Charged hadron fragmentation functions from collider data: NNPDF Collaboration.

We present NNFF1.1h, a new determination of unidentified charged-hadron fragmentation functions (FFs) and their uncertainties. Experimental measurements of transverse-momentum distributions for charged-hadron production in proton-(anti)proton collisions at the Tevatron and at the LHC are used to constrain a set of FFs originally determined from electron-positron annihilation data. Our analysis is performed at next-to-leading order in perturbative quantum chromodynamics. We find that the hadron-collider data is consistent with the electron-positron data and that it significantly constrains the gluon FF. We verify the reliability of our results upon our choice of the kinematic cut in the hadron transverse momentum applied to the hadron-collider data and their consistency with NNFF1.0, our previous determination of the FFs of charged pions, kaons, and protons/antiprotons.

Combined radiotherapy and chemotherapy in stage T3 and T4 nasopharyngeal carcinoma in children.

Twelve children younger than 16 years affected by undifferentiated nasopharyngeal carcinoma (NPC) with advanced primary tumor (T3, T4) were treated with chemotherapy consisting of Adriamycin (ADM [doxorubicin; Adria Laboratories, Columbus, OH]), vincristine (VCR), and cyclophosphamide (CYC), and radiotherapy. Preradiation chemotherapy produced partial responses in eight of ten evaluable patients. Eleven of 12 patients achieved a complete response following radiotherapy. The actuarial 3-year continuous relapse-free survival (CRFS) was 75%. This represents a significant improvement when compared with the 8% rate obtained in a previous series of patients treated with radiotherapy either with or without adjuvant CYC.

Curability of advanced Burkitt's lymphoma in children by intensive short-term chemotherapy.

The treatment programme (regimen I) we designed in 1982 for advanced Burkitt's lymphoma was modified in 1986 as regimen IIA and IIB for patients presenting without or with bone marrow (BM) and/or nervous system involvement, respectively. Following a 5-week course of cytoreductive chemotherapy, including vincristine (VCR), cyclophosphamide (CPM), doxorubicin (DXR), high-dose methotrexate (HDMTX) and intrathecal methotrexate and cytarabine (ARAC), high-dose ARAC and cisplatin were given as a 4-day continuous infusion. Regimen I continued with an additional 3-week course including VCR, CPM, DXR and HDMTX, which was omitted in regimen IIA. In regimen IIB the initial cytoreductive chemotherapy was complemented by adding etoposide and increasing HDMTX doses, and by modifying the high-dose ARAC administration modality and was followed, once the bone marrow had recovered, by ifosfamide that concluded the programme. A total of 44 children (22 in regimen I and 22 in regimens IIA and IIB) were treated, with an overall response rate of 98%. 4 patients died as a result of treatment related complications. Survival, progression-free and event-free survival rates were 73, 70 and 63%, respectively, for regimen I, and 82, 90 and 82%, respectively, for regimen IIA and IIB. A short chemotherapeutic regimen, using alternating phase-specific and non-specific agents, is able to cure the majority of patients with advanced Burkitt's lymphoma.

Advanced neuroblastoma: results of two treatment programs including sequential hemibody irradiation.

Results of two consecutive treatment programs for advanced neuroblastoma, including sequential hemibody irradiation, are analyzed and compared. The first treatment program (I-TP) included one single-fraction (7 Gy) irradiation to the upper and lower halves of the body as consolidation of remission achieved by previous chemotherapy with CDDP and VP16. A fractionated technique (2 Gy daily for 4 consecutive days to each hemibody) was used in the second treatment program (II-TP) for children in remission following a combination of CDDP + VP16 and ADM + VCR + CTX. In both treatment programs, chemotherapy was continued according to the same pre-radiation regimen following the two sessions of hemibody irradiation. Overall response rate to pre-radiation chemotherapy was 84% and 60% for I-TP and II-TP, respectively. Thirty-month overall progression-free survival was 0 for I-TP and 20% for II-TP. No treatment-related fatalities occurred. In the subsets of patients who reached complete or good partial remission during the pre-radiation chemotherapeutic phase, 30-month progression-free survival in I-TP and II-TP was 0 and 33%, respectively. The role of fractionated hemibody irradiation in prolonging the progression-free survival can be inferred.

Hypofractionated accelerated radiotherapy in osteogenic sarcoma.

A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients.

