[Disease-related knowledge acquisition through structured patient information in rheumatoid arthritis (StruPI-RA) : First results of the StruPI-RA study in Germany]. / Krankheitsbezogener Wissenserwerb durch strukturierte Patienteninformation bei Rheumatoider Arthritis (StruPI-RA) : Erste Ergebnisse der StruPI-RA-Studie in Deutschland.

BACKGROUND/OBJECTIVE: The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. METHODS: A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. RESULTS: The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. CONCLUSION: Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.

Fetal RHD detection from circulating cell-free fetal DNA in maternal plasma: validation of a diagnostic kit using automatic extraction and frozen DNA.

OBJECTIVE: This study aimed to validate non-invasive RHD genotyping of cell-free fetal DNA (cff-DNA) using different DNA extraction methods and of fresh and frozen extracted cff-DNA. BACKGROUND: Non-invasive RHD genotyping of cff-DNA predicts fetal RhD phenotype, allowing for the rational implementation of antenatal immunoprophylaxis and representing a big step forward in the management of RhD-immunised women. Validation of a diagnostic method is mandatory before its clinical application. METHODS: RhD-negative pregnant women were recruited at different gestational ages. The cff-DNA extraction was carried out using manual and automatic methods in order to improve cff-DNA yield and optimise the extraction. Fetal RHD genotyping was performed using a commercial real-time polymerase chain reaction (PCR) kit, and the results were compared with postnatal serological RhD determination on cord blood. RESULTS: Overall, 133 plasma samples were examined for the validation process, and a total of 423 tests were performed. No differences have been observed between the two extraction methods or between fresh or frozen cff-DNA regarding cff-DNA stability and quality parameters. There was 100% concordance between fetal RHD genotyping of cff-DNA and RhD phenotype on cord blood for both extraction methods on both fresh and frozen cff-DNA. CONCLUSION: Our study shows the reliability of automatic and manual cff-DNA extraction methods and the possibility of freezing extracted cff-DNA when performing RHD genotyping. This result might be relevant for improving laboratory work and organisation through the development of a standardised procedure for fetal RHD genotyping on cff-DNA, laying the foundations for evidence-based use of anti-D Ig prophylaxis in RhD pregnant women.

Survival prognostic factors in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: analysis from a single oncological center.

BACKGROUND: The aim of our study is to analyze survival, treatment-related morbidity, and safety in our experience of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Sixty-four patients were treated. Survival curves were calculated according to the Kaplan-Meier method. Univariate and multivariate analyses were done, and Cox's proportional hazard model was used to identify significant factors. RESULTS: Global 5-year overall survival was 55%. Overall survival was also evaluated according to neutrophils to lymphocytes ratio and neutrophils to platelets ratio. Overall survival according to pre-operative serum albumin level shows a difference in the two groups (P < 0.05). We observed minor or no adverse events in 53 cases (89.8%), while 3 patients (5.1%) showed a grade III-IV complication and 3 post-operative deaths (5.1%). Post-operative complication also influenced overall survival; patients in whom a minor complication occurred had a 3-year overall survival (OS) of 62% vs. a 3-year OS of 28% in patients who underwent a major complication (P < 0.1). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy (HIPEC) could be a valid and feasible option for selected patients affected by gastrointestinal malignancies' peritoneal carcinomatosis. Pre-operative parameters could be evaluated to choose patient who could benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Choroidal neovascularisation as an unusual ophthalmic manifestation of cat-scratch disease in an 8-year-old girl.

To report the first case of choroidal neovascularisation (CNV) that appeared during the primary Bartonella henselae infection in an 8-year-old girl. An 8-year-old girl was referred to our clinic complaining of a central scotoma in the right eye. Fundus examination revealed a bilateral disc oedema and in the right eye neuroretinitis with macular star and CNV, which was confirmed by fluorescein angiography. The optical coherence tomography revealed the presence of macular serous retinal detachment. Laboratory analysis showed rising IgM and IgG titres for B. henselae. Cat-scratch disease was diagnosed, and an 8-week treatment with azithromycin was initiated. In addition, an intravitreal injection of ranibizumab was performed in the right eye to treat the CNV. A month later, we decided to administer a systemic antibiotic again for an additional 5 months, due to the persistence of papillitis. Cat-scratch disease should be considered among the different causes of inflammatory CNV secondary to infectious uveitis. Our case was the first described in the literature in which a CNV appeared during the primary infection and not as a later complication. The combination of systemic antibiotic treatment with intravitreal anti-VEGF therapy was a successful choice because it allowed us to obtain the complete resolution of neuroretinitis, associated with the scarring of the choroidal neovascular membrane, with a final visual acuity of 20/20 in both eyes.

