保肝降酶方案治疗丙氨酸氨基转移酶升高的慢性乙型肝炎的经济学评价

目的：探讨4种不同保肝降酶治疗方案用于治疗丙氨酸氨基转移酶（ALT）升高的慢性乙型肝炎（CHB）患者的成本与效果。方法：通过建立一个基于Markov模型的决策树模型来模拟患者疾病进程,评价以下方案的成本与效果：无治疗;异甘草酸镁每日100mg;还原型谷胱甘肽每日1500mg;多烯磷脂酰胆碱每日465mg;异甘草酸镁每日200mg。临床数据、成本与效用数据等主要来自于已发表文献。结果：在ALT升高的CHB患者中,异甘草酸镁200mg方案可以获得4．504个质量调整生命年（QALYs）,而累积肝癌和死亡率分别为0．41％和1．99％。同其他治疗方案相比,异甘草酸镁200mg方案的健康获益最大。同无治疗方案相比,异甘草酸镁100mg方案在所有方案中最具成本效益比优势;同对照组相比,它可以在获得1个额外的QALYs时节省49320元。结论：ALT升高的CHB患者使用保肝降酶方案可以节约远期的卫生成本,其中异甘草酸镁100mg是最具优势的治疗方案。     

Antisecretory Activities of Orally Administered Loperamide and Loperamide Oxide on Intestinal Secretion in Rats

Abstract— In-vivo experiments in the rat jejunum have been performed to compare the antisecretory effect of orally administered loperamide with the effect of its pro-drug, loperamide oxide. Both loperamide and loperamide oxide, administered orally, reduced the secretory effect of prostaglandin E₂ (32 ng min^?1, intra-arterially) in the jejunum and the colon. Differences between the two drugs as to time course and dose response can be seen. Loperamide oxide shows its antisecretory effect in the jejunum, and at a dose of 2 mg kg^?1 also shows its effect in the colon 1 h after administration. The effect was maximal after 2 h and decreased after 4 h. A dose-response relationship was demonstrated at 2 h in the jejunum and the colon. In comparison, the effect of loperamide started later, and a good dose-response relationship was not observed in the jejunum or in the colon, higher doses always appearing less effective than lower doses.     

Morphological and cytochemical findings in 150 cases of T-lineage acute lymphoblastic leukaemia in adults

We evaluated the morphological findings in 150 consecutive cases of T-lineage acute lymphocytic leukaemia (T-ALL). Cytochemistry including PAS staining and acid phosphatase reaction proved of limited value for the diagnosis of ALL.
The diagnosis of acute leukaemia was easy to establish in most instances. However, in a few cases the leukaemic cells were difficult to recognize as blasts. The nuclei of such cells showed condensed chromatin and nucleoli were lacking, and was encountered particularly in thymic ALL.
Basophilic cytoplasm combined with prominent vacuolization suggestive of mature B-ALL (ALL-L3 type), was observed in 16 cases. Other features, however, such as cell size, polymorphism, chromatin structure, sparse cytoplasm or focal positivity for acid phosphatase, excluded a diagnosis of ALL-L3 in those cases.
Distinction from hybrid leukaemia was difficult in 20 cases, because of a low percentage of peroxidase-positive blasts or other features which suggested a separate myeloid leukaemia component. In nine of these the hybrid nature of the leukaemia was considered as certain on the basis of morphology. Seven cases had been diagnosed as biphenotypic with coexpression of myeloid and lymphoid markers by immunological techniques.
In conclusion, our analysis showed some serious pitfalls of the morphology in T-ALL, clearly indicating the need for immunological analysis of the leukaemic cells. However, morphology remains an essential component of the diagnostic repertoire, especially when the marrow is difficult to aspirate and in cases with equivocal immunological findings. Furthermore, recognition of a separate myeloid leukaemic component in addition to the lymphatic one requires a morphological analysis.     

Pain Threshold for Low Energy Intracardiac Cardioversion of Atrial Fibrillation with Low or No Sedation