Continuous cisplatin infusion in combination with vincristine and high-dose methotrexate for advanced osteogenic sarcoma.

Fifteen patients with metastatic osteogenic sarcoma (OS) were treated with a combination of Vincristine (1.4 mg/m2), high-dose Methotrexate (8 g/m2), and Cisplatin (120 mg/m2 as a 72-h continuous infusion). The overall response rate was 66% [5 complete response (CR) and 5 partial response (PR)]. Four of the six patients not previously treated had a CR. Toxicity from this regimen was moderate and never life-threatening. In no case was impairment of the renal function observed, and the clearance of high-dose Methotrexate was never delayed.

[Studies of cellular sensitization to BCG and PPD using leukocyte cell migration inhibition]. / Rilievo della sensibilizzazione cellulare al BCG ed al PPD mediante il test di inibizione della migrazione leucocitaria

Leucocyte inhibition migration test (LMT) with BCG and PPD was applied in pulmonary tuberculosis, lung cancer and sarcoidosis. No significant differences were noticed in the results obtained with each of the two antigenic materials; nevertheless, one case lobectomized of lung cancer successively treated with chemiotherapie and immunostimulation with BCG presented LMT positivity with BCG and negativity with PPD. The unpublished results of the former investigations carried out with brute tuberculin (LMT) on patients with pulmonary tuberculosis are here reported no significant difference was noticed between the results obtained with brute tuberculin, and the results with PPD. The still unsettled problem presented by the lack of inhibition in the presence of PPD in leucocyte migration test in patients with areactive (AA) and intermediate areactive (AI) tuberculosis is also briefly discussed. Finally, the existence of a dissociation between the cutaneous delayed test and the in vitro test for the detection of cellular sensibilisation is confirmed even when LMT is applied either in the presence of BCG or of PPD.

Immunological aspects of sarcoidósis.

The results are reported of an immunological study conducted on 37 cases of active sarcoidosis, in which some in vivo and in vitro tests related to the cell-mediated immunitary response were effected. The results are discussed, with relation to the clinical use of the immunological tests adopted, and their immunopathogenetic significance. In particular, the occurrence of false-positive and false-negative results in the in vitro Kveim antigen test (LMT) using the antigen preparations currently available, limit its use in clinical practice.

[Immunological diagnosis of hilarmediastinal lymphadenopathies (author's transl)]. / Sulla diagnostica immunologica delle linfoadenopatie ilomediastiniche

In the last few years, we have adopted the following immunological techniques for the study of hilarmediastinal lymphadenopathies: the E and EAC rosette tests (composition of the lymphocyte population) for an evaluation of the general immunological picture, the delayed-type cutaneous tests to reveal the specific picture of cell-mediated immune responses, and the leucocyte migration inhibition test against related and unrelated antigens. This cellular technique was integrated with the determination of precipitating and agglutinating antibodies against the same antigens. Data are reported regarding tubercular and sarcoid lymphadenopathies, Hodgkin's disease, and secondary neoplastic lymphadenopathy with prevalent intratoracic localization. The techniques used demonstrated that tubercular lymphadenopathy is associated with a well defined immunological profile which is both humoral and cellular. Sarcoid lymphadenopathy (thoracic sarcoidosis) showed a specific, well characterized immunological picture as regards cell-mediated immune responses. In Hodgkin's disease (hilarmediastinal lymphadenopathy) the immunological technique showed up a general, depressed immunological picture, particularly as regards the cell-mediated immunitary response, presumably partly due to the treatment given (physical and pharmacological therapy). Secondary neoplastic lymphadenopathy showed a similar pattern, as far as the immunological parameters used until now are concerned. On the basis of experience gained to date, we believe that the immunological techniques can make a contribution to diagnostic and clinical studies of tubercular and sarcoid lymphadenopathies.

The spectrum of human tuberculosis.

Clinical, morphological and immunological studies of human tuberculosis have enabled the spectrum of the disease to be determined. We have investigated the cell-mediated immune responses by means of skin tests and leucocyte migration inhibition to PPD, and the humoral immune responses by means of immunodiffusion and haemagglutination tests. Patients with tuberculosis can be classified into two polar groups--reactive (RR) and unreactive (UU), the former showing good cell-mediated immunity and little or no antibody formation and the latter poor cellular responses and exuberant antibody production. The intermediate forms show characteristics of the neighbouring polar groups. The existence of a spectrum of immune response in tuberculosis, which has long been suspected, is now demonstrated.

