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Biomedical subjects

D Hammond

Publications and source records attributed to D Hammond.

At least 109 records · Page 6Linked to original sources
PubMed1981

Comparison of vincristine utilized simultaneously or 24 hours before cyclophosphamide in maintenance regimen of acute lymphoblastic leukemia of children: a report of Childrens Cancer Study Group.

A controlled clinical study in children with lymphoblastic leukemia was conducted to measure the potential benefit of time sequencing vincristine and cyclophosphamide. Vincristine and cyclophosphamide were utilized in a maintenance regimen in children after a remission had been obtained. Patients received vincristine either 24 hours before cyclophosphamide or simultaneously with cyclophosphamide. The median time to relapse and the number of continued remissions was significantly increased for patients receiving vincristine 24 hours before cyclophosphamide when compared to those patients receiving both drugs simultaneously. The results of this comparative study indicate that the sequential use of vincristine and cyclophosphamide for maintenance of a second relapse in childhood ALL produces a greater duration of remission than when both are used simultaneously.

Adolescent↗
PubMed1980

Response to pneumococcal polysaccharide vaccine in patients with untreated Hodgkin's disease. Children's Cancer Study Group Report.

Patients with Hodgkin's disease (HD) have a high risk of overwhelming pneumococcal infections after splenectomy. Previous studies have shown that HD patients given polyvalent pneumococcal polysaccharide (PPS) vaccine after immunosuppressive therapy have a suboptimum antibody response. This study shows significant antibody response in HD patients to PPS vaccine given before radiation and chemotherapy. The same response was obtained whether the vaccine was given before or after splenectomy.

Adolescent↗
PubMed1980

Comparison of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia.

A retrospective comparison was made of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia; (1) intrathecal methotrexate only; (2) intermediate-dose methotrexate infusion and intrathecal methotrexate and, (3) 2400 rads cranial irradiation and intrathecal methotrexate. The incidence of primary meningeal relapse was statistically significantly lower in both standard-risk patients (age grear than 24 months and less than or equal to 120 months white-cell count less than 20,000) and increased-risk patients (age less than or equal to 24 months or greater than 120 months and/or white-cell count greater than 20,000) whose central-nervous-system prophylaxis included cranial irradiation. The disease-free and overall survival of irradiated increased-risk patients was significantly better than that of unirradiated increased-risk patients. The disease-free survival of standard-risk patients who received intermediate-dose methotrexate was statistically superior to that of the remaining standard-risk patients. There were no significant differences in overall survival between the three groups of standard-risk patients.

Adolescent↗
PubMed1980

Testicular relapse in childhood acute lymphoblastic leukemia: association with pretreatment patient characteristics and treatment. A report for Childrens Cancer Study Group.

Of 395 male pediatric patients with previously untreated acute lymphoblastic leukemia, 20 (5%) exhibited testicular infiltration prior to or concurrent with their first bone marrow relapse. Fourteen occurred as an isolated relapse and six occurred concomitant with bone marrow and/or central nervous system relapse. Nine of the 20 relapses were in patients who had discontinued therapy after completing three years of continuous complete remission. Factors found to be independently associated with an increased risk of testicular relapse during maintained remission included pretreatment lymphadenopathy, and to a lesser extent, initial hemoglobin level and initial platelet count. Pretreatment splenomegaly and lymphadenopathy appear to imply an increased risk of testicular relapse for those patients who have their maintenance therapy discontinued. Time from testicular relapse to bone marrow relapse or death was significantly shorter for patients with testicular involvement while receiving chemotherapy when compared to patients with testicular relapse after discontinuing therapy. In those patients achieving three years of continuous complete remission, subsequent testicular relapse occurred significantly more often in patients who discontinued therapy than a similar group who continued therapy. In a group of 76 males who received presymptomatic gonadal radiation immediately after achieving an initial marrow remission, protection appears to have been provided against the manifestation of testicular leukemia during maintained remission.