Recent studies have shown that internal cardioversion of atrial fibrillation is safe and effective. In this randomized prospective study, we have tried to evaluate the influence of different waveforms on the perception of pain during internal cardioversion in patients with chronic atrial fibrillation. Methods: Internal cardioversion was performed with minimal or no sedation in 31 consecutive patients, R wave triggered, biphasic shocks of 6 ms/6 ms or 3 ms/3 ms duration (randomly selected) and approximately 65% tilt were used starting with a 50-V test shock. The shock intensity was increased in 40-V steps up to a maximum voltage of 520 V. Shocks were applied via two custom-made catheters (Elecath, Rahway, NJ). In 16 patients (3 females, age 61 ± 11 years, left atrium diameter 58 ± 5 mm, duration of atrial fibrillation 4 ± 4 months), 6/6 waveforms were used, and in 15 patients (1 female, age 62 ± 5 years, left atrium diameter 59 ± 4 mm, duration of atrial fibrillation 5 ± 2 months), 3/3 waveforms were used. After cardioversion, each patient was asked to quantify their pain on a scale from 0–10 (0 = no pain, 10 = intolerable). Fourteen of the 15 patients in the 3/3 ms and 15 of the 16 patients in the 6/6 ms group were successfully cardioverted. Patients from the 6/6 waveform group were cardioverted with a lower mean voltage of 254/92 versus 355/127 V (P < 0.02), at lower pain score 1.8 ± 1.3 versus 4.2 ± 2.2 (P < 0.05) with equivalent energy (6.8 ± 2.8 versus 6.2 ± 1.5 J, n.s.) and required lower doses of midazolam of 2.2 ± 1.9 versus 4.0 ± 1.8 mg IV (P < 0.02). The waveform used in internal cardioversion seems to have a major impact on the patients’ perception of pain. These results imply that energy determines the success of a shock, but voltage determines the pain perceived by the patient. The use of waveforms that deliver greater energy at lower peak voltages offers the possibility of internal cardioversion with less sedation and greater patient tolerance.     

A New Mechanical Sensor for Detecting Body Activity and Posture, Suitable for Rate Responsive Pacing

In the past, thought about rate responsive pacing mainly focused on rate increase with exercise but did not consider that a rate increase with postural changes also is mandatory in order to prevent orthostatic reactions. A nightly decrease in pacemaker rate when the body is at rest and in a supine position is a further advantage for the patient's sleep and recovery. Therefore, we developed a sensor that could detect not only rest and body activity but also discriminate between a supine and an upright position. This sensor is a muiticontact tilt switch containing a small mercury ball, as shown in the left panel of the figure below. The principle of discrimination between rest and low and high body activity is realized by the movement of the mercury ball resulting from body motion, which causes openings and closures within the sensor as the ball touches the numerous sensor contacts. In the upright position, a distinct number of contacts at the bottom of the tilt switch are closed. In the supine position, there is no closure of the bottom contacts and a postural discrimination can he achieved. We studied 12 volunteers and 10 pacemaker patients with this new device both at rest and during physical exercise. The right panel of the figure illustrates that the contacts per second correlate to the increase of physical exercise, such as walking on the treadmill. Further studies with an external pacemaker containing a small sensor suitable to fit into the pacemaker are in preparation.     

A New Rate-Modulated Pacemaker System Optimized by Combination of Two Sensors

A new rate-modulated pacemaker system optimized by combination of two sensors is described. The parameter body activity and central venous blood temperature control the pacemaker rate. The specific characteristic of each parameter determines its role within the algorithm. While the motion sensor yields a fast reaction following the onset or a change of stress intensity, central venous blood temperature corresponds better to body metabolism. An indication of increased exercise from the motion sensor results in an accordingly rapid increase in the pacing rate. Unless this increased exercise is confirmed by an increase in central venous blood temperature within 2 or 3 minutes, the new motion level will be assumed to be the new baseline motion value and the pace rate will return to a basic pacing rate. Prolonged inappropriate responses are therefore avoided. Longer lasting exercise, fever and nonphysiological signals are recognized and handled safely. Exercise tests with five volunteers under various conditions showed pacing rate behavior that was close to normal.     

MLL2 mosaic mutations and intragenic deletion–duplications in patients with Kabuki syndrome

Kabuki syndrome (KS) is a rare multi‐system disorder that can result in a variety of congenital malformations, typical dysmorphism and variable learning disability. It is caused by MLL2 point mutations in the majority of the cases and, rarely by deletions involving KDM6A. Nearly one third of cases remain unsolved. Here, we expand the known genetic basis of KS by presenting five typical patients with the condition, all of whom have novel MLL2 mutation types– two patients with mosaic small deletions, one with a mosaic whole‐gene deletion, one with a multi‐exon deletion and one with an intragenic multi‐exon duplication. We recommend MLL2 dosage studies for all patients with typical KS, where traditional Sanger sequencing fails to identify mutations. The prevalence of such MLL2 mutations in KS may be comparable with deletions involving KDM6A. These findings may be helpful in understanding the mutational mechanism of MLL2 and the disease mechanism of KS.     

Feasibility of Using Intracardiac Impedance Measurements for Capture Detection

Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.     

A New Approach Towards Defibrillation Electrodes: Highly Conductive Isotropic Carbon Fibers

A new carbon fiber material was studied for its potential benefit in defibrillation electrodes. Miniaturization of the fiber production can result in small strands with extremely large surface areas. Two carbon fiber patches and a single carbon fiber bundle were used for the purposes of this study, and the results were compared to those obtained with conventional titanium/mesh patch electrodes. Tests performed in a saline filled tank revealed considerably lower resistances through the carbon material when compared to standard mesh electrodes. There was also a higher peak current flow with lower voltage. The carbon fibers exhibited lower impedance for defibrillation and this may be related to low polarization known to occur with carbon materials. This new carbon material may prove to be useful and further research is required.