6 mg/kg/day; per os, for periods ranging from 9 days to >8 weeks) in the initial neutropenic phase during induction treatment using corticosteroids and etoposide. Five of the 6 cases, in which CSA treatment was started early (before the second week of induction), survived the critical period with recovery of neutrophil counts within a week. The remaining 3 cases, in which CSA was introduced later or not at all, died of infection. Based on these results, we recommend a prompt short-term CSA infusion during neutropenic episodes in the most common treatment regimen of etoposide and corticosteroids in patients with HLH. Improved neutrophil recovery as a result of CSA treatment makes it possible to continue immunochemotherapy safely and obtain improved patient outcomes.

MDR1 gene overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment.

Overexpression of the multidrug resistance 1 (MDR1) gene is closely associated with the clinical outcome of hematopoietic malignancies, but the alteration of its expression during chemotherapeutic treatment and the precise mechanism underlying MDR1 gene overexpression in solid tumors remains unclear. We determined the expression and degree of methylation at the promoter of the MDR1 gene in bladder cancer. The mRNA levels of the MDR1 gene were found to be markedly enhanced, 3.5- to 5.7-fold higher in bladder cancers after chemotherapeutic treatment than those in untreated primary tumors. The MDR1 gene was overexpressed in recurrent tumors in 89% of patients who showed rerecurrence, whereas overexpression was observed in 25% of the patients without re-recurrence. A statistically significant inverse correlation existed between MDR1 expression and the methylation of 5'CpG sites at the promoter in patients with bladder cancer after chemotherapeutic treatment, with the degree of methylation at several CpG sites, rather than other specific sites, involved in this regulation. Consistent with the increase in MDR1 expression, the frequency of patients with a hypermethylated promoter decreased to 50 and 17% after intravesical and systemic chemotherapy, respectively. Thus, overexpression of the MDR1 gene might be a prognostic marker for intravesical recurrence, whereas methylation of the promoter region negatively regulates MDR1 expression and the appearance of multidrug resistance mediated by P-glycoprotein in bladder cancers.

Hematopoietic stem cell transplantation (HSCT) for Langerhans cell histiocytosis (LCH) in Japan.

There exists limited information about the usefulness of hemopoietic stem cell transplantation (HSCT) for the treatment of patients with refractory Langerhans cell histiocytosis (LCH). We report here four Japanese pediatric patients with multisystem LCH disease who underwent HSCT between 1994 and 1997. Two of the four patients are doing well without any relapse. However, neither of them shows improved sequelae 3 to 4 years after allogeneic HSCT, although the graft was rejected in one of the cases. The remaining two patients died of septic shock. A review of the literature of 11 patients revealed four fatalities after the use of HSCT in the treatment of LCH. Three of these were due to active LCH and three deaths occurred within 2 months after HSCT. To establish the usefulness of HSCT for refractory LCH, further studies are required.

Establishment of a new human megakaryoblastic cell line, CMY, with chromosome 17p abnormalities.

A new megakaryoblastic cell line CMY was established from a Down's syndrome patient suffering from acute megakaryoblastic leukemia. The karyotypes of CMY showed deletion of chromosome 17 or the translocation of 17p, whereas the blasts of the patient did not reveal these abnormalities of chromosome 17 by conventional karyotype analysis. Blasts of the patient failed to respond to chemotherapy and complete remission could not be attained. The abnormalities of 17p became progressively predominant in the patient. These results suggest that the blasts of a minor clone which had the abnormalities of chromosome 17p might have existed in the patient from the beginning and CMY was established from the minor clone. Investigation of p53 gene by PCR-SSCP analysis revealed that blasts of the patient showed normal patterns, while CMY showed an abnormally migrating band in exon 5 alone. This result suggests that another novel oncogenic factor(s) besides p53 might be present on chromosome 17p and other tumor suppresser genes need to be studied.

Identification of persistent trophoblastic diseases based on a human chorionic gonadotropin regression curve by means of a stepwise piecewise linear regression analysis after the evacuation of uneventful moles.

Among the 191 patients with complete hydatidiform moles who were diagnosed and treated at Kyushu University Hospital from 1982 until 1996, 167 patients were diagnosed with uneventful moles retrospectively. The serial beta human chorionic gonadotropin (hCG) values in the 167 patients with uneventful moles were analyzed by a stepwise piecewise linear regression analysis in order to establish a normal regression curve of a human chorionic gonadotropin after a molar pregnancy. This normal regression curve is considered to be excellent regarding sensitivity (24/24-100%) and to be equivalent to the identification based on a plateau or a rise regarding specificity (156/167-93.4%). To distinguish patients with persistent trophoblastic disease (PTD) from uneventful moles, this normal curve is thus considered to be accurate since the accuracy was 180/191 (94. 2%). The weeks exceeding the normal regression curve in 24 PTD patients were 5.04 +/- 3.85 weeks and were also earlier than the weeks based on a plateau or a rise (P = 0.01). Within 7 weeks after evacuation, in 21/24 (87.5%) of the PTD cases, the beta-hCG values exceeded the normal range, while in only 14/24 (58.3%) the beta-hCG showed a change in the shape of a plateau or a rise. In addition, in 19/24 (79.2%) of the PTD patients, the time exceeding the normal range was shorter than the time exhibiting a plateau or a rise in the beta-hCG change. The above findings thus led us to conclude that this normal regression curve was useful for discriminating PTD from uneventful moles more precisely and more quickly than by identification based on a plateau or a rise.

