Prevalence of Toscana virus antibodies in residents of two Ionian islands, Greece

The prevalence of Toscana virus (TOSV) IgG antibodies was determined among 128 residents of two Greek islands in the Ionian Sea, Corfu and Cephalonia. In total, 47.7% of tested persons had TOSV IgG antibodies; 51.7% among residents of Corfu and 39% among residents of Cephalonia. The prevalence was higher among persons older than 60 years, who were living in the coastal areas, while no relation with occupation was observed. The high seroprevalence, combined with the high antibody titers observed, suggest that TOSV, or an antigenically-related virus, circulates or has been circulating extensively in the region.     

Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2

Analysis of naturally occurring mutations that cause seizures in rodents has advanced understanding of the molecular mechanisms underlying epilepsy. Abnormalities of I_h and h channel expression have been found in many animal models of absence epilepsy. We characterized a novel spontaneous mutant mouse, apathetic (ap/ap), and identified the ap mutation as a 4 base pair insertion within the coding region of Hcn2, the gene encoding the h channel subunit 2 (HCN2). We demonstrated that Hcn2^ap mRNA is reduced by 90% compared to wild type, and the predicted truncated HCN2^ap protein is absent from the brain tissue of mice carrying the ap allele. ap/ap mice exhibited ataxia, generalized spike–wave absence seizures, and rare generalized tonic–clonic seizures. ap/+ mice had a normal gait, occasional absence seizures and an increased severity of chemoconvulsant-induced seizures. These findings help elucidate basic mechanisms of absence epilepsy and suggest HCN2 may be a target for therapeutic intervention.     

Hepcidin in iron overload disorders

Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin-ferroportin interaction in iron homeostasis.     

Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma.

BACKGROUND: The combination of vincristine and doxorubicin administered as a continuous infusion via an indwelling catheter together with intermittent high-dose dexamethasone (VAD) is an effective primary treatment for patients with symptomatic multiple myeloma. In order to avoid the need for an indwelling catheter, which imposes logistic problems for outpatient administration, several phase II studies have explored the feasibility and efficacy of VAD-like outpatient regimens. We designed a prospective randomized study to compare the objective response rates of two VAD-like outpatient regimens as primary treatment for symptomatic patients with multiple myeloma. PATIENTS AND METHODS: Patients were entered in a randomized study regardless of age, performance status and renal function. One hundred and twenty-seven patients received VAD bolus, which consisted of vincristine 0.4 mg i.v., doxorubicin 9 mg/m(2) i.v. and dexamethasone 40 mg p.o. daily for four consecutive days and 132 patients received VAD doxil, which consisted of vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v. on day 1 and dexamethasone 40 mg p.o. daily for 4 days. The two regimens were administered every 28 days for four courses and in courses 1 and 3, in both arms, dexamethasone was also given on days 9-12 and 17-20. RESULTS: An objective response was documented in 61.4% and 61.3% of patients treated with VAD bolus and VAD doxil, respectively. Hematological and non-hematological toxicities were mild or moderate and equally distributed between the two treatment arms with the exception of alopecia, which was more common after VAD bolus, and of palmar-plantar erythrodysesthesia, which was more common after VAD doxil. CONCLUSIONS: Our multicenter trial, which included an unselected patient population, indicated that both VAD bolus and VAD doxil can be administered to outpatients and can provide an equal opportunity of rapid response in many patients with multiple myeloma.     

