Hyperchloraemic metabolic acidosis.

Cholestyramine carries a risk of hyperchloraemic metabolic acidosis. Being cognisant of this drug-induced adverse event may reduce diagnostic delays. Emergency physicians should be alert about this condition, in particular among patients with pre-existing chronic kidney disease, or who are taking spironolactone.

Steroids administered after vacuum-assisted biopsy in the management of idiopathic granulomatous mastitis.

AIMS: The aetiology and treatment options for idiopathic granulomatous mastitis (IGM) are controversial. The aim was to study the clinical and diagnostic features and discuss medical and surgical treatment for IGM in our patients. METHODS: Sixty-five patients who met the histological criteria for IGM were retrospectively studied. The diagnosis of IGM was confirmed using Mammotome (an ultrasound-guided, vacuum-assisted biopsy system), core needle biopsy, quadrantectomy or segmental resection. Forty-five patients were treated with prednisolone (69.2%). Immunohistochemical (IHC) staining for immune-related antigens (CD3, CD4, CD8, CD79a, IgG, and IgM) was performed. RESULTS: Ultrasonography (USG) was carried out in all patients. Among them, 61 were considered to have an inflammatory mass and 15 had accompanying liquefaction. In four patients, the findings mimicked breast carcinoma (6.2%). The IHC results showed CD3, CD4, CD8 and CD79a lymphocytes diffusely distributed in the lesion. Stains for IgG and IgM were negative. Prednisolone was administered to the patients diagnosed with IGM. The success rate was 53 (81.5%) and the whole recurrence was 12 (18.5%). The median follow-up period was 12 months (range 4-42 months). CONCLUSIONS: The aetiology of IGM remains uncertain. The disease has no propensity for the right or left breast. It is a local autoimmune disease, involving humoral and cell-mediated immunity. Hyperprolactinaemia may play a role in some patients. Corticosteroids administered after complete removal of the IGM lesion using the Mammotome biopsy system is an effective treatment option.

Liver disease after bone marrow transplantation--the Taiwan experience.

To investigate the causes of impaired liver function (LF)* after BMT, 88 patients were included for analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, transplant methods, preconditioning regimens, and graft-versus-host disease (GVHD). Fifty of them (56.8%) developed abnormal LF after BMT and among them, 29 (32.9%) developed chronic hepatitis (CH). By univariate analysis, HCV infection, pretransplant abnormal LF, allogeneic BMT, and preconditioning regimen with total body irradiation were all significantly related to higher incidence of post-BMT impaired LF. However, only HCV infection, pretransplant abnormal LF, and acute GVHD were associated with higher incidence of CH. By multivariate logistic regression analysis, HCV infection and pretransplant abnormal LF were the two most significant interpreters for abnormal LF, especially for CH (odds ratios: 7.86 and 4.735, respectively) after BMT. Although the incidence of abnormal LF was found high in this study, there was no significant disadvantage in terms of survival for patients who developed abnormal acute and chronic liver function after BMT. However, a long-term follow-up is needed to evaluate survival pathology of CH, such as liver cirrhosis and hepatoma.

Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation.

BACKGROUND: Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS: Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS: After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS: Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.

Molecular cloning and characterization of a human brain-specific gene implicated in neuronal differentiation.

A 2.5 kb human cDNA clone containing a CAG trinucleotide repeat, designated HB20, was isolated from a human fetal brain library. Northern analysis on multi-tissue blots and various cell lines confirmed that HB20 is specifically expressed in the brain. Its expression is low in two glioma cells, moderate in a neuron precursor cell, NT2, but absent in lymphoma, cervical carcinoma, or colonic carcinoma cells. Significant increase of HB20 mRNA was shown along with retinoic acid-induced terminal differentiation of NT2 cells into neuron cells, hNT. Homology comparison of the predicted HB20 amino acid sequence with the current database revealed that it belongs to a newly recognized protein family composed of nucleosome assembly proteins and SET proto-oncogene, which has been shown to interact specifically with B-type cyclins involved in the control of cell proliferation. Together with the detection of nuclear localization signals and apparent nuclear distribution of expressed protein, HB20 is likely to be a brain-specific nuclear protein, functioning in the process of neuronal differentiation.

Reverse seroconversion of hepatitis B virus infectious status after allogeneic bone marrow transplantation from a carrier donor.

