Behavioral adjustment in children with asthma: a meta-analysis.

This study is a meta-analytic review of the behavioral adjustment of children and adolescents with asthma. Of 78 studies initially reviewed, 26 studies (encompassing 28 data sets), reflecting data on nearly 5,000 children with asthma (mean age = 8.4 years; 40% female), met criteria for inclusion. Effect size estimates were calculated across studies using standard methods. Separate effect sizes were calculated for internalizing and externalizing behavioral problems, degrees of asthma severity, and differences in control group used (i.e., sample controls or normative data). Results indicate that children with asthma have more behavioral difficulties than do healthy children, with the effect for internalizing behaviors being greater than that for externalizing behaviors (d(mn) = .73 vs .40). Increased asthma severity was associated with greater behavioral difficulties. Results did not differ by comparison group (healthy controls vs normative data). The findings suggest that patients with asthma, particularly children with severe asthma, should be considered at higher risk for behavioral difficulties that may necessitate psychosocial intervention.

The Perceived Illness Experience Scale (PIE): reliability and validity revisited.

This paper reports psychometric evaluation of the Perceived illness Experience Scale (PIE). This includes eight sub-scales developed to determine the impact of a chronic illness from the patient's perspective. The sample included 34 patients (mean age = 17 years) successfully treated by limb salvage procedures for a primary bone tumour. Patients also completed measures of well-being (the SF-36) and function. To determine the relationship between patient and proxy ratings, mothers also completed the PIE. Evidence of construct validity of the PIE was obtained from significant correlations between PIE and SF-36 scale scores. There were also significant correlations between function and three of the eight sub-scales of PIE. Good correlations between patients' and mothers' ratings suggests that mothers can be useful proxy raters where patients are unable to provide data themselves. These data suggest that evaluations of patients following limb salvage surgery should not be limited to function measures alone, but need to include assessment of the perceived impact of treatment.

Brief report: assessment of body image in survivors of childhood cancer.

OBJECTIVE: To establish preliminary reliability and validity data of the Body Image Instrument (BII), a 28-item self-report measure developed to assess body image in adolescents and young adults with cancer. METHOD: As part of a larger study assessing long-term adjustment in survivors of childhood cancer, 40 males and 27 females (mean age = 19.69 years, SD = 3.87) completed the BII and two validation measures: the SF-36 health survey and the Perceived Illness Experience measure. RESULTS: The five BII subscales--General Appearance, Body Competence, Others' Reaction to Appearance, Value of Appearance, and Body Parts--exhibited moderate to high internal reliability and concurrent validity. No significant sex differences in body image emerged, nor was age at diagnosis or time since diagnosis significantly correlated with body image. CONCLUSIONS: The measure may be of value in clinical settings, where it could be used to identify adjustment problems related to body image disturbance in pediatric cancer patients.

The role of monitoring in determining quality of life following treatment for a bone tumor.

Interviews were conducted with 34 young people who had previously been treated for a malignant bone tumor around the knee. These interviews focused on the impact of treatment on activities and perceptions of the risk of recurrence and need for future surgery A coding schema based on a "monitoring-blunting" framework was adopted (Miller, 1995). Quality of life was assessed using a generic and disease-specific measure. Based on interview data, respondents were categorized as negativistic monitors, adaptive monitors, and nonmonitors. There were no differences between groups in terms medical indicators (number of operations). Negativistic monitors reported poorer quality of life compared with the other two groups. There was no increase in nonmonitoring with time since diagnosis as reported in previous work. It is suggested that patients' self-ratings of quality of life are related to the way in which they monitor information and this may be independent of clinical function. Clinical implications, especially in terms of how potentially threatening information about late-effects of treatment are given to patients, are discussed.

Quality of life in children following treatment for a malignant primary bone tumour around the knee.

Purpose. We report on the quality of life following treatment for a malignant primary bone tumour around the knee in skeletally immature children.Patients. Patients (n = 41; mean age = 18 years; range 8-28) had all experienced chemotherapy in a neo-adjuvant setting, surgical excision of the tumour and endoprosthetic replacement.Methods. Interviews were conducted separately with the child and mother and focused on mobility, body image and the impact of treatment on schooling, employment and plans for the future.Results. Mobility in the group was variable. Only 12% reported that they could run with any confidence. The proportion who were able to swim (49%) or ride a bike (46%) was higher. All had experienced major disruption in schooling (mean absence following diagnosis = 12 months). Eight had repeated a school year and 41% patients reported that their schoolwork was affected. As a result of their experience, eight (six females and two males) chose health-related employment. Concerns for the future were highest among males and those with manual jobs. Three patients were receiving psychiatric support, in relation to extreme concern about the risk of recurrence. All expressed satisfaction with treatment, and older patients believed that the prosthesis gave a better quality of life than amputation.Discussion. Our data suggest that outcome following limb-salvage surgery is variable. Education is disrupted. Even so, only two left school with no qualifications. Employment is most restricted among males with few qualifications who may benefit from sensitive vocational counselling.