Age Factors↗
PubMed1980

Inactivation of purified rat liver cytochrome P-450 during the metabolism of parathion (diethyl p-nitrophenyl phosphorothionate).

The mechanism of the inactivation of purified rat liver cytochrome P-450 during the metabolism of parathion has been investigated with special reference to the covalent binding to the enzyme of the atomic sulfur (S) released upon oxidation of the compound. In addition to the previously reported loss of cytochrome P-450 detectable as its carbon monoxide complex, a loss of heme detectable as pyridine-hemochromagen, and a loss of enzymatic activity toward benzphetamine and ethoxycoumarin are shown. The loss of heme is 80% of the loss of cytochrome P-450, which in turn is less than the loss of benzphetamine demethylase activity, the turnover number of the modified enzyme being two-thirds that of the native based on the amount of cytochrome P-450 detectable as its carbon monoxide complex. Treatment with performic acid or dithiothreitol removes 75% of the 35S covalently bound to the cytochrome P-450 during parathion metabolism. However, the dithiothreitol treatment does not restore cytochrome P-450 detectable as its carbon monoxide complex or enzymatic activity. Likewise, no protection against the loss of heme, cytochrome P-450, or enzymatic activity is afforded by inclusion of 1 mM dithiothreitol during the incubation with parathion, although the amount of irreversibly bound sulfur, i.e. sulfur not dissociable by dithiothreitol, is significantly reduced. In the absence of dithiothreitol, 4 nmol of 35S become bound to the cytochrome P-450 for each nanomole of P-450 no longer detectable as its carbon monoxide complex. Evidence is presented for the covalent binding of sulfur to at least three other amino acids than cysteine. It is suggested that structural changes resulting from the covalent binding of atomic sulfur to cysteine residues are responsible for at least some of the loss of enzymatic activity observed.

Animals↗
PubMed1980

A farrowing management system using cloprostenol to control the time of parturition.

During a one year period, 1459 sows and gilts were treated with cloprostenol to induce farrowing during the night on a large commercial pig farm. A regular farrowing supervision programme was used during each farrowing period. The mean time from treatment to onset of farrowing was 25.7 hours (SD 5.36) and 95.3 per cent of aniamls commenced farrowing within 36 hours. There was a significant (P less than 0.001) increase in the proportion of piglets reared to weaning during the trial when compared with both the previous year and the average for the previous three years. The proportion of stillborn piglets and mortality of liveborn piglets up to weaning were significantly (P less than 0.001) reduced during the period of the trial. Similarly the number of piglets crushed by the sow was significantly (P less than 0.001) reduced. However, the proportion of piglets dying as runts increased significantly (P less than 0.001) and as a result of an isolated outbreak of scouring during one month of the trial, the number of piglets lost because of scouring also increased significantly (P less than 0.001). Several practical and economic benefits were identified as part of the new management system.

Agriculture↗
PubMed1980

A new therapy schedule for pediatric non-Hodgkin lymphoma toxicity with preliminary results.

A pilot study of the toxicity and efficacy of a new treatment schedule for childhood non-Hodgkin's lymphoma was conducted by members of the Children's Cancer Study Group (CCSG) prior to its use in a randomized phase III trial. Chemotherapeutic agents used were cyclophosphamide (CPM), vincristine (VCR), and prednisone, together with intravenous (IV) and intrathecal methotrexate (IT MTS). Radiation therapy was also employed. From September 1976 to April 1977, 27 eligible, newly diagnosed patients with non-Hodgkin's lymphoma were entered onto this pilot study. Toxicity was acceptable with minor adjustments in dosage and timing of the myelosuppressive agents. Fourteen of the 22 patients entered onto maintenance remain entirely disease-free, and all have completed the prescribed course of chemotherapy. None of the 12 patients characterized as having a "favorable" prognosis has relapsed, with a median follow-up of 27 months from on study.

Adolescent↗
PubMed1980

beta-Lactamase activity in human pus.

