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In view of recent knowledge on proteins regulating the cell cycle, we re-evaluated proliferative features of 98 diffusely growing non-Hodgkin's lymphomas. The combined use of 5 proliferation–associated variables (mitotic indices and percentages of Ki-67⁺, p34^cdc2+, cyclin A⁺ and cyclin B⁺ cells) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (1) low, (2) intermediate and (3) high proliferative activity. Conversely, bivariate plots exposed considerable cluster overlaps. Multivariate stepwise discriminant analysis of all cases revealed a decreasing order of discriminant power for % Ki-67⁺ cells > % p34^cdc2+ cells > mitotic index > % cyclin A⁺ cells > % cyclin B⁺ cells. The combined use of 2 variables only, mitotic index and % p34^cdc2+ cells, allowed a clear-cut separation of clusters 2 and 3. In bivariate plots, correlations were best between % Ki-67⁺ cells and % cyclin A⁺ cells and between mitotic indices and % cyclin B⁺ cells. Except for chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster 1), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cell lymphomas and diffuse follicular center lymphomas in cluster 1 and of diffuse large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. Anaplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy. Int. J. Cancer 83:203–209, 1999. © 1999 Wiley-Liss, Inc.

Total sleep deprivation (TSD) shows powerful but transient clinical effects in patients affected by bipolar depression. Pindolol blocks the serotonergic 5-HT1Aautoreceptor, thus improving the antidepressant effect of selective serotonin reuptake inhibitors. We evaluated the interaction of TSD and pindolol in the treatment of acute episodes of bipolar depression. Forty bipolar depressed inpatients were randomized to receive pindolol 7.5 mg/day or placebo for nine days in combination with three consecutive TSD cycles. Pindolol significantly improved the antidepressant effect of TSD, and prevented the short-term relapse after treatment. The response rate (HDRS scores <8) at the end of treatment was 15/20 for pindolol, and 3/20 for placebo. Coadministration of pindolol and TSD resulted in a complete response, which could be sustained for six months with lithium salts alone, in 65% of cases. This results suggest a major role for serotonergic transmission in the mechanism of action of TSD, and makes TSD treatment more effective in the treatment of bipolar depression.Neuropsychopharmacology (1999) 20 380–385.10.1016/S0893-133X(98)00129-8

A whole family of laser-plasma interaction experiments is based on the phase analysis of the laser pulse after the propagation in a plasma. Typically, this phase is obtained by means of interferometry. As pulsed interferometry is a much more difficult task than taking simple images of the beam, we developed a numerical code for extracting phase information from images. The technique, based on the algorithm of Gerchberg–Saxton, showed to be very effective in retrieving 2D phase distributions of simulated as well as real beams. The convergence of the algorithm is fast (some minutes on a personal computer). The electronic noise in real images is intrinsically discarded by the algorithm.

On the basis of a recent paper (Engeman, R. M., and Swanson, G. D. Comput. Biomed. Res. 24, 599 (1991)) on the choice of appropriate methods of 2 x 2 contingency table analysis, experimental results are reported and discussed in order to further clarify the real limits of the methods most commonly used in small sample size data situations. Copyright 1993, 1999 Academic Press

Purpose of this paper was to obtain a low-order identification-oriented model of the systemic vascular bed, with a future view to beat-to-beat monitoring and control applications. To this aim reduced models of the systemic bed were compared on the basis of Akaike Information Criterion (AIC). combined with parameter estimation accuracy and physical interpretability. These criteria have been applied to systemic pressure data generated by a cardiovascular simulator, implemented using a Computer Aided Design of Control System (CADCS) package. The results obtained show that only simple models can be accurately estimated, when signals with a limited frequency spectrum such as the physiological ones are used. In particular, the first-order model shows good properties in terms of accuracy of the estimates and physical interpretability. The use of a second-order model can provide less biased values for the diastolic and systolic time-constants even if accuracy of the estimates and convergence of the identification procedure are sacrified.

