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Biomedical subjects

T Kim

Publications and source records attributed to T Kim.

At least 253 records · Page 14Linked to original sources

Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation.

From December 1982 to January 1986, 57 patients received allogeneic bone marrow transplantation as therapy for Philadelphia chromosome (Ph') positive chronic myelogenous leukemia (CML). All patients were prepared for transplantation with cyclophosphamide 60 mg/kg (day -6, -5) and fractionated total body irradiation, 165 cGy twice daily (day -4, -3, -2, -1) and received major histocompatibility (MHC) matched donor marrow (day 0). All patients received graft-v-host disease (GVHD) prophylaxis with methotrexate, prednisone, and either antithymocyte globulin (ATG) (55 patients) or OKT3 infusion (two patients). The projected survival of 29 chronic phase patients is 64% (95% confidence interval [Cl] 42% to 86%); and of 28 accelerated phase patients, 30% (95% Cl, 12% to 48%) at 30 months (P = .005). Multivariate regression analysis of pretransplant patient characteristics demonstrated that the presence of chronic phase and age less than 30 years were the only prognostic features studied that independently predicted survival. No evidence of persistent or recurrent disease has occurred in chronic phase patients; however, reappearance of the Ph' was observed in seven accelerated-phase patients, and hematologic relapse occurred in three of these seven patients. The incidence of grade II to IV acute GVHD is 63% (95% Cl, 50% to 76%) at 100 days, and that of extensive chronic GVHD is 53% (95% Cl, 33% to 74%) at 30 months. The median Karnofsky activity assessment of survivors is 100% (range, 60% to 100%), and all activity assessments less than 100% can be attributed to complications of GVHD. Bone marrow transplantation therapy for CML after preparation with cyclophosphamide and fractionated total body irradiation results in a high proportion of disease-free survival in chronic-phase patients. Survival in accelerated phase is significantly worse and is associated with relapse. GVHD has emerged as a significant cause of morbidity and mortality in this study.

Antigens, Surface↗

[Effect of platonin on bone wound healing in rat calvaria--with special reference to the interaction of platonin and steroid hormones].

Interaction of Platonin (PI) and dexamethasone (DM) or testosterone propionate (TP) on bone wound healing was studied by measuring the areas of wound holes which were made in the rat parietal bone. The result was compared with that of the growth of the femur. 1) No significant difference was observed between the control group and pl groups (1, 10 and 100 micrograms/kg, s.c., for 4 weeks) on the wound hole area or the length, weight, calcium content (Ca) or hydroxyproline content (HP) in the femur. 2) The bone wound healing was delayed by DM (2 mg/kg, s.c., for the first 2 weeks). The inhibition of growth was also observed in the femur length and weight, but no significant effect of DM was observed in the Ca and HP of the femur. The combination of Pl and DM promoted the recovery from delayed bone wound healing and femur weight gain caused by DM. 3) No significant effects of TP (4 mg/kg, s.c., for the first 2 weeks) were observed on the wound healing and the femur growth, but an increase of the femur weight and Ca was observed by the combination of Pl and TP. These results indicate that Pl promotes the recovery from delayed bone wound healing and femur weight gain by DM, although no significant effects were observed in bone growth and bone wound healing by the administration of Pl alone. It is also suggested that a combination of Pl and TP promotes bone growth and mineralization.

Animals↗

Serum levels of interferons in patients with systemic lupus erythematosus.

Serum levels of alpha (alpha) and gamma (gamma)-interferons (IFN) were measured in 30 patients with untreated systemic lupus erythematosus (SLE) with a solid-phase, sandwich immunoradiometric assay using specific monoclonal antibodies. The serum levels of alpha-IFN were higher in patients with SLE than in normal subjects, and correlated with the clinical activity index (rs = 0.60, P less than 0.01), but not with renal histological activity. The serum level of alpha-IFN correlated with the serum level of immune complexes (r = 0.46, P less than 0.01) and the number of peripheral lymphocytes inversely (r = -0.49, P less than 0.01). Serum gamma-IFN levels were also higher in patients with SLE than in control subjects but no correlations were found between it and either clinical activity, renal histological activity or various laboratory parameters. Serum levels of both alpha-IFN and gamma-IFN were higher in SLE patients with erythema than in those without. These results suggested that serum levels of alpha-IFN were more closely related to clinical activity of SLE than were those of gamma-IFN, and that peripheral lymphocytes were probably not the source of the elevated serum IFN-alpha concentration.

