Usefulness of ATP-sensitivity-assay of intravesical instillation therapy of anti-cancer agents for superficial bladder cancer

Intravesical instillation of anti-cancer drugs for superficial urinary bladder cancer is generally carried out with the aim of prophylaxis against recurrence and chemotherapy against tumor. But since sensitivity of tumor cells to each anti-cancer drug differs individually, the anti-cancer drug to be used should also be decided individually. We selected a new sensitivity test, ATP-sensitivity-assay, which measures intracellular adenosine triphosphate (ATP) volume by Luciferin-Luciferase reaction, for the decision of the anti-cancer drug. In this paper, we evaluated the direct anti-tumor activity of the drugs that were decided by ATP-sensitivity-assay of intravesical chemotherapy. Six drugs, that are Doxorubicin (ADM), Mitomycin C (MMC), Pirarubicin (THP-ADM), Cytarabine (Ara-C), Bleomycin (BLM) and Cisplatin (CDDP) were tested in this research and size of tumors of six patients reduced to 34-93% after 6 times' installation. A woman got cystitis induced by ADM after 3 times' instillation but instillation was completed. ATP-sensitivity-assay is useful for deciding the anti-cancer drugs for intravesical chemotherapy and prophylaxis for superficial bladder cancer.     

Prophylactic effect of UFT on the recurrence of bladder cancer

To evaluate the effect of UFT, a mixture of ftorafur and uracil in a ratio of 1:4, in preventing postoperative recurrence of bladder cancer, we performed a randomized controlled study with a non-medication group as control. UFT was given orally 400 mg a day for 6 months. Of 111 patients, 56 were given UFT and 55 were followed up without any medication. The non-recurrence rate in the group treated with UFT was 62.8% after 1 year and 36.3% after 2 years of follow up, and that of the control group was 45.7% and 39.5%, respectively. The rate of non-recurrence in the UFT group was significantly higher (p less than 0.05) than that of the control group during the period of follow up for 2 years. The incidence of side effects was 6.8% in UFT patients. These results indicate the clinical usefulness of prophylactic administration of UFT for bladder cancer patients.     

Legg-Calvé-Perthes disease in hemophilia: incidence and etiologic considerations

A review of hip radiographs of patients with severe hemophilia showed Legg-Calvé-Perthes disease in four of 63 patients examined before the era of specific treatment. In another series of 44 patients receiving prophylactic treatment, there was no evidence of Legg-Calvé-Perthes disease. A case report of a boy with severe hemophilia with hip joint bleeding that caused joint capsule distention and greatly increased intracapsular pressure is presented. Based on our findings, and previously published results, we suggest that Legg-Calvé-Perthes disease in hemophilia is caused by increased intracapsular pressure secondary to hemarthrosis.     

Malignant schwannoma of acoustic nerve: a case report

During a routine physical examination in 1976, a 54-year-old man was noted to suffer from hearing difficulty and continuing tinnitus of his right ear. He had, however, no further consultations for the next five years, although the symptom persisted and gradually worsened. In May 1981, he experienced complete hearing loss in his right ear. A computed tomography disclosed no abnormalities, and other laboratory tests were unremarkable. In September 1981, the patient began to complain of paresthesia of the right angle of the mouth and tongue, right-sided facial paralysis, and walking difficulty. A repeated computed tomography showed a tumor at the right cerebellopontine angle region. A clinical diagnosis of acoustic schwannoma was made. The first operation was performed in December 1981. Complete removal of the tumor was impossible because of its unexpected, unusual hardness. The pathologic diagnosis was a malignant mesenchymal tumor, compatible with a malignant nerve sheath tumor of the acoustic nerve. A second operation was performed in January 1982, but the rapid postoperative regrowth of the tumor necessitated a third operation in March 1982. The patient died in the next month. Family histories did not show any evidence of von Recklinghausen's disease, and neither did the patient have any clinical stigmata of this disease.     

A methodological review of non-therapeutic intervention trials employing cluster randomization, 1979-1989

A methodological review is presented of 16 non-therapeutic intervention trials published over the last decade which have randomized intact clusters rather than individuals in treatment groups. Each of the trials was surveyed as to the information supplied on six methodological criteria. Although there is increasing recognition of the methodological issues associated with cluster randomization, many investigators are still not aware of the impact of this design on sample size requirements and analysis considerations. Investigators are urged to publish the cluster-specific event rates observed in their trials as a guide for the planning of future studies.     