Human T-lymphotropic virus type I/II infections in volunteer blood donors from Northern and Western Greece: increased prevalence in one blood bank unit

BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States, Canada, Japan, and some European countries. Previous reports from our group in relatively small numbers of donors have shown a zero prevalence of HTLV-I/II markers in our region. In this study, seven blood banks in the north and west of Greece participated in order to determine whether mandatory screening of blood donations for HTLV-I/II infection should be established. METHODS: Sera from 51,714 consecutive donors were investigated for anti-HTLV-I/II using two commercially available enzyme immunoassays (EIAs). Reactive samples in one or both EIAs were repeatedly evaluated further by Western blot, which is specific for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities. Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective of the WB result, using a combination assay based on the polymerase chain reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI 0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs. However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004-0.061%) was six times the prevalence found at the other blood banks combined (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant. None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very low prevalence of confirmed anti-HTLV-I/II infection markers in northern and western Greek blood donors, together with the negative PCR results in EIA-reactive subjects, indicates that anti-HTLV-I/I routine screening is not really justified in this area of our country. However, the increased prevalence of WB-confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further prospective and careful investigation in order to address whether this finding represents a real cluster phenomenon of HTLV infection.     

Homocysteine and C-reactive protein levels in Haemodialysis patients

Background: Mild to moderatehyperhomocysteinemia is very common amongpatients undergoing haemodialysis. There issufficient evidence that hyperhomocysteinemiais an independent risk factor forcardiovascular and or atheromatous disease inend stage renal failure patients. Vitaminsupplementation such as vitamin B6, B12 orfolate has been proposed to correct thismetabolic disturbance and it is to be proved ifthis intervention benefit these patients, butthere is no agreement whether oral folatesupplementation is capable to normalizehomocysteine levels in end stage renal failurepatients.Methods: In 53 patients, undergoinghaemodialysis, homocysteine levels (Hcy),folate, vitamin B12, ferritin and C-reactiveprotein (CRP) were estimated before and afterdialysis, without folate supplementation.Thirty voluntary blood donors were used ascontrols to compare homocysteine levels. Afterfour weeks of oral folate supplementation(10 mg/24 hours) the levels of homocysteine,serum folate and intra-erythrocyte folate wereestimated again. Eighteen months later thesurvival rate of our patients was recorded andanalyzed in relation to Hcy and CRP levels.Results: The results showed thathaemodialysis patients exhibited, almost,fourfold higher homocysteine levels thancontrols (27.39 ± 11.54 vs 7.38 ± 3.5, t = –8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly afterhaemodialysis where as homocysteine levelsdecrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03).Fourteen (14) patients suffered from coronaryheart disease (CHD) and they exhibited thehigher levels of homocysteine (Hcy1 vs. CHD: z =–3.4, p = 0.0006). All estimations performedrevealed a negative correlation betweenhomocysteine levels and plasma orintra-erythrocyte folate. No other variableexhibited any significant influence uponhomocysteine levels. After folatesupplementation homocysteine levels in thewhole number of patients were unchanged(Hcy(before) vs. Hcy(after): 27.39 ± 11.54vs. 26.95 ± 8.22, z = 0.3, p = 0.7, NS). Whenpatients with homocysteine levels higher than24 µmol/L were selected, a significantdecrease was observed (34.77 ± 9.32 vs.30.0 ± 8.05, z = 2.09, p = 0.02). Forty-twopatients were treated with erythropoietin fortheir anemia and we found a positivecorrelation between C-reactive protein levelsand rhu-Epo dose (CRP vs. Epo: r = 0.45,p = 0.002). Homocysteine levels did not exhibitany significant influence upon short-termsurvival (U = –0.37, p = 0.3, NS) where as CRPlevels exhibit a significant influence uponshort-term survival (U = 2.15, p = 0.005).Conclusions: Homocysteine levels inhaemodialysis patients are fourfold higher thanhealthy controls. Folate, vitamin B12 and CRPincrease significantly after dialysis. Patientswith coronary heart disease exhibit the highestlevels of homocysteine. The homocysteine levelsare inversely related with the folate levels.The exogenous folate supplementation increasethe serum folate levels but decreaseshomocysteine only in patients with higher thanmild hyperhomocysteinemia. Hcy doesn't exertany significant effect upon the short-termsurvival of the haemodialysis patients but CRPlevel is a god predictor of the short-termsurvival of these patients.     

Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study.

BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation after initial cytoreductive chemotherapy with the combination vincristine, doxorubicin and dexamethasone (VAD) is considered an effective therapy for many patients with newly diagnosed, symptomatic multiple myeloma. Response to initial cytoreductive chemotherapy is important for the long-term outcome of such patients. Thalidomide has recently shown significant antimyeloma activity. We studied the efficacy and toxicity of the combination of a liposomal doxorubicin-containing VAD regimen with thalidomide, administered on an outpatient basis, as initial cytoreductive treatment in previously untreated patients with symptomatic myeloma. PATIENTS AND METHODS: Thirty-nine myeloma patients were treated with vincristine 2 mg intravenously (i.v.), liposomal doxorubicin 40 mg/m(2) i.v. administered as single dose on day 1, and dexamethasone 40 mg per os daily for 4 days. Dexamethasone was also given on days 15-18 of the first cycle of treatment. The regimen was administered every 4 weeks for four courses. Thalidomide was given daily at a dose of 200 mg at bedtime. Response to treatment was evaluated after four cycles of treatment. After completion of four cycles, the patients were allowed to proceed to high-dose chemotherapy or to receive two additional cycles of the same treatment. RESULTS: On an intention-to-treat basis, 29 of the 39 patients (74%) responded to treatment. Four patients (10%) achieved complete and 25 (64%) partial response. Three patients (8%) showed minor response and seven (18%) were rated as non-responders. Major grade 3 or 4 toxicities consisted of neutropenia (15%), thrombocytopenia (15%), deep vein thrombosis (10%), constipation (10%), skin rash (5%) and peripheral neuropathy (5%). Two patients (5%) experienced early death due to infection. CONCLUSIONS: The combination of vincristine, liposomal doxorubicin, and dexamethasone (VAD doxil) with thalidomide is an effective and relatively well-tolerated initial cytoreductive treatment.Prospective randomized studies are required in order to assess the effect of this regimen on the long-term outcome of patients with multiple myeloma.     

Comparison of vincristine, carmustine, melphalan, cyclophosphamide, prednisone (VBMCP) and interferon-alpha with melphalan and prednisone (MP) and interferon-alpha (IFN-alpha) in patients with good-prognosis multiple myeloma: a prospective randomized study. Greek Myeloma Study Group

OBJECTIVES: The purpose of the study was to evaluate, in a selected group of myeloma patients with favorable prognosis, the effect, on response and survival, of polychymotherapy compared with melphalan prednisone, plus interferon in both arms. METHODS: Eighty-nine previously untreated patients with multiple myeloma and prognostic factors indicating a good prognosis were randomized to either oral melphalan plus prednisone (MP) in combination with recombinant interferon-alpha (rIFN-alpha) or combination chemotherapy with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with rIFN-alpha. The two treatment groups were comparable in terms of pretreatment characteristics. RESULTS: The overall response rate was 67.4% (2.3% complete remission, 65.1% partial response) in the MP/IFN-alpha group and 69.1% (14.3% complete remission, 54.8% partial response) in the VBMCP/IFN-alpha group (p=0.59). There were no differences also in response duration and overall survival between the two treatment groups. The median response duration was 39.1 months in the MP/IFN-alpha group and was not reached in the VBMCP/IFN-alpha group (p = 0.6). Overall survival was long in both treatment groups. The estimated 5-yr survival was 66% and 62% in the MP/IFN-alpha and VBMCP/IFN-alpha group, respectively (p=0.8). Toxicity was modest and treatments were well tolerated. Neutropenia (WHO grade 3 or 4) was higher, but not statistically significant, in the VBMCP/IFN-alpha group. CONCLUSIONS: The results of the study show that in myeloma patients with good prognosis, combination chemotherapy alternating with interferon-alpha has no advantage over conventional MP plus interferon-alpha, in regard to response rate, response duration, and overall survival of patients.