Using repeated exposure through hands-on cooking to increase children's preferences for fruits and vegetables.

Few children in the United States meet national fruit and vegetable intake recommendations, highlighting a need for interventions. Children's food preferences act as a barrier to fruit and vegetable consumption, but prior research has demonstrated that repeated taste exposures can increase children's acceptance of these foods. Prior research in this area has typically utilized controlled procedures in which children sample small tastes of target foods over repeated occasions. The primary aim of the present pilot study was to test whether children's preferences for target fruits and vegetables increased following repeated taste exposures to them through hands-on cooking in a community setting. Seventeen 6-to-8-year-old children participated in biweekly study sessions during six weeks of a summer camp serving lower-income families. Liking of (yummy, just OK, yucky) and rank-ordered preferences for nine fruits and vegetables were measured before and after exposure sessions (pre-test and post-test). Based on pre-test assessments, four relatively less liked foods (two fruits, two vegetables) were chosen to become target foods. Children were then exposed to target foods during nine hands-on cooking sessions; liking of target foods was also measured at a midpoint assessment. At each exposure session, children assisted with preparation of a different snack using a recipe involving target foods and then ate the prepared snack together. Preferences for target foods increased from pre-test (Median = 5.8) to post-test (Median = 5.5; p < 0.05). On average, the majority of children rated the prepared snacks favorably. Results from this pilot study demonstrate the potential of applying repeated exposure techniques via hands-on cooking in a community setting.

Predictive value of the fluorescent cytoprint assay (FCA): a retrospective correlation study of in vitro chemosensitivity and individual responses to chemotherapy.

The potential clinical usefulness of the fluorescent cytoprint assay (FCA) was assessed retrospectively in 73 cancer patients by correlating individual tumor chemosensitivity in vitro with responses to chemotherapy. The data show that the FCA has a sensitivity of 98%, specificity of 81%, and predictive accuracies of 85% and 97% for positive and negative clinical responses, respectively.

Advanced head and neck cancer: response to and toxicity of multimodality therapy.

This pilot study for resectable stage III and stage IV squamous cell carcinoma of the head and neck used a cytoreduction phase of preoperative radiation with cisplatin, followed by an eradicative treatment phase with radical surgery (group 1) or radical dose radiation and cisplatin (group 2), followed by adjuvant chemotherapy with 5-fluorouracil infusion and cisplatin delivered at 4-week intervals for six cycles following initial radiation therapy to the primary site. A total of 43 patients were treated between January 1984 and January 1987; 14 were classified with stage III carcinoma, 28 with stage IV, and one patient was not staged. Out of 43 patients, two did not complete therapy. Forty-one patients completed the eradicative phase of treatment. Complete tumor clearance at the end of the eradicative treatment phase was 88% (36 of 41 patients), 95% (18 of 19) in group 1 and 82% (18 of 22) in group 2. Actuarial recurrence-free survival was 61% at 3 years. Among 36 patients with complete tumor clearance after the eradicative treatment phase, there was no statistically significant difference for overall and recurrence-free survival between group 1 and group 2. In general, toxicity was not excessive, although mucositis, weight loss, and hematologic and neurologic toxicity were observed in varying degrees in these patients.

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

Accelerated radiotherapy followed by chemotherapy for locally recurrent small-cell carcinoma of the lung. A phase II study of Cancer and Leukemia Group B.

Recurrent or persistent small-cell carcinoma of the lung (SCCL) after chemotherapy (CT) alone has shown a poor response to conventional salvage radiotherapy (RT). Accelerated RT is judged more effective than conventional RT for rapidly growing tumors such as SCCL. The objectives of this study were: to determine the tolerability of accelerated RT; and to test the ability of accelerated RT plus CT to achieve local tumor control (LTC) of SCCL recurrent after CT. Patients whose localized tumor was not controlled were selected from Arm III of the Cancer and Leukemia Group B (CALGB) protocol 8083 (Proc. ASCO 2:230, 1984) as eligible for this study. The program of accelerated RT consisted of the delivery of 50.1 Gray (Gy) in 30 fractions over a period of 21 days to the chest. New chemotherapy different from the first began 2 weeks after the completion of RT and was repeated every 3 weeks for 18 months (M). Of 29 potentially eligible patients with locally recurrent SCCL after the first line CT alone from Arm III of the CALBG protocol 8083, 12 were enrolled initially in this study. The analysis of LTC included 11 patients excluding one patient who died 4 weeks after the start of RT from liver metastases. The LTC achieved was as follow: complete remission in 8/11 (72%) and partial remission in 3/11 patients. None of the patients was converted to CR by subsequent chemotherapy. Survival ranged from 2 to 20 M, with a median survival time of 6 M. Tolerance to the subsequent CT, normal tissue reaction to accelerated RT, and the theoretical advantage of accelerated RT over conventional RT for SCCL were evaluated.

Preoperative simultaneously administered cis-platinum plus radiation therapy for advanced squamous cell carcinoma of the head and neck.

