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ABSTRACTAutonomous navigation is currently subject to particular interest for naval and commercial vessels. In addition to the regulatory effort, several pieces of research tackled the development of new guidance laws, stable and robust control algorithms, methodologies to increase situational awareness, and collision avoidance algorithms. However, most of these systems blindly trust information from navigation sensors, which can malfunction or, even worse, have their data altered by cyber-attacks. This last scenario will be increasingly common shortly and represents a dangerous threat that future highly computerised ships must face. The proposed work shows an approach capable of hijacking a state-of-the-art collision avoidance algorithm route by feeding it with rogue data. The effects of such a cyber-attack are shown via an extensive simulation campaign, testing the methodology on three different COLREG scenarios: head-on, crossing, and overtaking. The study additionally highlights the susceptibility of forthcoming navigation systems to security breaches, which still needs to be addressed in the existing literature. According to the experimental findings, attackers can attract the autonomous ship guidance toward their objective at a mean distance of $ 133\,{\rm m} $ 133m. Finally, suggestions on how to harden these systems against this family of attacks are provided in the conclusion.

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4+CD25+FoxP3+regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4–21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 106/Kg), Tregs (2 × 106/Kg) and Tcons (0.5–1 × 106/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1–4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2–4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months–5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.

The third Naval Engineering and Ship Control special edition of the Journal of Marine Engineering and Technology aims to present cutting-edge research on naval engineering and ship control, as was presented during the International Naval Engineering Conference and Exhibition (INEC) and the International Ship Control Systems Symposium (iSCSS), held together in Delft in 2022.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities.Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACOP-B than among those given F-MACHOP (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) and of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B.The third-generation regimens, F-MACHOP and MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, serum lactate dehydrogenase, mediastinum involvement, bulky disease, histology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete response by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease are prognostic factors that increase the risk of a lower rate of complete response. These data confirm the important role of a pretreatment selection for the poor-risk patients and, on the basis of these parameters, it will probably be possible to consider these patients for high-dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support.

Objectives:Scope of this analysis was to estimate the cost-effectiveness of rituximab maintenance (r-maintenance) therapy vs. observation, in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from a large multicenter study, in the Italian public payer’s perspective.

To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia.

SummaryThe role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. We report the results of a series of 37 operated patients for primary gastric lymphoma (PGL). All patients underwent gastrectomy with D2 lymphadenectony and bilateral liver biopsies. Postoperative histopathological classification was compared to preoperative staging data. No mortality and low morbidity were observed in this series of patients. We found a high incidence of mixed grading of tumors and a relatively high incidence of lymph node metastases in low grade lymphoma. Relying on preoperative biopsies and imaging techniques could lead to preoperative staging inaccuracy and therefore to inappropriate treatment planning. For these reasons we advocate systematic primary surgery in PGL. Surgery could be useful for staging purposes and seems to be curative in stage IE.

Aim of this study was to evaluate the cost-effectiveness of rituximab + CHOP (R-CHOP) versus CHOP alone, in Italian patients with aggressive Non-Hodgkin lymphoma (NHL), in the NHS’ perspective.The economic analysis is based on an existing Markov model which was developed to evaluate costs and effects for two hypothetical cohorts of patients aged = 60 years or aged < 60 years respectively, over a time frame of 15 years after administration of chemotherapy. The model is based on five health states (start therapy, complete response, no response, progression, death) and combines efficacy data from published clinical trials (GELA-98-5) with costs of therapies and follow-up after chemotherapy, based on Italian treatment patterns. Costs and effects were discounted respectively at 6% and 1.5% per year. Extensive 1-way and Monte Carlo sensitivity analyses were conducted to test the robustness of results.For the two cohorts (age = 60 or age < 60 years), incremental discounted survival gains with R-CHOP vs. CHOP were respectively 1.08 and 1.02 years per patient; incremental QALYs were 1.15 and 1.04 per patient; incremental cost/patient was €14 838 and €13 938; the incremental cost per life-year gained (cost/LYG) was therefore €13 732 and €13 717, while the incremental cost/QALY gained was €12 879 and €13 362.The clinical advantage of R-CHOP is supported by values of incremental cost/LYG and cost/QALY gained, which are well below the thresholds commonly indicated both in the international and Italian literature. R-CHOP is a substantial improvement in the treatment of aggressive NHL, at a reasonable cost, in the perspective of the Italian NHS.

