Locomotor patterns during obstacle avoidance in children with cerebral palsy.

We investigated how early injuries to developing brain affect the interaction of locomotor patterns with the voluntary action required by obstacle clearance. This task requires higher cognitive load and specific anticipatory sensorimotor integration than more automated steady-state gait. To this end, we compared the adaptive gait patterns during obstacle clearance in 40 children with cerebral palsy (CP) (24 diplegic, 16 hemiplegic, 2-12 yr) and 22 typically developing (TD) children (2-12 yr) by analyzing gait kinematics, joint moments during foot elevation, electromyographic (EMG) activity of 11 pairs of bilateral muscles, and muscle modules evaluated by factorization of the EMG signals. The results confirmed generally slower task performance, plus difficulty in motor planning and control in CP. Thus ~30% of diplegic children failed to perform the task. Children with CP demonstrated higher foot lift, smaller range of motion of distal segments, difficulties in properly activating the hamstring muscles at liftoff, and a modified hip strategy when elevating the trailing limb. Basic muscle modules were generally roughly similar to TD patterns, though they showed a limited adaptation. Thus a distinct activation burst in the adaptable muscle module timed to the voluntary task (liftoff) was less evident in CP. Children with CP also showed prolonged EMG burst durations. Impaired obstacle task performance may reflect impaired or less adaptable supraspinal and spinal control of gait when a locomotor task is superimposed with the voluntary movement. Neurorehabilitation of gait in CP may thus be beneficial by adding voluntary tasks such as obstacle clearance during gait performance.NEW & NOTEWORTHY Previous studies mainly evaluated the neuromuscular pattern generation in cerebral palsy (CP) during unobstructed gait. Here we characterized impairments in the obstacle task performance associated with a limited adaptation of the task-relevant muscle module timed to the foot lift during obstacle crossing. Impaired task performance in children with CP may reflect basic developmental deficits in the adaptable control of gait when the locomotor task is superimposed with the voluntary movement.

Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer.

BACKGROUND: Currently used CA15-3 and CEA have found their clinical application particularly in the follow-up of patients with advanced disease. Novel biomarkers are urgent, especially for improving early diagnosis as well as for discriminating between benign and malignant disease. PATIENTS AND METHODS: In the present study, we used a proteomic approach based on surface-enhanced laser desorption/ionization-time of flight-mass spectrometry screening with the aim of identifying differentially expressed 2-30 kDa proteins in plasma of patients with malignant (65 cases) and benign (88 cases) breast lesions with respect to 121 healthy controls. RESULTS: We found that the most promising SELDI peaks were those corresponding to hepcidin-25 and ferritin light chain. We evaluated the capability of these peaks in predicting malignant and benign breast lesions using the area under the receiver operating characteristic curve (AUC). The results showed a good capacity to predict malignant breast lesions for hepcidin-25 [AUC: 0.82; 95% confidence interval (CI) 0.75-0.90] and ferritin light chain (AUC: 0.86; 95% CI 0.79-0.92). Conversely, a weak and satisfactory capability to predict benign breast lesion was observed for hepcidin-25 (AUC: 0.63; 95% CI 0.41-0.85) and ferritin light chain (AUC: 0.73; 95% CI 0.49-0.97). A significant association between HER2 status and hepcidin-25 was observed and the distribution of transferrin and ferritin were found significantly different in patients with breast cancer when compared with that of controls. CONCLUSIONS: This study provides evidence that hepcidin and ferritin light chain level in plasma may be of clinical usefulness to predict malignant and benign disease with respect to healthy controls.

Preventing weight gain during adjuvant chemotherapy for breast cancer: a dietary intervention study.

Adjuvant chemotherapy significantly decreases recurrences and improves survival in women with early breast cancer (BC). However, the side effects of chemotherapy include weight gain, which is associated with poorer prognosis. We have previously demonstrated that by means of a comprehensive dietary modification which aims at lowering insulin levels it is possible to reduce body weight and decrease the bioavailability of insulin, sex hormones and the growth factors linked to BC risk and prognosis. We are now going to present a randomized controlled study of adjuvant diet in BC patients undergoing chemotherapy. The diet was designed to prevent weight gain during chemotherapy treatment. Women of any age, operated for invasive BC, scheduled for adjuvant chemotherapy and without evidence of distant metastases, were randomized into a dietary intervention group and a control group. The intervention implied changing their usual diet for the whole duration of chemotherapy, following cooking classes and having lunch or dinner at the study centre at least twice per week. 96 BC patients were included in the study. The women in the intervention group showed a significant reduction in their body weight (2.9 kg on average), compared with the controls. They also significantly reduced body fat mass, waist and hip circumferences, biceps, underscapular and suprailiac skinfolds, compared with the women in the control group. Our results support the hypothesis that dietary intervention during adjuvant chemotherapy for BC is feasible and may prevent weight gain.

