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This article examines contemporary, mass migration from the perspective of human security. It tracks the development of the human security model of international relations, and compares it to the well-established state security model that has served as the dominant paradigm for international relations since the seventeenth century. The article argues that human security offers a more effective approach to many of the underlying problems and threats associated with mass migration, than does the traditional state-security model. It challenges national and international authorities to address threats to human security, in order to minimize forced migration and to create the conditions for migration by choice, not necessity.

This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.

Aims and Background Rarely are conclusions from clinical trials summarized in international consensus conferences and promptly transferred to patient care. The adjuvant therapy for colorectal cancer used in daily clinical practice in Italy is described and compared with the recommendations of the 1990 NIH Consensus Conference.Patients and Methods We audited prescriptions of adjuvant systemic therapies for Italian colorectal cancer patients in 82 centers during a fixed one-week period.Results Among 434 patients receiving adjuvant chemotherapy there were 139 (42.5%) colon cancer patients with N- and 169 (51.7%) with N+ regional nodal involvement. Treatment at academic centers, a young age, T4 and a low total number of lymph nodes removed at surgery were the factors potentially justifying the decision for adjuvant chemotherapy in stage II colon cancer patients. The most common chemotherapy used was a bolus of 5-fluorouracil/folinic acid for 6 months (75.8%). Adjuvant radiotherapy was not administered to 37 (38.5%) of 96 patients with stage II and III rectal cancer.Conclusions The study shows that a substantial proportion of patients on adjuvant treatment at a certain time point in a large enough sample of Italian centers are stage II (potential over-treatment) and that an under-treatment of stage II and III rectal cancer patients (lack of radiotherapy) occurs too often in daily clinical practice in this country.

To perform a phase 1 trial to determine the maximum tolerated dose and the dose-limiting toxicities of paclitaxel in children with refractory or recurrent solid tumors. Paclitaxel was administered twice weekly, increasing from four to six doses every 21 to 28 days.

To conduct a phase 1 trial of rebeccamycin analog (NSC 655649) in children with solid tumors to establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); to establish the pharmacokinetic profile in children, and to document any evidence of antitumor activity.

To establish the maximum tolerated dosage (MTD), the dose-limiting toxicities (DLTs), and pharmacokinetic parameters of CI-980, a novel tubulin binder, in children with solid tumors refractory to standard therapy. Patients 21 years of age or younger with adequate nutritional, hematopoietic, renal, and hepatic function were eligible. The patient must not have been pregnant. Patients with brain tumors were not eligible for any dosage level until it was demonstrated the level did not produce DLT in patients with extracranial solid tumors. The starting dosage level was 3.5 mg/m2/day, for 3 days, administered as a continuous intravenous infusion (80 of the adult MTD). If a dosage level was associated with dose-limiting myelotoxicity, growth factors were to be added. Thirty-three patients received CI-980. Twenty-four had solid tumor; 9 had brain tumor. The MTD achieved without granulocyte colony stimulating factor (G-CSF) was 3.5 mg/m2/day (DLT: neutropenia) and with G-CSF, it was as follows: patients with brain tumor, 4.2 mg/m2/day (DLT: myelosupression); and patients with solid tumor, 5 mg/m2/day (DLT: cortical toxicity). Several responses were seen, most notably prolonged stable disease in two of five patients with medulloblastoma. Pharmacokinetic data showed a mean steady state level of 1.74 ng/mL for two patients treated with the 5 mg/m2/day regimen, with rapid decay after the termination of the infusion. CI-980 showed preliminary evidence of activity in recurrent pediatric malignancies, with tolerable, reversible toxicities.