Synchronously administered cis-platinum (cis-DDP) and radiation therapy have been used to treat unresectable squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the efficacy and tolerance of preoperative adjuvant cis-DDP plus radiation therapy in operable stage III and IV head and neck cancers. Radiation therapy (4,500 rad) was delivered in 180-rad daily fractions. Cis-DDP (20 mg/M2) was given before radiotherapy on days 1-4 and 21-24. Eighteen patients began therapy; 16 completed the combined regimen. Toxicity included stomatitis and WBC below 2,500/mm3. One patient died from therapy of a cerebrovascular accident. Sixteen patients (89%) achieved a complete or partial response to therapy. Complete responses were observed in 13 of 18 primary tumors (72%), and in all three patients with cervical lymphadenopathy. Complete responses were noted for lesions of the nasopharynx, oral cavity, pharynx, hypopharynx, and larynx, for all histologic grades of squamous cell carcinoma. Twelve patients underwent curative surgery. Site-related morbidity occurred in two patients (15%) and a third patient developed postoperative pneumonia. Five of 10 resected primary tumors with preoperative complete responses were pathologically negative for tumor. Concurrent bolus cis-DDP and radiation therapy are well-tolerated and result in impressive tumor reduction. Morbidity after subsequent curative surgery is low, and histologic complete responses are frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Macrophage-histiocytes in malignant lymphoma, small lymphocytic type (well-differentiated lymphocytic lymphoma).

The authors studied the occurrence of Ricinus communis agglutinin (RCA)-binding macrophage-histiocytes in paraffin-embedded tumor tissue of 38 patients with malignant lymphoma, small lymphocytic type, a tumor of low-grade malignancy. Thirty-one patients (82%) had an indolent clinical course and were free of disease for a minimum follow-up period of 24 months. However, seven patients (18%) died within 24 months of biopsy, and six of the seven patients died of rapid progression of their tumor despite intensive treatment. Histologically, the tumors of these six short-term survivors were indistinguishable from those of the long-term survivors. RCA staining of paraffin-embedded tumor tissue of the 38 cases revealed three groups of tumors: (1) tumors with numerous (greater than 10/high-power field [HPF]) stromal macrophage-histiocytes (4 patients); (2) tumors with a moderate number (4-9/HPF) of macrophage-histiocytes (5 patients); (3) tumors with rare or no (0-3/HPF) macrophage-histiocytes, or only thin, anuclear variants (29 patients). Each of the six short-term survivors had readily demonstrable RCA-binding macrophage-histiocytes in their tumor; these were numerous in four and moderate in two. In contrast, macrophage-histiocytes were either rare or absent, or were anuclear variants, in 29 of the 31 patients who had an indolent clinical course. These observations suggest that in small lymphocytic type malignant lymphoma there is a subgroup characterized by an increased number of stromal macrophage-histiocytes and aggressive behavior of the tumor. Tumors of this subgroup can be detected by RCA staining.

A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study.

The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.

Hyperthermic adjuvant perfusion chemotherapy for Stage I malignant melanoma of the extremity with literature review.

Thirty-nine patients with clinical Stage I malignant melanoma of the extremities were treated with hyperthermic perfusion chemotherapy using melphalan followed by excision or wide re-excision of the area and regional lymph node dissection. Four patients with positive lymph nodes, on histologic examination, were considered pathologic Stage II. Seventy-two patients with clinical Stage I extremity melanomas, who were treated by conventional surgical methods, served as concurrent controls, and were comparable in the distribution of their various pretreatment characteristics. The actuarial survivals for clinical Stage I perfusion patients calculated by the life-table method at 5, 10, and 15 years were 91%, 86%, and 77%, respectively, and disease-free survivals were 85%, 80%, and 80%, respectively. These figures were significantly better than controls. A Breslow depth of invasion of greater than 1.5 mm showed a significant difference in both clinical and pathologic Stage I disease as compared with the controls. Similarly, perfused patients aged less than or equal to 50 years survived significantly better than controls in both clinical and pathologic Stage I disease. The literature has been reviewed.

A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer.

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).

Sclerosis in diffuse histiocytic lymphoma: a clinicopathologic study of 25 cases.

Sclerosis was observed in the lymph node specimens of 26 of 57 (46%) patients with diffuse histiocytic lymphoma. Two major types of sclerosis was observed: "compartmentalizing" (56%), in which the tumor was divided into many small compartments by anastomosing, hyalinized stroma; and "diffuse" (44%), in which the sclerosis occurred without evident partitioning of the tumor. The hyalinized stroma of the compartmentalizing sclerosis was frequently continuous with small vessels accompanied by aggregates of small lymphocytes, suggesting that the sclerosis was related to the occurrence of small lymphocyte-associated postcapillary venules. Compartmentalizing sclerosis was further divided into two groups: The first group (even pattern) was characterized by an orderly occurrence of the stromal network with no evidence of distortion, evenly spaced tumor cells showing no axis in their arrangement, and a sharp demarcation of tumor cells from the stroma. The second group (uneven pattern) was marked by either a disorderly occurrence of the stromal network with distortion of the overall pattern, tumor cells arranged along an axis, or poor demarcation of tumor cells from the stroma with individual envelopment of tumor cells by the stroma. Approximately two-thirds of the patients (9/14) with the compartmentalizing sclerosis survived two years or more after diagnosis; most patients (10/11) with diffuse sclerosis died within two years. Compartmentalizing sclerosis, even pattern, was associated with a consistently favorable prognosis; the uneven pattern was not. This study indicates a marked variation in the survival of patients with diffuse histiocytic lymphoma with sclerosis and demonstrates that prognostic subgroups may be delineated by additional morphologic features.