Functional taping applied to upper limb of children with hemiplegic cerebral palsy: a pilot study.

Functional taping with elastic bandages and adhesive tapes could limit the action of upper limb spastic muscles and sustain that of weaker muscles in children with hemiplegic cerebral palsy (CP). 16 young children with CP (3±2 years old) were enrolled in this pilot study including 5 months of taping in conjunction with conventional physical therapy, followed by 7 months of physical therapy alone (taping wash-out), and other 5 months of taping plus therapy. Large improvements in the Melbourne assessment score were found in the first period in which taping was used (+15.4%, p<0.001) and also in the second one despite 8 drop-outs (+8.4%, p=0.012), but not during the taping wash-out (- 4.6%; p=0.093). These results suggest that children with CP could benefit from the continuous correction provided by taping in order to limit the development of improper upper limb motor schemas and to favour that of proper ones.

Measuring interoception: The phase adjustment task.

Interoception, perception of one's bodily state, has been associated with mental health and socio-emotional processes. However, several interoception tasks are of questionable validity, meaning associations between interoception and other variables require confirmation with new measures. Here we describe the novel, smartphone-based Phase Adjustment Task (PAT). Tones are presented at the participant's heart rate, but out of phase with heartbeats. Participants adjust the phase relationship between tones and heartbeats until they are synchronous. Data from 124 participants indicates variance in performance across participants which is not affected by physiological or strategic confounds. Associations between interoception and anxiety, depression and stress were not significant. Weak associations between interoception and mental health variables may be a consequence of testing a non-clinical sample. A second study revealed PAT performance to be moderately stable over one week, consistent with state effects on interoception.

In soil radon anomalies and volcanic activity on Mt. Etna (Italy).

We present here the first attempt to understand the fast dynamics of an active basaltic volcano, namely Mt. Etna using soil gas radon measured in some sites located in strategic places around the volcano. Data were measured continuously from July 2015 to February 2017 and the raw signals were treated in order to filter out all possible periodic components that are normally due to non-volcanic factors, applying a method that does not require acquisition of other parameters, which are not always available. The residual signals highlighted seven anomalous changes, with radon values reaching levels from 2 to 5 times higher than the normal background. In six out of seven cases, anomalies were almost contemporaneous in all or almost all of the sites, indicating a common source for the observed radon variations. The pattern of anomalies suggests a transient wave-like propagation in the space/time domain, compatible with pressure-induced displacement of the gas. The observed patterns are most probably caused by the rapid upward motion of gas-rich magma into the volcano conduits, as almost all anomalies precede or accompany major volcanic events. In some cases, an alternative explanation could be the strong and sudden strain releases through earthquakes swarms, with consequent variations in the permeability of rocks at a large scale, given the apparent correlation between those anomalies and intense seismicity.

Multi-site, multi-country evaluation of analytical and operational performance of a low-mid volume chemiluminescent immunoassay analyzer.

BACKGROUND: A new automated immunoassay low-mid volume (< or = 250 immunoassays/day) chemiluminescent analyzer, Abbott Architect i1000sR, was evaluated by seven laboratories around the world (4 in Europe, one each in Canada, Japan, and the U.S.A.) to demonstrate equivalent performance for key operating characteristics (e.g., precision, turn around time, limit of detection, functional sensitivity, and linearity). METHODS: The laboratories followed standard protocols to assess precision, limit of detection (LoD), functional sensitivity, assay linearity, method comparison, and sample carryover. Turn around time for three stat assays (beta-hCG, BNP, and CK-MB) and the time required to complete workloads of 50 and 100 tests with a mixture of 75% routine tests and 25% stat tests was also evaluated. RESULTS: Total precision was typically < 5% CV for nine immunoassays. Analytical performance met design goals and demonstrated equivalency to package insert data for assays on market and in use for an existing high volume immunoassay system. Stat turn around times were consistent with the fixed analytical time of 15.6 minutes and met the expectations of the laboratories. Measured test throughput ranged from 47 - 54 tests per hour and demonstrated that the analyzer was fit for the intended purpose of supporting a laboratory that performs < or = 250 immunoassays per day. CONCLUSIONS: A multisite, international analyzer familiarization study is a practical means of confirming that a new instrument meets both a manufacturer's design specifications and users' real world expectations and provides a pragmatic test for the system. The experience of investigators at seven sites around the world indicates that a new fully automated chemiluminescent system is suitable for use.