Pus was obtained from patients with polymicrobial intraabdominal abscesses or polymicrobial empyema. Physical and chemical characteristics of 12 specimens were examined, and bacterial isolates were enumerated. Pus supernatant of six specimens rapidly inactivated penicillin, cephalothin, and cefazolin. Carbenicillin and ticarcillin were similarly degraded by supernatant of certain pus specimens. Cefoxitin, chloramphenicol, and clindamycin were not appreciably inactivated by pus supernatant. Degradation of penicillin and cephalosporin congeners in pus was due to the presence of beta-lactamase, as shown by chemical interaction with nitrocefin, chromatography, and inhibition by the beta-lactamase inhibitor clavulanic acid. Pus supernatant containing beta-lactamase activity reduced the bactericidal activity of carbenicillin against Bacteroides fragilis in whole pus in an abscess model in vitro. Bactericidal activity of clindamycin or cefoxitin was not impaired in pus containing beta-lactamase.

Bacteroides fragilis↗
PubMed1980

A study of the cross-resistance of vincristine and vindesine in reinduction therapy for acute lymphocytic leukemia in relapse. A report for Children's Cancer Study Group.

The vinca alkaloid modification product, vindesine, presents closely related molecular structure to vincristine. Although there are differences in capacity to bind tubulin dimer and inability to inhibit growth of several experimental tumors, there is a significant degree of overlap. In the clinical tests to date, vindesine has been used in treatment of children with relapse of acute lymphocytic leukemia considered to be resistant to vincristine. The study presented here was designed to assess the degree of overlap between vincristine and vindesine. The conclusion was reached that there is clinical cross-resistance.

Child↗
PubMed1980

The training of clinical trails statisticians: a clinician's view.

Clinical investigations today involves not only multidisciplinary teamwork but also investigators at multiple institutions observing the same criteria and standards in order to make possible the valid pooling of data in collaborative studies. As a result, there has been increasing awareness of the biostatistician's role, not simply in interpreting the data at the end of the study, but in every step of clinical investigation. This involvement ranges from study design and feasibility testing to data analysis and reporting. The problem is now a shortage of biostatisticians appropriately trained for clinical trials statistical methodology. As the statistician's role is of great importance, more graduate training programs in statistics should prepare statisticians for clinical trials work. This would pave the way to the many exciting and rewarding career opportunities which are available for statisticians in the area of clinical trails.

Career Choice↗
PubMed1979

Tumors of the pineal and suprasellar region: Childrens Cancer Study Group treatment results 1960--1975: a report from Childrens Cancer Study Group.

Tumors of the pineal and suprasellar region form a rare and interesting group of lesions with germinomas accounting for over 50% of all lesions in this anatomic region. The Brain Tumor Committee of Childrens Cancer Study Group (CCSG) recently surveyed all CCSG member institutions to determine treatment parameters and assess the techniques. A total of 140 patients were seen during the period from 1960 to 1975; 118 patients were evaluable, having adequate treatment records. One hundred and one patients were less than 30 years of age with a 2:1 male predominance. Thirty-six of the 57 biopsied patients (63%) were found to have germinomas. The survival of patients in the germinoma group (72%) was comparable to that of the patients without biopsy (71%). The overall survival rate for all patients (biopsied and unbiopsied) was 65% with follow-up times ranging from 2 to 15 years. Nine patients developed spinal cord metastases (8%), two of whom also had simultaneous primary recurrence; none of these patients had received adjunctive spinal irradiation.

Adolescent↗
PubMed1979

Eosinophilia, chloromas and a chromosome abnormality in a patient with a myeloproliferative syndrome.

The existence of eosinophilic leukemia remains controversial since many authors challenge the existence of this entity. We present a patient with a hypereosinophilic syndrome whose findings were consistent with a leukemic process. The patient's course was marked my signs and symptoms of myeloblastoma formation and his illness terminated in an acute blastic crisis. chromosome studies on peripheral blood leucocytes demonstrated aneuploidy and an abnormal number four chromosome with additional material on its long arm. This case appears to be an unusual example of a hypereosinophilic syndrome with both myeloblastoma formation and an abnormal leucocyte karyotype.