A 35-year-old man with acute promyelocytic leukemia received an allogeneic bone marrow transplant (BMT) in second complete remission. The donor was his 18-year-old brother, a chronic hepatitis B virus (HBV) carrier with detectable serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA (HBV DNA). Before BMT, the recipient was immune to HBV, with serum antibody to HBsAg (anti-HBs), antibody to HBeAg (anti-HBe) and normal liver function. Examination of the recipient serum drawn 2 months after BMT revealed reverse seroconversion from anti-HBs/anti-HBe to HBsAg/HBeAg, which remained positive thereafter. Upon reducing cyclosporin 6 months after BMT, acute hepatitis occurred with HBV DNA in serum as evidence of active HBV replication; the patient then developed chronic hepatitis which progressed to cirrhosis and hepatic decompensation within 8 months. Transfusion of HBV DNA/HBeAg-positive bone marrow is thus harmful even when the recipient has anti-HBs prior to BMT.

Bone marrow transplantation in Taiwan: low incidence of acute GVHD in patients with hematologic malignancies and severe aplastic anemia.

A total of 116 consecutive patients, including 82 cases of hematologic malignancies and 34 cases of severe aplastic anemia (SAA), were treated by allogeneic bone marrow transplantation (BMT). The conditioning regimens and post-graft immunosuppressive agents were as described by Thomas in Seattle and Santos in Baltimore. The incidence of grades II-IV acute GVHD in patients with hematologic malignancies with a full HLA match, with one locus and with two loci mismatches was 6.3% (4 of 63), 0% (0 of 11) and 37.5% (3 of 8), respectively. None of SAA patients developed grade II-IV acute GVHD. The low incidence of acute GVHD after BMT among Chinese patients may be associated with the use of isolation in laminar airflow rooms and a relatively low level of genetic diversity in histocompatibility antigens. This is an interesting issue for further study.

Withdrawal of immunosuppressive therapy in allogeneic bone marrow transplantation reactivates chronic viral hepatitis C.

A 28-year-old female patient with acute myelogenous leukemia and post-transfusion chronic viral hepatitis C received an allogeneic bone marrow transplantation (BMT) in first complete remission. The inflammatory activity of chronic hepatitis C decreased dramatically with the start of BMT and during the whole course of cyclosporin A treatment. After the immunosuppressive therapy was stopped, however, the chronic hepatitis C activity increased and the serum alanine amino-transferase levels thereafter remained as high as before BMT. Hepatitis C virus RNA was detected by polymerase chain reaction in serum drawn 60 days and 52 months after BMT. Since fulminant viral hepatitis B may take place after tapering of immunosuppressive therapy following BMT due to an excessive response of recovering immunity to the actively replicating virus during immune suppression, careful monitoring of liver function for patients with chronic viral hepatitis C in BMT is suggested.

Relapse of Graves' disease after successful allogeneic bone marrow transplantation.

As shown in many reports, allogeneic BMT can help cure autoimmune diseases. Conversely, we present a 24-year-old woman with Graves' disease, which was diagnosed just before BMT for CML. The Graves' disease remitted immediately after BMT but relapsed 18 months later. Since the donor was free from thyroid diseases and the patient showed a rapid shift to complete donor chimerism after BMT, the autoimmune problem seemed neither to arise directly from the donor nor simply from the recipient's residual lymphocytes. On the contrary, it was most likely compounded by chronic GVHD as suggested by the accompanying GVHD symptoms and the absolute donor karyotype in bone marrow cells. A Graves' disease-susceptible HLA allele was also shared between recipient and donor, possibly enhancing the chances of this condition developing. Thus, allogeneic BMT may facilitate relapses in autoimmune diseases as well as alleviating them.

Trisomy 21 in acute myeloid leukemia.

We report two cases of acute myeloid leukemia (AML), constitutionally normal, with trisomy 21. Trisomy 21 does not often occur as a sole numerical karyotypic abnormality in AML leukemia. The possible prognostic significance of the finding in acute leukemia is discussed.

Lack of mutations of BCL6 and BCL10 genes in mucosa-associated lymphoid tissue lymphomas of the orbital adnexa.

Knowledge regarding the molecular pathogenesis and progression of mucosa-associated lymphoid tissue (MALT) lymphomas of ocular adnexa is limited. Eleven cases of ocular MALT lymphoma were analyzed by clonal rearrangement of antigen receptor genes using Southern blot hybridization. Polymerase chain reaction-single stranded conformational polymorphism analysis and DNA sequencing was utilized to analyze the mutations of BCL6 and BCL10 genes. Clonal rearrangement of immunoglobulin heavy genes was found in all 11 patients. No point mutation was found in BCL6 or BCL10 genes in any of the samples analyzed. We suggest that mutations of BCL6 and BCL10 genes are rare in low-grade MALT lymphoma of ocular adnexa and are unlikely to be involved in the pathogenesis of the disease. But the role of alterations of both BCL6 and BCL10 genes in the disease progression of low-grade MALT lymphoma require additional study.

Prognostic significance of immunoglobulin and T cell receptor gene rearrangements in patients with acute myeloid leukemia: Taiwan experience.