Growth hormone enables effective nutrition by peripheral vein in postoperative patients: a pilot study

The purpose of this pilot study was to investigate the metabolic effects of growth hormone (GH) (Humatrope, Eli Lilly & Co., Indianapolis, IN) administration in postoperative (PO) patients receiving peripheral vein nutrition. Seven, well-nourished, nondiabetic patients undergoing elective surgical procedures were given either no drug (n = 3), GH 30 micrograms/kg/day (n = 2), or GH 60 micrograms/kg/day (n = 2) sub-Q daily until eating, up to 7 days PO. All the patients received 5% dextrose with electrolytes in the first 24 hours PO and then received calories at 80 +/- 5% of the measured resting energy expenditure (REE) and amino acid at 1 g/kg/day with electrolytes, vitamins, and minerals. There were no significant outcome differences between the 30 and 60 micrograms/kg/day groups and, therefore, these groups were analyzed together (n = 4). By day 6 of the study, the GH group had a significant reduction in the respiratory quotient (RQ) measured by indirect calorimetry; an increase in nitrogen retention; an increase in plasma transferrin concentrations; and an increase in plasma insulinlike growth factor (IGF1) concentration. There was no increase in blood glucose concentrations, or decrease in urinary 3-methylhistidine excretion; and no adverse effects occurred. We concluded that GH in PO patients on hypocaloric nutrition promoted protein synthesis, fat oxidation, and nitrogen retention. Effective parenteral nutritional support in postoperative adult patients can be achieved without the use of central vein access.     

T cell depletion with anti-CD5 immunotoxin in histocompatible bone marrow transplantation. The correlation between residual CD5 negative T cells and subsequent graft-versus-host disease.

Twenty-nine patients with advanced leukemias (median age 34 years) received histocompatible sibling marrow that had been depleted of T cells by ex vivo incubation with anti-CD5 monoclonal antibody-ricin immunotoxin (T101-R) for the purpose of graft-versus-host disease prophylaxis. Donor cell engraftment was documented in 28/29 patients by DNA restriction fragment length polymorphisms. In this pilot study the dose of T101-R incubated with donor marrow was increased in a stepwise manner from 300 ng (10 patients) to 600 ng (5 patients) to 1000 ng immunotoxin (IT)/10(7) bone marrow mononuclear cells (14 patients) in an attempt to achieve more effective GvHD prophylaxis. A statistically significant reduction in acute GvHD was achieved for patients receiving marrow pretreated with 1000 ng of immunotoxin (34%) compared to recipients of BM treated with 300 ng immunotoxin (100%, P = 0.0004). T-depleted marrow samples were evaluated for residual T cell activity using several in vitro assays including proliferation to the purified mitogen PHA (HA-17) and in mixed lymphocyte culture (MLC), T cell cytotoxicity, a limiting dilution assay for detecting precursors of proliferating T cells (LDApPTL), and phenotypic analysis of viable T cells expanded in 16-day culture with interleukin 2. The extent of T cell depletion determined by LDA assay varied widely at each immunotoxin concentration used. Thus, there was no correlation between the dose of T cells infused and subsequent GvHD. Phenotyping of lymphocytes recovered from immunotoxin-treated marrow demonstrated that residual T cells were CD5 negative in all cases tested. The only in vitro parameter that predicted subsequent acute or chronic GvHD was the demonstration of viable CD5 negative lymphocytes with T cell phenotype (CD2, CD3, and/or CD7 positive) after 16-day culture with IL-2 of the T-depleted bone marrow. We observed that such CD5 negative cells expressing other T cell markers have cytotoxic function and speculate that these cells may be capable of mediating GvHD in allogeneic transplantation.     

The flow cytometric crossmatch and early renal transplant loss

Data from this retrospective study indicate that a positive two-color T and/or B cell flow cytometric crossmatch (FCXM) is predictive of early renal allograft loss (less than 2 months) in cadaveric kidney donor recipients who had a negative crossmatch by the antihuman globulin complement-dependent cytotoxicity technique. Among 90 cadaveric kidney donor recipients (67 primary, 23 regrafts), 14 (8 primary, 6 regrafts) lost their renal allografts within 2 months, and 10 of the 14 were FCXM positive and HLA sensitized. The remaining 76 allografts survived beyond 2 months, 12 of which were FCXM-positive. Thus, the FCXM sensitivity rate for detecting early graft loss was 71%, and the specificity rate was 84%. Cadaveric graft-loss rates at 2 months were 33% for primary and 60% for FCXM-positive regrafts in contrast to 7% for primary and 0% for FCXM-negative regrafts. The difference in early graft loss between FCXM-positive and FCXM-negative recipients was statistically significant (P less than 0.0001). Subset analyses of FCXM-positive graft recipients indicate: (1) previous early graft loss contraindicates transplantation of an FXCM-positive regraft (P = 0.03); and (2) panel reactive antibody (PRA) less than or equal to 10% at crossmatch is not associated with early graft loss (P = 0.04). There was no significant difference in 1-year graft survival between primary and regrafts in either FCXM-negative recipients (85% vs. 77%, respectively) or FCXM-positive recipients (67% vs. 40%). All 12 of the FCXM-positive primary and regrafts that survived 2 months continued to function at 2 years. Stepwise logistic regression analysis of 5 independent predictor variables (FCXM status, gender, primary vs. regraft status, PRA level, and HLA mismatched antigens) indicated that the FCXM test was the best predictor of early graft loss. When FCXM results of the 90 cadaveric graft recipients were ranked in three groups, an FCXM channel shift of 29 or greater (third tertile) on a 1024 channel log scale was associated with a 7.0-fold (95% confidence interval 1.9-25.5) increased risk of early graft failure when compared to the first two tertiles. These data indicate that the FCXM offers an additional approach for identifying sensitized patients at risk of early renal allograft loss.