Seventy-eight of 362 children with acute lymphocytic leukemia (ALL) had leukemic cells similar in phenotype to normal pre-B cells. When the clinical and laboratory features of patients with pre-B and “null” cell phenotypes of ALL were compared, no significant differences were noted, except that the pre-B cell ALL phenotype had a higher percentage of black children. In contrast, patients with T cell ALL had a higher median age at diagnosis, frequent thymic involvement, and higher WBC counts. Patients with pre-B and “null” cell ALL were treated identically and patients with T cell ALL differently. Although no difference in remission induction rates was noted between patient groups with pre-B and “null” cell ALL, the remissions were of shorter duration for patients with pre-B cell ALL (p = 0.004). Similarly, overt leukemic involvement of both the central nervous system (CNS) and bone marrow was noted sooner in the patient group with pre-B cell ALL. Univariate and multivariate Cox life table regression analyses demonstrate the independent prognostic significance of the pre-B phenotype and illustrate that the prognostic influence of potential relapse risk factors, such as WBC, sex, and age, are specific for leukemia phenotype. These findings may have importance for the design and tailoring of therapy for children with acute leukemia.

The prognostic significance of chromosomal translocations, particularly t(1;19) (q23;p13), was evaluated in children with pre-B and early pre-B acute lymphoblastic leukemia (ALL). Patients were treated on a risk-based protocol of the Pediatric Oncology Group (POG) between February 1986 and May 1989. An abnormal clone was detected in 46% (130 of 285) of pre-B cases and 56% (380 of 679) of early pre-B cases. Translocation of any type was associated with a worse treatment outcome than other karyotypic abnormalities: 15 of 66 versus 3 of 64 failed therapy in the pre-B group (P= .001), and 37 of 141 versus 23 of 239 failed in the early pre-B group (P< .001). The t(1 ;19) (q23;p13) occurred significantly more often in cases of pre-B ALL with a clonal abnormality than in early pre-B ALL cases (29 of 130 v5 of 380. P< .001). Among the 285 pre-B cases in which bone marrow was studied cytogenetically, those with t(1;19) had a significantly worse treatment outcome than all others (11 of 29 v 27 of 256 have failed therapy, P<.001). This difference is significant (P< .001) after adjustment for leukocyte count, age, and other relevant features. Cases with the t(1;19) also had a worse prognosis than pre-B patients with other translocations (4 of 37 have failed, P< .01) or with any other karyotypic abnormality (7 of 101 have failed, P< .001). We conclude that chromosomal translocations confer a worse prognosis for non-T, non-B-cell childhood ALL, and that the t(1;19) is largely responsible for the poor prognosis of the pre-B subgroup.

Many children with acute lymphoblastic leukemia (ALL) develop a marrow relapse during or shortly following initial continuation chemotherapy. Achievement of a second complete remission is the initial step in a successful retreatment effort. Reinduction results using two or three drugs have been unsatisfactory, and previous reports of four-drug reinduction programs have included relatively small numbers of patients. Pediatric Oncology Group protocol 8303 was designed for patients with ALL in first marrow relapse during or within 6 months after cessation of chemotherapy. The results of reinduction therapy in 297 study patients are described here. Four-drug reinduction therapy consisted of daily oral prednisone, weekly vincristine and daunorubicin, and asparaginase three times weekly for 4 weeks (PVDA). CNS retreatment consisted of two doses of triple intrathecal chemotherapy. Of the 297 patients receiving reinduction, 245, or 82%, entered second complete remission, six died of infection or progressive disease, and 46 others still had M2or M3bone marrow status. Forty of these latter patients received four doses (during a 2-week period) of teniposide and cytarabine, after which 13 (32%) achieved complete remission status. Thus, the overall second complete remission rate with PVDA with or without teniposide/cytarabine was 258 of 297, or 87%. The treatment program was generally well tolerated. Among the numerous factors analyzed by using logistic regression, only female sex (P= .035), the presence of blasts on the blood smear at the time of relapse (P= .0002), and a length of initial complete remission less than 12 months (P= .021) were independent predictors of failure to enter second remission. We conclude that the intensive reinduction program described here is a highly effective first step in the delivery of salvage therapy to patients with ALL in first marrow relapse. The current challenge is to develop improved continuation treatment for these children.

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.

