A day care program and evaluation of animal-assisted therapy (AAT) for the elderly with senile dementia.

We conducted a survey to clarify the evaluation methods of animal-assisted therapy (AAT) for the elderly with senile dementia in an adult day care center. AAT was implemented for a total of six biweekly sessions. The AAT group consisted of seven subjects and the control group numbered 20 subjects. In a comparison between Mini-Mental State Exam (MMSE) scores at baseline and those measured three months later, the average MMSE score before AAT (baseline) was 11.43 (+/- 9.00), and three months later it was 12.29(+/- 9.69). In the AAT group, the average score on Nishimura's Activities of Daily Living (N-ADL) at baseline was 28.43(+/- 14.00), and after ATT it was 29.57(+/- 14.47). In the AAT group, the average baseline score on behavioral pathology of Alzheimer's disease (Behave-AD) was 11.14(+/- 4.85), and three months after AAT it was 7.29(+/- 7.11) (p < 0.05). In the control group, the average baseline score was 5.45(+/- 3.27) and three months later it was 5.63(+/- 3.59). The evaluation of salivary CgA, as a mental stress index, showed a decreasing tendency in the AAT group. Our findings demonstrate the usefulness of using several methods for evaluation of the changes in patients given AAT.

[Treatment outcome in elderly patients with aggressive non-Hodgkin's lymphoma].

Seventy-one patients aged 61-84 years with previously untreated aggressive non-Hodgkin's lymphoma were treated with a doxorubicin-containing regimen and evaluated retrospectively. The patients comprised 49 men and 22 women with a median age of 68 years. The median observation period was 544 days. Histological examination revealed 17 cases of diffuse small cleaved, 11 cases of diffuse mixed, 40 cases of diffuse large, and 3 cases of immunoblastic lymphoma, classified according to the International Working Formulation. When the patients were divided according to the age-adjusted international index, group A (61-64 years; n = 21) comprised 5 low (L)-, 4 low-intermediate (LI)-, 7 high-intermediate (HI)-, and 5 high (H)-risk patients. The corresponding numbers in group B (> or = 65 years; n = 50) were 14, 12, 16, and 8, respectively. The overall three-year survival rate was 50%, being 78% in group A and 36% in group B (P = 0.02), and 77% for L + LI patients and 34% for HI + H patients (P = 0.003). The respective three-year survival rates for L + LI and HI + H patients were 100% and 67% in group A, and 68% and 16% in group B. HI + H patients in group B showed shorter survival than L + LI patients in group B (P = 0.002) and HI + H patients in group A (P = 0.03). The cause of death in most group B HI + H patients was lymphoma, although the dose intensity of doxorubicin, cyclophosphamide and vincristine did not differ significantly from that in the other groups. Thus, HI + H patients aged 65 and over had an essentially poor prognosis.

Predictive factors for central nervous system involvement in non-Hodgkin's lymphoma: significance of very high serum LDH concentrations.

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.

Facile synthesis of optically active gamma-lactones via lipase-catalyzed reaction of 4-substituted 4-hydroxybutyramides.

Lipase-catalyzed transesterification of racemic 4-substituted 4-hydroxybutyramides with succinic anhydride proceeded enantioselectively to afford (S)-succinic acid monoester and unreacted (R)-4-hydroxybutyramide derivative, which were separated easily by treatment with an alkaline solution. Both enantiomers were converted easily to optically active gamma-substituted gamma-butyrolactones.

Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia.

Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.

Long-term liver function of recipients with hepatitis G virus infection after bone marrow transplantation.

To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Eradication of minimal residual disease during graft-versus-host reaction induced by abrupt discontinuation of immunosuppression following bone marrow transplantation in a patient with Ph1-ALL.

We observed a patient in whom graft-versus-host disease (GVHD) appeared to induce a positive effect. This 32-year-old male with Philadelphia chromosome-positive acute lymphoblastic leukemia received a bone marrow transplant (BMT) from an HLA-identical sibling donor. We analyzed the bone marrow with the reverse transcriptase-polymerase chain reaction to screen for the minor bcr/abl transcript, which indicates the presence of minimal residual disease (MRD). MRD was present in the pre- and post-transplant phases. There was no evidence of acute GVHD by post-transplant day 45. We abruptly discontinued the immunosuppressive therapy in an attempt to eliminate MRD by inducing an antileukemic reaction during GVHD. GVHD associated with diarrhea and liver dysfunction developed on day 64. On day 105, MRD disappeared and GVHD was treated with prednisolone and cyclosporin. The disappearance of MRD may have been due to the graft-versus-leukemia (GVL) effect mediated by the alloimmune response of donor T lymphocytes. These findings suggest that induction of the GVL effect may be useful for eliminating MRD after BMT in leukemia patients at high risk of recurrence of the disease.