Whole blood rotation thromboelastometry (ROTEM(®)) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V.

Severe factor V (FV) deficiency (parahaemophilia) is a rare congenital hemorrhagic disorder characterized by very low or undetectable plasma FV levels and bleeding phenotype ranging from mild to severe. We evaluated whole blood (WB) rotation thromboelastometry (ROTEM) in parahaemophilia patients and the contribution of intraplatelets FV, if any, to clot formation. Standard ROTEM(®) assays were performed in WB from nine parahaemophilia patients and 50 healthy controls. In addition, platelets poor plasma from one parahaemophilia patient (PPP-Pt) or normal subjects (PPP-N) was reconstituted with washed platelets obtained either from one patient with parahaemophilia (Plts-Pt) or normal subjects (Plts-N) and ROTEM assays were performed in platelets rich plasma (PRP) samples. There was a prolongation of the WB clotting time (CT) in all assays in patients as compared with controls. However, maximum clot firmness (MCF) was similar in patients and controls. ROTEM in PPP-Pt showed both a prolongation of CT and a reduction of MCF as compared with PPP-N. The addition of either Plts-Pt or Plts-N to PPP-Pt resulted in similar increase in MCF and a decrease of CT which was more evident for PPP-Pt + Plts-N than PPP-Pt + Plts-Pt. In contrast, the addition of Plts-Pt or Plts-N to PPP-N had superimposable effects on both CT and MCF. In parahaemophilia patients, WB ROTEM(®) presents mainly with prolongation of CT and no relevant effect on MCF. Residual intraplatelets FV in parahaemophilia contributes significantly to thrombin generation as shown in artificially reconstituted PRP models.

Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand.

Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety. By contrast, the producers of PDMPs have developed pathogen reduction techniques for inactivating the microorganisms in (pooled) plasma, but little attention has been paid to the pertinence of the clinical indications for these products. The use of blood, and of erythrocytes in particular, has declined by almost 40%, but the use of immunoglobulins (IG) tripled between 2004 and 2018, making it necessary to pay donors to obtain sufficient blood to meet the market demand for these products. We analyzed the reasons for this increase to unsustainable levels of use, by investigating (practice) guidelines, recommendations, Cochrane data analyses and systematic reviews for clinical indications for IG over time. We found no new evidence explaining the huge increase up to 2018 or the predicted 5-7% yearly annual increase until 2024. For some former evidence-based indications, biologics have largely replaced IG, but the administration of IG for doubtful indications (up to 40%) has not decreased in recent decades. The main development since 2004 is that IG use in Europe has become market-driven rather than evidence-guided. As transfusion specialists and blood therapists, we must raise the alarm that this situation is likely to continue in the absence of good clinical studies determining the place of IG alongside other treatments, and for as long as market profitability remains the dominant driving force. We discuss here approaches for reversing this trend and moving towards European self-sufficiency through non-remunerated voluntary blood donation.

EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab.