A different reactivity of the demosponge Chondrosia reniformis pinacoderm with regard to crystalline and amorphous silica is described. Following the crystalline quartz particle settlement, the pinacoderm breaks and exopinacocytes contract to form a rim around this foreign material that becomes gradually incorporated. Instead, amorphous opaline spicules elicit a motile response of exopinacocytes. At the onset of this process they lay a thin homogeneous matrix on the spicule, while afterwards several exopinacocytes join together forming a cellular coat covering the spicule. The sinking of both kinds of foreign material is allowed by the malleable organization of the collagenous ectosome. The effect of different silica crystalline forms on sponge cells is discussed by considering similar phenomena in other animals.

We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients ≥1 year and ≤21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (±SE) was 63% ± 2% (pre-B = 51 % ± 5% and early pre-B = 66% ± 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P= .0004); this association included both bone marrow and CNS remissions (P= .0004 and P= .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk-specific treatment protocols.

The comparative effectiveness of intrathecal (IT) combination chemotherapy using two agents, methotrexate (MTX) and hydrocortisone (HDC), and three agents, MTX, HDC, and cytosine arabinoside (CA), in treating meningeal leukemia was determined in a randomized Southwest Oncology Group study. Following central nervous system (CNS) remission induction the same regimen was used for periodic maintenance until CNS relapse supervened. Complete CNS remission was achieved in 100% of 43 children given two-agent therapy and in 96% of 48 children given three-agent therapy. Length of CNS remission for two-agent therapy was 1-150+ wk, median, 47.2 wk; for three-agent therapy, remissions were 1-190+ wk, median 64.6 wk. Differences in length of remission curves were not of statistical significance (p= 0.71). Toxicity of combination IT chemotherapy in the two- and three-agent regimens was reduced compared to that of IT MTX alone for CNS remission induction and maintenance. The additive effects of the IT drug combinations have been less than expected. The cytocidal activity of these agents when administered simultaneously or sequentially is not fully understood. Further studies are clearly indicated to determine optimum doses, schedules, and sequences for the chemotherapeutic agents which can be given intrathecally in combination.

We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.

We report the prognostic significance of the pre-B-cell immunophenotype and other presenting features, including blast cell karyotype, in a randomized clinical trial conducted from 1981 to 1986 for children with early pre-B (n = 685) or pre-B (n = 222) acute lymphoblastic leukemia (ALL). Patients greater than or equal to 1 year and less than or equal to 21 years of age who attained complete remission were stratified by conventional risk criteria and immunophenotype and then randomized to receive continuation therapy with either of two regimens of intensive chemotherapy, designated S (standard) and SAM (standard plus intermediate-dose methotrexate, 1 g/m2 every 8 weeks). The proportions of subjects achieving complete remission in the two phenotypically defined subgroups were identical, 96%. At a median follow-up time of 42 months, the overall probability of 4-year event-free survival (+/- SE) was 63% +/- 2% (pre-B = 51% +/- 5% and early pre-B = 66% +/- 3%). Children with pre-B ALL had significantly shorter durations of continuous complete remission (P = .0004); this association included both bone marrow and CNS remissions (P = .0004 and P = .02, respectively). In a univariate Cox regression analysis of potentially important prognostic factors, the pre-B immunophenotype was significantly related to a poorer outcome, as were other recognized biologic and clinical features (eg, pseudodiploidy, older age, male sex, black race, and a higher WBC). It retained its prognostic strength in a multivariate model based on age, WBC, ploidy, and sex. The risk of failure at any point in the clinical course of a child with the pre-B immunophenotype was 1.8 times as great as that in a patient lacking this feature but otherwise having an equivalent risk status. It should be stressed that the predictive value of any of the significant characteristics identified in this study could diminish in the context of another, more effective treatment program. Nevertheless, our major conclusion, that children with pre-B ALL fare worse than those with early pre-B disease in a contemporary clinical trial has implications for stratified randomization of patients and the design of risk- specific treatment protocols.