Adult↗
PubMed1979

Relapse rates following cessation of chemotherapy during complete remission of acute lymphocytic leukemia.

The therapeutic benefit of maintenance chemotherapy beyond three years for children with acute lymphocytic leukemia (ALL) in continuous complete remission was evaluated by the investigators of Childrens Cancer Study Group (CCSG). Two hundred and twenty leukemic children in first remission for three years or longer and who had received at least three years of continuous chemotherapy were eligible. One hundred and one patients were randomized to either continue chemotherapy for an additional three years or to discontinue therapy, and 119 patients nonrandomly continued or discontinued therapy. The patients had received a variety of chemotherapy regimens. The study period extended from April 1970 until December 1977, with a median follow-up time of 25 months. Relapses occurred in 15 randomized patients (15%). Randomized patients remaining on chemotherapy experienced a statistically significant lower relapse rate than patients randomized to discontinue therapy. Also among randomized patients, bone marrow relapse was significantly more frequent in males than in females. Considering the total patient group, age and white blood count at diagnosis had no significance in predicting relapse. Of relapse events in males, 21% were isolated testicular relapses, identifying the testicles as a major risk site in males completing three years of continuous complete remission. This study demonstrates that continuing chemotherapy beyond three years results in a significant prolongation of remission in males, although the eventual survival outcome for later discontinuance of therapy will require longer follow-up.

Bone Neoplasms↗
PubMed1979

Improved remission induction rate with D-ZAPO but unimproved remission duration with addition of immunotherapy to chemotherapy in previously untreated children with ANLL.

In 163 children with acute nonlymphocytic leukemia (ANLL), a D-ZAPO induction program consisting of daunomycin, 5-azacytidine, cytosine arabinoside, prednisone, and vincristine resulted in a remission rate of 71.8%. Immunologic therapy was employed during maintenance with the aim of prolonging remission and improving survival. The administration of immunotherapy consisting of a mixture of bacillus Calmette-Guérin (BCG) and allogenic acute myelomonocytic leukemic cells injected intradermally on day 14 of each of the first three monthly cycles of 6-thioguanine for ten days, 5-azacytidine and cytosine arabinoside for four days, and vincristine for one day did not improve remission duration or survival compared to that due to chemotherapy alone. Important prognostic factors identified in this study included a remission induction rate significantly better for females than males (P = 0.04), for children between the ages of 5 and 10 years compared to those greater than this age group (P = 0.01), and a prolonged remission duration (P = 0.04), and survival (P less than 0.01) for patients with initial white blood counts of less than 20 x 10(9)/liter.

Adolescent↗
PubMed1979

Histiocytosis X: clinical trial of chlorambucil: a report from Childrens Cancer Study Group.

A prospective study for histiocytosis X was designed to determine whether "good risk" patients, ie, those without evidence of dysfunction of liver, lung, or hemopoietic system, would respond to single agent therapy; in this case chlorambucil (CMB) used in a dose of 5 mgm/m2/day. If there was no response after an adequate trial period, treatment was initiated with four drugs using a combination of prednisone, vinblastine, cyclophosphamide and methotrexate. There were 26 evaluable patients, 57% of whom were less than two years of age at onset of therapy. There were three complete and four partial responses to CMB for a response rate of 26.9%. Sixteen patients received an adequate trial of four-drug therapy with three complete and two partial responses for a response rate of 33%. These responses were inferior to those previously reported for either single agents or combined therapy in histiocytosis X.

Adolescent↗
PubMed1979

An initial report of a phase-III trial comparing vindesine and vincristine for acute lymphocytic leukemia of childhood.

The initial results from the Children's Cancer Study Group (CCSG) study on vindesine are the subject of this report. Vindesine was shown to be active in the treatment of acute lymphocytic leukemia (ALL) in children in a phase-II clinical trial conducted by the CCSG. A phase-II trial is now in progress. The aim of this is to compare the use of vincristine and of vindesine with reference to induction rate, toxicity, and cross-resistance.

Adolescent↗