What are the motivational needs behind volunteer work?

Identification of an individual's motivational need and desired volunteer work enables volunteer administrators to capitalize on the motivation a person brings to the organization as well as to make effective use of the role by being cognizant of the levels of participation behind the differing volunteer assignments. The Motivation by Maslow Questionnaire was used to identify motivational needs of 35 helpline (crisis) volunteers, and three categories of volunteer work were used to classify their levels of participation. Implications for improving volunteer commitment to the formal voluntary organization and recruitment and retention strategies relative to volunteer motivational needs are discussed.

A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B.

Between 1982 and 1986, 326 evaluable patients with acute myeloid leukemia (AML) were randomized to receive cytarabine (Ara-C) at 200 mg/m2 (A200) or 100 mg/m2 (A100) for induction and maintenance therapy. Cycle 1 of induction therapy consisted of 7 days of continuous intravenous (IV) Ara-C and 3 days of i.v. daunorubicin (DNR); cycle 2, if needed, consisted of 5 days of Ara-C and 2 days of DNR. Complete responders (CR) then received monthly subcutaneous (SC) Ara-C at the respective doses (A100 or A200) with 6-thioquanine (6TG) at months 1 and 5, with vincristine (VCR) and prednisone at months 2, 4, 6, and 8, and with DNR at months 3 and 7. Complete response rates were 58% (A100) and 64% (A200) (P = .29). Median survival was 46 weeks (A100) and 38 weeks (A200) (P = .64); 5-year survival was 10% (A200) and 8% (A100). Median time to remission was 6.7 weeks (A200) and 8.1 weeks (A100) (P = .18). Median disease-free survival was 41 weeks (A200) and 44 weeks (A100) (P = .86). Deaths were attributed to therapy-related toxicities in 21% (A200) and 13% (A100) (P = .05). The 5-year survival was 15% for patients with performance status (PS) 0, 8% for PS 1 to 2, and 2% for PS 3 to 4, 18% for patients less than 40 years, 8% for ages 40 to 59, and 3% for age 60 or greater. Stratification of data by age and PS suggested that A200 may improve survival in patients less than 60 years with a good PS 0 (P = .05). This trial does not support the superiority of A200 over A100 in the treatment of AML.

Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer--preliminary report.

Tamoxifen (TAM), a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Recent reports suggest that TAM may cause endometrial neoplasia. This study is designed to evaluate the oncogenic potential of low-dose TAM on the endometrium. Initially, endometrial screening of patients with breast cancer who had received TAM therapy for at least 12 months was conducted. Seventy patients were interviewed and office endometrial biopsies were obtained from thirty-eight patients. Seven (18%) had hyperplastic changes, ranging from simple hyperplasia through complex hyperplasia with atypia. The following prospective study was conducted: after breast surgery and prior to initiation of TAM therapy, an office endometrial sampling was obtained as a control. After initiation of TAM therapy, biopsies were repeated every 4 to 6 months as long as the patients remained asymptomatic. Nineteen patients were interviewed. Twelve patients were biopsied and followed from 3 to 15 months. One patient refused additional biopsies. Eleven patients had repeat biopsies after initiation of TAM. New hyperplastic changes were found in 3/11 (27%) patients. The preliminary results of this study (although with a small number of patients) indicate that TAM may have some neoplastic effect on the endometrium of postmenopausal patients with breast cancer. This study is still in progress. Additional prospective studies are warranted before a significant correlation between TAM and endometrial neoplasia is confirmed.

A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.

Effect of cyclophosphamide and levan treatment on bone marrow and peripheral blood cells in B16-F10 melanoma-bearing mice.