Antibodies, Monoclonal↗

Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation.

During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TLI). All recipients were previously transfused. Comparison of post-bone marrow transplantation events in adults and children reveals equivalent median time to engraftment, median duration of hospitalization, median Karnofsky assessment of activity, and equivalent low rejection rate. Although the incidence of moderate and severe acute graft-v-host disease (GVHD) and of extensive chronic GVHD was greater in adults than in children, the projected survival at 4 years of adults (67%; 95% confidence interval [CI] 49% to 85%) and of children (73%; 95% CI 57% to 89%) was equivalent. All survivors are transfusion-free and have normal peripheral blood counts. One of 28 adults and 2 of 30 children have experienced rejection, and 1 of these patients survives after a second transplant. No malignancies have been identified following transplantation. An unexpectedly high incidence of hypothyroidism has been detected and may be attributable to preparation of recipients with TLI. Therapy of severe aplastic anemia with allogeneic BMT after preparation with cyclophosphamide and TLI offers a high rate of transfusion-free survival and a low rejection rate in previously transfused young adults and children.

Acute Disease↗

Do protozoa conceal a high potency of nucleoside triphosphate hydrolysis present in Toxoplasma gondii?

ATP hydrolytic activity in whole cell homogenates of some protozoa was assayed in the presence or absence of dithiothreitol. The activities in all protozoan cell homogenates, except Toxoplasma gondii, ranged from 0.6 to 32 mumol/mg protein/hr, irrespective of the presence or absence of dithiothreitol. A remarkably higher activity, 11,690 mumol/mg protein/hr, was observed for T. gondii in the presence of dithiothreitol. These results indicate that the higher ATP hydrolytic potency observed for T. gondii is not universal to protozoa, rather it is unique to T. gondii.

Adenosine Triphosphate↗

Comparison between the effects of dexamethasone and indomethacin on bone wound healing.

The area of wound holes made in the parietal bone of 4-week-old rats was measured at 1, 2 and 4 weeks after the operation using Alizarin red S staining without the use of histological sections. Dexamethasone and indomethacin were administered s.c. after the operation every day except Sunday. The inhibitory action of dexamethasone on bone wound healing was stronger than that of indomethacin, as was its inhibitory action on skin wound healing. Inhibition of the age-related decrease in radiolucency of femurs and some changes in serum calcium level were also observed by dexamethasone administration, but not by indomethacin. These results suggest that dexamethasone inhibits bone wound healing through its effects on calcium metabolism in addition to its general inhibitory action on wound healing which is shared with indomethacin. Dexamethasone also strongly inhibited the decrease in Alcian blue stainability which occurs with an increase in age, both in the normal portion and in the wound hole portion of the calvaria, whereas indomethacin showed a weak inhibitory effect only in the wound hole portion. This result suggests that one of the mechanisms by which dexamethasone inhibits bone wound healing may be based on the retardation of mineralization caused by the inhibition of removal of acid mucopolysaccharide.

Animals↗

Genetic predisposition to acute lymphocytic leukemia in American blacks. A Pediatric Oncology Group study.

Recent reports have shown an association between genes lying within the major histocompatibility complex (MHC), particularly HLA and factor B (Bf), and acute lymphocytic leukemia (ALL) in white children. The frequencies of Bf and complement component C4 phenotypes in 90 black American children with ALL were examined to determine if a genetic association existed. The Bf and C4 results for the black children with ALL were compared with frequencies in healthy black Americans from the same geographic region. The BfF allele was carried by 95.6% of the black ALL patients compared with 86.1% of the controls (P = 0.017; relative risk = 3.5). In contrast, only 2.2% of the patients with ALL were homozygous for BfS compared with 9.8% of the controls (P = 0.043; relative risk = 0.2). These findings are similar to those observed in white American children. The C4A6 phenotype was found in 11.9% of the black children with ALL compared with 0.6% of the controls (P = 0.0026; relative risk = 22.7). These findings represent the first reported association of a particular allele whose gene lies within the MHC with ALL in black American children. The results suggest that the occurrence of ALL in black American children may be partially due to a genetic influence.