We investigated the prognostic significance of lymphoid antigen receptor gene rearrangement in patients with newly diagnosed acute myeloid leukemia (AML). Thirty-nine patients were included in the study. Clonal gene rearrangement of immunoglobulin heavy chain (IgH) and T cell receptor beta chain (TCRbeta) was found in leukemic cells in 11 (28.2%) and 10 (25.6%) patients, respectively. Five (12.8%) had both IgH and TCRbeta gene rearrangements. Three of the seven (42.9%) B-lymphoid marker-positive and eight of the 32 (25%) B-lymphoid marker-negative patients had clonal IgH gene rearrangements. Five of the 11 (45.5%) T-lymphoid marker-positive and 5 of the 28 (17.9%) T-lymphoid marker-negative patients had clonal TCRbeta gene rearrangements. All patients were treated with similar regimens. The complete remission rate (62.5% vs 65.2%, p=1.000) and median survival (13 vs 14 months, p=0.366) were similar in patients with and without clonal IgH or TCRbeta gene rearrangements. In conclusion, while clonal rearrangements of IgH or TCRbeta genes were found in AML patients, they did not appear to effect the prognosis.

Molecular analysis of mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexa.

Lymphomas of mucosa-associated lymphoid tissue (MALT) are a distinct subgroup of extranodal B-cell non-Hodgkin's lymphomas. Most studies have failed to demonstrate the clonal rearrangement of BCL-1, BCL-2 or c-MYC genes for MALT lymphomas. Further, alteration of the p53 gene is rarely demonstrated in low-grade MALT lymphomas, but can be detected in high-grade disease. Lymphomas of the ocular adnexa represent approximately eight percent of all extranodal lymphomas, most of which are MALT lymphomas, but few studies had explored the alterations of BCL-1, BCL-2, c-MYC and p53 genes specifically for ocular MALT lymphomas. We investigated the changes to BCL-1, BCL-2, c-MYC and p53 genes in these lymphomas for Taiwanese patients. Clonal rearrangement for immunoglobulin heavy-chain (IgH), BCL-1, BCL-2, c-MYC and p53 genes was examined for 16 cases of ocular MALT lymphoma. Restriction-length polymorphism and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the DNA, corresponding to exons 5 through 9, followed by DNA sequencing, were utilized to analyze the possible mutations of the p53 gene for these tumors. Thirteen of the cases revealed rearranged IgH genes using Southern blotting or PCR. No rearrangement of BCL-1, BCL-2, c-MYC or p53 genes was discovered, with point mutation of the p53 gene in one case. As for other types of MALT lymphomas, BCL-1, BCL-2 and c-MYC genes are not implicated in the pathogenesis of the ocular sub-group. Although alteration of the p53 gene is rare for low-grade ocular MALT lymphoma, its role in disease progression merits further research.

Randomized trial comparing weekly bolus 5-fluorouracil plus leucovorin versus monthly 5-day 5-fluorouracil plus leucovorin in metastatic colorectal cancer.

BACKGROUND/AIMS: The purpose of this study was to compare the efficacy and toxicity profiles of weekly intravenous (i.v.) bolus injection of 5-fluorouracil plus low-dose leucovorin with the Mayo Clinics' monthly 5-day schedule of 5-fluorouracil and leucovorin in the treatment of metastatic colorectal cancer. METHODOLOGY: A total of 96 patients with previously untreated metastatic colorectal cancer were randomized to receive either a weekly i.v. bolus injection of 5-fluorouracil 400 mg/m2 plus leucovorin 20 mg/m2 (weekly arm), or i.v. bolus injection of 5-fluorouracil 425 mg/m2 plus leucovorin 20 mg/m2 for 5 consecutive days every 4 or 5 weeks (monthly arm). Therapy was continued until disease progression or unacceptable toxicity appeared. In the presence of disease progression, the study regimen was stopped and second-line treatment was instituted after the patient was discontinued from this study. RESULTS: There was no significant difference of response rates between both regimens. The response rate were 14.3% in the weekly arm (2 CR and 5 PR, 95% CI: 2.6-25.2%) and 10.6% in the monthly arm (1 CR and 4 PR; 95% CI: 6.5-32.3%), respectively (P = 0.8957). The survival times were also similar between the two (P = 0.4207, log-rank test). The median survival were 15.8 months in the monthly arm and 18.4 months in the weekly arm. Hematologic toxicity was minimal in both arms. However, the monthly arm produced a higher toxicity in severe (grade 3-4) diarrhea (14.9% vs. 2%; P = 0.029) and stomatitis (8.5% vs. 0; P = 0.054). CONCLUSIONS: Weekly bolus injection of 5-fluorouracil and low-dose leucovorin achieved a similar response rate and survival as compared with the Mayo Clinics' monthly 5-day schedule, but severe toxicity was less commonly seen using the weekly regimen. As current chemotherapeutic treatment for metastatic colorectal cancer is largely palliative rather than curative, the weekly bolus regimen may be a more favorable approach in managing metastatic colorectal cancer.

