Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.     

Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS

OBJECTIVE: B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) has been increasingly reported in Asia and is regarded as a variant of intravascular lymphomatosis (IVL). Recently CD5 was reported to be expressed in some cases of diffuse large cell lymphoma and IVL. We therefore examined the expression of CD5 on lymphoma cells in B-LAHS and compared the clinical and laboratory data between CD5+ and CD5- B-LAHS. METHODS: The expression of CD5 on lymphoma cells was examined using flow cytometry and immunohistochemical analysis of paraffin sections. The clinical records were reviewed to characterize clinical features. PATIENTS: Twelve patients with B-LAHS; ten men and two women, age ranging from 41 to 82 years (median, 63.5 years) were included in this study. RESULTS: B-LAHS is characterized by fever and hepatosplenomegaly without lymphadenopathy at the initial presentation. Histological examination showed hemophagocytosis and infiltration of lymphoma cells in the bone marrow, and in some cases intravascular proliferation of lymphoid cells characteristic of IVL. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. In eight of the twelve patients, lymphoma cells were positive for CD5. But no differences were observed in the clinical or laboratory findings between CD5+ B-LAHS and CD5- B-LAHS. CONCLUSION: No clinical differences were observed between CD5+ B-LAHS and CD5- B-LAHS. Further studies are required to elucidate the differences in pathogenesis between these two subgroups of B-LAHS.     

Relationships between diurnal blood pressure variation, physical activity, and health-related QOL

The aim of this study is to clarify the associations between diurnal blood pressure variation, physical activity and health-related quality of life (HRQOL). Ninety-seven volunteers, including 52 hypertensive patients and 45 healthy subjects (average age, 48 years) participated in this study. Twenty-four hour ambulatory blood pressure and heart rate variability were measured using TM2425 (A&D Co). Physical activity was measured using actigraphy, and HRQOL was assessed by a Medical Outcome Study Short-Forum 36-Item Health Survey (SF-36). Awake mean physical activity positively correlated with the nocturnal dip in systolic blood pressure (SBP) (r = 0.242, p < 0.02) and diastolic blood pressure (DBP) (r = 0.219, p < 0.04). The score of physical functioning positively correlated with awake mean physical activity (r = 0.265, p < 0.02). The score of role-emotional also correlated with awake mean physical activity (r = 0.269, p = 0.01). Using multiple regression analysis, the nocturnal dip in SBP was found to be correlated with awake and sleep mean physical activities (p < 0.05, p < 0.05, respectively). In conclusion, physical activity is associated with the nocturnal dip in blood pressure. Moreover, physical activity correlates with some of the factors of HRQOL.     

Phenotypic analysis of plasma cells in bone marrow using flow cytometry in AL amyloidosis.

AL amyloidosis is an intractable disease resulting from a plasma cell dyscrasia which has a wide clinical spectrum. To investigate the phenotype of plasma cells in the bone marrow, a flow cytometric analysis was carried out in 10 patients with this disease (mean age, 57.8 +/- 7.9 years) and controls with M-protein (positive controls, n = 4) and without it (negative controls, n = 8). All patients were shown to have either A kappa- or A lambda-immunoreactive amyloid deposits on the biopsied tissues. On flow cytometry CD38++CD19+CD56- cells (polyclonal plasma cells) showed no significant difference between patients (0.59 +/- 0.37%) and either negative (2.25 +/- 2.84%) or positive controls (0.38 +/- 0.20%), while CD38++CD19-CD56+ cells (monoclonal plasma cells) showed a significantly higher level in the patients (1.34 +/- 1.54%) than in either negative (0.041 +/- 0.004%, p < 0.005) or positive controls (0.11 +/- 0.09%, p < 0.05). With respect to maturation of plasma cells, five of the patients (50%), three of the positive controls (75%) and all of the negative controls showed a dominant proliferation of mature subtype (CD45+MPC-1+CD49e- or CD45+MPC-1+CD49e+). Immature (CD45+MPC-1- or CD45-MPC-1-) and intermediate (CD45-MPC-1+CD49e-) subtypes were dominantly present in the bone marrow in 2 and 3 patients, respectively. In AL amyloidosis monoclonal plasma cells producing M-protein can be easily and reliably detected in the bone marrow by flow cytometry. This analysis might provide plasma cell phenotypic markers useful for assessing the prognosis and for monitoring the response to treatment.     

A case of hepatosplenic cat scratch disease]

A 43-year-old man was admitted with idiopathic fever. Abdominal ultrasonogram demonstrated multiple hypoechoic lesions in the spleen. Abdominal CT scan showed multiple hypodense lesions in the liver and spleen. The patient had a cat in his house, and the presence of a very high serous antibody titer for Bartonella henselae led to the diagnosis of hepatosplenic cat scratch disease. It is important to consider this disease in the differential diagnosis of idiopathic fever when multiple lesions are detected in the liver and spleen.     