Adenosine Monophosphate↗

Radiation therapy for advanced head and neck squamous cell carcinoma using twice-a-day fractionation. A long-term follow-up.

Twenty-one patients with massive advanced squamous cell carcinoma of the head and neck received radiation therapy under the twice-a-day fractionation regimen. One hundred ten rad tumor dose was delivered twice daily with a 4-hour gap between the fractions, 5 days/week, to a total tumor dose of 7480 rad. The purpose was to increase the therapeutic ratio by minimizing sublethal radiation damage to normal tissue while allowing reoxygenation of radioresistant hypoxic tumor cells. Fifty-three percent of the patients showed no evidence of primary tumor at the end of the therapy and 60% showed complete regression of massive cervical lymphadenopathy. The 2-year recurrent-free rates for patients with tumors of the tonsillar region were 36% of T4 (4/11) and 33% (2/6) of N3a. The experience with conventional fractionation in similar cases was previously reported by others from this institution. They reported 2-year recurrent-free rates of 0% of T4 (0/10) and 17% (1/6) of N3. The higher recurrent-free rates in our series suggests better local and regional tumor control by the twice-a-day fractionation.

Carcinoma, Squamous Cell↗

Allogeneic bone marrow transplantation with related donors other than HLA MLC-matched siblings, and the use of antithymocyte globulin, prednisone, and methotrexate for prophylaxis of graft-versus-host disease.

Fifteen patients ranging in age from 1-29 years (median age 9 years) had bone marrow transplantations (BMT) from related donors other than HLA mixed lymphocyte culture (MLC) identical siblings. Donors were selected on the basis of HLA similarity and low reactivity in the MLC. Posttransplant immunosuppression consisting of methotrexate (MTX), antithymocyte globulin (ATG), and prednisone was used in an effort to decrease graft-versus-host disease (GVHD). Seven children were treated for aplastic anemia, 7 for hematologic malignancy, and 1 for osteopetrosis. Primary engraftment failure contributed to death in 3 patients, all of whom had aplastic anemia. Nine of 12 engrafted patients developed moderate-to-severe acute graft-versus-host disease. Of the 15 patients, 7 developed interstitial pneumonitis. Three patients demonstrated mixed chimerism (at or beyond 3 months posttransplant). Two of the seven patients treated for aplastic anemia are currently alive six months and more than five years posttransplant; the latter patient has chronic GVHD. Four of the seven patients treated for hematologic malignancy are currently alive more than 500 days posttransplantation. Three have chronic GVHD. Analysis of patient outcome according to the degree of similarity in histocompatibility testing revealed that patients with low reactivity in the MLC (less than 5% relative response in both directions) had a better prognosis (5/6, 83% long-term survival) than patients with maximum donor vs. recipient mixed lymphocyte culture relative response greater than 5% (1/9, 12% long-term survival), P = .016.

Adolescent↗

Bone marrow transplantation for acute nonlymphocytic leukemia in first remission: analysis of prognostic factors.

Prognostic factors were reviewed retrospectively for 39 children and adults aged 1 to 40 years (median 14 years) with acute nonlymphocytic leukemia (ANLL) who attained a first remission and underwent bone marrow transplantation from November 1976 to July 1983. The preparation regimen for transplantation was cyclophosphamide (60 mg/kg/d for two days) followed by total body irradiation (either 750 cGy single dose at 26 cGy/min, n = 37, or 1,320 cGy fractionated at 10 cGy/min, n = 2). Twenty-three patients are surviving disease free with a median followup of three years. The three-year estimated disease-free survival is 55% +/- 17% (+/- 2 SE). Five patients have relapsed from 92 to 756 days after transplantation for an estimated relapse rate of 21% +/- 18%. Two factors, the white blood cell (WBC) count and the French-American-British (FAB) classification at leukemia diagnosis were found to be of prognostic importance. Patients with a WBC of less than 20,000/microL at diagnosis had a three-year estimated disease-free survival of 74% +/- 18% v 26% +/- 24% for those with a WBC of greater than or equal to 20,000 (P = .008). The estimated relapse rate was 6% +/- 12% for patients with a WBC at diagnosis less than 20,000 v 53% +/- 38% for patients with a WBC at diagnosis of greater than or equal to 20,000 (P = .01). Patients with myeloid morphology at diagnosis (FAB M1,2,3) had an estimated relapse rate of 9% +/- 12% v patients with monocytoid morphology (FAB M4,5a) whose estimated relapse rate was 58% +/- 44% (P = .05). Our data suggest that a high WBC count at poor prognostic factors for patients with ANLL who undergo bone marrow transplantation in first remission after conditioning with cyclophosphamide plus total body irradiation.

