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Biomedical subjects

D Hammond

Publications and source records attributed to D Hammond.

At least 55 records · Page 3Linked to original sources
PubMed1989

Acute nonlymphocytic leukemias of childhood. Inter-observer variability and problems in the use of the FAB classification.

The French-American-British (FAB) classification system and some recent modifications were applied to 486 children with a diagnosis of acute nonlymphocytic leukemia (ANLL) to determine the distribution of the subtypes in children, to document the extent of inter-observer variation in assigning subtypes, and to examine the reasons for the differences. The distribution of FAB subtypes of childhood ANLL was similar to that reported for adults. In the initial year of the study, the inter-observer concurrence between the institutional diagnosis and the reviewing pathologists was 50%, but in the more recent years, concurrence between institutions and the review pathologist has approached 80%, averaging around 73% for the entire study. Many problems remain to be solved with this classification system, including the imprecision in wording, the subjectiveness of the interpretation, errors due to the random distribution of cells, and the current lack of evidence that certain FAB subtypes, such as M1 and M2, differ significantly in terms of biological behavior and prognosis.

Adolescent↗
PubMed1989

The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group.

Fifty-eight patients with high-grade astrocytoma were treated by members of the Childrens Cancer Study Group in a prospective randomized trial designed to study the effectiveness of chemotherapy as an adjuvant to standard surgical treatment and radiotherapy. Following surgical therapy, patients were assigned randomly to radiotherapy with or without chemotherapy consisting of chloroethyl-cyclohexyl nitrosourea, vincristine, and prednisone. Treatment with chemotherapy prolonged survival and event-free survival. Five-year event-free survival was 46% for patients in the radiotherapy and chemotherapy group, and 18% for patients in the radiotherapy-alone group. Five-year survival was similarly improved. The differences in outcome due to treatment were statistically significant after correcting for imbalances in important prognostic factors (event-free survival, p = 0.026; survival, p = 0.067). The presence of mitoses or necrosis in the tumor specimen was associated with poorer outcome. Patients whose initial surgery was limited to biopsy, and patients with basal ganglia lesions, also had significantly worse outcome. Chemotherapy administered at the time of recurrence in a small number of patients did not produce any long-term survivors. This study is to our knowledge the only randomized trial to investigate effectiveness of chemotherapy in the treatment of high-grade astrocytoma in children.

Adolescent↗
PubMed1989

Personality types of women attending an STD clinic: correlation with keeping first review appointments.

One hundred and eighty new women patients attending a sexually transmitted disease (STD) clinic answered the Eysenck personality questionnaire (EPQ) which measures psychoticism, extraversion, neuroticism, and a tendency to "fake good". These personality scores were correlated with the patients' attendance or non-attendance for their first review appointments. The results showed that the mean psychoticism scale scores of the 41 non-attenders was significantly higher than that of the 139 who kept their first appointment. This relation was confirmed using point biserial correlations. The mean scores of non-attenders on the other three EPQ scales were not significantly different from those of attenders, and none of the correlations between the other EPQ scales and this behavioural criterion was significant. The psychoticism scale is tentatively recommended for identifying women patients who may need special counselling about the importance of keeping their first review appointment.

Adult↗
PubMed1989

Current neurosurgical treatment of medulloblastomas in children. A report from the Children's Cancer Study Group.

To determine the current neurosurgical treatment of children with medulloblastomas, we reviewed the operative reports and neurosurgical report forms from 141 children with posterior fossa medulloblastomas treated on two current Children's Cancer Study Group (CCSG) protocols, CCG-921 for high-stage and CCG-923 for low-stage medulloblastoma. Most medulloblastoma operations were performed in major medical centers: 61% of the operations were performed in CCSG member institutions, 23% in CCSG affiliates and 16% in other institutions. The tumor T stage distribution was as follows: T1-4%, T2-15%, T3A-35%, T3B-36%, and T4-10%. Tumors infiltrated the brainstem in 38% of cases and were associated with hydrocephalus in 91% of cases. Hydrocephalus was managed by external ventricular drains in 50% and by shunts in 60%. Adjunctive instruments (e.g., microscope, ultrasonic aspirator) were used in 93% of the operations. Tumor removals were as follows: biopsy only 3%, partial removals 13%, subtotal removals 13%, near total removals 41% and gross total removals in 40%; 90% or more of the tumor was removed in 81% of the operations. Forty-seven percent of the operations were performed by pediatric neurosurgeons. Near total and gross total removals were performed significantly more often (p less than 0.05) by pediatric neurosurgeons than by general neurosurgeons. Postoperative morbidity was reported in 46% of cases, including neurologic morbidity in 26% of cases. There was no significant difference in patient morbidity between pediatric and general neurosurgeons.

