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Some 16th century religious buildings provide evidence of the influence of European treatises on architecture in the New World. Many early Dominican monasteries in the central-southern regions of modern-day Mexico are part of the remarkable repertoire of this phenomenon. This paper provides in-depth analysis of the dissemination mechanisms of treatises on architecture in the ecclesiastical realm.

IMPORTANCE: The PCSK9 inhibitor evolocumab reduced major vascular events in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, yet the types and sizes of myocardial outcomes in FOURIER have not been previously explored. OBJECTIVE: To assess the types and sizes of myocardial infarction (MI) and the effect of evolocumab on MI by subtype. DESIGN, SETTING, AND PARTICIPANTS: A prespecified analysis of a multicenter double-blind randomized clinical trial. Patients were randomized to evolocumab or placebo and followed up for a median of 2.2 years. The study included 27 564 patients with stable atherosclerotic disease receiving statin therapy. Clinical end points were evaluated by the Thrombolysis in Myocardial Infarction clinical events committee. Rates presented are 3-year Kaplan-Meier estimates. Data were collected from 2013 to 2016 and analyzed from June 2017 to December 2019. MAIN OUTCOMES AND MEASURES: Myocardial infarction was defined based on the third universal MI definition, and further classified according to MI type (universal MI subclass, ST-segment elevation myocardial infarction [STEMI] vs non–STEMI) and by MI size (determined by peak troponin level). RESULTS: A total of 27 564 patients were randomized, with a mean (SD) age of 62.5 (9.0) years, and 20 795 (75%) were male. Of these, 1107 patients experienced a total of 1288 MIs. Most MIs (68%) were atherothrombotic (type 1), with 15% from myocardial oxygen supply-demand mismatch (type 2) and 15% percutaneous coronary intervention–related (type 4). Sudden death (type 3) and coronary artery bypass grafting–related (type 5) accounted for a total of 21 MIs (

Many new photovoltaic (PV) applications, such as the concentrating PV (CPV) systems, are appearing on the market. The main characteristic of CPV systems is to concentrate sunlight on a receiver by means of optical devices and to decrease the solar cells area required. A low CPV (LCPV) system allows optimizing the PV effect with high increase of generated electric power as well as decrease of active surface area. In this paper, an economic analysis and a life cycle assessment (LCA) study of a particular LCPV scheme is presented and its environmental impacts are compared with those of a PV traditional system. The LCA study was performed with the software tool SimaPro 8.0.2, using the Econinvent 3.1 database. A functional unit of 1 kWh of electricity produced was chosen. Carbon Footprint, Ecological Footprint and ReCiPe 2008 were the methods used to assess the environmental impacts of the LCPV plant compared with a corresponding traditional system. All the methods demonstrated the environmental convenience of the LCPV system. The innovative system allowed saving 16.9% of CO2 equivalent in comparison with the traditional PV plant. The environmental impacts saving was 17% in terms of Ecological Footprint, and, finally, 15.8% with the ReCiPe method.

Background Most patients with hereditary hemochromatosis in the Caucasian population are homozygous for the p.C282Y mutation in the HFE gene. The penetrance and expression of hereditary hemochromatosis differ largely among cases of homozygous p.C282Y. Genetic factors might be involved in addition to environmental factors. Design and Methods In the present study, we analyzed 50 candidate genes involved in iron metabolism and evaluated the association between 214 single nucleotide polymorphisms in these genes and three phenotypic outcomes of iron overload (serum ferritin, iron removed and transferrin saturation) in a large group of 296 p.C282Y homozygous Italians. Polymorphisms were tested for genetic association with each single outcome using linear regression models adjusted for age, sex and alcohol consumption. Results We found a series of 17 genetic variants located in different genes with possible additive effects on the studied outcomes. In order to evaluate whether the selected polymorphisms could provide a predictive signature for adverse phenotype, we re-evaluated data by dividing patients in two extreme phenotype classes based on the three phenotypic outcomes. We found that only a small improvement in prediction could be achieved by adding genetic information to clinical data. Among the selected polymorphisms, a significant association was observed between rs3806562, located in the 5'UTR of CYBRD1, and transferrin saturation. This variant belongs to the same haplotype block that contains the CYBRD1 polymorphism rs884409, found to be associated with serum ferritin in another population of p.C282Y homozygotes, and able to modulate promoter activity. A luciferase assay indicated that rs3806562 does not have a significant functional role, suggesting that it is a genetic marker linked to the putative genetic modifier rs884409. Conclusions While our results support the hypothesis that polymorphisms in genes regulating iron metabolism may modulate penetrance of HFE-hereditary hemochromatosis, with emphasis on CYBRD1, they strengthen the notion that none of these polymorphisms alone is a major modifier of the phenotype of hereditary hemochromatosis