Seedlings of guayule (Parthenium argentatumGray) were successfully grown on a milled and composted pine bark medium. Liming and saturation of the medium was carried out for a 4-week period, prior to the addition of a VAM fungal inoculum and guayule seeds. This was done to permit an increase and stabilization of pH. Rock phosphate was incorporated into the medium at levels of 1.5, 3, 6 and 12mgdm−3, while other nutrients were provided by a modified Hoagland’s solution (lacking phosphate) with a nitrogen level of 70mgdm−3. Although poor seedling growth was recorded, it is suggested that seedlings may be pre-adapted to transplantation in a potentially hostile environment.

In order to plan an optimal anticancer therapeutic regimen, the physician must consider many factors such as the biochemistry, cellular composition, and proliferative state of the tumor; the physiological status of the host; and the toxicity of the chemotherapeutic agent on normal and malignant tissues. The biophysical and biochemical characteristics of these factors are discussed, and mechanisms of action and significant side effects of major chemotherapeutic agents are elucidated.

Analysis of remission induction rates for 1,117 children 18 months to 10 years of age (group 1) and 90 infants <18 months of age (group 2) with acute lymphoid leukemia (ALL) and of duration of continuous complete remission (CCR) for 454 in group 1 and 33 in group 2 revealed that infants fared significantly worse in both measures of outcome (P =. 03 and P <. 0001). To examine potential reasons for the poor prognosis of affected infants, clinical and biologic features of their ALL were compared. Infants had higher WBC counts [P <. 001), a higher incidence of massive splenomegaly (P <. 001), massive hepatomegaly (P <. 001), more central nervous system (CNS) disease at diagnosis (P <. 01), and lower platelet counts (P< .001). Also, their blasts were less often PAS+(P =. 02). The incidence of non(T, B, pre-B), T and pre-B immunopheno-types of ALL did not differ significantly between the two groups. However, in patients with non(T, B, pre-B) ALL, the majority (51 %) of infants had common ALL antigen (CALLA)-negative blasts, as compared with only 7% in group 1 (P < .001). Furthermore, infants with non(T, B, pre-B) cell ALL who were <12 months of age were almost always CALLA- (18 of 21). The blasts of children from both groups usually expressed la-like antigens. These data illustrate that infants with ALL have extensive and bulky disease more often than do older children and are more often affected with a prognostically unfavorable phenotype of acute leukemia (AL) which expresses la-like antigens but is more often PAS- and CALLA-. We believe that these clinical and biological differences predict and explain in part the observed poor response to treatment of infants with ALL.

• A number of chemotherapeutic agents have been shown to have antitumor activity against childhood medulloblastoma. Ten-year survival with optimal surgery and radiation therapy ranges from 5% to 25%. Carefully controlled clinical trials utilizing a combination of surgery, radiation therapy, and chemotherapy should be employed in the early stages of the disease in an attempt to define which drugs are most effective, and to improve the survival rate.(Am J Dis Child 130:639-642, 1976)

The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin's lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80); stage IV, 5/12 (42); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75); stage IV, 2/3 (67). Event-free survival (EFS) at >2 years was similar for patients with DUL and LCL, i.e., 65 and 61, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p= .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy. Poor outcome related to renal failure at diagnosis, and to CNS or BM or the involvement of both at diagnosis. The lactic dehydrogenase (LDH) levels were not significantly associated with treatment outcome.

The Intergroup Rhabdomyosarcoma Study (IRS) initiated an escalating-dose cyclophosphamide (Cyc) pilot without hematopoietic growth factor (HGF) support in combination with vincristine (Vcr) and actinomycin-D (Amd), known as VAC, to establish a Cyc dose with myelotoxicity comparable to an ifosfamide (Ifos), Vcr, and Amd combination regimen (VAI). A Cyc dose equivalent to Ifos was to be determined when comparable myelotoxicity was achieved.

The monoglyceryl ester (1) of a new halimane diterpenoic acid has been isolated as diacetyl derivative (2) from the mantle tissue of the Antarctic nudibranch Austrodoris kerguelenensis. The structure and the relative stereochemistry have been established by means of spectroscopic and chemical methods and by comparison with model compounds. An analysis of conflicting NMR data reported in literature for molecules related to the diterpenoic part of 1 has also been made.