Biopsy↗
PubMed1988

Opportunities for cancer prevention and early detection among children.

The tumors of infants, children, and adolescents are generally deep seated rather than superficially located cancers of epithelial structures. Appropriate mass screening techniques (i.e., pap smear, mammogram, hemoccult test, or chest radiograph) have not been available for the early detection of childhood tumors. It is widely believed that the tumors of children are not suitable for mass screening tests. Therefore, they are diagnosed most often at an advanced stage. An inexpensive urine test has been found to be effective in detecting neuroblastoma at an early, preclinical stage in infants as young as 6 months. The tumors detected in this manner have a high rate of curability. This test appears to be suitable for wide application and has been shown to be both cost-effective and medically effective. Much less is known about the possible causes of the cancers of children than about the cancers of adults, so preventive measures are less well defined. Children in whom cancer develops are more likely to have a genetic predisposition due to one of the rare but numerous heritable genetic defects associated with more than 100 such known syndromes or an acquired genetic defect. Such children are predisposed to cancer because they already have an inherited or acquired somatic genetic lesion and are more susceptible to another genetic insult that results in neoplasia. Such children should be screened regularly for the early detection of cancer. They also constitute a special population to which maximal preventive efforts should be applied, both because they are at high risk and because they constitute a unique population for testing the effectiveness of proposed preventive measures. Cancer is a multifactorial, multistep process that results in the highest incidence of cancer among older adults after a lifetime of exposure to known and presumed cancer risks. Current efforts at cancer prevention are aimed primarily at adults. A greater challenge, which should be even more effective, is to motivate children, their parents, and teachers to prevent the cancers of adults during childhood.

Child↗
PubMed1988

The Intergroup Rhabdomyosarcoma Study-I. A final report.

The results of treatment of 686, previously untreated patients younger than 21 years with rhabdomyosarcoma or undifferentiated sarcoma, who were entered on Intergroup Rhabdomyosarcoma Study-I (IRS-I) were analyzed after a minimum potential follow-up time of 7 years. Patients in Clinical Group I (localized disease, completely resected) were randomized to receive either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC + radiation. At 5 years, approximately 80% of patients given either treatment were still disease-free and there was no significant difference between treatments in the overall percentages of patients surviving of 93% and 81%, respectively (P = 0.67). Patients in Clinical Group II (regional disease, grossly resected) were randomized to receive either vincristine and dactinomycin (VA) + radiation or VAC + radiation. At 5 years, 72% and 65% of the patients, respectively, were disease-free and there was no evidence of a difference between treatments (P = 0.46). The overall survival percentage at 5 years was approximately 72% for both treatments. Patients in Clinical Groups III (gross residual disease after surgery) and IV (metastatic disease) were randomized to receive either "pulse" VAC + radiation or "pulse" VAC + Adriamycin (doxorubicin) + radiation. The complete remission (CR) rate was 69% in Clinical Group III and 50% in IV, with no statistically significant difference in CR rates between treatments in either group. Those who achieved a CR had a nearly 60% chance of staying in remission for 5 years in Clinical Group III compared with approximately 30% in Clinical Group IV. The overall survival percentage at 5 years was 52% in Clinical Group III compared to 20% in Clinical Group IV (P less than 0.0001). The 5-year survival percentage for the entire cohort of 686 patients was 55%. Survival after relapse was poor, being 32% at 1 year and 17% at 2 years. The risk of distant metastasis was much greater than the risk of local recurrence within each clinical group, and there was no evidence of differing types of relapses between treatments. Primary tumors of the orbit and genitourinary tract carried the best prognosis, whereas tumors of the retroperitoneum had the worst prognosis. The authors conclude that for the therapeutic regimens evaluated there was no therapeutic advantage to including radiation in the treatment of Clinical Group I disease, or cyclophosphamide given as a daily low-dose oral regimen in the treatment of Clinical Group II disease or Adriamycin in the treatment of Clinical Groups III and IV diseases.

Adolescent↗
PubMed1987

Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (ALL).

