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Biomedical subjects

C K Tebbi

Publications and source records attributed to C K Tebbi.

At least 19 recordsLinked to original sources
PubMed1991

Modulation of drug resistance in homoharringtonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole.

The development of resistance accounts for therapy failure in the majority of advanced cases of neuroblastoma in children. A new transplantable murine C-1300 neuroblastoma cell line was developed in vitro, by repeated exposure of a sensitive cell line to increasing, but sublethal, doses of Homoharringtonine (HHT). The ED50 of the highly resistant cells for HHT, using a standard agar colony assay, is 480 ng/ml, compared with 13 ng/ml for the sensitive parental line. The resistant cells have cross-resistance to a number of other agents, including adriamycin, vinca alkaloids, melphalan, and CCNU. Western blot analysis revealed progressive increases in P-glycoprotein, parallel to the graded development of resistance with a 29-fold elevation in the highest resistant cells. High-performance liquid chromatography (HPLC) indicated that resistant cells have a significantly lower uptake of HHT than parental sensitive cells. cyclosporine A (CsA) and dipyridamole (DPM) could modulate the acquired resistance and completely restore the cytotoxic effects of HHT and adriamycin as determined by the clonogenic assay. The reversal of resistance by CsA and DPM was dose dependent. With the relative low toxicity of dipyridamole and CsA in doses required for modulation of resistance, these agents may be candidates for clinical utilization in chemotherapy of resistant neuroblastoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

1-beta-D-arabinofuranosylcytosine conjugates of ether and thioether phospholipids. A new class of ara-C prodrug with improved antitumor activity.

The 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates 1-O-alkyl (ether) and 1-S-alkyl (thioether) phospholipids, being analogues of ara-CDP-sn-1,2-O-dipalmitoylglycerol (1), showed significant antitumor activity against L1210 and P388 leukemia in vivo. The more active conjugates include the 1-O-alkyl analogues, ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (2) and ara-CDP-rac-1-O-octa-decyl-2-O-palmitoylglycerol (3), and the corresponding 1-S-alkyl analogues, ara-CDP-rac-1-S-hexadecyl-2-O-palmitoyl-1-thioglycerol (4) and ara-CDP-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (5, Cytoros). The conjugates were formulated by sonication, in which the conjugates existed as discs (size 0.01-0.04 microns). Among the conjugates of the three different phospholipids, the 1-S-alkyl analogues 4 and 5 displayed the strongest antitumor activity against L1210 leukemia in mice, followed by the 1-O-alkyl (2 and 3) and the 1-O-acyl (1) analogues. The 1-S-alkyl analogue 5 was considerably more effective than the 1-O-acyl analogue 1 against myelomonocytic WEHI-3B leukemia in mice. Conjugate 5 (Cytoros) showed a significant therapeutic activity in mice with colon 26 carcinoma, M5076 sarcoma, and C-1300 neuroblastoma. Furthermore, this agent inhibited liver metastases of M5076 sarcoma. Conjugates 3 and 5 also inhibited the metastasis of 3-Lewis lung carcinoma to the lungs of mice. Cytoros (5) and its analogues, with other ether and thioether phospholipids, appear to offer increased therapeutic benefit to mice with tumors.

Analysis of Variance↗
PubMed1990

Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study.

Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity.

Child↗
PubMed1990

Vocational adjustment and general well-being of young adults with IDDM.

The vocational experiences and general well-being of 58 young adult subjects (mean age 24.3 yr) with insulin-dependent diabetes mellitus (IDDM) diagnosed during their adolescence were compared with that of 55 healthy matched control subjects with linear logistic discriminant function analyses. Assessment measures included the Rand General Well-Being Scale and the Rand Functional Limitations and Physical Abilities Batteries. Diabetic subjects, on average, reported significantly lower general well-being than control subjects, particularly in terms of health-related fears and feelings of depression. However, diabetic subjects did not report a pervasive functional deficit relative to control subjects and experienced similar employment rates and problems in the workplace. These results suggest that this group of young adult diabetic subjects has adjusted well to the demands of the workplace despite lower reports of general well-being. The results are discussed in light of relevant sampling issues.

Adaptation, Psychological↗
PubMed1989

Long-term vocational adjustment of cancer patients diagnosed during adolescence.