Immunotherapeutic agents have often been found to provoke opposite effects on tumor growth--inhibitory or stimulatory--depending on dose, timing or route of administration. The reason for these opposite effects is not yet known. Levan (polyfructose), an immunomodulatory polysaccharide, has been found to exert opposite effects on the growth of the F10 variant of B16 melanoma. Low doses inhibit and high doses enhance the growth of this tumor. Cyclophosphamide (CY) augments the inhibitory effect of the polysaccharide. In order to elucidate the mechanism of these opposite effects, we tried to determine the changes induced by levan at inhibitory and stimulatory doses, alone or in conjunction with CY, on the lymphatic and hematopoietic systems of B16-F10 melanoma-bearing mice. In a previous study we reported the effect of these treatments on the morphology of spleen and lymph nodes (Leibovici, Kopel, Siegal & Gal-Mor (1986). Int. J. Immunopharmac., 8, 391). In the present study, we examined the effect of the treatments on bone marrow and peripheral blood composition. The growth of the tumor itself, as well as the various treatments, induced very marked changes in both bone marrow and blood. Tumor inoculation produced a sharp leukopenia and anemia followed by a restoration of both white and red blood cells. In the bone marrow, the tumor caused a gradual decrease in lymphocyte number. CY accentuated the severe leukopenia caused by the tumor. Lymphocyte depletion was prolonged, while restoration of granulocytes was achieved by day 7. A similar pattern of changes was observed in the bone marrow. With levan, opposite effects were observed in blood and bone marrow with the two doses in relation to the number of the cells of the lymphoid and myeloid lines: while 0.1 mg (tumor inhibitory) doses caused a more active restoration of lymphocytes as compared to 10 mg (tumor stimulatory) doses, an opposite effect was seen on the myeloid series--the high dose induced a more pronounced granulocytosis than the low dose. In the combined treatment, the low levan dose accelerated lymphocyte restoration in bone marrow compared to CY, while the high dose delayed the recovery of these cells. The results of the present study in conjunction with our previous study may explain the basis of the intriguing tumor inhibitory-stimulatory effects of some immunomodulators. Moderate increases in myeloid cell series appear to favor tumor inhibition and high increases favor tumor stimulation. In addition, the results of this study suggest that a regulatory relation might exist between the proliferation of the lymphoid and myeloid cell series.

Bone marrow and peripheral blood modifications in C57BL mice administered with cyclophosphamide and levan.

The effects of cyclophosphamide (CY) and levan at low (0.1 mg) and high (10 mg) doses (previously found to inhibit and stimulate, respectively, B16 melanoma growth) were studied. in single and combined administration, on the blood and bone marrow of C57BL mice. Very marked changes in the cellular composition of blood and bone marrow were induced by the various treatments. CY caused a sharp depletion of leukocytes in blood and bone marrow followed by a restoration of granulocytes while lymphocytes remained low. Levan caused a sharp dose-dependent depletion in bone marrow lymphocytes. Blood lymphocytes were not affected, however, by the polysaccharide. With the high levan dose, after a temporary granulocytopenia and monocytopenia, prominent granulocytosis was observed. While CY affected equally the different types of cells, levan decreased the number of lymphocytes and erythroblasts to a greater degree than the number of granulocytes. In the combined CY-levan treatments, the low levan dose generally attenuated the suppressive effect of CY, while the high concentration aggravated it.

COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma.

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.

Relationship of estrogen and progesterone receptors to prognosis in breast cancer.

To ascertain the role of estrogen (ER) and progesterone (PR) receptors as prognostic indicators of resectable breast cancer, the records of 204 patients were analyzed whose receptor studies were done at the Maimonides Medical Center from 1975 to 1983. All patients had radical or modified radical mastectomies and did not show any evidence of distant metastases at the time of operation. Median follow-up was 37 months. An additional 117 patients received some form of adjuvant therapy, mainly chemotherapy, and were analyzed separately. Life table analysis using the log rank test for measuring significance, and a Cox multivariate analysis was performed. At 48 months, 22% of the ER positive (ER+) group versus 33% of the ER negative (ER-) group had recurred as compared to 16% and 35% for the PR+ versus PR- groups, respectively. Life table analysis of the disease free interval (DFI) showed that the difference between the ER+ and ER- groups was not significant (p greater than 0.1), while the difference in DFI between the PR+ and PR- groups was significant (p less than 0.05). Multivariate analysis revealed that the most important factors in predicting the DFI were nodal status (p less than 0.001), tumor size (p less than 0.025), and progesterone receptor status (p less than 0.05). Estrogen receptor status was not found to be significant. In conclusion, PR- patients have a shorter DFI than PR+ patients and that PR status is a more valuable predictor of DFI than ER status.

Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081.

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.

Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a cancer and leukemia group B study.

Patients with acute nonlymphocytic leukemia were randomized to receive remission induction therapy consisting of seven days of cytosine arabinoside and three days of daunorubicin ("7 + 3") or to receive the same regimen intensified by either the addition of 6-thioguanine or by extension of the administration of cytosine arabinoside to ten days. Additionally, all patients were randomized to receive or not to receive cotrimoxazole antibacterial prophylaxis during the remission induction phase. Neither an increase in intensity of chemotherapy nor the antibacterial prophylaxis increased the remission rate above the 53% for patients treated with the standard "7 + 3" regimen. The second part of this study addressed the issue of the utility of long-term maintenance chemotherapy. To this end, patients were randomized to discontinue all treatment after 8 months of maintenance chemotherapy or to continue maintenance therapy for a total of 3 years. Although there was a transient increase in the relapse rate for patients who discontinued therapy, the proportion of long-term remitters was identical in the two patient groups. Additionally, there is a suggestion of a survival advantage for patients randomized to discontinue all therapy at 8 months.

