The Problem of Intractability: The Continuing Need for New Medical Therapies in Epilepsy

Summary: Treatment of epilepsy, one of the most common neurologic disorders, has evolved from "institutional" poly-therapy to "dogmatic" monotherapy, and, most recently, to "rational" polypharmacy. The introduction of bromides for the treatment of epilepsy was followed first by phenobarbital and then by phenytoin as therapeutic options. Although attempts to combine medications were legion, none was supported by studies that demonstrated the benefit of such combinations. The issue of adverse effects became a principal argument in favor of monotherapy. Monotherapy, using newly developed drugs, avoided problems due to drug interactions but was ineffective in 20–30% of patients. A greater understanding of basic disease mechanisms and developments in molecular biology have led to an increased number of effective drugs for the estimated 6–12% of patients with epilepsy whose condition is intractable. Clinical research continues to build on the work of basic scientists in attempting to develop treatments based on a desire to move beyond the palliative and to affect the causative mechanisms of the disease. Novel medical approaches now under exploration include the use of drugs with complementary mechanisms of action, stimulation of various components of the nervous system, biochemical manipulations, focal intracerebral drug perfusion, and gene therapy.     

Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms

Summary One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances.More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p<0.04); the reverse was true for the placebo patient (p<0.05).     

Grip and pinch strength among selected adult occupational groups

A survey of 402 normal subjects (203 men, 199 women) was conducted to assist in distinguishing potential differences in norms of hand strength. Norm data had previously been collected from mixed occupational groups, but in the present study it was hypothesised that people involved in heavy manual work on a daily basis might possess greater hand strength than others. The volunteers were adults working in industry and agriculture; they were subdivided into occupational categories. Measurements of grip, key and palmar pinch using the Jamar dynamometer and B and L pinch gauge were collected, using the protocol described by Mathiowetz. Volunteers also rated their individual hand strength job requirements subjectively. Mean values were established with regard to age, sex, dominance, occupational group and subjective rating. Significant differences were found with regard to age and sex but not to dominance; there was no evidence of differences between occupational groups or between subjective rating and individual scoring, i.e. volunteers who perceived their job as requiring a high degree of strength did not achieve higher test measurements than others. A high interrater reliability was demonstrated when comparing these follow-up measurements with the original data. It was concluded that, for clinical and rehabilitative purposes, therapists can interpret assessment of outcome most accurately by comparing patients' results with the existing norm data.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.     

屈光性调节性内斜视综合治疗的效果

①目的:探讨综合治疗屈光性调节性内斜视的效果及其相关因素。②方法:对随机收集78例屈光性调节性内斜视病儿的综合治疗效果进行回顾性分析。③结果:经5年随访，73例(93．6％)维持正常眼位，149只(97．4％)弱视眼治愈，72例(92．3％)获得立体视功能。④结论:及时对屈光性调节性内斜视病儿进行综合治疗，建立和恢复其双眼单视功能，预后较好。     

Geste antagonistes in idiopathic lower cranial dystonia.

Geste antagonistes, or sensory tricks, are well described in focal dystonia affecting the neck, hand, and face. Improvement in dystonic movements is typically maintained while the trick is performed, but disappears when the geste ends. We investigated the phenomenological features of geste antagoniste maneuvers in 19 patients with idiopathic lower cranial dystonia who were prospectively evaluated over a period of 6 years. Of the 19, 10 were men, mean age of onset was 49.8 years, and the most commonly involved lower cranial area was the jaw (10 patients). In most patients, dystonia was task-specific. Taking advantage of the improvement with a sensory geste, we manufactured oral appliances that mimicked the geste in 8 patients, and 3 continue to use it.     

Treatment of hepatitis B and C after liver transplantation. Part 2, hepatitis C

Abstract End-stage liver disease caused by the hepatitis C virus is a major indication for liver transplantation. However, recurrence of hepatitis in the graft is a major issue. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 60%–80% of patients, and 6%–28% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by antiviral drug side effects. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25% of patients, but indications, modality and duration of treatment should be assessed.     

浅谈基因治疗的现状及其面临的困境

基因治疗将在未来的疾病治疗中扮演重要的角色，然而这一新颖的技术却面临着诸多问题，本文论述了基因治疗的发展现状及其所面临的技术难题。