BACKGROUND: In an attempt to identify markers of resistance to trastuzumab, we evaluated both the profiling of human epidermal growth factor receptor 2 (HER2)-positive tumor cells measuring the relative levels of EGFR, pMAPK, pAkt and PTEN and their correlations with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab. PATIENTS AND METHODS: Tumor tissues for this retrospective analysis were available from 45 out of 76 patients with metastatic breast cancer treated from April 1999 to March 2006 with trastuzumab-based therapy at our Institution. Evaluations of EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry (IHC) were carried out on all 45 tissue samples and their correlations with response to trastuzumab, incidence of central nervous system (CNS) metastases, time to progression (TTP), overall survival from diagnosis of breast cancer (OS1), from diagnosis of metastatic disease (OS2) and from the start of trastuzumab (OS3) were analyzed. RESULTS: We observed that TTP (P = 0.001) and median OS2 and OS3 were significantly longer in patients responsive to trastuzumab-based regimen compared with nonresponsive patients. EGFR, pMAPK, pAkt and PTEN status by IHC were not significantly associated with response to trastuzumab, TTP, overall survival (OS1, OS2, OS3) and CNS metastases incidence. A trend for shorter OS3 was observed for pMAPK-positive patients compared with pMAPK-negative patients (22.8 versus 31.2 months; P = 0.076). Median OS1 resulted shorter in 22 pAkt-positive patients (69.8 months) compared with 23 pAkt-negative patients (108.2 months); P = 0.091. It is likely that high expression of pMAPK (pMAPK-positive status) or pAkt (pAkt-positive status) could identify a subgroup of HER2-positive tumors with high activity of proliferation and survival pathways and with resistance to trastuzumab. CONCLUSIONS: In HER2-positive metastatic breast cancers, EGFR, pMAPK, pAkt and PTEN status evaluated by IHC was not significantly associated with response to trastuzumab, TTP, OS and CNS metastases incidence. However, HER2 status determined by IHC and/or FISH assays may not be sufficient to predict response to trastuzumab-based therapy.

Daily bathing with 4% chlorhexidine gluconate in intensive care settings: a randomized controlled trial.

OBJECTIVES: To investigate whether daily bathing with a soap-like solution of 4% chlorhexidine (CHG) followed by water rinsing (CHGwr) would decrease the incidence of hospital-acquired infections (HAI) in intensive care settings. METHODS: Randomized, controlled trial; infectious diseases specialists were blinded to the intervention status. All patients admitted to the Intensive Care Unit (ICU) and to the Post-operative Cardiosurgical Intensive Care Unit (PC-ICU) of the University Hospital of Perugia were enrolled and randomized to the intervention arm (daily bathing with 4% CHGwr) or to the control arm (daily bathing with standard soap). The incidence rate of acquisition of HAI was compared between the two arms as primary outcome. We also evaluated the incidence of bloodstream infections (BSI), central-line-associated BSI (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI), and 4% CHGwr safety. RESULTS: In all, 449 individuals were enrolled, 226 in treatment arm and 223 in control arm. Thirty-four individuals of the 226 (15%) and 57 (25.6%) suffered from at least an HAI in the intervention and control arms, respectively (p 0.008); 23.2 and 40.9 infections/1000 patient-days were detected in the intervention arm and control arm, respectively (p 0.037). The incidence of all bloodstream infections (BSI plus CABSI) was significantly reduced in the intervention arm (9.2 versus 22.6 infections/1000 patient-days, p 0.027); no differences were observed in the mortality between the two arms. CONCLUSIONS: Daily bathing with 4% CHGwr significantly reduced HAI incidence in intensive care settings. CLINICALTRIAL. GOV REGISTRATION: NCT03639363.

Inflammatory Markers as Prognostic Factors of Survival in Patients Affected by Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

INTRODUCTION: Transarterial chemoembolization (TACE) is a good choice for hepatocellular carcinoma (HCC) treatment when surgery and liver transplantation are not feasible. Few studies reported the value of prognostic factors influencing survival after chemoembolization. In this study, we evaluated whether preoperative inflammatory factors such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio affected our patient survival when affected by hepatocellular carcinoma. METHODS: We retrospectively evaluated a total of 72 patients with hepatocellular carcinoma that underwent TACE. We enrolled patients with different etiopathogeneses of hepatitis and histologically proven HCC not suitable for surgery. The overall study population was dichotomized in two groups according to the median NLR value and was analyzed also according to other prognostic factors. RESULTS: The global median overall survival (OS) was 28 months. The OS in patients with high NLR was statistically significantly shorter than that in patients with low NLR. The following pretreatment variables were significantly associated with the OS in univariate analyses: age, Child-Pugh score, BCLC stage, INR, and NLR. Pretreated high NLR was an independently unfavorable factor for OS. CONCLUSION: NLR could be considered a good prognostic factor of survival useful to stratify patients that could benefit from TACE treatment.