Factors predictive of survival in patients with node-positive colorectal cancer in Taiwan.

BACKGROUND/AIMS: Preoperative CEA levels, depth of tumor penetration, and the number of positive lymph nodes were reported as independent factors prognostic of survival in colorectal cancer patients. This study was carried out in an effort to evaluate the prognostic significance of these three factors in patients with Dukes' C colorectal cancer in Taiwan. METHODOLOGY: Between 1992 and 1994, a total of 112 patients with node-positive colorectal cancer were evaluated retrospectively at the Veteran General Hospital-Taipei. All patients underwent potentially curative surgery and received 5-fluorouracil based adjuvant chemotherapy. Reference to the Dukes' classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on the location of the tumor, depth of penetration, number of positive lymph nodes, degree of tumor differentiation, and preoperative CEA levels were analyzed to understand their association with survival. Blood samples for CEA measurement were taken a few days before operation. A multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the most important independent predictors of survival among all the possible variables. RESULTS: Using univariate analysis the number of positive lymph nodes (P < 0.001), penetration of the bowel wall (P < 0.001), and preoperative CEA levels (P < 0.001) were found as significant prognostic factors, while the degree of tumor differentiation, location of the tumor, age and sex were not significant. Using multivariate Cox analysis the number of positive lymph nodes, penetration of the bowel wall, and preoperative CEA levels were still found as independent prognostic factors in node-positive colorectal cancer patients. CONCLUSIONS: Data obtained from our study indicates that preoperative CEA levels, depth of tumor penetration, and the number of positive lymph nodes were independent prognostic factors in Dukes' C colorectal cancer patients. They could serve as appropriate modifications of the initial Dukes scheme in node-positive diseases.

[Diagnosis and treatment of small intracerebral abscess].

Diagnosis and treatment of 39 cases of small intracerebral abscess are reported. All of them were proved pathologically. The main symptom was epilepsy. It may be due to hemorrhagic infection, occurred more in teenagers, and located around the parietal lobe. Some diagnostic characters and essential points on surgery are also presented in the paper. Finally, the authors suggest two-stage management for the disease is the best choice. About 89.7% of patients obtained good results.

1,25-Dihydroxyvitamin D3 suppresses cell growth, DNA synthesis, and phosphorylation of retinoblastoma protein in a breast cancer cell line.

Cells of a breast adenocarcinoma cell line, CAMA-IEe, were found to contain a moderate concentration of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] receptors. The receptors' dissociation constant calculated by Scatchard analysis was 4.1 x 10(-10) M. These receptors sedimented at around 4.0 S position on a linear 5-20% sucrose density gradient and exhibited an apparent molecular weight of about 46 kDa. Receptor concentration was found to be highest in the early stages of cell growth, decreased continuously when cells were actively growing, and reached the lowest level at confluence. Suppression of cell growth, of DNA synthesis, and of the phosphorylation of retinoblastoma protein by 1,25(OH)2D3 at concentrations about 10(-7) M were observed. Treatment with 10(-7) M 1,25(OH)2D3 for 12 hr or longer caused elevation of cytosolic free calcium in CAMA-IEe cells. These results show that CAMA-IEe cell growth is suppressed by 1,25(OH)2D3 and that the suppression is possibly mediated through calcium mobilization.

Intramedullary spinal cord metastasis: a case report.

Intramedullary spinal cord metastasis is a rare condition of systemic malignancy. We report a case of breast cancer with thoracic spinal cord intramedullary metastasis. The patient suffered from neurological deficit in both lower extremities. Magnetic resonance imaging (MRI) examination showed two soft tissue lesions located in the medullary region of thoracic spinal cord at T3 to T5 vertebral level. She was treated with local radiotherapy and systemic corticosteroid treatment with much improvement of the symptoms.

The application of immunocytochemistry in diagnosis of meningeal carcinomatosis in a patient with unknown primary site.

A 55-year-old female with meningeal signs was suspected to have carcinomatosis meningitis based on cytospin cytology study of cerebrospinal fluid (CSF) with Wright stain. There was no primary site of any malignancy which could be identified as the source of metastasis. Immunochemical staining for cytokeratin and carcinoembryonic antigen on suspicious large immature cells in the CSF gave positive results and confirmed the malignant nature of her disease. Intrathecal chemotherapy with methotrexate and whole brain irradiation then eradicated the symptoms rapidly. Immunocytochemistry was considered to be a very powerful diagnostic tool in management of this patient.