Dynamic balance assessment during gait in children with Down and Prader-Willi syndromes using inertial sensors.

Down (DS) and Prader-Willi (PWS) syndromes are chromosomal disorders both characterized by obesity, ligament laxity, and hypotonia, the latter associated with gait instability. Although these shared features may justify a common rehabilitation approach, evidence exists that adults with DS and PWS adopt different postural and walking strategies. The development of an instrumented protocol able to describe these strategies and quantify patients' gait stability in the current clinical routine would be of great benefit for health professionals, allowing them to design personalized rehabilitation programs. This is particularly true for children with DS and PWS, where motor development is dramatically constrained by severe hypotonia and muscle weakness. The aim of this study was, thus, to propose an instrumented protocol, integrated with the clinical routine and based on the use of wearable inertial sensors, to assess gait stability in DS and PWS children. Fifteen children with DS, 11 children with PWS, and 12 typically developing children (CG) were involved in the study. Participants performed a 10-meter walking test while wearing four inertial sensors located at pelvis, sternum, and both distal tibiae levels. Spatiotemporal parameters (walking speed, stride frequency, and stride length) and a set of indices related to gait symmetry and upper-body stability (Root Mean Square, Attenuation Coefficient and Improved Harmonic Ratio) were estimated from pelvis and sternum accelerations. The Gross Motor Functional Measures (GMFM-88) and Intelligence Quotient (IQ Wechsler) were also assessed for each patient. A correlation analysis among the GMFM-88 and IQ scales and the estimated parameters was then performed. Children with DS and PWS exhibit reduced gait symmetry and higher accelerations at pelvis level than CG. While these accelerations are attenuated by about 40% at sternum level in CG and DS, PWS children display significant smaller attenuations, thus reporting reduced gait stability, most likely due to their typical "Trendelenburg gait". Significant correlations were found between the estimated parameters and the GMFM-88 scale when considering the whole PWS and DS group and the PWS group alone. These results promote the adoption of wearable technology in clinical routines to monitor gait patterns in children with DS and PWS: the proposed protocol allows to markedly characterize patient-specific motor limitations even when clinical assessment scores provide similar results in terms of pathology severity. This protocol could be adopted to support health professionals in designing personalized treatments that, in turn, could help improving patients' quality of life in terms of both physical and social perspectives.

Soil radon monitoring in the NE flank of Mt. Etna (Sicily).

Soil radon has been monitored at a fixed location on the northeastern flank of Mt. Etna, a high-risk volcano in Sicily. The aim of this study was to evaluate the effects of the recent volcanic activity on soil radon concentration. Continuous radon measurements have been performed since July 2001. While comparison between the trend in in-soil radon concentration and the acquired meteorological series (temperature, humidity and pressure) appear to confirm a general seasonal correlation, nevertheless particular anomalies suggest a possible dependence of the radon concentration on volcanic dynamics.

Oral administration of anti-doxorubicin monoclonal antibody prevents chemotherapy-induced gastrointestinal toxicity in mice.