Supplemental Material, DS2_VET_10.1177_0300985815626573 for Histological Classification and Immunohistochemical Evaluation of MDM2 and CDK4 Expression in Canine Liposarcoma by G. Avallone, P. Roccabianca, L. Crippa, E. Lepri, B. Brunetti, C. Bernardini, M. Forni, A. Olandese, and G. Sarli in Veterinary Pathology

Objective: The aim of this study is to report on the role of neuroendoscopy during the management of hydrocephalus that led to the diagnosis of intracranial tumoral dissemination and the subsequent finding of a spinal cord glioma. Methods and Results: We present two children each with an intramedullary astrocytoma that presented initially with hydrocephalus without spinal cord symptoms. In both cases leptomeningeal gliomatous dissemination was asserted during routine endoscopy for the management of hydrocephalus. The diagnosis of a cervical and a lower thoracic intramedullary tumor was made soon after on magnetic resonance imaging. Conclusions: Spinal cord MRI with contrast should be considered initially in selected cases of hydrocephalus without evident diagnosis. The intraoperative diagnosis of gliomatous dissemination and secondary hydrocephalus due to unrecognized spinal cord gliomas was possible, in our experience, with the routine use of the neuroendoscope.

In this work we establish a relationship between Cartan's geometric approach to third order ODEs and the 3-dim Null Surface Formulation (NSF). We then generalize both constructions to allow for caustics and singularities that necessarily arise in these formalisms.

The Null Surface Formulation of General Relativity is developed for 2+1 dimensional gravity. The geometrical meaning of the metricity condition is analyzed and two approaches to the derivation of the field equations are presented. One method makes explicit use of the conformal factor while the other only uses conformal information. The resulting set of equations contain the same geometrical meaning as the 4-D formulation without the technical complexities of the higher dimensional analog. A canonical family of null surfaces in this formulation, the light cone cuts of null infinity, are constructed on asymptotically flat space times and some of their kinematical aspects discussed. A particular example, which nevertheless contains most of the generic features is explicitly constructed and analyzed, revealing the behavior predicted in the full theory.

This review outlines the present state of applications of seismic isolation to civil buildings in Europe (with particular reference to Italy), including the countries formerly belonging to the USSR. Some information is also given on the use of other passive innovative antiseismic devices, like energy dissipators and shock transmitters, as well as on applications to bridges, viaducts and industrial plants. The adopted innovative antiseismic systems are described. Research projects, mainly in the framework of Programmes funded by the European Commission, which have been completed recently or are in progress, are briefly outlined. The available or proposed design rules and guidelines and statistics of applications (based on the outcome of recent international seminars) are included. Some examples of applications are briefly illustrated. Finally, the perspectives for future applications are discussed, highlighting the issues which have so far restrained a wider use of innovative antiseismic techniques in Europe.

The meaning of ataxia is failure of coordination. Ataxic patients are not able to define the width, velocity, and rhythms of muscle contractions and cannot coordinate more muscle groups which are synchronously activated. The ataxia can be determined by (1) injury of the proprioceptive afferences, (2) labyrinthic injury, and (3) injury of cerebellum or its connections which are reciprocally connected to the cerebral cortex (neocerebellum), the spinal cord (paleocerebellum), and the vestibular system (archeocerebellum).

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.

Cavernous angiomas are common lesions of the CNS characterized by abnormally dilated blood vessels lined by a thin endothelium, closely clustered together and not separated by normal neural tissue. They are more frequently found intracranially. In the spine, a common location is the vertebral bodies. Intradural extramedullary and intramedullary cavernous angiomas are less frequent lesions, while purely epidural locations are uncommon. Spinal dumbbell-shaped epidural cavernous angiomas are exceedingly rare, and only six cases have been reported in the literature. We describe one additional case whose MRI appearance was indistinguishable from that of a neurinoma, which is a much more common lesion. Surgical treatment is advised and complete radiological evaluation is necessary to rule out concomitant localizations in other organs.