Calcareous spicule formation was studied using tetracycline and 45Ca++ tagging in Clathrina cerebrum (Haeckel), Ascandra falcata Haeckel and Sycon ciliatum (Fabricius) (Porifera: Calcispongiae). The percentage of fluorescent spicules 24 h after the start of the experiment was similar in C. cerebrum and A. falcata (about 13% of the whole spicular population), while no fluorescence occurred in S. ciliatum. Results from 45Ca++ labelling experiments were similar in C. cerebrum and S. ciliatum. Estimated rates of spicule production by tetracycline labelling (30 mg/g/day and 34 mg/g/day for Clathrina and Ascandra, respectively) were about four times greater than those by 45Ca++ tagging (8.2 mg/g/day and 8.1 mg/g/day for Clathrina and Sycon, respectively). Our data show that about 1-3% of sponge calcite in the three species examined reforms in 24 h, suggesting that a constant deposition rate of from one to three months is needed for a complete turnover of the total spicular population.

For the construction of their skeleton, several species of Demospongiae utilise foreign material such as sand grains, sponge spicules, diatom oozes and other particles. Even though selection mechanisms were widely debated, no investigation comparing en vironmental sedimentation and particle incorporation had been carried out. The aim of this work is to compare the environmental sedimentation, studied by traps, with the particles found inside the body of the common demosponge, Chondrosia reniformis, collect ed along a depth transect on the vertical rocky cliff of the Portofino Promontory (Ligurian Sea, Italy). The mineralogical analysis eviden ces an active choice regarding the quality of the incorporated matter, with a strong affinity for siliceous particles. The size of the particles incorporated by the sponges at different depths is similar to that of the fine inorganic fraction in the water column. This phenomenon involves two mechanisms: (1) a physical uptake related to the mucous surface of the sponge and (2) the etching action on quartz particles typical of Chondrosia.

Scores for severity grading of childhood poisoning may be useful in comparing different causes of poisoning, in order to identify the main risks and their changes over time. The Multicentre Study of Poisoning in Children score is based on four levels of severity (1 - mild, 2 - moderate, 3 - severe, 4 - very severe) involving nine target groups: seven relating to organ systems (gastrointestinal, nervous, respiratory, circulatory, renal, hepatic, skin), one to metabolic abnormalities and one to injuries from corrosive substances. Each patient is classified by the highest level attributed to any one of the nine groups. The score has been prospectively tested in 644 symptomatic children, aged 0-13 years, admitted to six pediatric hospitals of Northern Italy from January 1, 1991 to December 31, 1993. Poisoning was categorized as mild (1) in 357 children (53.8%), moderate (2) in 285 (42.9%), severe (3) in 18 (2.7%) and very severe (4) in 4 (0.6%). No deaths occurred, Severity grading according to The Multicentre Study of Poisoning in Children score confirms the prevalence of mild and moderate poisonings in children; the score seems to be an objective method suitable for epidemiological studies in direrent countries. Its clinical usefulness deserves more investigation.

Purpose: This study reviewed the Pediatric Oncology Group experience with phase II clinical trials in children (<21 years of age) with refractory tumors.

A phase I trial was conducted in children with refractory solid tumors to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and pharmacodynamics for topotecan administered by a 30-min infusion for 5 consecutive days.

During the 2nd Italian Oceanographic Antarctic Expedition (1989–90) a small number of nudibranchs was collected at Terra Nova Bay (Ross Sea, Antarctica). In addition to well known species (such as Austrodoris kerguelensis Bergh, 1884 and Tritoniella belli Eliot, 1907) other, more unusual, species were also recorded, including Pseudotritonia gracilidens Odhner, 1944 and Cuthona georgiana (Pfeffer, 1884). Comparative information on the principal diagnostic features of the numerous species of Cuthona from the Sub-Antarctic and Antarctic waters is also tabulated and discussed.