Five hundred four children with low risk acute lymphocytic leukemia (previously untreated, age 3 to 6 years with white blood counts less than 10,000/mm3 at diagnosis) were randomized into two different central nervous system prophylaxis regimens. One regimen (250 patients) consisted of cranial radiation and intrathecal methotrexate (IT MTX). The second regimen (254 patients) consisted of IT MTX only. Median follow-up time for surviving patients is currently 54 months from randomization. Life table analysis of central nervous relapse, marrow relapse, disease-free survival, and survival shows very similar outcome for both treatment groups. The results indicate that maintenance IT MTX as described in this report can be substituted for cranial radiation in children with low risk ALL.

Central Nervous System↗
PubMed1987

The effect of methotrexate on the bioavailability of oral 6-mercaptopurine.

Fourteen children (aged 3 to 14 years) with average-risk acute lymphoblastic leukemia were studied after an oral dose of 6-mercaptopurine (6-MP) (75 mg/m2) administered alone and, on the next day, concurrently with oral methotrexate (20 mg/m2). When 6-MP was administered alone, both the peak plasma concentration (15 to 150 ng X ml-1) and the AUC (36 to 340 ng X ml-1 X hr) were highly variable. Concurrent methotrexate resulted in a 31% increase in the AUC (P less than 0.01) and a 26% increase in peak plasma levels (P less than 0.05) of 6-MP. The AUC of methotrexate correlated with the degree of increase in 6-MP plasma concentrations. These findings are consistent with previous in vitro studies demonstrating that methotrexate is an inhibitor of xanthine oxidase, the enzyme that catabolizes 6-MP to the inactive metabolite thiouric acid. Although the increases in 6-MP AUC and peak plasma concentrations resulting from concurrent methotrexate administration were statistically significant, this interaction is probably not clinically significant at standard low oral doses of methotrexate in light of the wide interpatient variability in these pharmacokinetic parameters of 6-MP.

Administration, Oral↗
PubMed1987

[Progress in the study, treatment and cure of hematologic malignancies in children in North America].

Progress in the study, treatment and cure of hematologic malignancies in children is one of the most gratifying accounts in the entire history of cancer therapy. It is important to note that progress in treatment and cure have been the direct result of formal study of childhood cancers and the development and clinical trial of new treatments designed to improve the response and cure rate. In the experience of the Children's Cancer Study Group (CCSG), approximately half of the children with cancer which are registered have hematologic malignancies. By far the most significant of these is acute lymphoblastic leukemia (ALL), which accounts for 33% of all the cancers registered with the Group. Acute non-lymphoblastic types of leukemia have amounted to 6% of all cancers in our experience, non-Hodgkin's lymphoma for another 6% and Hodgkin's disease for approximately 5%. The cancer death rate in children under the age of fifteen years has declined very significantly in the United States since 1950. In 1955 the National Cancer Institute organized the first national cooperative groups in order to develop and test new treatments for acute lymphoblastic leukemia. The CCSG was the first of these. The success which has been achieved in treating acute leukemia is remarkable, particularly when one recalls that in 1950 the disease was 100% fatal. The death rate due to Hodgkin's disease has also shown a sharp decline, and more recently, deaths due to non-Hodgkin's lymphomas have also declined.

Child↗
PubMed1986

Clinical implications of oncogene activation in human neuroblastomas.

Amplification of the oncogene N-myc has been identified in almost all human neuroblastoma cell lines tested. Eighty-nine primary neuroblastomas from untreated patients were studied to determine the frequency and clinical significance of N-myc amplification. Tumor DNA was analyzed by hybridization with the radiolabeled probe pNB-1 for N-myc. Amplification (3-300 copies) of the N-myc gene was found in 34 of the 89 tumors (38%). Amplification was not found in 8 Stage I or 5 Stage IV-S tumors, but it was found in 2 of 16 with Stage II, 13 of 20 with Stage III, and 19 of 40 with Stage IV tumors (P less than 0.01). Correlation of N-myc amplification with progression-free survival (PFS) indicated that N-myc amplification was associated with a worse prognosis (P less than 0.0001). The PFS at 18 months was 70%, 30%, and 5% for patients whose tumors had 1, 3-10, and more than 10 copies, respectively. Even within individual stages, the presence of N-myc amplification correlated with rapid progression. For instance, of 16 patients with Stage II disease, the 2 with N-myc amplification developed progressive disease rapidly, whereas only 1 of 14 without amplification progressed (P = 0.03). Similarly, those with Stage III and IV disease whose tumors have multiple copies of N-myc had a substantially worse prognosis. The correlation between N-myc amplification and age at diagnosis was also analyzed. Although N-myc amplification was detected in only 4 of 28 infants less than 1 year of age, compared to 30 of 61 older patients (P less than 0.005), this difference disappeared when corrected for disease stage. The results suggest that N-myc amplification is a powerful prognostic indicator, and that this gene may play an important role in the progression of certain neuroblastomas.