5-Aza-2'-deoxycytidine (Decitabine) induces trilineage response in unfavourable myelodysplastic syndromes.

The preliminary results of a disease-oriented phase I-II study aimed at evaluating the clinical activity of 5-aza-2'-deoxycytidine (Decitabine) in patients affected by advanced myelodysplastic syndromes (MDS) are reported. Two patients affected by refractory anemia with excess of blasts (RAEB) and eight with RAEB in transformation (RAEB-T) were treated with Decitabine at a daily dose of 45 mg/m2, divided into three 4 h infusions for 3 days (six patients) or as continuous infusion of 50 mg/m2 for 3 days (four patients). Treatment with Decitabine resulted in a significant increase in circulating neutrophils, platelets, and hemoglobin with respect to pretreatment values in over 50% of patients. These changes were accompanied by the improvement of the marrow myeloid relative differentiation index (median fivefold increase in the whole group of patients) and of the myeloid to erythroid cell ratio (median twofold increase) in most of the patients. In four out of ten patients a complete normalization of peripheral blood (PB) and bone marrow (BM) picture (complete hematologic response) was obtained. The evaluation of the percentage of CD34-positive BM cells showed a slow but progressive reduction of early leukemic progenitors in most of the patients. A transient slight BM hypoplasia was obtained in less than 50% of patients while a severe marrow aplasia was never observed in our group of MDS patients during treatment with Decitabine. Extra-hematological toxicity was very mild in all the patients. The preliminary results of our study indicate that Decitabine is able to induce trilineage hematological responses in advanced MDS patients along with a stable normalization of the PB and BM picture in some of the subjects. Decitabine appears an active agent in advanced MDS and this deserves careful investigation in this heterogeneous group of disorders.

[SLE: Extra-renal clinical manifestations and lupus nephritis]. / LES: Manifestazioni cliniche extra-renali E nefrite lupica.

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting multiple organ systems, skin and joints the most involved. Lupus Nephritis occurs in Approximately 50% of patients, sometimes it may be the first manifestation of SLE. Clinical features range from asymptomatic urinary abnormalities to full-blown nephrotic syndrome or rapidly progressive renal failure. Because of the heterogeneity of clinical renal manifestations, renal biopsy plays an important role in the management of patients with SLE: it provides information about the class, severity, activity and chronicity of the renal disease that cannot be accurately predicted on the basis of clinical parameters. The complexity of protean renal manifestation of SLE can be approached using the original WHO classification (1982), recently revised (2004).

Simvastatin protects against long-lasting behavioral and morphological consequences of neonatal hypoxic/ischemic brain injury.

BACKGROUND AND PURPOSE: Recent studies suggest that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) not only reduce the incidence of stroke by lowering cholesterol levels but may also exert neuroprotective effects via a mechanism not related to their lipid-lowering effect. Despite the growing body of evidence, however, the neuroprotective effect of statins in stroke is still controversial. Herein, we studied whether a prophylactic administration of simvastatin (Sim) provides significant protection against brain damage, and we sought to determine its long-lasting behavioral consequences in a neonatal model of hypoxia/ischemia. METHODS: Newborn male rats were injected daily from postnatal days 1 to 7 with activated Sim (20 mg/kg) or an equivalent volume of vehicle. On postnatal day 7, the rats were subjected to ligation of the right common carotid artery, followed by 3 hours of hypoxia or by sham operation. The neuroprotective effect of Sim was evaluated after the rats had achieved adulthood by using a battery of behavioral tests and histological analysis. RESULTS: Sim-treated ischemic rats performed the circular water maze, the radial arm maze, and the multiple-choice water maze significantly better than did vehicle-treated ischemic rats. Furthermore, in contrast to the ischemic rats, hypoxia/ischemia-injured rats pretreated with Sim were not hyperactive at weaning and showed less behavioral asymmetry. Consistently, it was found that brain damage was significantly attenuated. CONCLUSIONS: These findings indicate that prophylactic administration of statins may provide a potential neuroprotective strategy leading to an improvement in functional outcome in ischemic stroke. However, toxicity concern must be addressed before these agents can be directed to the asphyxiated fetus or newborn.