Central nervous system infiltrates have become a major cause of morbidity among leukemic children and may constitute a site from which a remission marrow is again infiltrated. Conventional intrathecal methotrexate (IT MTX) therapy produces excellent palliation and complete reversal of abnormal cerebrospinal fluid findings for periods ranging from 6 to 414 days (median 87 days). The CNS remission maintenance potential of (1) IT MTX, 12 mg/sq m, every 6-8 wk, and (2) bis-nitrosourea (BCNU), 100 mg/sq m intravenously, every 6-8 wk were compared with "no therapy" maintenance. Only those children in CNS remission 6-8 wk following induction therapy were eligible for randomization to the maintenance study. The duration of CNS remission for BCNU-maintained and "no therapy" patients was similar, with a median length of remission of 96 days and 112 days, respectively. The median duration of remission for the MTX maintenance group was 472 days. The differences in length of CNS remission between the MTX group and the other two groups were statistically highly significant (p < 0.01 for both comparisons). Headache, fever, and/or vomiting occurred in 38% of the children after one or more of the intrathecal maintenance treatments and, in general, symptoms tended to worsen as maintenance continued.

INTEREST in the use of chemotherapeutic agents for palliating the clinical effects of malignant neoplasms is increasing. Cancer chemotherapy is especially useful when recurrence or metastasis follows surgery, or radiotherapy, or both and when massive size or the presence of distant metastases at the time of discovery precludes the use of these conventional methods. Most childhood cancers have some degree of responsiveness to one or more of the various available chemical compounds.Sarcomas of the soft tissues in children tend to be highly malignant and to have a rather discouraging outlook. Bowden's1 five-year survival rate for 602 patients with soft-part sarcomas was 37%. Other mortality figures are higher. Lawrence et al2 reported 9 of 48 patients with embryonal rhabdomyosarcoma surviving and Masson and Soule3 found that 88% of traced patients with embryonal rhabdomyosarcoma of the head and neck died within five years. A number of agents have

1. Using IT MTX as standard therapy for CNS leukemia, the comparative effectiveness of three radiation therapy regimens and a combination radiation-IT MTX regimen was determined by the Pediatric Division of the Southwest Cancer Chemotherapy Study Group. 2. IT MTX, 0.5 mg./Kg. every 2-3 days until the spinal fluid mononuclear cell count decreased to 10/mm3 or less, produced spinal fluid remissions in 78 per cent of 51 children experiencing their first episode of CNS leukemia. The duration of remission ranged from 6-414 days (median 87 days). These figures are comparable to those previously reported for IT antifol therapy. 3. Radiation therapy to the entire cranium using tumor doses of 500 rads and 1000 rads was ineffective in normalizing the CSF, although symptomatic relief was often obtained. 4. Radiation of the entire cerebrospinal axis using a tumor dose of 1000 rads resulted in a spinal fluid remission rate of 92 per cent. Remissions persisted for 13-527 days (median 52 days). Six of seven children in marrow remission when radiation therapy was administered showed evidence of myelosuppression. 5. A combination therapy regimen with two injections of MTX preceding radiation of the entire cerebrospinal axis (750-1000 rads tumor dose for children in marrow remission and 250-500 rads tumor dose for children in marrow relapse) and one injection of MTX intrathecally following radiation resulted in spinal fluid remission in 100 per cent of the evaluable children in the treatment group. Symptomatic remissions occurred in 94 per cent of the children. The duration of remission, however, was similar to that obtained with conventional IT MTX therapy. Evidence of myelosuppression appeared in half of the children in bone marrow remission. 6. None of the radiation regimens was superior to IT MTX when the following parameters were considered: (1) duration of CNS remission; (2) duration of existing bone marrow remission; (3) survival from onset of meningeal leukemia; and (4) number of CNS relapses.