Gastrointestinal mucositis is a common and painful condition that afflicts a proportion of cancer patients receiving chemotherapeutic drugs including anthracyclines, and it has become the dose-limiting toxicity for a number of chemotherapeutic regimens. The murine monoclonal antibody MAD11 recognizes the anthracycline doxorubicin, and systemic administration of this antibody in mice treated with doxorubicin was found previously to prevent the toxic effects of the drug. The purpose of this study was to determine whether gastrointestinal toxicity associated with doxorubicin can be reduced by oral administration of anti-doxorubicin MAD11 in mice. Our experiments show that orally administered MAD11 antibodies: (a) are essentially not absorbed in the blood circulation since less than 0.5% of protein-associated radioactivity was recovered from blood samples; (b) reduce the extent of doxorubicin-induced apoptosis in murine intestinal crypts, as determined by labeling strand breaks with modified nucleotides in an enzymatic reaction; and (c) reduce the body weight loss in mice treated with 12 mg/kg body weight of doxorubicin and decrease the early mortality in mice treated with 16 mg/kg body weight. This type of treatment may be useful in preventing anthracycline-induced gastrointestinal mucositis in cancer patients.

The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage.

A molecule that is immunologically related to the c-erbB-2 oncogene product (p185HER2/neu) was detected in the conditioned culture medium from neu-overexpressing tumor cell lines and in sera of advanced-stage breast carcinoma patients. Using a sensitive (in the range of 0.5 ng ml-1) double-determinant radioimmunoassay (DDIRMA) with two monoclonal antibodies (MAbs) directed against the neu extracellular domain (ECD), soluble oncoproteins were detected in supernatants from several neu-positive tumor cell lines, independent of the levels of membrane p185HER2 expression. The molecule detected did not react with a MAb directed against an intracytoplasmic epitope of the p185HER2. Western blot analysis of the concentrated supernatant revealed a protein of approximately 110 kDa molecular mass, which closely matches the predicted size of the glycosylated p185HER2 ECD. Immunoprecipitation of culture supernatant from cell surface-radioiodinated cells confirmed the 110 kDa molecular mass of the glycosylated shed protein, which migrated to 86 kDa after deglycosylation. Proteolytic cleavage of the p185HER2 molecule was demonstrated in release assays carried out with protease inhibitors. The combined use of leupeptin and EDTA completely inhibited release of the molecule. Analysis of sera from breast carcinoma patients and healthy donors by DDIRMA revealed the presence of soluble neu in 15% of pathologic sera but none of the normal sera. A good correlation was found between neu-overexpression in the primary tumor and the soluble marker in serum of patients with advanced disease; sera of early-stage patients were always negative, independent of neu-overexpression in the tumor. These results suggest the usefulness of soluble neu as an indicator of tumor aggressiveness but not as a diagnostic marker of breast cancer.

Evaluation of the balance between angiogenic and antiangiogenic circulating factors in patients with breast and gastrointestinal cancers.

Angiogenesis is a critical determinant of tumor growth. Tumor cells produce or induce angiogenic molecules that act specifically on endothelial cells (ECs) but also release angiostatic molecules. Thus, tumor angiogenesis represents a net balance between positive and negative regulators of neovascularization. Sera from patients with breast or gastrointestinal cancers were evaluated for their capacity to selectively modulate the proliferation of human umbilical vein ECs; sera from 15 of 78 (19%) breast cancer patients and 8 of 53 (15%) gastrointestinal cancer patients induced human umbilical vein EC growth, whereas sera from 4 of 78 (5%) breast cancer patients and 1 of 53 (2%) gastrointestinal cancer patients inhibited EC proliferation. Growth-stimulatory sera were significantly more frequent among postmenopausal (14 of 53) than premenopausal (1 of 25) breast cancer patients; inhibitory activity was observed in 3 of 25 premenopausal patients versus 1 of 53 postmenopausal individuals. The half-life of serum-stimulating and -inhibiting factors seemed to differ, because stimulatory activity but not inhibitory activity was decreased at 5 days after surgery. The levels of vascular endothelial growth factor were elevated in about 45% of patients with growth-stimulatory sera, whereas the serum inhibition of EC growth was found to be due, at least in part, to high levels of soluble thrombospondin.

Differential sensitivity to non-major histocompatibility complex-restricted recombinant interleukin 2-activated lymphocyte killing of human mammary epithelial MCF-10A cells overexpressing oncogenes or protein kinase A subunits.