Peripheral T-cell lymphomas (PTCL) are usually characterized by aggressive clinical behaviour and poor clinical outcome, but their biological background has not been extensively investigated to date, due to their low incidence, about 10% of all non-Hodgkin's lymphoma cases in Western countries, and also to the paucity of specific molecular-genetic abnormalities. Neverthless, there is increasing biological and clinical evidence that primary nodal PTCL should be considered separately from extra-nodal cases, but little is known about biological factors of possible clinical and prognostic impact. This immunohistochemical study has analysed the expression of p53, Mdm2, p21^WAF1, BCL-2 and p-glycoprotein (MDR-1 gene product) in a series of 45 cases of nodal peripheral T-cell lymphomas (PTCL) with 'high-grade' histology. The immunohistochemical findings were then correlated with proliferative activity and clinical outcome. p53 was over-expressed in 13 cases (28.9%). p53 positive cases showed significantly higher proliferative activity (p&lt;0.01), more frequent expression of Bcl-2 (p&lt;0.01) and less frequent expression of p21^WAF1 than p53 negative cases. Mdm2 and p-glycoprotein were expressed in 4/13 (30.8%) and 8/13 (61.5%) p53 positive cases respectively, and in none (0%) of the p53 negative cases (p&lt;0.01). Analysis of the survival curves showed that p53 positive cases were associated with a significantly poorer clinical outcome than p53 negative cases, in terms of both overall survival (p=0.0032) and event-free survival (p=0.0004). Furthermore, multivariate analysis showed that p53 expression was the most important independent prognostic variable. These findings indicate that p53 over-expression identifies a subset of nodal PTCL cases with a distinctive biological profile (higher proliferative activity, less frequent expression of p21^WAF1 and more frequent expression of Bcl-2, Mdm2 and p-glycoprotein than p53 negative cases) and poor clinical outcome. The immunohistochemical analysis of p53 expression is a simple, rapid and low-cost method which may provide information of potential clinical and prognostic value in nodal peripheral T-cell lymphomas. Copyright © 2001 John Wiley & Sons, Ltd.

There is very little experience regarding recurrences following videothoracoscopic (VATS) treatment of primary spontaneous pneumothorax. We report our experience with 19 patients who underwent redo-VATS to evaluate the feasibility of such surgical approach.

The CD2 co-receptor expressed on the surface of T lymphocytes is able to stimulate T cell activation, proliferation and cytokine production in the absence of direct engagement of the antigen-specific TCR. Engagement of human CD2 by mitogenic pairs of anti-CD2 mAb induces tyrosine phosphorylation of a number of intracellular proteins including a 120 kDa phosphoprotein that we identify as the proto-oncogene c-Cbl. Rapidly tyrosine phosphorylated following stimulation of a number of cell surface receptors, c-Cbl is an adaptor protein that has been shown to associate with a complex of intracellular signaling molecules, and to mediate both positive and negative regulatory effects. Here we show that, like TCR-CD3 stimulation, stimulation of CD2 enhanced the association of c-Cbl with both Crk(L) and the p85 subunit of phosphatidylinositol-3 kinase. Overexpression of wild-type c-Cbl protein inhibited both CD2and CD3-induced NF-AT transcriptional activity, suggesting that CD2 signaling is also negatively regulated by c-Cbl. The inhibitory effect of c-Cbl depended upon its N-terminal phosphotyrosine-binding domain, the domain that has been shown to be required for inhibition of the Syk/ZAP-70 family kinases. In Syk(-) Jurkat T cells stably expressing wild-type ZAP-70, CD2 stimulation induced only a minimal increase in ZAP-70 tyrosine phosphorylation. Nevertheless, ZAP-70 kinase was required for CD2-mediated NF-AT transcriptional activity. Thus, CD2-mediated NF-AT transcriptional activity appears to depend upon ZAP-70/Syk kinases and to be negatively regulated by c-Cbl.