Long-term vocational achievements of 40 survivors of cancer diagnosed during adolescence were examined and compared with 40 healthy sex-matched and age-matched controls. Patients' ages at diagnosis ranged from 13 to 19 years (mean, 16.15). Study subjects had survived cancer for over 5 years and were on no cancer therapy. Assessment measures included the Rand General Well-Being Scale, the Rand Functional Limitations and Physical Abilities Batteries, and a semistructured interview. The relation of physical disability and limitations caused by cancer to patients' achievements also was evaluated. Although cancer patients, on the average, were more concerned about their health and reported lower general spirits than controls, no differences were found between control and study groups with regard to overall general well-being. More cancer patients than controls reported that their health limited their ability to engage in vigorous activities. A greater functional deficit was found among unemployed than employed cancer patients. Employers and co-workers often were aware of the patient's diagnosis (85% and 67%, respectively). Cancer patients reported disease-related discrimination in hiring (7.4%), induction into the military (66.7%), and obtaining health, life, and disability insurance (31.5%). There was no significant relationship between health status and employment. Nevertheless, cancer patients had a higher average income than controls. Sixty-four percent of patients believed that changes in certain physical features of the workplace were necessary to facilitate readjustment to the job. Despite the disabilities experienced by cancer patients and generally negative public attitudes, long-term survivors have a good outlook on life and are competitive members of the workplace and society.

Adolescent↗
PubMed1989

The significance of the ratio of blood to marrow hematopoietic progenitors (CFU-GM and CFU-GEMM) in relation to disease state of patients with acute lymphoblastic leukemia.

We studied a total of 143 patients with 231 assays of CFU-GM, of these, 45 patients were studied with 58 simultaneous assays of CFU-GEMM in an attempt to correlate progenitor colony growth with disease state. Blood and marrow leukocytes were cultured in a standard methylcellulose culture system using normal human leukocyte colony stimulating activity. Results are expressed as natural logarithm of the ratio of blood colonies to marrow colonies. A high ratio of blood to marrow (greater than 1) was seen in active disease while a low ratio occurred during remission. Eighty-seven per cent of CFU-GM matched pair samples with active disease had high ratios while less than 1% of remission samples were high. In addition, patients with suspected relapse or relapse up to 14 months after this test often had high ratios indicating this test could be of prognostic value. It is not known if this effect of ALL is unique to ALL or if it occurs as a reaction to any hematopoietic stress.

Bone Marrow↗
PubMed1989

Attributions of responsibility in adolescent cancer patients and their parents.

Attributions of responsibility have been shown to be important determinants of illness behavior in adults. This study examines the salience of attributional judgements among adolescents with cancer. Patients and their parents were categorized according to their attributions of responsibility for the cause of and solution to the adolescent's health problems into one of four attributional models. Of the four possible models, only two were represented: the medical and compensatory. Only 37.5% of parent/child pairs were concordant for model choice. Patients whose attributions conformed to those of the compensatory model sought more information (F = 5.1, (P = .03), were satisfied with the information supplied (F = 3.5, P = .07), and expressed the belief that a greater percentage of prescribed medications needed to be taken if a cure was to result (F = 4.1, P = .05). Side effects were more often experienced by patients whose responsibility attributions exemplified the medical model (F = 5.09, P = .03). Model concordance did not relate to parent/child agreement on health-related beliefs, patient age, sex, or compliance measures (P greater than .05). No relationship was found between parent-child model concordance and patient's self-reported medication compliance. The present data do not support the notion that attributions of responsibility for cause and solution of cancer should be important targets of interventions designed to increase medication compliance among cancer patients.

Adolescent↗
PubMed1989

Adjustment to amputation among adolescent oncology patients.

With increased patient survival, the psychosocial consequences of amputation in cancer patients has become increasingly important. The following study examined the psychosocial correlates of amputation in 16 male and 17 female Brazilian adolescent patients aged 10-20 years who had lost a limb to cancer. Interviews were conducted within 12 months of amputation. Eighty-two percent indicated that they were involved in preoperative decision making, but only 58% understood the limitations in functioning after undergoing an amputation. Before surgery, the most frequently chosen confidante was the mother, followed by a sibling, staff member, and a friend. The major postoperative problems in these patients were walking, pain, and social issues. Overall, 75% of the amputees felt they were independent in and out of the home. Most individuals (66.6%) had, but fewer (58%) wore, their prosthesis. Prior to amputation, 30 patients were enrolled in school and 13 had a job. Of 15 who returned to school, 67% could not keep up with the school work and 93% had problems getting along with their classmates. Of five patients who returned to their jobs, no one reported discrimination in hiring or promotion; however, four workers felt they had lost a job because of their amputation, and two reproted having to change jobs. Many had altered their lifestyles to suit their disability, but the social and educational adjustment of these patients appears promising. Proper education of school faculty, classmates, and medical staff may enhance the adjustment of adolescent cancer amputees.

Adaptation, Psychological↗
PubMed1988

Self-reported depression in adolescent cancer patients.