Downregulation of CPI-17 contributes to dysfunctional motility in chronic intestinal inflammation model mice and ulcerative colitis patients

Background  Chronic intestinal inflammation is frequently accompanied by motility disorders. We previously reported that proinflammatory cytokines, such as tumor necrosis factor α and interleukin (IL)-1β downregulate CPI-17, an endogenous inhibitor of serine/threonine protein phosphatase in smooth-muscle cells, which results in the inhibition of myosin light chain phosphorylation and contractility. However, its clinical relevance has not been clarified. Methods  The present study examined the changes in CPI-17 expression in chronic intestinal inflammation using smooth-muscle tissues from IL-10 knockout mice and from patients with ulcerative colitis (UC). Results  The IL-10 knockout mice developed spontaneous and chronic colitis accompanied by immune cell infiltration, submucosal fibrosis, and thickening of the muscularis externa. The expression of α-smooth muscle actin protein in the smooth-muscle layer did not change, whereas that of CPI-17 protein was decreased by about 40% compared with healthy wild-type controls. Consistent with this observation, smooth-muscle contractile force and myosin light chain phosphorylation induced by a muscarinic agonist were reduced in the knockout mice. Moreover, we observed that CPI-17 protein expression was decreased in smooth-muscle tissues from patients with UC compared with controls. Conclusions  CPI-17 downregulation might contribute to the decreased motor function in chronic inflammatory bowel diseases.     

Evaluation of intensive chemotherapy in AL amyloidosis: usefulness of flow cytometric analysis of plasma cells in bone marrow.

To investigate whether monoclonal plasma cells in the bone marrow are useful as a therapeutic marker in AL amyloidosis, serial flow cytometry was performed in five patients with this disorder before and after chemotherapy. Four patients were treated with 2 or 3 courses of VAD (vincristine, doxorubicin and dexamethazone) and subsequently with high-dose melphalan followed by auto-PBSCT. The remaining one patient was treated with two courses of VAD alone. Before treatment all patients exhibited a CD19- CD56+ subpopulation, which indicated monoclonal plasma cells, in varying degrees. After treatment all patients showed a decrease in monoclonal plasma cells in accordance with the disappearance of M-protein in serum and/or urine. In two patients treated with VAD followed by auto-PBSCT, polyclonal (CD19+ CD56-) and total plasma cells gradually increased in the follow-up study, while monoclonal plasma cells stayed at less than 0.3% nine months after treatment. No apparent correlation was found between altered maturation of plasma cells and disappearance of M-protein. With respect to easy detection of monoclonal plasma cells producing amyloidogenic M-protein, flow cytometry of bone marrow aspirates is useful and reliable in the follow-up of patients with AL amyloidosis and in the evaluation of the effects of chemotherapy.     

Modified laparoscopic splenectomy: a beneficial technique for ABO-incompatible living donor renal transplantation candidates on hemodialysis

Advances in laparoscopy have enabled minimally invasive surgical treatment of splenic diseases. Even with these advances, laparoscopic splenectomy in patients on dialysis can be difficult because of tissue fragility due to the underlying renal disease. We report a safe surgical technique for laparoscopic splenectomy in patients on maintenance dialysis that is suitable for use before ABO-incompatible living donor renal transplantation (LDRTx). Between June 1972 and December 2006, a total of 800 patients underwent LDRTx in our department, including 82 patients who underwent ABO-incompatible LDRTx. Between April 2001 and December 2006 we performed laparoscopic splenectomy in 48 hemodialysis patients as a pretreatment before ABO-incompatible LDRTx. Under general anesthesia the operation was performed using a new technique, referred to as the "splenic hilum lump method." We evaluated the surgical outcomes, such as the operative time, amount of blood loss, efficacy, and complications. The mean operative time was 131.6 +/- 38.4 min and mean blood loss was 126 +/- 395 mL. Blood transfusion was required in three patients. All cases had satisfactory kidney function after LDRTx and none developed kidney graft failure due to acute rejection. Almost all patients could walk the day after laparoscopic splenectomy and were satisfied with the cosmetic appearance of the scar after wound healing. The surgical technique we report here can be safely performed on patients with renal failure who require caution because of tissue fragility. Laparoscopic splenectomy is a safe, effective and less invasive operative procedure as a pretreatment for ABO-incompatible LDRTx.     

Thyroglobulin release-stimulating activity in immunoglobulin G from patients with Graves' disease studied by human thyroid cells in vitro

The ability of TSH or immunoglobulin G (G-IgG) from untreated patients with hyperthyroidism due to Graves' disease to stimulate thyroglobulin (Tg) release from human thyroid cells was studied. Thyroid tissue obtained from antithyroid drug-treated Graves' hyperthyroid patients was dispersed enzymatically and cultured in monolayers; medium was changed every 3 days. The cultured cells initially released large but declining amounts of Tg, independent of the presence of TSH (approximately 5 micrograms/dish on day 3 and approximately 1.5 micrograms/dish on day 6). After 6 days, TSH had a dose-dependent stimulatory effect on Tg release, and the peak response occurred on day 15. G-IgG-induced Tg release was found on the 12th day of culture and was maximal on day 18. Thyroid cells cultured for 12 days in the absence of TSH responded to TSH and G-IgG in a time- and dose-dependent fashion. Using 12-day cultures, Tg release-stimulating activity (Tg-RSA) was tested using 5 mg/ml (7.5 mg/dish) G-IgGs from 20 patients and 72-h incubation. The Tg-RSA of individual patients varied. However, significant correlations were found between Tg-RSA values and serum Tg concentrations or Tg-RSA and thyroid-stimulating immunoglobulin activities. No correlation was found between Tg-RSA and TSH binding inhibitor immunoglobulin activities. These results suggest that Tg-RSA can be an indicator of abnormal IgG of hyperthyroid Graves' patients. Whether the activity is identical with thyroid-stimulating activity remains to be clarified.