[Low-grade non-Hodgkin's lymphoma: intensive combined chemotherapy].

The efficacy of various combination chemotherapies employed for the 37 patients with low-grade non-Hodgkin's lymphoma between 1981 and 1994 was evaluated retrospectively. The overall survival at 5 years was 68%. The 5-year survival of the 27 patients achieving complete response (CR) was 87%, which was significantly higher than that of 9 patients with partial response (p = 0.0005). The CR rate of stage III and IV patients was 64% for the 22 patients treated with ACOMP-B (D), and was 38% for 8 others treated with milder chemotherapy regimens including VEPA. The 22 advanced stage patients had a 5-year survival of 88% after the treatment with ACOMP-B (D) and 69% of them remained free of disease at 5 years. In this group no relapse occurred beyond 1.6 years after treatment. These findings suggest a possible role of third generation chemotherapy in the treatment of patients with advanced-stage low-grade non-Hodgkin's lymphoma.

[Therapy related leukemia].

Eleven therapy related leukemias (TRL) who were hospitalized in the Department of Hematology and Chemotherapy, Kanagawa Cancer Center between October 1983 and December 1993 were identified. Six of the patients were males and five were females. Their median age was 62 years (range from 14 to 75). Three patients had previously received treatment for breast cancer and two patients for malignant lymphoma. The other patients had received treatment for lung cancer, urinary bladder cancer, gastric cancer, brain tumor, maxillary sinus cancer and macroglobulinemia, respectively. Seven patients had been treated with chemotherapy and four patients had been treated with chemotherapy and irradiation for the primary tumor. The TRL cases consisted of 8 acute non-lymphoid leukemias, two acute lymphoid leukemias and one hypoplastic leukemia, respectively. The status of primary tumors at the development of TRL was complete remission in ten patients and partial remission in one patient. Three of the 10 patients who received anti-leukemic therapy entered complete remission and the median survival time was 36 days (from 7 days to 489 days). One patient expired of pneumonia before he received anti-leukemic therapy. TRL patients showed poor response to chemotherapy and had poor prognosis. These data suggest that the use of reduced doses of carcinogenic drugs for primary tumors might be required to prevent the development of TRL.

[Intermittent-dose ara-C/daunomycin therapy combined with cyclosporin-A and G-CSF led to a fourth remission in a patient with acute promyelocytic leukemia].

A 50-year-old female was admitted with acute promyelocytic leukemia (APL) in August, 1988. She was treated with behenoyl-ara-C, daunomycin, 6-mercaptopurine and prednisolone (BH-AC.DMP), which led to a complete remission. Thereafter, she was treated with 2 courses of BH-AC.DM and discharged from hospital. Intensification therapy was performed twice a year, with 1 course of BH-AC.DM and 5 courses of intermittent-dose ara-C/mitoxantrone which ended in March, 1992. She had a relapse in September, 1993 and was treated with all-trans retinoic acid, which led to a second remission. A second relapse occurred in May, 1994, and intermittent-dose ara-C/mitoxantrone, combined with granulocyte colony-stimulating factor (G-CSF), led to a third remission. However, she had a third relapse in September, 1994. She was treated with a trial of G-CSF (300 micrograms/body, day 1-7), to stimulate dormant leukemic cells to enter the cell cycle, and cyclosporin-A (78 mg/kg, day 2-5), in order to overcome daunomycin resistance in refractory leukemia, combined with daunomycin (45 mg/m2, day 3-5) and ara-C (1.4 g/m2, day 3-7), after obtaining informed consent. The fourth remission needed 46 days after combination chemotherapy because of severe myelosuppression. It was suggested that intermittent-dose ara-C/daunomycin therapy combined with G-CSF and cyclosporin-A may be useful for relapsed and refractory leukemia.

[Treatment for elderly patients with acute non-lymphocytic leukemia].

A retrospective analysis was performed on forty nine elderly (34 males and 15 females) patients aged 65 years or more (median age 73, range 65-82) with acute non-lymphocytic leukemia (ANLL). Patients were studied to examine factors according to age group (65-69 years, 70-74, 75-79 and 80 or over), respectively. Patients were treated with either low dose Ara-C therapy or BHAC-DMP therapy according of the choice of their attending physicians. Complete remission (CR) was obtained in 20 of 49 patients (43%), and in 6 of 14 patients (43%) aged 65-69, in 8 of 18 (44%) aged 70-74, in 5 of 12 (42%) aged 75-79 years and in 1 of 3 (33%) aged 80 or over, respectively. The median survivals of these groups were 263, 298, 260, 168.5 and 38.5 days, respectively. Multivariate analysis revealed that the achievement of CR was associated with normal karyotype, and serum GOT level < or = 30 mu/ml and GPT < or = 40 mu/ml. Prolonged survival was related to the achievement of CR. The results indicated that liver function before chemotherapy was an important prognostic factor.