Tropisetron (ICS 205-930) in pediatric oncology: first results in patients refractory to antiemetic metoclopramide-based treatments.

PURPOSE: We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its compassionate use in children with malignant disease who during previous chemotherapy cycles experienced emesis refractory to metoclopramide-based treatments. PATIENTS AND METHODS: Tropisetron was given to 15 children (eight boys and seven girls 18 months to 18 years of age) with miscellaneous neoplasms. Generally 5 mg/day of tropisetron was administered i.v. the first day of cisplatin-based chemotherapy and i.v. or orally each subsequent day of chemotherapy. The dose of tropisetron was reduced to 2 mg/day in children < 2 years of age and weighing < 20 kg. RESULTS: Vomiting was well controlled (no more than two episodes per day) on 118 of the 184 days of treatment with tropisetron (64%). No clinically important variations were observed in blood pressure, heart rate, body temperature, or electrocardiographic findings attributable to tropisetron. Transient, mild to moderate side effects (headache, constipation, abdominal pain, diarrhea) occurred in five patients on 11 of the 184 days of tropisetron treatment (6%). CONCLUSION: The results obtained during compassionate use of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of pediatric patients.

Studies on bronchoalveolar cells in humans. I. Preliminary morphological studies in various respiratory diseases.

A preliminary investigation has been carried out on bronchoalveolar cells obtained following lavage in various respiratory diseases. Of 23 cases observed, 7 have been studied in detail, 6 cases provided insufficient material for investigation, and the data obtained from the remaining 10 cases were inconclusive. Considerations are made with regard to the value of bronchial lavage in clinical diagnosis and cell studies.

Studies on bronchoalveolar cells in human diseases. II. General morphology and ultrastructure of pulmonary macrophages and small mononuclear cells in sarcoidosis.

Data are presented from light and electron microscopic studies on bronchoalveolar lavage (BAC) in sarcoidosis, with particular emphasis on the ultrastructural morphology and functional characteristics of pulmonary macrophages (PM) and small mononuclear cells (SMC). Light microscopy showed an average of over 77% of the BAC to be PM, range 99-51%. SMC populations were also extremely variable. These variations may relate directly to the degree of disease activity. Electron microscopy demonstrated a wide range of morphological and implied functional (biosynthetic and phagocytic) characteristics of PM. Some of these are morphologically comparable to cells found in tissue granulomata. Our ultrastructural study has shown that the SMC population is made up of lymphocytes, monocytes and cells with intermediate characteristics (precursors).

Alveolar lymphocytes in the follow-up of sarcoidosis.

Bronchoalveolar lavage (BAL) was performed in a group of 25 patients with pulmonary sarcoidosis in order to monitor variations in alveolar lymphocytes (AL) in comparison to the clinical evolution of the disease. Two BAL were performed in each patient, the second 6-12 months after the first (8.9 +/- 3, M +/- SD). Twelve patients were classified as improved and 13 as unimproved on the basis of a score of changes in the clinical picture, x-ray, respiratory function, immunological and biochemical tests. There was a significant decrease (p less than 0.001) of the percentage of AL in 66% of cases in the improved group, but not in the unimproved group, where, on the contrary, it was possible to observe an increase in the percentage of AL in 46% of these cases (n.s.). In 9 of 11 patients followed for 1-5 years with at least 3 BAL, AL behaviour correlated with clinical evolution. On the basis of the parameters studied, it was possible to show a correlation between lymphocytes, alveolitis and clinical evolution, especially in patients with an improved course. While a single BAL does not seem to be sufficient to show the course of the disease, repeated long-term washings allow a more accurate staging of sarcoidosis and can give early warning of relapses even when the conventional parameters (clinical, radiological and functional) are unchanged. Our aim was to look for a simpler parameter, which could be used routinely by even unspecialized laboratories, who are not able to type lymphocytes.

Acute monoblastic leukemia as a second malignancy following chemotherapy for osteogenic sarcoma: a case report.

A patient with well-differentiated monoblastic leukemia (ANLL FAB-M5b) is described in whom acute leukemia was diagnosed 25 months after having completed postoperative adjuvant chemotherapy for osteogenic sarcoma of the femur. All analyzed metaphases showed 48xy, dup 1(q12), +3, +9.

