Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience

When a high titre inhibitor develops in a patient with haemophilia, attempts are made to eradicate it through immune tolerance induction therapy (ITI) involving the frequent and regular administration of factor, usually for months to years. ITI is successful in only two thirds of patients prompting investigators to explore alternate regimens to use in haemophiliacs failing conventional ITI. Rituximab is an anti-CD20 monoclonal antibody, which has shown promise in the treatment of B-cell-mediated disorders. We developed a protocol for the use of rituximab in haemophilia A (HA) patients failing conventional ITI or in those haemophiliacs where the likelihood of success of conventional ITI is poor. Patients receive 375 mg m(-2) of intravenous rituximab weekly for 4 weeks followed by monthly (up to 5 months) until inhibitor disappearance and establishment of normal FVIII pharmacokinetics (recovery and half-life). Patients are concurrently placed on recombinant FVIII (100 U kg(-1) day(-1)). We have placed five haemophiliacs (four children with severe HA, and one adult with mild HA) on this protocol. In three patients (two with severe HA and one with mild HA) inhibitors disappeared although in neither severe haemophiliac did FVIII pharmacokinetics completely normalize. The fourth patient had a significant drop in inhibitor titres although not a complete disappearance of the inhibitor. All four of these patients ceased bleeding following rituximab. The fifth patient had no response to rituximab. This non-responding patient was not placed on concurrent FVIII. Our five cases suggest that rituximab may hold promise in the eradication of inhibitors. Prospective randomized studies are required to determine the value of this agent in inhibitor management.     

Central haemodynamics in acute myocardial infarction in relation to mortality and peak enzyme activity

The relation of central haemodynamic changes to subsequent mortalityand peak enzyme activity was investigated in 190 patients withacute myocardial infarction. The mean delay time from onsetof symptoms to the haemodynamic study was 7.2 hours. Major exclusioncriteria were heart rate < 65beats min^–1, systolicblood pressure < 105 mmHg and lung rales to a distance of> 10 cm above the lung bases. Nine patients (4.7%) died within15 days and 16 patients (8.4%) within 90 days after the infarction.Compared to survivors, non-survivors were characterized by baselinedepression of cardiac index, stroke volume index and left ventricularstroke work index, while pulmonary capillary wedge pressureand peripheral resistance were increased. However, a wide overlapbetween survivors and non-survivors makes the predictive valuelow in the individual patient. Peak serum aspartate aminotransferase (S-ASAT) activity wasweakly related to baseline pulmonary capillary wedge pressure(r = 0.28; P< 0.001) and stroke volume index (r = –0.22;P7lt;0.01). The correlation to pulmonary capillary wedge pressurewas only found in anterior (r = 0.34) infarcts. Peak serum lactatedehydrogenase (LD¹) was not correlated with baseline haemodynamics.     

The transition from injecting to smoking heroin in three Spanish cities

Aims. To measure the current prevalence of different routes of heroin administration among users and to describe the most frequent patterns in the evolution of the main route from the time of first use to the present and their implications for the control of the HIV epidemic. Design. Cross-sectional study. Face-to-face interviews using a structured questionnaire. Setting and participants. Nine hundred and nine regular heroin users from Madrid, Barcelona and Seville (about 300 per city), half of them recruited in treatment centres and the other half out of treatment. Measurements. Socio-demographic characteristics, current and historical behaviours related to route of administration. Findings. Before 1980 injection was the first main route of heroin administration for most users in Barcelona and Madrid; in Seville smoking already predominated, although 40% of users began by injecting. Sniffing subsequently became predominant in Barcelona, while smoking became the predominant first route in Madrid and Seville (smoking has been the only first route in Seville since 1991). The prevalence of injection as the main route of administration during the last 30 days was 77.3% in Barcelona, 24.3% in Madrid and 23.9% in Seville; smoking predominated in the latter two cities. The factors most strongly associated with injection as the preferred route were city of recruitment and having a partner who injected. Some 73% of those who stopped injecting in their last change of route stated that the results of their HIV test or fear of becoming infected had been important in making this decision. Conclusions. The change from injecting to smoking will greatly facilitate the control of HIV infection in Spain. However, the main causal factor does not appear to be the perception of HIV risk, but rather other, ecological factors (cultural or market-related). The absence of these factors in some areas may impede the spread of smoking.     

Obliterative portal venopathy: A comparative study of 184 cases of extrahepatic portal obstruction and 469 cases of idiopathic portal hypertension

Abstract A total of 184 cases of extrahepatic portal obstruction (EHPO), mostly demonstrated by intraoperative portography and studied at 17 institutes during the period 1957–1983, were compared with 469 cases of idiopathic portal hypertension (IPH) similarly studied. Of the cases of EHPO, there were 101 males and 83 females; 93 were under 20 years of age and the average age was 25.9 years (i.e. much younger than that of IPH cases). There were two age peaks, one before age 19 years and the other at age 40–49 years. One out of three adult cases had a history of abdominal surgery, but otherwise the aetiologic factor was difficult to elicit. Bleeding was the initial symptom in the majority, and splenectomy and haematological findings of hypersplenism were less pronounced compared with IPH. Liver function tests were almost always normal. The liver appeared normal macroscopically in 69% and histologically in 35%. The changes seen in the remainder were similar to those in IPH; they were less frequent in young patients than in cases above age 20 years. Compared with IPH, the wedged hepatic venous pressure in patients with EHPO was lower and the gradient from the portal venous pressure was greater. It is concluded that extrahepatic portal obstruction is less common compared with IPH in Japan, and that there are cases particularly among adults that present clinicopathological features very similar to those of IPH. It is unclear at present whether these two disorders represent two different disease entities, or whether they represent one disorder with differences in the site of involvement along the portal vein system.     