The sensitivity of human tumor cells to activated lymphocytes is considered to play an essential role in the antitumor activity of recombinant interleukin-2 (rIL-2)-based immunotherapy. We have investigated the effects of several genes involved in the regulation of cell growth and transformation on the sensitivity of human mammary epithelial MCF-10A cells to non-MHC-restricted, rIL-2-activated lymphocytes. Therefore, the lysability of MCF-10A cells overexpressing activated oncogenes (Ha-ras, erbB-2, and a mutated p53), growth factors [transforming growth factor alpha (TGFalpha)], or cAMP-dependent protein kinase A subunits (RIalpha, RIIbeta, and Calpha) was evaluated comparatively at different effector:target ratios by a 51Cr release assay. Parental MCF-10A, MCF-10A p53-mutated, and MCF-10A RIIbeta cells showed an intermediate sensitivity. Lysability was increased significantly in MCF-10A Ha-ras, MCF-10A TGFalpha, and MCF-10A RIalpha cells, reduced in MCF-10A Calpha cells, and completely abrogated in MCF-10A erbB-2 cells. These differences could not be explained by simple changes in the cell surface expression of MHC class I and intercellular adhesion molecule-1 proteins or by secretion of TGFbeta. Treatment with TAb 250, a mouse anti-p185(erbB-2) monoclonal antibody, or down-regulation of p185(erbB-2) expression resulted in circumvention of MCF-10A erbB-2 cell resistance. We conclude that molecular changes at the single-gene level resulting in alterations of intracellular signaling and/or cell transformation modulate sensitivity of human mammary epithelial cells to non-MHC-restricted, rIL-2-induced cytotoxicity, regardless of MHC class I and/or intercellular adhesion molecule-1 expression or TGFbeta secretion. Furthermore, anti-p185(erbB-2) monoclonal antibodies may be useful as adjuncts to rIL-2 treatment in patients with erbB-2-overexpressing tumors.

Radon transport: laboratory and model study.

In order to exploit radon profiles for geophysical purposes and also to estimate its entry indoors, it is necessary to study its transport through porous soils. The great number of involved parameters and processes affecting the emanation of radon from the soil grains and its transport in the source medium has led to many theoretical and/or laboratory studies. The authors report the first results of a laboratory study carried out at the Radioactivity Laboratory of the Department of Physics and Astronomy (University of Catania) by means of a facility for measuring radon concentrations in the sample pores at various depths under well-defined and controlled conditions of physical parameters. In particular, radon concentration vertical profiles extracted in low-moisture samples for different advective fluxes and temperatures were compared with expected concentrations, according to a three-phase transport model developed by Andersen (Risø National Laboratory, Denmark), showing, in general, a good agreement between measurements and model calculations.

Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.

BACKGROUND: Previous studies reported controversial results about the efficacy of video-game based therapy (VGT) in improving neurorehabilitation outcomes in children with cerebral palsy (CP). AIM: Primary aim was to investigate the effectiveness of VGT with respect to conventional therapy (CT) in improving upper limb motor outcomes in a group of children with CP. Secondary aim was to quantify if VGT leads children to perform a higher number of movements. DESIGN: A cross-over randomized controlled trial (RCT) for investigating the primary aim and a cross-sectional study for investigating the secondary aim of this study. SETTINGS: Outpatients. INCLUSION CRITERIA: clinical diagnosis of CP, age between 4 and 14 years, level of GMFC between I and IV. EXCLUSION CRITERIA: QI<35, severe comorbidities, incapacity to stand even with an external support. METHODS: Twenty-two children with CP (6.89±1.91-year old) were enrolled in a cross-over RCT with 16 sessions of VGT (using Xbox with Kinect device) and then 16 of CT or vice versa. Upper limb functioning was assessed using the Quality of Upper Extremities Skills Test (QUEST) and hand abilities using Abilhand-kids score. According to the secondary aim of this study a secondary cross-sectional study has been performed. Eight children with CP (6.50±1.60-year old) were enrolled into a trial in which five wireless triaxial accelerometers were positioned on their forearms, legs and trunk for quantifying the physical activity during VGT vs. CT. RESULTS: QUEST scores significantly improved only after VGT (P=0.003), and not after CT (P=0.056). The reverse occurred for Abilhand-kids scores (P=0.165 vs. P=0.013, respectively). Quantity of performed movements was three times higher in VGT than in CT (+198%, P=0.027). CONCLUSION: VGT resulted effective in improving the motor functions of upper limb extremities in children with CP, conceivably for the increased quantity of limb movements, but failed in improving the manual abilities for performing activities of daily living which benefited more from CT. CLINICAL REHABILITATION IMPACT: VGT performed using the X-Box with Kinect device could enhance the number of upper limb movements in children with CP during rehabilitation and in turn improving upper limb motor skills, but CT remained superior for improving performances in manual activities of daily living.