20 consecutive patients with nausea and vomiting secondary to cisplatin chemotherapy uncontrolled by serotonin-antagonist and corticosteroid prophylaxis during their first cycle received adjuvant prop

Using data from the Geneva Cancer Registry, we found that in 2002–2004, breast cancer incidence in women aged 25–39 years increased by 46.7% per year (95% CI: 7.1–74.0, P=0.015), which surveillance or detection bias may not fully explain.

In this article, we describe the morphologic and immunophenotypic features of 75 cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World Health Organization classification, 49 cases were common subtype ALCL, and respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7% of the tumors and, using a panel of 9 T-cell surface markers, 88% could be assigned to the T-cell lineage. A molecular analysis for the T-cell receptor γ (TCR- γ) and the heavy chain of the immunoglobulin H rearrangements was performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56. Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's lymphomas.

There is evidence that spontaneous blinking correlates with cognitive functions. This arises from the observation that blinking rate (BR) is modulated by arousal levels, basic cognitive processes (e.g., attention, information processing, memory, etc.) and more complex cognitive functions (e.g., reading, speaking, etc.). The aim of this work was to test the role of BR evaluation in the assessment of cognitive network functioning in awake patients with consciousness deficits. Thirteen patients were recruited for the study, and were assessed by the Glasgow coma scale (GCS) and Glasgow outcome scale (GOS) on admittance and discharge, respectively. A level of cognitive functioning scale (LCFS) score was assigned at every change in awareness or at least every 2 weeks. At the same time as the clinical tests, the BR was observed for a 5-min period. Ten healthy subjects, observed throughout three non-consecutive days, formed the control group. The BR underwent a different temporal behaviour in the two diagnostic categories. In the persistent vegetative state (PVS) group it remained stable throughout time and linked with the clinical conditions of the patients; whereas in the non-persistent vegetative state (NPVS) group it decreased over time as the cognitive conditions improved. Moreover, a strong inverse correlation was found between overall BR values and LCFS scores. We have concluded that the blinking behaviour changes manifested in PVS and NPVS patients reflect different evolution phases of a cholinergic-dopaminergic imbalance, and that a reduced BR characterizes the early stages of consciousness recovery.

The c-fos promoter is negatively regulated by the retinoblastoma (Rb)-suceptibility-gene- encoded protein as well as by other genes involved in the control of transcription, cell cycle regulation and neoplastic transformation. We have examined by immunohistochemistry the c-Fos and c-Jun proteins in five cases of retinoblastoma in order to evaluate eventual alterations in their expression in vivo, possibly related to a gene mutation or to loss of Rb negative control.

During its long history, the Clinica del Lavoro Luigi Devoto has produced numerous internationally recognized scientific contributions in the specific field of occupational medicine and health, and in other broader areas as, for example, immunology, toxicology, cytogenetics. Pivotal in this activity was the figure of Enrico C. Vigliani, director of the Clinica for over 35 years. We mention here, in particular, the results of the study of "early" markers of lead intoxication; the research on the carcinogenicity of benzene and aromatic amines; the study of the pathogenesis of silicosis and byssinosis; the study of cytogenetic damage after exposure to industrial toxic chemicals; the technical research for dust abatement in mines. Such research also played a major role in the development of pulmonary medicine, toxicology and immunology in Italy, and conferred scientific dignity on the newborn "industrial hygiene" discipline thanks to the work of Nicola Zurlo. Today, the Clinica's research is maintained at international standards especially by the work of thematic Research Centers recently established within the Clinica, covering fields such as occupational and environmental toxicology, occupational oncology, ergonomics, respiratory disease and allergy, psycho-social risk factors. These Centers are also devoted to the development of innovative methods in epidemiology, toxicology, psychology, molecular biology, and ergonomic measurement for the identification and evaluation of health risks at work.

Summary Mucositis is still a leading side effect of high dose chemotherapy and irradiation delivered in autologous and allogeneic bone marrow transplantation. In this double blind randomised study, we tested the efficacy of sucralfate for the prevention of mucositis induced by such conditioning treatments. Treatment was started one day before conditioning regimen and patients were prospectively evaluated. The main endpoint was severe mucositis that was more frequent in the placebo group than in the sucralfate group (47% vs. 29%, P = 0.07). This trend was confirmed after adjustment on total body irradiation (TBI) (P = 0.06), the sole stratification parameter. Interestingly, patients receiving sucralfate showed a significant reduction of diarrhoea (25% vs. 53%, P = 0.005). Overall, the preventive administration of sucralfate appears to be an effective procedure to diminish the occurrence of severe oral and intestinal mucositis in patients treated by high dose chemotherapy alone or combined with TBI before bone marrow transplantation.

