Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort

Summary.  Background and objectives:  he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed. Methods:  A national survey of all Comprehensive Care Haemophilia Cente in the UK. Results:  A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethedsa assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL⁻¹ and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded. Conclusions:  hese data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.     

松果腺对血清皮质酮的影响及其作用部位分析

松果腺对血清皮质酮有抑制作用，对其昼夜节律的中值及峰值位相亦产生影响．松果腺抑制肾上腺增重，切除松果腺使血浆ＡＣＴＨ升高，注射地塞米松或戊巴比妥钠均阻断了松果腺激素褪黑素的降皮质酮作用。提示：松果腺对血清皮质酮的抑制作用是通过其激素——褪黑素实现的，而褪黑素则主要是通过下丘脑－垂体－肾上腺皮质轴起的作用．     

Evaluating a new approach to selecting medical students

Summary. Dissatisfaction with the traditional methods of selecting Australian medical students, which use only secondary school achievement, led to an innovative alternative method at the Newcastle Medical School. This multistage approach uses tests of problem-solving ability, empathy, creativity and moral dilemmas to screen applicants otherwise suitable on academic achievement. In the 5-year trial since its inception, this process appears reasonably reliable and valid. There is some merit in using a composite score for ranking applicants, based on weighted contributions from the psychological tests used in its multifactorial battery. However, the ultimate effectiveness of individual tests of a composite score will depend on their predictive validity, which is yet unmeasured.     

Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure?: Lessons from a multicentre randomized placebo-controlled trial

‘Anaerobic threshold’ (AT), proposed as a non-invasiveindex of exercise tolerance, independent of patient motivation,is considered more reliable than exercise duration in assessingthe effect of drug therapy in chronic heart failure (CHF). However,inter-observer variation in patients may be more difficult thanin normal subjects. In a multicentre study, 85 patients from10 centres performed a total of 331 bicycle maximal tests (rampprotocols, 10 watts. min^–1) with respiratory gas analysisby different systems. A central committee reviewed all the tests.Percentages of AT determination ranged from 34% to 71% dependingon the method used. Apart from the respiratory exchange ratio(RER=1) method, which yielded the lowest rate of determination.and the crossing point (when RER=1), which yielded the highestrate, 71%, other methods of determination, such as carbon dioxide(42%), minute ventilation (52%) or ventilatory equivalents plottedvs time (57%), did not dtffer in the rate of AT determination. Thus, even among trained physicians, AT determination was notreliable. The crossing point may nevertheless be a valuableindex from a pragmatic standpoint, although it occurs afterthe actual AT Peak oxygen uptake should remain the main end-pointin assessment of exercise capacity.     

Use of a New Fallback Function to Prevent Endless-Loop Tachycardias: First Clinical Results

The methods used for preventing endless-loop tachycardias (ELTs) most often consist of initiating a long postventricular atrial refractory period (PVARP) with the sensing of every event likely to induce ELTs, such as sensed premature ventricular contractions (PVCs). A new fallback function may be useful to prevent the initiation of ELTs. A window of atrial rate acceleration detection (WARAD) is initiated with the sensing of every sinus event and equals 75% of the preceding PP interval. If an atrial event is sensed during this period, as are premature atrial contractions (PACs), no atrioventricular (AV) delay is initiated, but an atrial puise output is delivered and a subsequent 31-msec AV delay is started. Theoretically retrograde P waves are premature compared to sinus rhythm. They are therefore detected as PACs, and do not initiate AV delay, thus prohibiting the induction of ELTs. This function was tested in six patients, using external or implanted Chorus 2 pacemakers. Short PVARP (203 msec) and high atrial sensibility were programmed. Retrograde conduction was induced either by inefficient atrial pacing or a long programmed AV delay. Two different dual chamber settings were tested: dual chamber pacing with the fallback function On or Off. In every situation, the function proved effective in preventing ELTs: the number of tachycardia episodes went from 124 with the function programmed Off to 5 with the function programmed On for comparable durations. More than 75 ELTs effectively prevented by fallback have been recorded.     

先天性胆总管囊肿的诊治体会

目的 通过对47例先天性胆总管囊肿诊疗的回顾性分析提出理想的手术方法。方法 全部病例采用囊肿切除加胆肠吻合术重建胆道。结果 随访46例，其中24例采用短段空肠间置，同时加抗返流术式者20例；22例行Roux—Y肝总管空肠吻合术，同时加抗返流术式17例，均疗效满意，而加抗返流术式者疗效更优。结论 先天性胆总管囊肿的诊疗，应明确囊肿的分型及胆胰解剖，采用囊肿彻底切除，再行胆肠重建时应加抗返流术式。     

Leukocyte-technetium-99m uptake in Crohn’s disease: Does it show subclinical disease?

AIM: To evaluate inflammatory activity in patients with Crohn’s disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn’s Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes.RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% ± 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20).CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.