Effects of amlodipine on transient myocardial ischaemia in patients with a severe coronary condition treated with a beta-blocker

The purpose of this trial was to study the additional anti-ischaemiceffects of amlodipine in coronary patients with ambulant ischaemiadespite beta-blocker therapy. Beta-blockers are the most effectivedrug therapy for reducing the frequency and duration of ambulatoryischaemic episodes. However, the therapeutic advantage of combinedcalcium antagonist-beta-blocker treatment remains questionable. Three hundred and thirteen patients with documented coronaryartery disease, a positive exercise test within 6 months beforeentry and background beta-blocker therapy, were screened. Inclusioncriteria (4 episodes of transient ST segment depression of 1.0 mm and/or 20 min of ischaemia) were demonstrated in a 48h ECG during the placebo run-in period in 84 (25%) of the patients.Eighty-nine percent of the ischaemic episodes were silent. Theeligible patients were then randomized in a 2-week, double-blind,parallel group study comparing placebo to amlodipune 10 mg dailyadded to the beta-blocker. The anti-ischaemic efficacy of thecombination therapy was assessed by 48 h ECG monitoring andexercise tests. Compared to placebo, amlodipine did not significantly reduceeither the frequency (3.7±4.3 vs 4±4.8 episodesin the amlodipune group) or the duration of ambulatory ischaemia(mean duration: 43.9±57.1 vs 39.6±65.7 min, totalduration 3.1±6.7 vs 2.8±6.1 h). Exercise-inducedST segment depression tended to decrease with amlodipine (58%vs 73% in the placebo group) and the ischaemia-free workloadcapacity was increased (+1.7 stage vs 0.7 stage in the placebogroup, P=0.08). These results suggest that 2 weeks treatment with amlodipinemay not provide any additional anti-ischaemic benefit in patientswith ambulant ischaemia resistant to a beta-blocker therapy.     

苦参生物碱的高效液相色谱法测定

报道了苦参中五种主要生物碱——槐果碱、苦参碱、槐定、氧化槐果碱和氧化苦参碱的高效液相色谱测定法。用氨基键合相柱,乙腈—磷酸水溶液(pH 2)—无水乙醇(80:8:10)为流动相,220nm为检测波长。方法简便易行,可在15 min内完成测定。     

Allergy and the risk of sudden infant death syndrome

Background and Objective There are several sources that suggest that there is a link between allergy and sudden infant death syndrome. We endevavoured to look for evidence of an association between allergic disease and the risk of sudden infant death syndrome (SIDS). Methods A nationwide case-control study covering a region with 78% of all births in New Zealand during 1987–90. Interviews were completed with the parents of 393 (81.0% of total) infants who died from the sudden infant death syndrome (SIDS), and 1592 (88.4% of total) control families who were a representative sample of all hospital births in the study region. Results Eczema was reported in 13.9% control infants compared with only 8.0% of the SIDS infants, univariate odds ratio for this in terms of risk for SIDS was 0.56 (95% confidence interval 0.37, 0.84) for infants with eczema compared with those without. This lesser risk for SIDS was unchanged when adjusted for potential confounding factors. The risk of SIDS was not associated with reported cow's milk reactions or a family history of allergic symptoms once adjustments were made for possible confounding factors. Conclusion Infants with skin disorders identified by their parents as eczema had a low risk for SIDS. Families can be reassured that atopy is not a risk factor for SIDS.     

不同剂量低强度激光血管内照射对实验性糖尿病兔红细胞变形能力的影响及其时间效应

本研究首次采用了较大的功率和剂量（５ｍＷ、１０ｍＷ、１８ｍＷ和２５ｍＷ×６０ｍｉｎ）的Ｈｅ－Ｎｅ激光对实验性糖尿病新西兰兔进行了血管内照射，观察了其红细胞变形能力（ＲＣＤ）随剂量和时间的变化。结果发现：①在未实验所选用的功率和剂量范围内，大剂量的照射对ＲＣＤ的影响能较早地表现出来，且更持久。②在改善ＲＣＤ的程度上，剂量（功率）越大，则越表现出优越性，特别是在照射后第１天和第３天，剂量越大的组其平均ＩＦ指数越小。③而照射１２天以后各组无显著性差异，则说明一次照射不可能使ＲＣＤ彻底恢复正常，所以在临床应用时，应进行多次照射。④从照后各天结果的相互比较可以看出，第三天的效果最好，这一结果可为疗程设计提供参考。未次实验过程中未发现溶血现象。     

Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison

BACKGROUND: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. OBJECTIVES: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. RESULTS: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. CONCLUSIONS: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.