Summary. It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/ d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n ¼ 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n ¼ 34) treated with AmB (P ¼ 0·09); P ¼ 0·03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P ¼ 0·05 and P ¼ 0·096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P ¼ 0·03). More patients on AmB had a >100% increase of their baseline serum creatinine (P < 0·001).The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Please be advised that this information was generated on 2018-05-12 and may be subject to change.11 Snyder PJ, Utiger RD. Response to thyrotropin-releasing hormone (TRH) in normal man. J Clin Endocrinol Metab 1972; 34: 380-85. 12 Rooney S, Marino P, Gobrau L, Gross I, Warshaw J. Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis? M artin den Heijer, Henk J Biom , Wim B J G errits, F rits R Rosendaai, Hans L H aak, P ie rre W W ijerm ans, Gerard M J Bos SummarySeveral studies have shown a relation between » hyperhomocysteinaemia and arterial vascular disease. We looked at the association between hyperhomocysteinaemia and venous thrombosis which could be clinically important as hyperhomocysteinaemia is easily corrected by vitamin supplementation.We studied 185 patients with a history of recurrent venous thrombosis and 220 controls from the general population. Homocysteine concentrations were measured before and 6 h after oral methionine loading. We defined hyperhomocysteinaemia as the homocysteine concentration above the fasting or the postmethionine value found for the 90th percentile of the controls. Of the 185 patients with recurrent thrombosis, 46 (25%) had fasting homocysteine concentrations above the 90th percentile or the controls (odds ratio is 3-1 [1-8-5-5]). After adjustment for age, sex, and menopausal status the odds ratio was 2-0 (l-5-2*7). Similar results were found for the post-methionine value (unadjusted odds ratio 3-1 [1-7-5-5], adjusted 2*6 [1-9-3-5]).Hyperhomocysteinaemia is a common risk factor for recurrent venous thrombosis and can lead to a two-fold or three-fold increase in risk.

SummaryPlasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial. We report on a series of 33 patients with TTP who were splenectomised because they were plasma refractory (n ¼ 9) or for relapsed disease (n ¼ 24). Splenectomy generated prompt and unmaintained remissions in all except five patients, in whom remission was delayed (n ¼ 4) or who died with progressive disease (n ¼ 1). Four postoperative complications occurred: one pulmonary embolism and three surgical complications. Median follow-up after splenectomy was 109 months (range 28-230 months). The overall postsplenectomy relapse rate was 0AE09 relapses/patient-year and the 10-year relapse-free survival (RFS) was 70% (95% CI 50-83%). In the patients with relapsing TTP, relapse rate fell from 0AE74 relapses/patient-year before splenectomy to 0AE10 after splenectomy (P < 0AE00001). Two patients died from first postsplenectomy relapse. Although these results are based on retrospective data and that the relapse rate may spontaneously decrease with time, we conclude that splenectomy, when performed during stable disease, has an acceptable safety profile and should be considered in cases of plasma refractoriness or relapsing TTP to reach durable remissions and to reduce or prevent future relapses.

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Abstract-Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis and is inversely related to plasma folate and vitamin B12 levels. We assessed the effects of vitamin supplementation on plasma homocysteine levels in 89 patients with a history of recurrent venous thrombosis and 227 healthy volunteers. Patients and hyperhomocysteinemic (homocysteine level Ͼ16 mol/L) volunteers were randomized to placebo or high-dose multivitamin supplements containing 5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine. A subgroup of volunteers without hyperhomocysteinemia was also randomized into three additional regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg hydroxycobalamin. Before and after the intervention period, blood samples were taken for measurements of homocysteine, folate, cobalamin, and pyridoxal-5Ј-phosphate levels. Supplementation with high-dose multivitamin preparations normalized plasma homocysteine levels (Յ16 mol/L) in 26 of 30 individuals compared with 7 of 30 in the placebo group. Also in normohomocysteinemic subjects, multivitamin supplementation strongly reduced homocysteine levels (median reduction, 30%; range, Ϫ22% to 55%). In this subgroup the effect of folic acid alone was similar to that of multivitamin: median reduction, 26%; range, Ϫ2% to 52% for 5 mg folic acid and 25%; range, Ϫ54% to 40% for 0.5 mg folic acid. Cobalamin supplementation had only a slight effect on homocysteine lowering (median reduction, 10%; range, Ϫ21% to 41%). Our study shows that combined vitamin supplementation reduces homocysteine levels effectively in patients with venous thrombosis and in healthy volunteers, either with or without hyperhomocysteinemia. Even supplementation with 0.5 mg of folic acid led to a substantial reduction of blood homocysteine levels. (Arterioscler Thromb Vasc Biol. 1998;18:356-361.)