This paper describes a nonstandard procedure for total knee replacement (TKR), based on the use of modern tools such as computers, electronic sensors, and robots, to achieve accurate and optimal implant results. The intervention is planned on a standard PC connected to the CT scanner. Dedicated software shows the surgeon limb alignment and knee status and assists in the choice of the best prosthesis. The intervention is then performed with a new device and surgical procedure. At first the femur and the tibia are fixed to the operating table with a special clamp and the knee bones are exposed with the standard technique; then the surgeon digitizes the shape of the joint and the computer transfers the planned surgical strategy to a dedicated surgical robot. Resections are performed by the surgeon on a constrained guide held by the robot. In this paper we summarize the main results on the system performances, and discuss the clinical implications of this new technology in the operating room. Preliminary experiments on cadavers and volunteers show that this methodology can improve the accuracy of the implant to 2.5 mm and 2°, reduce operating time and surgical errors, and may represent a challenging alternative methodology for TKR. © 2000 Biomedical Engineering Society. PAC00: 0707Tw, 8780-y

This paper focuses on the use of linear logic as a specification language for the operational semantics of advanced concepts of programming such as concurrency and object-orientation. Our approach is based on a refinement of linear logic sequent calculi based on the proof-theoretic characterization of logic programming. A well-founded combination of higher-order logic programming and linear logic will be used to give an accurate encoding of the traditional features of concurrent object-oriented programming languages, whose corner-stone is the notion of encapsulation.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hcdgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemother-apeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were cvaluable: 52 received CH(doxorubicin)OP and 51 received CI(Idaruhicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%. with complete response in 62%: 638 in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 868 of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced Severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse event (I moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and I severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .OOO1). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduccd clinical toxicity in comparison to the standarddoxorubicin-containing CHOP rcgimen in patients with intcrmediate-grade non-Hodgkin's lymphoma.

In the paper stator faults are analyzed by means of a procedure based on the space-vector theory. The used approach, due to Stepina, allows to consider separately each conductor of every single slot and therefore to take easily into account the winding dissymmetry.The interactions among the different harmonic fields are studied by starting from the topological structure of windings and the harmonic analysis of the currents and of torque Is carried out.The method is tested to numerical computations of steady-state currents for an induction machine with different positions of stator short-circuits.Finally the procedure is validated by using an experimental squirrel cage machine, having stator windings constructed so as to realize different short-circuits.

Summary Interferon alpha (a-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid a-IFN (a n-1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of a n-1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during a-IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of a-IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that a-IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.

Abstract: An extension of the class of logic programs for which the Negation as Failure rule is equivalent to the Closed World Assumption is presented. This extension includes programs on infinite domains and with recursive definitions. For this class of programs with ground (positive or negative) queries the Query Evaluation Process is complete. A characterization of this class of programs is given, and a decision algorithm, which recognizes a subclass of these programs, is presented. The algorithm is based on showing the correspondence between a program and a primitive recursive function.

Smooth acceleration during the start-up is important in some industrial applications of induction motors. An example is given by texile machines, where the breaking fibre threas during the start-up must be avoided.An asymmetrical starting scheme, implemented by means of an external resistance inserted in one of the motor phases, can provide a simple, but elective, solution to this problem; the value of the resistance Mill depend on the assigned value of the maximum torque developed. To compute the transient behavior during the start-up, a dynamical motor model, effective also of describe asymmetrically connected machines has been used to study the torque control problem. The present paper reports the results obtained with reference to a 70 W induction motor supplied by a frequency converter. A comparison between experimental data and simulation is presented.

