Impact of negative line tension on the shape of nanometer-size sessile droplets.

The sign and value of the line tension has been measured from the size dependence of the contact angle of nanometer-size sessile fullerene (C60) droplets on the planar SiO2 interface, measured with atomic force microscopy (AFM). Analysis according to the modified Young's equation indicates a negative line tension, with a magnitude between -10{-11} and -10{-10} N/m, in good agreement with theoretical predictions. The experiments also indicate that droplets with contact area radii below 10 nm are in fact two-dimensional round terraces.

Low-molecular-weight heparin as bridging therapy during interruption of oral anticoagulation in patients undergoing colonoscopy or gastroscopy.

Nowadays, most patients under oral anticoagulant therapy (OAT) require invasive procedures such as colonoscopy (CC) or gastroscopy (GC). The goals of the management of OAT are to minimise the risk of thromboembolism and bleeding. We have performed the first prospective, observational study to evaluate these parameters using fixed-dose high-risk thromboprophylactic therapy with sodic bemiparin (Hibor) as bridging therapy. From January 2004 to January 2005, patients under OAT were included. Periprocedure prophylaxis consisted of: Acenocumarol patients: Day -3: withdrawal acenocumarol. Days -2,-1,0: Hibor 3500 UI/d sc and days +1,+2,+3: Hibor 3500 U/I + acenocumarol. And day +5: acenocumarol only. Warfarin patients: Days -5,-4: withdrawal warfarin, -3,-2,-1, 0; Hibor 3500 UI/day sc, days +1,+2,+3,+4: Hibor 3500 UI/day sc and warfarin and day +5; warfarin only. Thromboembolic complications and bleeding were recorded in a 3 month follow-up. We included 100 consecutive patients in the intention-to-treat group. The remaining 98 patients were 50 women and 48 men. Mean age of women was 71.1 (range: 46-87) years and 70.7 (range: 39-86) years in men. Eighty-three took acenocumarol, and 15 warfarin. Thirty-two gastroscopies and 61 colonoscopies were performed and in five patients both were performed. No thromboembolic and bleeding complications related to bemiparin were observed in the 103 endoscopies. Two patients developed pruritus at the punction site. Fixed-dose high-risk thromboprophilactic therapy with bemiparin (Hibor) is safe and effective as a bridging therapy in patients under OAT who require GC or CC.

Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse.

PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.

Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT. PATIENTS AND METHODS: We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16-66), and 90 patients (57%) were >45 yr of age. RESULTS: Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P < 0,001), respectively. Cumulative incidence of TRM at 2 yr was 30% [95% confidence interval (CI) 22-41%] for the STAND group and 22% (95% CI 13-37%) for the RIC group [non-significant (NS)]. Factors associated with a higher TRM in multivariate analysis were: STAND vs. RIC conditioning regimen [relative risk (RR) 5.4; 95% CI 2.3-12.8; P < 0.001]; age > or =45 yr vs. <45 yr (RR 5; 95% CI 2.4-10.8, P < 0.001); second vs. first HSCT (RR 2.8, 95% CI 1.3-6.3, P = 0.01) and non-T-cell-depleted vs. T-cell-depleted graft (RR 2.7, 95% CI 1.3-5.8, P = 0.009). Overall survival (OS) at 2 yr was 52.5 +/- 10.4% for STAND group and 59 +/- 16.8% in RIC group. Factors associated with poorer OS in multivariate analysis were: STAND vs. RIC conditioning regimen (RR 3.4, 95% CI 1.7-6.9, P = 0.001); age > or =45 vs <45 yr (RR 2.5, 95% CI 1.4-4.5, P = 0.002) and diagnosis [other than chronic myeloid leukemia (CML) vs. CML] (RR 2.6, 95% CI 1.2-5.7 P = 0.02). CONCLUSIONS: Our results indicate that the introduction of RIC allogeneic HSCT for patients at high risk for TRM (advanced age, prior HSCT and non-T-cell depletion) leads to a reduction in the TRM and improvement in the OS.

Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.

BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.

Potentiation by TRH of the effect of antidepressants in the forced-swimming test, involvement of dopaminergic and opioid systems.

1. It has been shown that thyrotropin releasing hormone (TRH) can potentiate the effects of the antidepressant, imipramine, as measured by the mouse forced-swimming test. This potentiation is not associated with an increase of effective levels of noradrenaline in the synaptic clefts, but depends upon the integrity of opioid systems. The present study was designed to investigate: (a) the potentiation by TRH of the effects of other antidepressants, using the same test; (b) the possible involvement of other neuronal systems, such as the 5-hydroxytryptaminergic and dopaminergic systems; (c) the contribution of the opioid and dopaminergic systems to the potentiation of the actions of other antidepressants by TRH. 2. The effects of nortriptyline, amineptine, maprotiline, nomifensine and mianserin, but not that of clomipramine, were potentiated by TRH (2 mg kg-1, i.p.). The inhibitor of 5-hydroxytryptamine synthesis, p-chlorophenylalanine (PCPA), did not prevent the effect induced by imipramine plus TRH. Blockade of dopaminergic systems by gamma-butyrolactone (GBL) (37.5 mg kg-1, i.p.), alpha-methyl-p-tyrosine (AMPT) (125 mg kg-1, i.p.) and apomorphine (0.025 mg kg-1, i.p.) antagonized the effects induced by various antidepressants alone (at high, effective doses) or at lower ineffective doses in association with TRH. The effect induced by imipramine plus TRH was also blocked by sulpiride (16 mg kg-1, i.p.). Pretreatment with the opioid antagonist, naloxone, inhibited the effects induced by nomifensine plus TRH or mianserin plus TRH but not those induced by nortriptyline plus TRH, maprotiline plus TRH or amineptine plus TRH. When high active doses of the antidepressants were used alone, only the clomipramine effect was blocked by naloxone. 3. These data indicate that TRH is able to potentiate the effect not only of imipramine but of other antidepressants in the mouse forced-swimming test, although these other antidepressants act in various ways on cerebral amines. The antagonism of the effects induced by the antidepressants alone or in association with TRH after blockade of dopaminergic systems may indicate a reversal of the effect of the antidepressants by blockade of dopaminergic systems. Hence, the same mechanisms would be involved in the effects induced by antidepressants alone or in association with TRH, with respect to dopaminergic systems. However, different mechanisms of action seem to be responsible for the potentiation of TRH of the effect of the various antidepressants, since the involvement of the opioid systems varies according to the antidepressant tested.