This paper focuses upon the use of simple mathematical models in estimating total pulmonary compliance for clinical investigation and attempts to quantify the estimation errors that may be expected in presence of significant and sustained gas leakage from lungs. To this end, simulation experiments were made and mechanically ventilated patients were analyzed. The results obtained in both cases demonstrate that, in spite of good reproducibility, systematic overestimation of the compliance (ranging from 6% to 50% for normal and stiff subjects, respectively) occurs when the presence of gas leakage is neglected. Consequently, a monocompartmental extended model of respiratory mechanics is proposed and tested. This model provides reproducible and unbiased estimation of compliance and can be seen as an appropriate representation of respiratory mechanics also in presence of gas leakage.

Analysis of the spatial distributions of objects is fundamental to biomedical image interpretation. Nearest-neighbor (NN) methods are generally used to assess whether objects are arranged at random or in a deterministic manner. Simple standard NN techniques, however, may fail to identify complex spatial organizations. To overcome this problem the present study proposes a NN iterative algorithm that enables deterministic spatial patterns to be detected by identifying the distances between objects for which there is the greatest deviation from randomness and hence the amplitude of the areas of maximum reciprocal influence between objects. The performance of the algorithm is evaluated by applying it to both manufactured and experimental data. The manufactured data example showed that the proposed procedure produced neither false positives or negatives. The method proved to be extremely sensitive, detecting even small deviations from randomness. The experimental analysis was applied to the study of the spatial distribution of apoptotic structures in malignant neoplastic tissue. It showed that the apoptotic cells and bodies are characterized by a complex spatial pattern, and aggregate closely.

The purpose of the present study was to compare the efficacy of clozapine with that of chlorpromazine in an open label manner (both given in association with lithium salts) in the treatment of acute mania. Thirty hospitalized manic patients were entered into the study. All patients met DSM-IV criteria for bipolar disorder, Manic Episode; 27 patients completed the study and three patients dropped for noneompliance. The duration of the study was 3 weeks. Patients were randomly assigned to two treatment groups: group 1 (n=15) was treated with clozapine at a mean dose of 166 mg/day and group 2 (n =12) was treated with chlorpromazine at a mean dose of 310 mg/day. Manic symptomatology was rated on Young Rating Scale for Mania (YRSM) each week; side effects were recorded on dosage records and treatment emergent symptoms; extrapyramidal acute side effects were rated on the Simpson-Angus Rating Scale performed at the beginning of the study and after 3 weeks of treatment, A two-way repeated measures analysis of variance on YRMS scores showed a significant time effect (p< 0.0001) and a significant time-group interaction (p< 0.0001). Post-hoc comparison between the two groups showed a significant difference after 2 weeks of treatment (P= 0.00001), with clozapine treated patients showing lower YRSM scores than chlorpromazine treated patients, YRSM scores at the end of the study were not significantly different, Patients treated with clozapine showed a more rapid trend toward amelioration. No clinically relevant side effect was observed during the study.

Our study was designed to compare cellular kinetic parameters of classical Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C, common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M transition. These disorders share some phenotypic properties, e.g., CD30 positivity of putative neoplastic cells. The percentages of cells expressing p34^cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also registered. Highly significant differences between HD and ALCL-C were recognized: a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the metaphase stage) and consequent multinucleation and/or deletion of CD30⁺ cells was prominent, in contrast to ALCL-C. This was associated with a markedly lower fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of CD30⁺ cells in HD, but not in ALCL-C, was correlated with the %p34⁺ LAC; c) the proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to the percentages of cyclin-B (C + N)⁺ LAC in ALCL-C but not in HD; d) in HD, in contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)⁺ LAC did not correlate with the ana/telophase indices (ATI, reflecting successful completion of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34⁺ LAC were positively correlated with ATI or the degree of CD30⁺ cell deletion, but inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to take an intermediate position between HD and ALCL-C, but sided more with the latter. In conclusion, our present results suggest a derangement of MPF kinetics and functions that is more profound in HD than in ALCL-C. Int. J. Cancer 77:408–414, 1998. © 1998 Wiley-Liss, Inc.