Macrophage-histiocyte lysozyme activity in relation to the clinical presentation of Hodgkin's disease. An immunohistochemical study.

The clinical presentation of 71 untreated patients with Hodgkin's disease was studied in relation to immunohistochemically demonstrable lysozyme in the lymph node biopsy material. Sixty-one patients (86%) showed a positive staining reaction of varying degree, while ten (14%) showed no demonstrable lysozyme. The clinical features of lysozyme-positive patients differed markedly from those of lysozyme-negative patients. Stain-positive patients were younger (29 vs. 46), were more often in clinical Stage I or II disease (69% vs. 10%, P less than 0.001), and less frequently had constitutional symptoms (34% vs. 70%, P less than 0.02). Moreover, within the stain-positive group, patients who had the most intense staining reaction (mottling pattern) also had the most favorable clinical and histopathologic features at the time of diagnosis. The observations suggest that in Hodgkin's disease the lysozyme secretory activity of macrophage-histiocytes may be an important element of host resistance to neoplasia and that a depression of this secretory activity corresponds with disseminated disease.

Occurrence and patterns of muramidase containing cells in Hodgkin's disease, non-Hodgkin's lymphomas, and reactive hyperplasia.

The occurrence and pattern of cytoplasmic muramidase containing histiocytes were studied by the unlabeled antibody peroxidase-antiperoxidase method in biopsy material from patients with Hodgkin's disease, non-Hodgkin's lymphomas, and reactive hyperplasia. The majority of lymph nodes from patients with Hodgkin's disease, nodular lymphoma, and reactive hyperplasia gave positive staining reactions when tested in this manner. Differences in the staining pattern were observed for the different conditions studied. In general, stain positive cells occurred in one of the following four patterns: nodular, dispersed, aggregating without background stain, or aggregating with background stain (mottling pattern). The nodular and aggregating without background stain patterns were not specific and were seen in various conditions. The dispersed pattern, however, was observed only in some cases of non-Hodgkin's diffuse lymphomas, suggesting a subgroup of tumors characterized by active participation of reactive histiocytes. The mottling pattern was virtually limited to Hodgkin's disease. Since the mottling pattern appeared to be produced by virtue of a large amount of extracellular muramidase, the elevation of the serum muramidase level in Hodgkin's disease may be related to enzymatically active secretory histiocytes. Moreover, the mottling staining pattern was observed frequently in the lymphocytic predominance and nodular sclerosis type of Hodgkin's disease, but relatively infrequently in the mixed cellularity or lymphocytic depletion types, suggesting that the variation in histiocytic activity may be related to the course of the disease. The decreased staining reaction observed in the latter two categories could not be accounted for by a decrease in the numbers of histiocytic cells in hematoxylin and eosin stained sections, suggesting that release or synthesis may be defective in those unfavorable types of Hodgkin's disease.

Clinical trial of VP 16--213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B.

The epipodophyllotoxin derivative VP 16--213 (NSC 141540) was studied by the Cancer and Leukemia Group B in a broad phase II trial at three dose levels: 60 mg/m2, 90 mg/m2, and 135 mg/m2 I.V. twice weekly. No correlation between dose of VP 16--213 and response frequency in a particular disease category could be demonstrated. Of the 382 patients, 8% obtained a complete (CR) or partial remission (PR), 8% showed improvement, and 14% had stable disease. By tumor type the best responses were obtained in lymphomas (8/31 CR + PR), uterus (2/9), prostate (1/5), rhabdomyosarcoma (2/6), neuroblastoma (2/4), colon/rectum (5/81), other gastrointestinal (4/32). In lung tumors, 4/80 patients obtained CR or PR. VP 16--213 has definite antineoplastic activity but the response frequency with the twice weekly schedule may be lower than that reported with other schedules.

Procarbazine, vinblastine, and actinomycin D in stage III and IV melanoma with or without methanol-extracted residue of Bacillus Calmette-Guérin.

Patients with stage III and IV melanoma were randomly assigned to receive procarbazine (100 mg/m2, Days 1--10), vinblastine (5 mg/m2, Days 1 and 8), and actinomycin D (0.5 mg/m2, Days 1 and 8) with or without methanol-extracted residue (MER) of bacillus Calmette-Guerin (200 micrograms in five sites). In patients with measurable disease, 20% (eight of 40 patients) responded with only the combination chemotherapy while 15% (six of 39 patients) responded with the MER added. Toxicity was tolerable except for some instances of severe, gastrointestinal toxicity associated with procarbazine. MER as given in this study, failed to either increase the response rate or prolong survival.