Summary In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-crossresistance with other alkylating compounds warrants further studies.

This study analyzes the value of surgery in the treatment, staging and long-term survival of 17 patients affected with primary gastric lymphoma. In 7 patients the neoplasm was localized to the lower third of the stomach, in three to the middle third, in two to the upper third, while in 5 patients there was involvement of the entire stomach. Patients were classified according to the Ann-Arbor classification. Nine patients were stage Ie, five stage Ile, and three stage IVe. A partial gastrectomy was carried out in ten patients and total gastrectomy in 7. In all cases surgical excision of the gastric lymphoma was performed together with intraoperative staging including bilateral hepatic biopsies, and exploration of all abdominal lymph nodes.Two postoperative deaths occurred among the 7 patients who underwent total gastrectomy but no major complications were observed in the remaining 5 patients. No deaths occurred among the 10 patients who underwent partial gastrectomy, but in one case an acute complication developed. Staging laparotomy permitted the correction of clinical staging, and showed that three cases were understaged and one overstaged.All patients received adjuvant chemio-radiotherapy. All but one patient are currently alive, well and free of disease. Survival was correlated significantly with the stage of the disease and extent of gastric involvement, but there was no correlation between survival, histological grade, and the type of gastrectomy performed.

This paper describes a new approach to the analysis of the electromechanical transient behavior of induction motors using the generalized rotating-field theory. The equation set is written on the basis of the representation of the electrical variables of the real circuits using the general theory of linear static networks -for every speed value. The supplied voltage waveform is partitioned into segments with constant or sinusoidal shape; this allows an easy computation of the system's initial state imposing dynamical steady-state conditions.The subsequent integration of the electromechanical equation then enables one to compute (by means of a step by step procedure) the whole dynamical behavior of the system.The procedure out lined, unlike d-q transformation methods, can also be applied to motors with asymmetrical windings.The performed machine simulation has -been validated by means of some experimental tests. A very close agreement has been obtained between the computed and the measured results.

In this paper we define a new notion or truth on Herbrand interpretations extended with variables which allows us to capture, by means of suitable models, various observable properties, such as the ground success set, the set of atomic consequences, and the computed answer substitutions. The notion of truth extends the classical one to account for non-ground formulas in the interpretations. The various operational semantics are all models. An ordering on interpretations is defined to overcome the problem that the intersection of a set of models is not necessarily a model. The set of interpretations with this partial order is shown to be a complete lattice, and the greatest lower bound of any set of models is shown to be a model. Thus there exists a least model, which is the least Herbrand model and therefore the ground success set semantics. Richer operational semantics are non-least models, which can, however, be effectively defined by fixpoint constructions. The model corresponding to the computed answer substitutions operational semantics is the most primitive one (the others can easily be obtained from it).Copyright 1993, 1999 Academic Press

We propose a new negation rule for logic programming which derives existentially closed negative literals, and we define a version of completion for which this rule is sound and complete. The rule is called "Negation As Instantiation" (NAI). According to it, a negated atom succeeds whenever all the branches of the SLD-tree for the atom either fail or instantiate the atom. The set of the atoms whose negation is inferred by the NAI rule is proved equivalent to the complement of Tc↓ ω, where Tcis the immediate consequence operator extended to non-ground atoms (M. Falaschi et al., 1989, Theoret. Comput, Sci.69(3), 289-318). The NAI rule subsumes negation as failure on ground atoms, it excludes floundering, and can be efficiently implemented, We formalize this way of handling negation in terms of SLDNI-resolution (SLD-resolution with Negation as Instantiation). Finally, we amalgamate SLDNI-resolution and SLDNF-resolution, thus obtaining a new resolution procedure which is able to treat negative literals with both existentially quantified variables and free variables, and we prove its correctness.

Using elementary ideas and techniques, we prove (Theorem 2) that for a nonconstant differentiable function , a< b, the set S(f) = {xϵ [a, b] : f'(x) ≠ 0} cannot be negligible. This result remains valid if ffails to be differentiable on a countable subset of [a, b].