The prevalence of depression was studied, using the Beck Depression Inventory (BDI) and Schedule for Affective Disorders and Schizophrenia (SADS), in a sample of 30 adolescent cancer patients. BDI scores revealed that 26 patients (87%) were not depressed, 4 (13%) were moderately depressed and no one had severe depression. Similarly, SADS data indicated no history of depression in 75% of the sample, and histories of minor and major depression in 14 and 10% of the sample, respectively. Females scored significantly higher (p less than .05) than males on BDI physical, but not psychological, items. The average response to BDI physical items was significantly greater (p less than .05) than to psychological items, suggesting that somatic symptoms are more salient than psychological symptoms of depression among adolescent cancer patients. Overall, however, as compared with norms, the rate of major depression among adolescent cancer patients is not greater than that for the population at large. These data do not exclude the possibility of masked symptoms, which only under stringent conditions will become obvious.

Adolescent↗
PubMed1988

Osteosarcoma.

Osteosarcoma is the most common bone tumor of children and adolescents. The peak incidence of the disease is in the 15 to 19 year age group. The disease is more commonly seen in males than females. While several factors, including exposure to radiation, genetic disorders such as retinoblastoma, and high rate of bone growth, have been associated with osteosarcoma, in most cases no definite etiology can be established. Osteosarcoma usually originates in the metaphyseal region of long bones and extends through the cortex, causing varying degrees of bone destruction and expansion of periosteum. The radiographic appearance caused by this process is often referred to as "sun burst" sign. Positive diagnosis of osteosarcoma is made by histopathology. The histopathological classification of osteosarcoma can also predict the degree of aggressive behavior of this tumor and thus has prognostic significance. Surgery, including amputation or limb-salvage procedure, is the mainstay of treatment of osteosarcoma. It is now unequivocally established that adjuvant chemotherapy will prolong the survival of patients with this disease. Chemotherapy agents often used include platinum derivates, methotrexate, vincristine, cyclophosphamide, adriamycin, actinomycin D, bleomycin and DTIC. Depending on surgical decision, these agents can be used prior to or after the operation. Immediate fitting with prosthesis and provision of appropriate medical and psychological support in the care of these patients is essential.

Adolescent↗
PubMed1988

The role of parent-adolescent concordance in compliance with cancer chemotherapy.

In an attempt to examine factors affecting compliance with orally administered chemotherapy agents, we have examined the relation of agreement of parents and their adolescent children on various treatment-related issues and compliance with cancer chemotherapy. In a longitudinal study, 16 parent/cancer patient pairs were interviewed regarding their knowledge and understanding of illness, medications, and treatment, and their medication compliance. Adolescent responses matched closely those of parents on topics pertaining to medication dose, frequency, number, and purpose. Age was positively correlated with agreement for medication instructions. Disagreements were more commonly found in patients under 17 years of age. Compliance was greater when parents and patients agreed on who was responsible for medication administration, and on their understanding of medication instructions, number, and effectiveness. Treatment of the adolescent oncology patient should include consideration of psychosocial developmental factors, encourage parent-child communication, and place less reliance on self-administered therapy.

Adolescent↗
PubMed1987

Acute megakaryoblastic leukemia associated with mosaic Down's syndrome.

There have been several reports of the association between Down's Syndrome and acute megakaryoblastic (M7) leukemia (AMKL). The diagnosis of this rare form of leukemia has been better delineated by the use of the platelet peroxidase reaction and the antifactor VIII antibody immunoperoxidase test. In the past, the prognosis of patients with a combination of Down's Syndrome and AMKL has been extremely poor, with a median survival of 6.9 months for 11 reported cases in the literature. The present report reviews the previously reported cases and describes a unique patient with mosaic Down's syndrome and AMKL with favorable response to therapy.

Amsacrine↗
PubMed1987

Toxicity of high dose Ara-C in children and adolescents.

The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.

Adolescent↗
PubMed1987

Malignant histiocytosis. Complete remission in two pediatric patients.

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.

Adolescent↗
PubMed1986

Compliance of pediatric and adolescent cancer patients.

Compliance with self-administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age, 6.85 years) and 40 parents were extensively interviewed at 2 weeks, 20 weeks, and 50 weeks post-diagnosis. The results of self-reported compliance were corroborated by serum bioassay of the prescribed medications. A significant correlation between the age of patient and compliance with chemotherapeutic agents and nonchemotherapeutic medications was found (P less than 0.05 and P less than 0.02, respectively), with adolescent patients being compliant less often. Over the course of therapy, compliance among patients decreased, but not significantly. A significant negative correlation was found between compliance and the number of children in the family. Compliers and noncompliers did differ significantly in how well they understood instructions concerning how to take their medication (P = 0.04). No significant correlations between compliance and stage of the disease, number or type of drugs used, complexity of the regimen, degree of satisfaction with information given to the patient, understanding of disease, treatment, or belief in medication efficacy were found. The main reasons given for noncompliance were forgetfulness, busy schedules, and nonavailability of medication. More compliers than noncompliers were in agreement with their parents regarding who was responsible for the administration of the medication. Compliance is a complex and multifaceted issue which interrelates with a large number of medical and social factors.

Administration, Oral↗