[Defining trials of medicinal products according to the revised Dutch Medical Research in Human Subjects Act (WMO)]. / Afbakening van geneesmiddelenonderzoek volgens de gewijzigde wet Medisch-wetenschappelijk Onderzoek met Mensen (WMO).

The revised Dutch Medical Research in Human Subjects Act (WMO), which implements the European directive regarding 'good clinical practice in the conduct of clinical trials on medicinal products for human use' (2001/20/EC), became effective on March 1, 2006. The revision places additional requirements on trials of medicinal products. Whether a trial should be regarded as a trial of a medicinal product is therefore an important question. The law does not provide adequate guidance for the classification of trials in which biological samples are collected, e.g. for genomic, proteomic or pharmacokinetic studies, while a medicinal product is given for a registered indication. Classifying these types of trials as trials of medicinal products does not enhance the safety of the participants. Therefore, these studies should not be considered as trials of medicinal products to avoid the increased administrative burden required by the revised WMO.

[Effects and costs of adjuvant chemotherapy for operable lymph node positive breast cancer with HER2/neu overexpression]. / Effecten en kosten van adjuvante chemotherapie bij operabele lymfklierpositieve borstkanker met HER2/neu-overexpressie.

Newer forms ofadjuvant chemotherapy can considerably improve the prognosis for breast cancer. The benefits that can be achieved are particularly high for young women (< 50 years) with an unfavourable risk profile (tumour-positive axilliary nodes). The recent application of taxans and trastuzumab has sharply increased the costs of an adjuvant treatment for high-risk mammary breast carcinoma. The cost increase can especially be attributed to trastuzumab. The additional costs of cytostatics (10,079 Euro per life-year gained) appear to be justified if the following is taken into account: women under the age of 50 years still have a life expectancy of approximately 33 years, many have socially relevant positions, and that cure also prevents such things as absence through illness and inability to work as well as expensive palliative care. The pharmaceutical industry spends approximately the same amount on research and innovation as it does on advertising. By reducing marketing costs, there will be more room to lessen the costs of new and socially relevant medications. Ultimately, the pressing question remains on why the Dutch government does not fully compensate hospitals in the Netherlands for the introduction of new, potentially life-saving medications. At present, a substantial percentage of the costs has to be paid by the hospitals themselves out of the regular hospital budget, which is not meant for this. This is happening at the expense of other care to an increasing extent.

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer.

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25-71) years and a rectal tumor at a mean of 3 (range, 0-5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1-8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1-60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n = 2) and incontinence (n = 3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 3.5 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1-5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0-30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome.

Electromechanical delay during knee extensor contractions.

The purpose of this study was to investigate the magnitude of electromechanical delay (EMD) and its possible dependence on muscle type, type of contraction, fatigue, level of force, initial muscle length, and muscle contraction velocity. This was achieved using an experiment that measured voluntary knee extensor torques and surface EMG activity for a variety of different contractile conditions in seven male subjects. EMD values were obtained using a cross-correlation technique in three experimental KIN-COM dynamometer conditions of vastus medialis, rectus femoris, and vastus lateralis. In the first condition, a series of 10 repetitive submaximal (50% and 70% MVC) isometric knee extensor contractions were performed at knee angles of 90 degrees and 130 degrees extension. In the second condition, 10 maximal isokinetic knee extensor contractions were performed during passive shortening and lengthening. As such, the dynamometer was used to passively move the knee joint at 30 degrees.s-1 and 60 degrees.s-1. Both during lengthening and shortening, the contractions occurred at an angular position of 110 degrees. In the last condition, a repetitive submaximal isometric knee extensor fatigue test was performed for 100 s (150 contractions). At 10, 40, and 90 s during the time course of this fatigue test, a series of 10 contractions were recorded. To avoid a phase lag, which is introduced with one-way filtering, the EMG was processed with a bidirectional low-pass filter application. A significant main effect in EMD for the factor level of force was found. The EMD values obtained at a force level of 50% MVC were longer than at 70% MVC (107 vs 98 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Electromechanical delay in the vastus lateralis muscle during dynamic isometric contractions.

Electromechanical delay (EMD) values were obtained using a cross-correlation technique for a series of 14 repetitive submaximal dynamic isometric contractions of the vastus lateralis performed by five subjects. To avoid a phase lag, which is introduced with one-way filtering, the EMG was processed with a bi-directional application of a second-order Butterworth filter. A mean EMD value of 86 ms (SD = 5.1 ms) was found. Moreover, contraction and relaxation delays were computed and compared. There was a significant difference between the contraction and relaxation delays (P less than 0.005). The mean contraction delay was 81.9 ms and the mean relaxation delay was 88.8 ms. Despite this significant difference, the computed contraction and relaxation delay values lie in the same range as the total phase lag, calculated with the cross-correlation technique. The magnitude of EMD values found supports the need to account for this delay when interpreting temporal aspects of patterns of intermuscular coordination.