SEVERAL HEMOLYTIC anemias are characterized by deficiency of the enzyme glucose-6-phosphate dehydrogenase (G-6-PD) in the erythrocyte. Among these are the primaquinesensitive anemias found in Negroes, a group of nonspherocytic anemias found in Caucasians, and the anemia secondary to the ingestion of fava beans in sensitive individuals. Although they share a similar defect in erythrocyte metabolism, these anemias are otherwise different.1-5When primaquine-sensitive individuals have a severe infection or are exposed to various chemicals and drugs, a hemolytic process may ensue. The mechanism of erythrocyte destruction has not been completely established but a demonstrable and major factor is the deficiency of G-6-PD in the erythrocyte which becomes critical as the cell ages.5The purpose of this report is to emphasize the variability of clinical manifestations and the diagnostic problems encountered in 14 Negro children and their families with primaquinesensitive anemia. Some clinical patterns of expression are delineated under the

A series of experiments was conducted to clarify the role of the autonomic nervous system in the acquisition and maintenance of the conditioned emotional response (CER). In Exp. 1 the reactivity of either the sympathetic or the parasympathetic system was altered by drugs during maintenance testing of the CER. 12 rats were trained to bar-press for sugar water on a VI 30-sec. schedule; 6 CER trials were administered during each 2-hr. session. The intensity of the unconditioned stimulus (electric shock) was adjusted for each Sso as to suppress responding during the CER signal (tone) to approximately 50% of normal pressing rate. Neither the sympathetic agents (adrenalin, Chlorpromazine, Dibenzyline), nor the parasympathetic agents (methacholine chloride, propantheline, atropine sulfate) reliably altered bar-press rates during the CER trials. Exp. 2 demonstrated that the autonomic agents, in the dosages used, were in fact altering autonomic reactivity as indexed by heart-rate measures. In Exp. 3 acquisition of the CER by 18 rats was found not to be affected by autonomic alteration as produced by drugs.

Desferrioxamine, a new, specific iron chelating agent, was used in the successful treatment of a child with acute iron intoxication due to ferrous gluconate. The dosage of desferrioxamine was 92 mg/kg given intravenously on three occasions at 12-hour intervals after an initial oral dose of 5 gm. Prompt improvement in the child's clinical status was accompanied by rapid fall in serum iron concentration to normal levels and excretion of about 25 mg of iron in the urine. Further trials of desferrioxamine in the treatment of acute iron intoxication are warranted on the basis of this experience.

Dal confronto tra il quadro istologico del pronefro di larve di Rana temporaria normali o trattate con prolattina, in stadi avanzati di prometamorfosi, risulta che, in linea generale, i fenomeni degenerativi (regressione dei tubuli renali, invasione del territorio pronefrico da parte dei macrofagi e dei leucociti acidofili) sono piu evidenti nelle larve di controllo che in quelle trattate con prolattina. Tali reperti confermerebbero dati biochimici precedenti i quali sembrerebbero dimostrare che la prolattina, pur attivando la tiroide eserciterebbe un'azione antagonista rispetto all'ormone tiroideo a livello di alcuni organi bersaglio periferici.

We report the use of vincristine sulfate, vinblastine sulfate, and cyclophosphamide in the treatment of children with histiocytosis X. No children with solitary eosinophilic granulomas are included in this study. The complete remission rates for the three drugs were 50%, 20%, and 36%, respectively; and the complete remission plus partial remission rates are 50%, 55%, and 63%, respectively. Because of the small numbers of patients involved, and the design of the study, we could reach no conclusions regarding the relative efficacy of the drugs. We discuss factors influencing the response and present tabulated data regarding age, degree of involvement, duration of therapy, and result of therapy for each patient.

VINCRISTINE sulfate, an alkaloid of the periwinkle plant, was made available for clinical use in 1961. Early data suggested activity of this drug in the treatment of children with acute leukemia1-3 and a variety of solid tumors.4-6 In children with generalized neuroblastoma, one of three reported by Selawry and Hananian4 and three of seven children studied by James and George5 demonstrated favorable tumor response to vincristine. The effectiveness of vincristine in children with generalized neuroblastoma was investigated by a co-operative protocol study of the Pediatric Division of the Southwest Cancer Chemotherapy Study Group. The results of this study constitute the basis for this preliminary report. MATERIALS AND METHODS Twenty children under 15 years of age with a tissue diagnosis of neuroblastoma were registered for the study within a 25-month period. Criteria for admission into this study included measurable lesions with evidence of progressive disease no longer