Mast cells in bronchoalveolar lavage in sarcoidosis: correlation with alveolar lymphocytes.

Today it is believed that mast cells (MC) are important not only in IgE-mediated reactions, but also in delayed hypersensitivity reactions, and that their functions are mediated by factors released by T lymphocytes. Recent studies have shown their presence in bronchoalveolar lavage (BAL) of patients with asthma and interstitial lung disease. MC have been identified by us in the BAL of patients with sarcoidosis and lung cancer, and in controls. A statistically significant correlation has been found between MC and lymphocytes, CD3+ and CD4+ cells present in BAL, thus supporting the hypothesis of interactions between T lymphocytes and MC in immune reactions at the alveolar level.

Hypersensitivity to pets in Italy.

Eight hundred and two consecutive symptomatic outpatients (with asthma and rhinitis) were studied to evaluate the incidence of prick test positivity to cat and dog danders and the association of exposure to these animals in the home, as revealed by a standard questionnaire. 14.3% were found to be skin positive to cat and/or dog danders. The incidence of cutaneous hypersensitivity to cat and/or dog danders was 25% in the 216 subjects who kept animals, significantly higher (p less than 0.0005) than the 10.4% of 586 subjects who did not keep animals. In the 57 subjects who owned both dogs and cats, a significantly higher incidence of skin hypersensitivity was found compared to the other subjects. Our data does not demonstrate a greater incidence in sensitivity to cat danders compared to dog danders, or increased sensitization to dermatophagoides pteronyssinus, nor a different incidence of clinical manifestations (asthma and rhinitis) between those with animals in the house and those without.

Protective effect of inhaled furosemide on allergen-induced early and late asthmatic reactions.

The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen. We studied 11 subjects with mild allergic asthma, who had both early and late asthmatic responses to a specific inhaled allergen in a preliminary challenge. After placebo administration, the maximal changes (mean +/- SE) from base line in the forced expiratory volume in one second (FEV1) and specific airway resistance were, respectively, a decrease of 35 +/- 4 percent and an increase of 288 +/- 56 percent between 0 and 60 minutes after inhalation of the allergen (early response) and a decrease of 35 +/- 5 percent and an increase of 301 +/- 40 percent between 4 and 12 hours (late response). After furosemide administration (4 ml; 10 mg per milliliter), the early response to inhaled allergen was markedly attenuated in all the subjects, and the late response in all but one. The maximal changes in the FEV1 and specific airway resistance were, respectively, a decrease of 11 +/- 2 percent and an increase of 61 +/- 2 percent between 0 and 60 minutes and a decrease of 20 +/- 4 percent and an increase of 178 +/- 25 percent between 4 and 12 hours (P less than 0.05 for all comparisons). No significant differences were seen in the bronchoconstrictor response to inhaled methacholine after furosemide or placebo administration. We conclude that a furosemide-sensitive mechanism in the airways is involved in the pathogenesis of the reactions of patients with allergic asthma. Whether inhaled furosemide might be useful in the treatment of allergic asthma is uncertain and will require further study.

Experience with palliative [131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Our experience with palliative [131I]metabenzylguanidine (131I-MIBG) therapy in 7 patients (6 children and 1 adult) affected by advanced neuroblastoma is reported. All patients (classified as IV stage) showed a progression following initial intensive therapy, including chemotherapy and, in some cases, hemi-body irradiation and surgery for their primary tumor. 131I-MIBG activity ranged for a single course between 2.77 GBq to 5.55 GBq on the basis of age, intensity of uptake, and the hematological assessment. Four patients received only one course of therapy due to progressive disease (2), early death (1) or persistent thrombocytopenia unrelated to 131I-MIBG therapy (1). Two patients received two courses and showed a partial response lasting 4 months and stable disease lasting 3 months respectively. Therapy was thereafter discontinued due to progression. One patient received 4 courses of therapy (cumulative activity = 19.61 GBq) in 5 months. A partial response for 9 months in the bone metastases was documented, but the therapy was discontinued due to persistent thrombocytopenia (58,000 plts/microL) lasting 4 months. Thrombocytopenia was the major side-effect, occurring in 5/7 patients over 8 courses of therapy for a mean period of 37 days (7-120 d). Thus, in our experience thrombocytopenia is the major factor limiting the therapeutic effect of 131I-MIBG therapy in palliative treatment.