[Necrotizing sarcoid granulomatosis diagnosed by video thoracoscopic lung biopsy].

A 28-year-old woman was admitted to our hospital because of chest pain. A chest roentgenogram and a chest computed tomogram revealed many nodular shadows on both sides. Examinations of specimens obtained by and by transbronchial lung biopsy during fiberoptic bronchoscopy were not diagnostic, and therefore video thoracoscopic lung biopsy was done. The lung lesion was characterized by aggregates of epithelioid cell granulomas, along with granulomatous and necrotizing angitis. We therefore diagnosed necrotizing sarcoid granulomatosis, and began to administer prednisolone. The nodular shadows disappeared within four weeks. In this case video thoracoscopic lung biopsy was useful in the diagnosis of necrotizing sarcoid granulomatosis in the lung.

Case of a child with paroxysmal nocturnal hemoglobinuria diagnosed by flow cytometry.

A case of a child with paroxysmal nocturnal hemoglobinuria (PNH) is characterized by an increased sensitivity of the erythrocyte to hemolytic action of complement. The widely used Ham test may not always be reliable. Recently, a panel of monoclonal antibodies has become available to detect various glycosylphosphatidylinositol (GPI)-linked proteins by flow cytometry (FCM) and the deficiency of GPI-anchored proteins on the various kinds of cell membranes is implicated as the pathogenesis of PNH. We diagnosed a case of a child with PNH by FCM and complement lysis sensitivity (CLS) test, which showed the increased sensitivity of PNH erythrocytes to complement. His diagnosis was delayed because of Ham test negativity and rarity of PNH cases in children.

[Hyperkalemia in a cyclosporine A-treated allogeneic bone marrow transplant recipient].

A 9-year-old boy was admitted with the diagnosis of myelodysplastic syndrome (FAB RAEB in T). The patient was treated with busulfan and cyclophosphamide and transplanted with bone marrow cells from an HLA identical sister. Cyclosporin A (CyA) and short term methotrexate (MTX) was given for prophylaxis against graft versus host disease (GvHD). The serum potassium value was observed to increase to 6.3 mEq/l during the period of CyA therapy. The serum potassium value returned to 4 mEq/l when CyA treatment was decreased to a serum concentration of less than 50 ng/ml (FPIA). On day 90 post transplantation the patient was diagnosed as relapsed. The patient was preconditioned with cyclophosphamide and total body irradiation and a second bone marrow transplantation was performed using cells from the same donor. He was treated again with CyA and short term MTX for the prevention of GvHD. Once again the patient became hyperkalemic with 6.8 mEq/l. The serum creatinine level was 0.9 mg/dl, the GFR was 52.1 ml/min, FEK was 7.1%. Pseudohypoaldosteronism or hyporeninemic hypoaldosteronism was suspected. To investigate this possibility a renin/aldosterone stimulation test was performed. We speculate that an idiosyncratic response to CyA resulted in pseudohypoaldosteronism and produced a defect in potassium secretion.

Treatment for B-cell-type lymphoma in a girl associated with Bloom's syndrome.

A 12-year-old girl suffering from Bloom's syndrome developed B-cell-type lymphoma in the epipharynx. She was identified as having Bloom's syndrome at the age of 3. While the tumor was eradicated completely by induction chemotherapy, the bone marrow suppression was severe and persistent. For this reason, we modified subsequent chemotherapy to a milder form. Thus the remaining therapy could be safely completed. This is the first case clearly diagnosed as having epipharyngeal B-cell-type lymphoma in the Bloom's Syndrome Registry.

Epstein-Barr virus infection in Chediak-Higashi syndrome mimicking acute lymphocytic leukemia.

We have had the opportunity to study a case of Chediak-Higashi syndrome (CHS) in the accelerated phase that was associated with Epstein-Barr virus (EBV) infection. The clinical course of a 12-year-old boy was characterized by fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia. However, in the terminal stage, the appearance of an atypical lymphoblastic leukocytosis was morphologically indistinguishable from acute lymphocytic leukemia, accompanied by benign histiocytosis with hemophagocytosis. Autopsy examination revealed an atypical lymphoid infiltration favoring EBV infection as the primary diagnosis. This case underscores the fatal consequences of EBV infection in CHS.

Beneficial effects of high-dose intravenous gammaglobulin on the accelerated phase of Chediak-Higashi syndrome.

The Chediak-Higashi syndrome (CHS) is a rare, autosomal-recessively inherited disease characterized by giant cytoplasmic granules in neutrophils, monocytes and lymphocytes. It has been reported that a lymphoma-like illness develops in the accelerated phase of the syndrome and that early death ensues. Treatment of CHS has not been established, particularly when the accelerated phase develops. We treated a 15-year-old boy, who had entered into the accelerated phase, with high-dose intravenous gammaglobulin. The treatment was beneficial in the management of accelerated phase of CHS.