Summary We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600×109/l in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600×109/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET.

The current study represents one of the first psychological investigations that attempts to describe the untreated course of late onset characterological dysthymia. Of 34 dysthymic subjects who were studied for 9 months, six women remitted (18). Twenty-eight subjects (82) remained unchanged. Among the nonremitters, we found stable patterns of functioning in the cognitive, coping, personality, interpersonal, and environmental spheres. The destructive nature of these refractory patterns appeared to predispose the individual to a depressionogenic lifestyle. These unchanging features were not found among the remitters. The small size of the remitting group makes our speculations tentative but we did find consistent changes over time across measures of functioning. While the symptom-affective features of the nonremitters remained at clinically significant levels throughout, the depressive symptom levels of the six remitters decreased to nonsignificant clinical levels during the last half of the study. It was noted that, based on these preliminary data, DSM-III-R may be “underdescriptive” in regard to relevant symptom features of characterological dysthymia.

At each menstrual cycle, the uterine endometrium undergoes intense remodelling. Of the many factors implicated in tissue remodelling, the matrix metalloproteinases (MMPs) play a central role owing to their capacity to degrade the extracellular matrix. The aim of this study was to examine the nature and cellular origin of endometrial proteases as evaluated in culture systems with clearly characterized cell types. Endometrial cells from hysterectomy specimens were prepared using collagenase digestion. Bone-marrow-derived cells (a known source of proteases) were removed by immunopurification. Cells were cultured on different substrates (matrigel, agarose, glass or plastic). Purity of cell preparations was examined by immunocytochemistry, and proteases were characterized by zymography on SDS-PAGE containing gelatin. The cell phenotype in culture was largely influenced by the type of substrate. Gelatindegrading enzymes detected in culture supernatants of stromal and epithelial cells had molecular masses ranging from 42 to 248 kDa, and were identified as metalloproteinases. We conclude that human endometrial stromal and epithelial cells express several matrix metalloproteinases, the expression of which clearly depended on the purity of cell preparation, on cell adhesion and on the nature of the substrate on which the cells grew. These enzymes might be involved in endometrium remodelling, blastocyst implantation and trophoblast invasion.

Allogeneic bone marrow-engrafted adults immunized with meningococcal types A and C and pneumococcal type 14 polysaccharide antigens showed only low antibody titers of the IgM class, no antibody titers of the IgG or IgA classes, and no bactericidial activityin vitro. The analytical isoelectrofocusing showed the appearance of a restricted pattern of clonotypes in a minority of subjects. These observations are consistent with the hypothesis that B cells in bone marrow transplant patients express some characteristics of neonatal B cells and suggest that polysaccharide-protein conjugates, rather than isolated polysaccharide, might be utilized in the setting of bone marrow transplantation.

Summary In a prospective randomized trial parenteral trimethoprim/sulphamethoxazole was added to amikacin plus piperacillin in order to compare triple-drug antibiotic combination with a standard regimen as empiric therapy of fever in patients with granulocytopenia. One hundred and sixty-one episodes were evaluated; 74 episodes with amikacin plus piperacillin and 87 episodes with amikacin plus piperacillin plus trimethoprim/sulphamethoxazole. The overall response to therapy (63% vs. 84%) as well as the response of microbiologically documented infections (60% vs. 82%) was significantly better in patients treated with the triple-drug combination (p < 0.05). However, no statistically significant differences in response to antibiotics at different infection sites or with regard to any single pathogen was found between the two groups. Trimethoprim/sulphamethoxazole seemed to be responsible for additional toxicity (nausea and vomiting) when added to amikacin plus piperacillin, but these side-effects were clearly related to the rate of infusion of trimethoprim/sulphamethoxazole. The findings of this study support the use of a three-drug versus a two-drug combination as empiric antibiotic regimen in febrile granulocytopenic patients.