Effect of splenectomy on treatment of Lewis lung carcinoma by an immunomodulatory polysaccharide and a cytotoxic agent.

The effect of the spleen on the efficiency of chemotherapy (cyclophosphamide) and immunotherapy (the polysaccharide levan) of C57BL mice bearing the Lewis lung carcinoma was studied. The development of Lewis lung carcinoma caused a gradual splenomegaly in the C57BL mice. Splenectomy did not, however, affect tumor growth in the nontreated host. Levan induced a pronounced splenomegaly. Splenectomy reduced markedly the antitumoral effect of the polysaccharide. These results indicate that spleen elements participate in the inhibitory activity of levan. By contrast, splenectomy had no effect on the efficiency of treatment of cyclophosphamide.

Histological changes in spleen and lymph nodes of mice administered cyclophosphamide and levan.

Morphological changes in spleen and lymph nodes of C57B1 mice induced by the cytotoxic agent cyclophosphamide and the polysaccharide levan, separately and in combination were studied. In the spleen, an early decrease (phase 1) and a late increase (phase 2) in weight were found to result from all drug administrations. The hypocellularity of phase 1 was due to a depletion in the white pulp affecting mainly the B-region. Splenic weight decrease was parallel to B-cell depletion and most marked in animals exposed to cyclophosphamide with levan. The splenomegaly observed during phase 2 with all treatments was due to extramedullary hematopoiesis in the red pulp. In the lymph nodes, administration of cyclophosphamide and levan produced opposite effects on the B-cell region: cyclophosphamide eliminated the germinal centers for 8 days, but levan seemed to enhance B-cell activity. In animals given both cyclophosphamide and levan, inhibition of B-cell activity began earlier than with cyclophosphamide alone. Levan does not antagonize the suppressive effect of cyclophosphamide on the B-cell component at the early phase when the drugs are given together.

Effect of tumor inhibitory and stimulatory doses of levan, alone and in combination with cyclophosphamide, on spleen and lymph nodes.

Immunotherapeutic agents are often reported to induce opposite effects -- inhibitory and stimulatory -- on tumor growth, depending on the dose, timing or route of administration of the drug. The reason underlying these opposite effects is not yet known. The immunomodulatory polysaccharide levan (polyfructose) has been found to exert such opposite effects on the growth of the F10 variant of B16 melanoma. Low doses inhibit and high doses enhance tumor growth. Cyclophosphamide (CY) augment the inhibitory effect of levan. In order to clarify the mechanism of this switch, we tried in the present study to determine the changes induced by levan at inhibitory and stimulatory treatments, alone or with CY, on the morphology of spleens and lymph nodes of the melanoma-bearing mice. The growth of the tumor in non-treated mice was found to induce a moderate splenomegaly. Microscopically, two main changes were observed: a mild extramedullary hematopoiesis and a sharp increase in the number of germinal centers. A parallel increase in germinal center number was found in the lymph nodes. The data presented suggest that the immune system plays a role in both the inhibition and stimulation of tumor growth by levan. Levan induced a dose dependent splenomegaly, even more pronounced in combination with CY, due to an extramedullary hematopoiesis. Levan reduced the B cell activity caused by the tumor, proportionally to its dose. In combination with CY, levan accelerated the recovery of the B cell activity at the low dose, while the high dose prevented it. A similar trend was found in the lymph nodes. The changes involved in the switch inhibition-stimulation could be either the degree of reduction in B cell activity or the degree of extramedullary hematopoiesis or some interplay between the myelocytic and lymphocytic series, which was found to change in an opposite fashion under the influence of various treatments. Since the immune system is a finely equilibrated system, it is possible that immunomodulation rather than immunostimulation should be aimed at in cancer immunotherapy. However, the conditions required for achieving this equilibrium have to be defined.

Opposite effects on tumor growth depending on dose of an immunomodulatory polysaccharide with or without cyclophosphamide.

Opposite effects on the growth of the F10 variant of B16 melanoma--inhibitory and stimulatory--were found with varying doses of the polysaccharide levan. Low (0.1 and 1 mg) daily doses inhibited, while high (5 and 10 mg) doses enhanced tumor growth. In combined cyclophosphamide-levan treatment, these opposite effects were more pronounced.

Different biological behavior of AKR lymphoma cells from primary and metastatic tumors.

AKR lymphoma cells derived from primary s.c. tumors (PT) and cells from their metastases (MT) were inoculated into recipient mice in order to compare their malignant behavior. A higher malignant potential of MT compared to PT cells was found. The results support the hypothesis that metastasis is a process of selection of cells possessing a potential to metastasize, which preexist in the primary tumor. In the model used, both the selection of 'variants' of malignancy and the assay of malignancy were as close as possible to natural tumor progression.