Multiple intestinal atresia is a rare disorder with vascular or hereditary etiology. So far, the occurrence of this malformation along with omphalocele has not been reported. We describe a boy born from a nonconsanguineous gypsy couple with intrauterine growth retardation, omphalocele, and multiple intestinal atresia from the pylorus to the rectum. The microscopic examination of the intestine shows multiple small lumina with a sieve-like appearance. This is characteristic of the hereditary atresias and suggests development of a defect in (re)canalization during embryogenesis. The association with omphalocele indicates a common developmental defect may be present.

Angiogenesis is the process that drives blood vessel development in growing tissues in response to the local production of angiogenic factors. With the present research the authors have studied vascular endothelial growth factor (VEGF) production in ovarian follicles as a potential mechanism of ovarian activity regulation. Prepubertal gilts were treated with 1250 IU equine chorionic gonadotropin (eCG) followed 60 h later by 750 IU of human chorionic gonadotropin (hCG) in order to induce follicle growth and ovulation. Ovaries were collected at different times of the treatment and single follicles were isolated and classified according to their diameter as small (4 mm), medium (4-5 mm), or large (5 mm). VEGF levels were measured in follicular fluid by enzyme immunoassay, and VEGF mRNA content was evaluated in isolated theca and granulosa compartments. Equine chorionic gonadotropin stimulated a prompt follicular growth and induced a parallel evident rise in VEGF levels in follicular fluid of medium and large follicles. Analysis of VEGF mRNA levels confirmed the stimulatory effect of eCG, showing that it is confined to granulosa cells, whereas theca cells maintained their VEGF steady state mRNA. Administration of hCG 60 h after eCG caused a dramatic drop in follicular fluid VEGF that reached undetectable levels in 36 h. A parallel reduction in VEGF mRNA expression was recorded in granulosa cells. The stimulating effect of eCG was also confirmed by in vitro experiments, provided that follicles in toto were used, whereas isolated follicle cells did not respond to this hormonal stimulation. Consistent with the observation in vivo, granulosa cells in culture reacted to hCG with a clear block of VEGF production. These results demonstrate that while follicles of untreated animals produce stable and low levels of the angiogenic factor, VEGF markedly rose in medium and large follicles after eCG administration. The increasing levels, essentially attributable to granulosa cells, are likely to be involved in blood vessel development in the wall of growing follicles, and may play a local key role in gonadotropin-induced follicle development. When ovulation approaches, under the effect of hCG, the production of VEGF is switched off, probably creating the safest conditions for the rupture of the follicle wall while theca cells maintained unaltered angiogenic activity, which is probably required for corpus luteum development.

Background: In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines. However, this dose-response question for doxorubicin was never carefully addressed in OC patients. These data and the more favorable toxicity profile of the anthracycline analogue epirubicin prompted us to study high-dose epirubicin (HDE) in relapsed OC patients. Patients and Methods: This phase I study included 19 OC patients with measurable or evaluable disease and no more than one prior (cisplatin-containing) chemotherapy regimen. Dose escalation was not allowed in individual patients. Epirubicin was administered by rapid intravenous infusion (2 (at least 3 patients per dose level). None of the patients received hematopoietic growth factors. We defined the maximum tolerated dose (MTD) as the dose at which we observed WHO grade 4 hematologic toxicity in ≥50% and/or WHO grade 3 nonhematologic toxicity in ≥30% of the patients. Results: The MTD was 200 mg/m2, with DLT being both hematologic (leukopenia and/or thrombocytopenia) and nonhematologic (mucositis). Objective responses were observed in 6 patients (response rate 32%), 3 of them occurring in 10 patients with primary platinum resistance. Conclusions: HDE is tolerable and has activity in second-line after cisplatin-based chemotherapy in OC patients. The recommended dose for phase II trials in such patients is 150 mg/m2, with escalation to 180 mg/m2 if toxicity permits.

