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Biomedical subjects

R J Wells

Publications and source records attributed to R J Wells.

At least 55 records · Page 3Linked to original sources

Interferon-alpha n1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance.

Twelve children ages 3-15 years with relapsed acute lymphocyte leukemia (ALL) were treated over 25 days by intravenous or intramuscular administration of interferon-alpha n1 (IFN-alpha n1). Single doses ranged from 2.5 to 15 MU/m2, total doses from 60 to 200 MU/m2. Serum pharmacokinetics were determined following administration of two different doses. Calculation of area under serum concentration curve (AUC) values showed increased AUC with increased dose. Mean AUC (h x U/ml) ranged from 735 to 3986 at doses of 2.5 and 15 MU/m2, respectively, when given intramuscularly. AUC for i.v. and i.m. administration were similar. Side effects reported most commonly were fever and chills in 11 of 12 patients, nausea/vomiting in 7, mild lethargy in 3, and injection site pain in 4 of 9 treated i.m. Reversible hepatotoxicity occurred in the 3 patients receiving the highest doses, 10 then 15 MU/m2. Three patients had clinically significant bleeding associated with mildly increased coagulation studies and an additional three patients had increased coagulation parameters without bleeding. Four patients were considered to have stable disease; one treated at the highest dose level had clearance of peripheral blasts but remained in bone marrow relapse. IFN-alpha n1 as used in this study produced detectable blood levels with associated side effects. A Phase II intramuscular trial is recommended.

Adolescent↗

Neuropsychologic and academic functioning of children with sickle cell anemia.

This study compared neuropsychologic test results and academic functioning among 28 school-age children with sickle cell anemia (SCA), and 28 healthy, age-, sex-, and socioeconomically matched black peers followed at a tertiary care center. Children with SCA scored significantly lower on reading and spelling achievement scores than healthy matched peers. Also, older children with SCA performed significantly less well on tests of visual-motor and attention skills than younger children with SCA. These results were unrelated to most measures of physical illness severity. The data suggest that sickle cell anemia may be associated with subtle neuropsychological and learning deficits that can contribute to decreased school performance.

Adolescent↗

Sequential high-dose cytosine arabinoside-asparaginase treatment in advanced childhood leukemia.

Sequential high-dose cytosine arabinoside (ara-C) and asparaginase were given to 41 children age six months to 21 years of age with advanced leukemia. Ten of 22 patients with acute lymphocytic leukemia (ALL) and eight of 19 patients with acute nonlymphocytic leukemia (ANLL) obtained complete remissions. The most significant toxicity seen was infection in 22 patients. In addition, patients given intrathecal chemotherapy within 24 hours of ara-C developed neurologic toxicity. The high response rate seen in these patients with advanced leukemia indicates that a trial of this regimen is warranted in children with less advanced ALL and ANLL.

Acute Disease↗

Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae.

A battery of neuropsychologic tests was administered "blindly" to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

Brain↗

Utilization of an immunostaining technique to demonstrate heterogeneity in the content of dihydrofolate reductase in peripheral blast cells from a patient with acute lymphocytic leukemia.

Cultured human KB cells which developed resistance to increasing concentrations of methotrexate showed increased levels of dihydrofolate reductase (DHFR) as demonstrated by an immunobridge staining technique. Peripheral blast cells from a leukemic patient were examined for DHFR content during several courses of methotrexate therapy. The number of cells which demonstrated high levels of DHFR increased at the end of treatment. The content in each individual cell was heterogeneous, based on varied intensity of staining in each cell. This immunostaining technique, which utilizes an antibody to DHFR, may have the potential to be a useful tool in the clinic for predicting a patient's possible response to methotrexate therapy.

Animals↗

Congenital juvenile chronic myelogenous leukemia: case report and review.

The case of a patient with ecchymosis, hepatomegaly, leukocytosis, thrombocytopenia, and anemia at birth is presented. Throughout his course, thrombocytopenia, anemia, and leukocytosis without a marked increase in the number of blast forms in either peripheral blood or bone marrow persisted until the patient developed a blast crisis shortly before his death at age 4 months. This patient is the youngest reported to have the juvenile form of chronic myelogenous leukemia and the first that in the present era can be considered congenital in origin.

Diagnosis, Differential↗

The impact of cranial irradiation on the growth of children with acute lymphocytic leukemia.

Heights, height velocities, weights, and weight velocities were measured serially in 21 patients with acute lymphocytic leukemia (ALL) who had survived three to five years in continuous complete remission. These patients were assigned randomly to treatment regimens that varied according to whether cranial irradiation was used. Patients receiving cranial irradiation had lower height velocities during therapy than normal subjects and patients not receiving cranial irradiation. Twenty-two other children with ALL, who were irradiated but not randomized, exhibited similar alterations in growth. These results indicate that cranial irradiation, and not leukemia or antileukemia chemotherapy, causes reduced growth.

Body Height↗

Enrichment by counterpart centrifugal elutriation of human lymphocytes cytotoxic to human tumour cells.

The enriched fractions of cytotoxic cells responsible for natural killer (NK) activity against both human sarcoma and neuroblastoma (LA-N2) cell lines were readily obtained by countercurrent centrifugal elutriation (CCE). The NK cells were obtained in the larger lymphocyte fractions (fraction 6 +/- 1), having a mean cell volume of 180 u3. The cytotoxic-enriched fraction contained 51% large lymphocytes having cytoplasmic granules. On the other hand, monocytes were purified to greater than 90% and isolated in another fraction (final fraction) and these cells had the lowest NK activity against both human tumour cell lines. However, compared with the lymphocyte fractions, small and large monocytes displayed greater antibody-dependent cellular cytotoxicity (ADCC) activity against human B erythrocytes. These results indicate that NK found to have activity against both tumour cells lines were larger lymphocytes, not small monocytes. Thus, countercurrent centrifugal elutriation (CCE) can provide a sensitive method to obtain enriched fractions of large lymphocytes contained tumoricidal activity against human sarcoma and neuroblastoma cell lines.

Antibody-Dependent Cell Cytotoxicity↗

Normal glucocorticoid receptor numbers in a child with glucocorticoid-resistant relapsed acute lymphocytic leukemia.

Glucocorticoid receptors were quantified in circulating lymphoblasts from a child with relapsed acute lymphocytic leukemia refractory to multiple glucocorticoid containing drug regimens. The number of receptor sites in this patient's lymphoblasts was found to be similar to the number of receptor sites in lymphoblasts from a group of newly diagnosed children with acute lymphocytic leukemia. This patient differs from previous reported cases of relapsed acute lymphocytic leukemia in that all previous relapsed patients with normal receptor numbers obtained complete remissions when glucocorticoid containing treatment regimens were employed.

Antineoplastic Agents↗

Glucocorticoid receptors in the lymphoblasts of patients with glucocorticoid-resistant childhood acute lymphocytic leukemia.

Glucocorticoid receptor sites were measured in lymphoblasts of six patients with childhood acute lymphocytic leukemia in relapse who were resistant to glucocorticoid therapy and compared to the number of receptor sites found in the lymphoblasts of 12 patients with acute lymphocytic leukemia who achieved initial complete remissions on glucocorticoid-containing chemotherapy regimens. Resistant patients as a group were found to have lower receptor site levels. This data supports the hypothesis that reduction in the number of receptor sites per cell is one mechanism by which cells become resistant to glucocorticoids. However, the clinical usefulness of these measurements to prospectively select glucocorticoid-resistant patients appears limited because four of the six resistant patients had measurements within one standard deviation of the mean for the 12 patients who achieved remission.

Adolescent↗