The role of baseline inflammatory-based scores and serum tumor markers to risk stratify pseudomyxoma peritonei patients treated with cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

AIMS: Inflammation-based scores such as neutrophil-lymphocyte ratio (NLR) and Onodera nutritional index (ONI) have been identified as new prognosticators in several tumors. We conducted a prognostic analysis of these markers and performed a risk stratification of PMP patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: 226 patients from two peritoneal surface malignancies centers participated in this study. Cox proportional modeling was used to select predictors of overall survival (OS) among baseline inflammation-based scores, serum tumor markers, clinical and surgical variables. Risk stratification was done using conditional inference tree model. RESULTS: One hundred eighty-two cases had diffuse peritoneal adenomucinosis subtype. Fifty-four cases had received previous systemic chemotherapy. The means of ONI and NLR were 51.4 (SD = 9.8) and 3.2 (SD = 2.3), respectively. Two hundred ten cases were optimally cytoreduced. Cox analysis identified completeness of cytoreduction, histological subtype, previous systemic chemotherapy, NLR, and CA 19-9 as independent prognosticators. Conditional inference tree method identified two poor prognostic subsets: NLR ≤2.7 and CA 19-9>336 (5yr-OS = 15%) and NLR >2.7 and ONI ≤42 (5yr-OS = 30%). CONCLUSIONS: NLR, ONI, and CA 19-9 are new prognosticators that contributed to improve prediction of OS in PMP patients treated by CRS and HIPEC. These markers allowed a risk stratification that could optimize therapeutic management of PMP patients.

Purification of interleukin-2 antibodies from healthy individuals.

By covalent binding of recombinant interleukin-2 (rIL-2) to Sepharose, it was possible to immunopurify specific human anti-IL-2 antibodies from a pool of immunoglobulins obtained from healthy subjects. Since low quantities of the ligand released by the matrix could interfere with the evaluation of the biological activity of anti-IL-2 antibodies, the antibody preparation was subjected to pepsin digestion which is known to destroy the IL-2 molecule. Purified human anti-IL-2 antibodies were found to be mostly IgG1 and able to neutralize IL-2 induced peripheral blood lymphocytes (PBL) proliferation in vitro. The availability of purified anti-IL-2 antibodies, obtained from healthy individuals, able to modulate IL-2 activity, could be important in several therapeutic approaches.

A new monoclonal antibody recognizing anthracyclinic molecule.

The immunosuppressive effect of Doxorubicin (DXR) has been circumvented so that monoclonal antibodies (MAbs) reacting with DXR and other anthracycline derivatives have been obtained. The MAb described here (MAD11) belongs to the IgG2 class and selectively recognizes epitopes located at or near the aromatic ring D of the anthracycline molecule. MAD11 differs from another MAb (MAD2) obtained from the same somatic hybridization and previously described which preferentially reacts with aliphatic ring A of anthracycline.

Antibody response after vaccination with antigen-pulsed dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.

Daily low-dose subcutaneous recombinant interleukin-2 by alternate weekly administration: antitumor activity and immunomodulatory effects.

A phase II clinical trial of subcutaneous recombinant Interleukin 2 (rIL-2) given by 5 days pulses followed by a 9 days rest has been performed in patients affected by renal cell carcinoma, malignant melanoma and colorectal cancer. A total of 25 patients entered the study, completed at least six courses of treatment, and were evaluable for toxicity and response to treatment. This schedule of subcutaneous rIL-2 was well tolerated and no World Health Organization grade 3 side effects were observed. A 33.3% response rate was recorded in patients affected by renal cell carcinoma, although no major responses were achieved in patients with malignant melanoma and colorectal cancer. A durable increase of natural killer activity retained by poeripheral blood mononuclear cells was demonstrated in these patients and was paralleled by increased serum levels of interferon gamma and tumor necrosis factor a without changes of circulating interleukin-1d. It is concluded that this schedule of pulse administration of subcutaneous rIL-2 has antitumor activity in renal cell carcinoma and produces durable biomodulatory effects.