Familial clustering of Helicobacter pylori infection has been reported. We tested the hypothesis that simultaneously treating all Helicobacter pylori positive family contacts of infected symptomatic children results in lower treatment failure.Relatives of 47 children (index) with Helicobacter pylori gastritis had endoscopy to assess prevalence of infection in first degree cohabiting relatives. Controls included 60 children with dyspepsia and Helicobacter pylori gastritis whose infected family contacts were not treated. Index children, siblings younger than 18 years of age and control children received a 2-week course of amoxicillin and tinidazole. Parents of index children and their siblings over 18 years of age received a 2-week course of Colloidal Bismuth Subcytrate and tinidazole. The eradication rate in index children and their relatives was compared to controls whose infected family contacts were not treated.Helicobacter pylori was found in 67% of 31 siblings younger than 18, in 82% of 22 siblings older than 18 years, and in 87% of 92 parents. Endoscopy, repeated four to six weeks after the end of treatment, showed Helicobacter pylori eradication in 94% of children and siblings younger than 18, and in 70% of parents and siblings over 18 years in the family treatment group, compared with 75% of control children (p.01).The high prevalence of the infection in family members suggests that person-to-person spread of Helicobacter pylori takes place. Furthermore our results show that if (or when) required, simultaneous treatment given to the whole family results in lower treatment failure, since it may promote compliance to treatment.

Summary Background The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) – and advanced (FIGO ffl – IV) – stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinical CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%–73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c = clinical, p = pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients < = 55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p = 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p = 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (33%) or incompleteness (33%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are needed.

Nuclear DNA content was determined on paraffin blocks of 28 neuroblastic tumors retrieved from Surgical Pathology files. In 26 cases cytofluorimetric analysis for DNA content was satisfactory. 8 tumor were diploid, 12 were aneuploid and 6 tetraploid. All but one of the children with diploid neuroblastoma (NB) died after a survival ranging from 14 to 32 months. The only surviving child had a Stage I thoracic ganglioneuroblastoma (GNB) and was alive after 27 months. Conversely 11 of 12 patients with aneuploid tumors were alive with prolonged follow-up. Two children are alive after a period exceeding 146 months. The only exception in this group of aneuploid tumors was a child with Stage IV neuroblastoma of the adrenal gland with pleuro pulmonary metastasis who died after 6 months. In the group with tetraploid tumors 3 patients died (2 children with Stage III and IV died early while the third, with thoracic Stage II GNB, survived for 72 months). Two patients with tetraploid GNB Stage II and III are alive 65 and 72 months after diagnosis respectively. Another child with Stage IV adrenal NB is alive after 14 months but with metastatic spread to bones, bone marrow and lymph nodes. Cox analysis of the cases demonstrated ploidy as an independent prognostic factor. These results are in agreement with other molecular analysis linking near-ploidy of Neuroblastic tumors to poor prognosis. Ploidy, as detected by flow cytometry for nuclear DNA content, may represent an important prognostic factor in Neuroblastic tumors. The advantage of flow cytometry over other techniques of molecular analysis is represented by the simple methodology suitable for fixed and paraffin embedded tissue, even on retrieval material.

A dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines has been demonstrated in vitro. However, this has never been carefully addressed in the clinic. These data and the more favourable toxicity profile of the anthracycline analogue epirubicin were reasons to study high-dose epirubicin (HDE) in OC patients who relapsed on/after platinum-based chemotherapy. This was done both in a phase I/II feasibility study (n = 27; HDE dose 120-200 mg/m2 q3 weeks) and a still ongoing straightforward phase II study (n = 91; HDE dose 150-180 mg/m2 q 3 weeks).Responses were observed at all dose levels. Overall 24 of the 118 patients responded (20%), which is much higher than reported with lower doses (7% with doses of 60-110 mg/m2). The most important side effects were myelosuppression, alopecia, nausea and vomiting and mucositis.HDE is tolerable and has activity in second-line after platinum-based chemotherapy in OC patients.

Nausea and vomiting remain one of the most distressing and unpleasant side-effects of cancer chemotherapy [1, 2]. These symptoms cause significant delayed psychological morbidity such as anticipatory nausea/vomiting or depression [3] and are the most frequently cited reasons patients give for not wanting to continue chemotherapy or even start treatment. Recently, selective serotonin antagonists (5HT3-antagonists) have shown considerable antiemetic potency during highly emetogenic therapies with fewer side-effects [4, 5]. Despite these improvements, 20–30 % of patients undergoing Cisplatin chemotherapy still remain unresponsive to the most efficient antiemetic regimens available i.e. 5HT3-antagonists plus Dexamethasone [6].