Epirubicin versus CMF as adjuvant therapy for stage I and II breast cancer: a prospective randomised study.

We compared a relatively short regimen of monochemotherapy with epirubicin versus polychemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as adjuvant treatment for stage I and II breast cancer patients. 348 patients with oestrogen receptor negative (ER-) node negative and ER- or ER+ node-positive with <10 nodes were accrued. CMF was given intravenously (i.v.) on days 1 and 8, every 4 weeks, for six courses; epirubicin was given weekly for 4 months. Postmenopausal patients received tamoxifen for 3 years. The primary endpoints were overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS). Outcome evaluation was performed both in eligible patients and in all randomised patients according to the intention-to-treat principle. 8 randomised patients were considered ineligible. At a median follow-up of 8 years, there was no difference in OS (Hazard Ratio (HR)=1.11, 95% Confidence Interval (CI): 0.77-1.61, P=0.58), EFS (HR=1.14, 95% CI: 0.78-1.64, P=0.48), and RFS (HR=1.14, 95% CI: 0.8-1.64, P=0.48) between the two arms for all of the patients. At 8 years, the RFS percentages (+/-Standard Error (S.E.)) were 65.4% (+/-4%) in the CMF arm and 62.7% (+/-4%) in the epirubicin arm; for EFS these were 64.2% (+/-4%) for CMF and 60.8% (+/-4%) for epirubicin, respectively. A significant difference in RFS (P=0.015) was observed in patients with 4-9 positive nodes in favour of the CMF arm. Toxicity in the two arms was superimposable except for more frequent grade 3 alopecia in the epirubicin-treated patients (P=0.001). Overall, at a median follow-up of 8 years, there were no differences between the two arms in terms of OS, EFS and RFS.

Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain.

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

Autoradiographic localization of [3H]thiocolchicoside binding sites in the rat brain and spinal cord.

Thiocolchicoside is used in humans as a myorelaxant drug with anti-inflammatory and analgesic activity. Recently we established the experimental conditions that allowed the identification of [3H]thiocolchicoside binding sites in synaptic membranes of rat spinal cord and cerebral cortex. The pharmacological characterization of these sites indicated that GABA and several of its agonists and antagonists, as well as strychnine, were able to interact with [3H]thiocolchicoside binding in a dose-dependent manner and with different affinities. In order to gain more insight into the nature and the anatomical distribution of the binding sites labeled by [3H]thiocolchicoside, in the present study we examined the localization of these sites on parasagittal and coronal sections of the rat brain and spinal cord, respectively, using receptor autoradiography. In the spinal cord an intense signal was observed in the gray matter, with the highest density occurring in the superficial layers of the dorsal horns. Strychnine completely displaced [3H]thiocolchicoside binding, whereas GABA only partially removed the radioligand from its binding sites. In the brain, specific binding occurred in several areas and was displaced by both GABA and strychnine. The distribution of [3H]thiocolchicoside binding sites in brain sections, however, did not match that found for [3H]muscimol. Furthermore, cold thiocolchicoside was not able to completely displace [3H]muscimol binding, and showed a different efficacy in the various areas labeled by the radioligand. We conclude that thiocolchicoside may interact with a subpopulation of GABA(A) receptors having low-affinity binding sites for GABA. Furthermore, the observed sensitivity to strychnine in the spinal cord indicates an interaction also with strychnine-sensitive glycine receptors, suggesting that the pharmacological effects of thiocolchicoside may be the result of its interaction with different receptor populations.

Immunochemical studies on red cell auto antigens: use and limits of immunoprecipitation from biotinylated erythrocyte membrane.

Erythrocyte surface was labelled by means of biotin; immunoprecipitation technique was then used to localise antigens recognised on red cell membrane proteins by: a) autoantibodies from 13 patients with antierythrocyte autoimmunity; b) commercially available anti-D and anti-k (Cellano) antierythrocyte alloantibodies. Results with alloantibodies are comparable to those obtained using radiochemical probes. Immunoprecipitations with autoantibody containing eluates showed reactivity at different molecular weights (the most common at 34-50 kD, others at 100 and 45 kD and a newly described one at 80 kD), thus confirming that many membrane proteins may act as target antigens for erythrocyte autoimmunity. We found a higher percentage of reactive immunoprecipitates than previously reported using the same labelling method. However, critical conditions to allow valuable results seem to be a threshold amount of autoantibody to precipitate any recognisable band and the sensitivity of the detection method. Hence methodological variables must be taken into consideration before concluding that "non protein" antigens trigger the autoimmune process.

IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb.

EDTA-dependent pseudothrombocytopenia (PTCP) consists of an inappropriate low platelet count caused by autoantibodies present in the serum samples reacting with platelets only in EDTA-anticoagulated blood. By using immunoprecipitation and Western blot techniques, we studied the immunochemical specificity of platelet agglutinating autoantibodies in the serum samples of 10 patients with PTCP. Furthermore, to evaluate a possible role of PTCP-associated IgG autoantibodies in increased platelet turnover, we assayed the plasma glycocalicin (GC) level and calculated the GC index for every patient. Our results provide direct evidence that an epitope located on platelet membrane glycoprotein IIb is recognized by PTCP-associated IgG antibodies; moreover GC levels in patients with EDTA-dependent PTCP were similar to control levels, thus excluding an increased platelet turnover. We conclude that antiplatelet antibodies directed against platelet cryptantigens are unlikely to have a major role in the increased removal of cells from circulation.

Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats.

The characterization of motor and cognitive dysfunctions following a neonatal ischemic injury is a prerequisite to investigate putative pharmacological interventions. To this end, in the present study, we evaluated the long-lasting behavioral alterations occurring after a hypoxic/ischemic injury obtained by the combination of monolateral carotid ligation and exposure to 8% oxygen for 3 h in 7-day-old rats. These animals show a different degree of damage in the side ipsilateral to the occluded artery. Motor coordination, tested both before and after weaning, was not affected, whereas spontaneous activity was increased at weaning but not in the adult age. When tested in an open field after apomorphine administration, most ischemic animals showed a marked turning behavior ipsilateral to the lesioned side. They also had a reduced rate of spontaneous alternation and a marked tendency to visit the arm of the T-maze ipsilateral to the lesion. Injured rats were deficient in performing water maze and T-maze acquisition tests but, when evaluated in a passive avoidance paradigm, no difference from controls was observed. These data indicate that an ischemic insult in neonatal rats causes long-lasting learning deficits and motor behavior asymmetry. These behavioral alterations may represent a useful endpoint for studying the efficacy of potential pharmacological treatments that may improve the behavioral consequences of a perinatal hypoxic/ischemic insult in humans.

Antithrombin III deficiency as a risk factor for catheter-related central vein thrombosis in cancer patients.

The fibrin sleeve of venous catheters (VC) and parietal thrombi represent frequent and dangerous side-effects of central venous catheterization (CVC), due to the risk of embolism. Reduced levels of coagulation clotting factors inhibitors (such as Antithrombin III) are known to be associated with increased thrombogenic risk. The aim of this study was to evaluate the role of Antithrombin III (AT III) deficiency as a risk factor for thrombosis in cancer patients undergoing CVC. The study groups included patients with a reduced AT III activity (< 70%, 20 consecutive patients) and with normal AT III values (> 70%, 20 randomly selected patients), requiring a VC for chemotherapy and/or total parenteral nutrition. The study protocol included evaluation of Hb, PLTs, PT (INR), aPTT, Fibrinogen and AT III at days 0, 1, 3 and 8 after CVC and upon VC removal. Peripheral and pullout phlebographies were performed in all patients on catheter withdrawal. A quantitative scale was developed to evaluate both VC and parietal thrombus degree in each catheter-containing venous segment (subclavian, innominate, superior vena cava); the sum of the mean values was defined as overall thrombus. The average VC dwelling time was similar in both groups. There were no significant differences in Hb, PLTs, PT (INR), aPTT, Fibrinogen and in the remaining parameters of the study between the two groups. The group with AT III deficiency presented a higher degree of both parietal (p < 0.05) and overall thrombus (p < 0.02). Data showed a higher severity of CVC-related thrombosis in patients with AT III deficiency than in the control group. Further studies are needed to evaluate whether the therapeutically-induced normalization of AT III levels can reduce the thrombosis degree.