Liver function tests of recipients with hepatitis C virus infection after bone marrow transplantation.

We used the polymerase chain reaction (PCR) to determine the presence of hepatitis C virus (HCV)-RNA in serum samples obtained from 19 patients with leukaemia or severe aplastic anaemia and investigated the correlation between HCV status and the results of liver function tests after bone marrow transplantation. PCR analysis of serum samples obtained before transplant showed that 10 of 18 patients were HCV-RNA-positive; 5 of these patients had developed acute post-transfusion hepatitis 1-11 months before transplant. An additional patient was HCV-RNA-positive on post-transplant day 62. Eight HCV-RNA-positive patients had pre-transplant GPT levels above the upper limit of normal. In these patients the GPT decreased significantly from a median of 104 IU/l (54-822 IU/l) pre-transplant to 23 IU/l (15-56 IU/l) on post-transplant days 8-12. In 9 of 11 HCV-RNA-positive patients, the GPT increased transiently from days 40 to 50 and again increased after day 100. Two of these patients died from hepatic failure; the GPT levels normalised in 3 patients after day 300 but continued to fluctuate in 4 patients. In the remaining 2 HCV-RNA-positive patients, the GPT remained close to the normal range throughout the follow-up period. Three HCV-RNA-positive patients became HCV-RNA-negative after 1-3 years. In these patients, the GPT remained normal for > 3 years after day 300.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of chimerism after bone marrow transplantation with single locus minisatellite DNA probes.

The origin of cells in almost all allogeneic donor-recipient pairs can be determined through the use of highly polymorphic minisatellite DNA probes. Single-locus probes were cloned from hypervariable fragments in a human DNA fingerprint detected with a multi-locus probe. While each probe is highly polymorphic and locus specific, they all contain repetitive sequences. The properties of single-locus probes have improved the sensitivity of detecting mixed chimerism in comparison with multi-locus probes. The use of single-locus probes permitted detection of mixed chimerism (MC) at levels as low as 0.625%, approaching that obtained by PCR methods. In the present study, five patients who received allogeneic BMT for hematologic malignancies were analyzed. Two patients exhibited MC after BMT. One developed acute GVHD and chronic GVHD and remained in CR while the second patient who had no signs of GVHD suffered a relapse.

[Neutrophilic myelofibrosis; a case report].

A 53-year-old male was admitted to our hospital with abdominal pain. Physical examination revealed marked splenomegaly. The white blood cell count increased to 5.8 x 10(4)/microliters. Bone marrow biopsy showed hypercellularity with a moderate increase in reticulin fiber. Chromosomal analysis showed 47, XY, +9q-, -9q- without Ph1 chromosome and bcr-abl rearrangement. MCNU therapy was successful in reducing the white blood cell count and splenomegaly. It is likely that the diagnosis of our patient is compatible with the neutrophilic myelofibrosis described by Stewart, et al.

Phase IV group study of natural human interferon alpha (HLBI) on chronic myelogeneous leukaemia.

Under the control of Kanagawa CML/HLBI phase IV study group in Japan, 18 cases out of registered 30 cases of chronic myelogeneous leukaemia consisting of 17 chronic phase and 1 accelerated phase, during July, 1991 to January, 1992, were analyzed for their hematological responses and cytogentic responses preliminarily. Hematological response rate (PR + CR) was 83.3% including 50.0% of CR, as judged by Kimura's criteria after treatment with HLBI alone (16 cases) or/and with other chemotherapy (2 cases). The dosage and duration of HLBI therapy required to get into the complete remission ranged from 212 to 1272 millions IU and between 6 to 42 weeks (mean value was 20 weeks), respectively. The clonally proliferated leukocytes and decreased physiological hematopoiesis started to recover from 2 to 4 weeks and reached their normal ranges from 16 weeks after 6 millions IU of HLBI were administered every day. In the 4 cases examined, 3 cases showed minimal cytogenetic responses and a case showed no cytogenetic response. Slight and temporary adverse effects were observed in 15 out of 18 cases (83.3%) including fever, general malaise, appetite loss, eruption, diarrhea, glossitis, hypogustation, weight loss and local muscle pain.

[Adult T-cell leukemia with various pulmonary complications].

A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.

[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.