20 consecutive patients with nausea and vomiting secondary to cisplatin chemotherapy uncontrolled by serotonin-antagonist and corticosteroid prophylaxis during their first cycle received adjuvant propofol. This new anesthetic agent was added at subhypnotic doses, i.e. 1 mg/kg/h, as a continuous intravenous infusion during the two subsequent chemotherapy cycles. In 85 and 90% of patients, nausea and vomiting were prevented in the first 24 h following the first and second propofol-supplemented chemotherapy cycles respectively. 24-72 h postchemotherapy, this side effect remained suppressed in 75 and 70% of patients, respectively. Patients' comfort and appetite were improved. All 20 subjects preferred the propofol-containing regimen.

Granular acute lymphoblastic leukemia (ALL) is a rare morphological variant of ALL, characterized by cytoplasmic azurophil granules or inclusions, positive for aspecific esterase and acid phosphatase, with heterogeneous features at the ultrastructural level.In an attempt to determine whether the presence of granules or inclusions marks a biologically distinct variety of ALL with peculiar clinical features, a prospective morphological review was undertaken of children entering AIEOP protocols for ALL in the period from 1985 to 1989.Of 531 cases examined, 16 (3%) were found to have greater than 1% granular bone marrow blasts, with 7 cases (1.3%) having greater than 10%. The presence of granules or inclusions was associated with the immunophenotype of "common" ALL. There was no clear association with FAB type L1 or L2 nor with particular clinical or hematological findings at presentation. Complete remission was achieved in all cases; one patient died of infection in remission at 3 months and 2 patients relapsed after 12 and 32 months, respectively, while the others are still in remission after a minimum follow-up of 24 months.In conclusion, granular morphology seems to have no prognostic importance in children ALL.

Both antacids and H2 receptor antagonists have a potential role in treating peptic oesophagitis associated with acid reflux. The aim of this study is to assess the efficacy and tolerability of famotidine and alginate-antacid in children with endoscopically documented peptic oesophagitis. We compared clinical, endoscopic and histological response to alginate-antacid (1 tablet to be chewed 30 min after each meal and at bed time) or famotidine (1 mg/kg before supper at 7 pm) in 49 children (mean age 9 years, 34 males). Twenty-four of them were randomly allocated to alginate-antacid treatment (group A), twenty-five to famotidine (group B). Both treatments were protracted for six months and endoscopy was then repeated. Symptoms disappeared in 43.4% and improved in 47.8% of children of group A and disappeared in 91.6% of those of group B (p less than .05). Mean time for symptom disappearance was 17 weeks for group A and 5 weeks for group B (p less than .01). After six months, at endoscopy oesophagitis was healed in 43.4% in group A and in 41.6% of group B, the difference between the two groups was not significant, however the improvement of endoscopic grades induced by famotidine was significantly better (p less than .05). Histology showed a healed peptic oesophagitis in 52.2% of the children in group A and in 70.8% of group B (p less than .001). No toxicity was observed with either treatment. We conclude that famotidine is superior to alginate-antacid in treating peptic oesophagitis associated with acid reflux, since it induces a better symptomatic response and a greater improvement of endoscopic lesions.

Various strategies for local immunotherapy performed by using lymphokines and lymphocytes are presented. In experimental mice models, the antitumor reaction elicited through the injection of little amounts of IL-2 and gamma-IFN at the tumor growth site is significantly enhanced by the concurrence of lymphocytes from tumor bearing mice artificially admixed to challenging tumor cells. These lymphocytes act as initiator or helper cells that elicit both a local and a systemic long lasting immune reaction by the release of additional lymphokines. The reaction activated mostly involves draining lymph nodes, where multiple reaction mechanisms are induced. The local injection of cocktails of molecularly defined lymphokines can also mimic the helper action of lymphocytes and trigger a similarly effective anti-tumor reaction. A set of pilot clinical trials with IL-2 or gamma-IFN injected perilymphatically were initiated in patients with advanced primary or recurrent localized tumors of the head and neck and the bladder. This treatment appears to elicit a local reaction by activating a few pathways of patients immunoreactivity, whose efficiency may well be high, as shown by the tumor inhibition often observed.