Acute Disease↗

Autologous bone marrow transplantation for patients with acute lymphoblastic leukemia in second or subsequent remission: results of bone marrow treated with monoclonal antibodies BA-1, BA-2, and BA-3 plus complement.

Autologous bone marrow transplantation (BMT) was utilized as therapy for 23 patients with acute lymphoblastic leukemia (ALL) in second or greater remission. Bone marrow was treated in vitro with a combination of monoclonal antibodies, consisting of BA-1, BA-2, BA-3, and baby rabbit complement (BRC'). All patients were prepared for transplantation with cyclophosphamide and fractionated total body irradiation. Engraftment occurred in all 23 patients. Seven of 23 patients remain relapse-free from six to 32 months (median, 21.4 months) posttransplant. Failures were due to relapse with the exception of one patient who died of infection. This study demonstrates that autologous BMT using in vitro marrow treatment with BA-1, BA-2, BA-3, and BRC' is safe, allows engraftment, and results in prolonged survival for some patients with ALL in second or greater remission.

Adolescent↗

Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia.

Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216-806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501-732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.

Adolescent↗

Acid-fast bacilli in sputum smears of patients with pulmonary tuberculosis. Prevalence and significance of negative smears pretreatment and positive smears post-treatment.

We studied 977 patients with culture-proved pulmonary tuberculosis retrospectively to determine the frequency with which patients were sputum smear negative but culture positive (S-C+) prior to treatment, the frequency with which patients developed the smear positive but culture negative (S+C-) status during treatment, and the implication of these 2 phenomena to the success of treatment. One fourth (25.6%) of the patients were repeatedly S-C+ prior to treatment; the frequency of this phenomenon was inversely proportional to the extent of disease and the presence of cavities. Patients who were S-C+ prior to treatment, and whose organisms were drug-sensitive, had the fastest sputum culture conversion rate. Patients who were S+C+ without far-advanced cavitary disease had a significantly slower conversion rate after 1 month of treatment, and those with far-advanced cavitary disease had the slowest conversion rate. Patients with drug-resistant organisms had slower conversion rates than did their counterparts with drug-sensitive organisms, but in all but 4 of these, sputum smears and cultures ultimately converted to negative. The S+C- phenomenon was observed in 20.4% of patients; its frequency was related to the extent of disease and to treatment regimens that contained rifampin. In all patients who exhibited the S+C- phenomenon, sputum smears converted to negative with continuation of the same treatment regimen.

Adult↗

Effect of synthetic chicken vasoactive intestinal peptide on pancreatic blood flow and on exocrine and endocrine secretions of the pancreas in dogs.

This study was undertaken to determine the effect of synthetic chicken vasoactive intestinal peptide (VIP) on pancreatic blood flow, exocrine and endocrine secretions of the pancreas, and biliary secretion in dogs. The effect of synthetic chicken VIP on pancreatic blood flow and systemic arterial pressure was identical to that of natural chicken VIP in dogs. The present study demonstrated that synthetic chicken VIP induces significant increases in pancreatic blood flow, pancreaticobiliary secretion, and blood levels of insulin and glucose in dogs. Both the volume of pancreatic juice and blood levels of insulin were increased in consonance with the increase of pancreatic blood flow. This study suggests that the stimulatory effects of synthetic chicken VIP on exocrine and endocrine secretions of the pancreas may be related to the increased pancreatic blood flow elicited by synthetic chicken VIP.

Animals↗