A research program aimed at developing an EHD pump for insulating liquids is in progress at the Electrical Engineering Department of the University of Genova. The initial part of this program considered a single stage ion drag pump and was aimed at the optimization of the relevant electrodes (materials and geometry) and interelectrode gap to obtain a high hydrostatic pressure. The experimental data on three different technical grade liquid dielectrics (oils) are reported. They allow a comparison with two different theoretical pressure vs. voltage relations, due to Stuetzer and to Pickard, for each tested liquid. The general validity of such relations is discussed and questioned. The latter point and the experimental data here reported illustrate that, at present, it is necessary to introduce, early in the design process of this kind of EHD pumps, an experimental stage, specific to each liquid to be used.

A method was developed that allows the determination of benomyl, carbendazim (MBC), thiophanate methyl (TFM) as carbendazim and thiabendazole (TBZ) by HPLC with UV detection. After extraction and cyclization of TFM into MBC, the conversion of benomyl into MBC is carried out by absorbing the raw extract on a ready-to-use, disposable column of a macroporous Kieselghur-type material and percolating 0.1 M HCl through it. Benzimidazolic residues are partitioned into the acid solution whereas most of the co-extractives are retained on the column. The final clean-up is performed on a strong cation-exchange (SCX) cartridge. The determination of MBC and TBZ is carried out by HPLC-UV detection on a polymeric reversed-phase column eluted with a water-ecetonitrile (70 : 30). Recoveries of MBC and TBZ from pear, apple, orange, grape, kiwi, tomato and lettuce, spiked at levels of 0.22 and 0.88 mg/kg, were satisfactory (70%). The main features of the method include high selectivity towards MBC and TBZ, reduced consumption of reagents and solvents, reduced handling operations, lack of emulsions and the use of disposable items.

In this study our aim was to determine the biophysical values of constitutive skin color in Caucasians and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Constitutive skin color was measured on the buttock, with a Minolta CR‐200 colorimeter, in a population of 557 consecutive subjects belonging to phototype categories I, II, III and IV. The colorimeter expresses the results in five different color systems. We used the “Yxy” and L*a*b* systems, which are the most widespread in dermatology. Statistical analysis of the data showed that the “Yxy” system is even more discriminant than the L*a*b* system when the Fitzpatrick classification scheme is adopted as the reference and shows a poor ability to correctly classify the intermediate phototypes (II and III). On the contrary the “Yxy” system performs well in distinguishing phototypes I and IV. To establish whether this low discriminating capacity for phototypes II and III is related to a low discriminating capacity of the method suggested by Fitzpatrick or by our procedure, an objective technique (minimal erythemal dose) should be used to evaluate the percentage errors of classification of both the Fitzpatrick method and instrumental measurement of skin color. The results of such a study are extremely important because the evaluation of skin color is objective, simple and has potential applications in dermatology and cosmetology.

Before beginning PUVA‐therapy it is important to accurately gauge an individual's degree of psoralen photosensitivity. This determination is usually based on an individual's skin phototype or minimal phototoxic dose. Since minimal phototoxic dose is technically complex and time consuming to measure, sun reactivity skin phototype is often used instead; however, it has recently been shown that skin phototype lacks specificity as a predictor of an individual's minimal phototoxic dose. In this study, an artificial neural network was developed to attempt to predict the minimal phototoxic dose from skin colour measurements combined with skin phototype. Our results showed that minimal phototoxic dose was predicted with an error less than 1 J/cm2in only about half the subjects. In conclusion, minimal phototoxic dose probably cannot be predicted with sufficient accuracy on the basis of skin colour and skin phototype alone.

In the present study histologic, clinical and follow-up data of 37 cases of retinoblastoma were statistically analyzed by means of a multivariate method. The evaluated histological parameters were: growth pattern, degree of differentiation, number of mitoses, presence of necrosis, pseudorosettes, blood vessel basophilia, calcification, extension to anterior chamber, invasion of optic nerve and ocular coats (choroid and sclera). The analysis was based upon the Cox proportional hazards regression model. Invasion of ocular coats proved to be highly correlated to the prognosis (p < 0.0002). None of the other parameters showed a significant relation to survival.

The experimental apparatus exposed to the positive pion beam of the LEALE Laboratory of Frascati is described. It consists in a diffusion cloud chamber filled with helium at the pressure of 15 atm. Also, the results of the μ+and e+contamination and energy distribtioon of the π+beam are reported.