Age Factors↗
PubMed1986

Analysis of prognostic factors in acute lymphoblastic leukemia.

Children with ALL who have a high probability of excellent response, long-term survival, and cure when treated with widely available standard therapy can be identified at the time of diagnosis. Others can be identified who are at high risk of failure to respond, early relapse, and death. The importance of such prognostic characteristics is so great that they should be considered in the selection of appropriate treatment for each patient. Prognostic factors also must be considered in the design and analysis of clinical trials. All prognostic factors are not equally significant and many of them are closely associated. It is possible to rank them in importance and usefulness by appropriate statistical methods. As additional prognostic factors are identified, and as more effective and more specific therapies are developed, the relative importance of prognostic factors will change.

Adolescent↗
PubMed1985

Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.

Eighty-nine patients with untreated primary neuroblastomas were studied to determine the relation between the number of copies of the N-myc oncogene and survival without disease progression. Genomic amplification (3 to 300 copies) of N-myc was detected in 2 of 16 tumors in Stage II, 13 of 20 in Stage III, and 19 of 40 in Stage IV; in contrast, 8 Stage I and 5 Stage IV-S tumors all had 1 copy of the gene (P less than 0.01). Analysis of progression-free survival in all patients revealed that amplification of N-myc was associated with the worst prognosis (P less than 0.0001); the estimated progression-free survival at 18 months was 70 per cent, 30 per cent, and 5 per cent for patients whose tumors had 1, 3 to 10, or more than 10 N-myc copies, respectively. Of 16 Stage II tumors, 2 with amplification metastasized, whereas only 1 of 14 without amplification did so (P = 0.03). Stage IV tumors with amplification progressed most rapidly: nine months after diagnosis the estimated progression-free survival was 61 per cent, 47 per cent, and 0 per cent in patients whose tumors had 1, 3 to 10, or more than 10 copies, respectively (P less than 0.0001). These results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas.

Adolescent↗
PubMed1985

Comparison of stage IV and IV-S neuroblastoma in the first year of life.

Clinical staging and factors related to survival were evaluated in 44 stage IV-S and 44 stage IV patients with neuroblastoma, ages 0 to 12 months, seen at Children's Cancer Study Group (CCSG) institutions from 1972 to 1979. In 73 patients with complete surgical staging, the life-table projected survival at 3 years was 91% for stage IV-S and 44% for stage IV. The only deaths in stage IV-S disease occurred in three patients less than 2 months old at diagnosis. In stage IV-S, 3 to 12 months old at diagnosis, the disease-free survival was 97%. Chemotherapy or radiation therapy did not appear to improve the survival rate in stage IV-S. These studies further document a significant clinical and biologic difference between patients with stage IV and stage IV-S neuroblastoma and suggest that they require different therapeutic management.

Actuarial Analysis↗
PubMed1985

Microcomputers and consultation psychiatry in the general hospital.

The microcomputer allows for the design of a system that functions integrally with both the day-to-day and long-term needs of a consultation-liaison psychiatric service. This article describes a microcomputer system and data structure that can accomplish many of the same research tasks as a minicomputer system. In addition, the same data item inputs can be used to develop management reports that can facilitate the administrative as well as the pedagogic needs of a consultation-liaison service. Because of the daily availability and review of output reports, supervisors' corrections are made that enhance the reliability of the data. The program format provides 1) an intake form with pertinent identifying demographic data; 2) an activity file that contains every encounter between the consultant and the patient as well as research, supervisory, and liaison activities (which permit cost-effectiveness analysis); 3) a master clinical data base containing 255 variables for each case seen; 4) a computer-generated chart note; 5) letters to referring physicians; 6) clinical activity descriptions for billing; and 7) a file for pertinent literature searches. Since certain analyses may be limited in the microsystem, its interactive capacity with mainframe computers allows for complex functions. The microsystem described presently emphasizes flexibility, accessibility, and step-by-step development of files as needed by a particular consultation-liaison service. Finally, microcomputers are available at a fraction of the cost of the minicomputer or mainframe systems.

Adult↗