A phase II trial with RFS2000 (rubitecan) in patients with advanced non-small cell lung cancer.

Rubitecan (RFS2000, 9 nitrocamptothecin,) is a new oral topoisomerase I inhibitor. We report a phase II, single-arm, open-label study of RFS2000 as first line treatment for non-small cell lung cancer (NSCLC). Seventeen treatment-naïve patients with stage IIIB (9/17) and IV (8/17) NSCLC (11 male and 6 female) were treated, the median age was 62 years (range 52-86), and the majority of patients (14/17) were of performance status 1. RFS2000 was given orally, daily for 5 days, repeated every week. The starting dose was 1.5 mg/m(2)/day, and dose adjustment was permitted based upon toxicity. Fifteen patients had a dose escalation to 1.75 mg/m(2)/day and 7 had a second dose escalation to the protocol maximum level of 2.0 mg/m(2)/day. RFS2000 was tolerated well. Almost all adverse events were grade 1 and 2. The most frequently encountered adverse events were diarrhoea, nausea, anorexia, and lethargy. Neutropenia and thrombocytopenia were not observed in any patient. There were no responders to RFS2000 treatment, 10 patients had stable disease as their best response, whilst five had tumour progression. Two patients were not assessable for tumour response. The median survival time was 257 days (95% CI = 222-352). RFS2000 appears to be inactive at dose levels of 1.5-2.0 mg/m(2)/day in advanced NSCLC patients. Since only mild toxicity and no myelosuppression were encountered, these dose level are too low for this treatment-naïve patient population with NSCLC. Further studies at an increased dose would be required to identify whether this agent has merit in the treatment of NSCLC.

Does lowering of cholesterol levels influence functional properties of large arteries?

Hypercholesterolaemia is a risk factor for atherosclerosis and induces endothelial dysfunction. Endothelial dysfunction may increase vascular tone and arterial stiffness and as a consequence may decrease arterial distensibility (DC) and arterial compliance (CC). It is hypothesized that lipid-lowering therapy may enhance DC and CC. Therefore, the present study investigates the effect of lipid-lowering therapy with pravastatin on the haemodynamics, DC and CC of the elastic common carotid artery (CCA), and the muscular femoral (FA) and brachial (BA) arteries in patients with primary hypercholesterolaemia. After an 8-week placebo run-in period with a low-cholesterol diet, 19 patients with total cholesterol concentrations of between 6.5 and 9.0 mmol.l-1 and triglyceride concentrations < 4 mmol.l-1 entered a double-blind placebo controlled crossover study. Patients received pravastatin 40 mg o.d. or placebo, each for 8 weeks. Throughout the study the lipid-lowering diet was continued. With pravastatin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides were decreased (total cholesterol 26%, LDL-C 35%, triglycerides 16%), while high-density lipoprotein cholesterol (HDL-C) was not changed. Other laboratory values remained within the normal range. Blood pressure, heart rate, cardiac function and systemic vascular resistance were not influenced by pravastatin. Compared to placebo, diameter, distensibility and compliance of all arteries were not statistically significantly changed with pravastatin. These data suggest that, in patients with mild to moderate primary hypercholesterolaemia, short-term lowering of plasma cholesterol does not alter the haemodynamics and vessel wall properties of large arteries.

[Reconstruction of the tibial plateau fracture with arthroscopic monitoring without arthrotomy]. / Reconstructie van de tibiaplateaufractuur onder artroscopische controle zonder artrotomie.

In the period from October 1986 to November 1988 in the Medisch Spectrum Twente of Enschede, 25 patients were treated for a tibial plateau fracture by means of arthroscopic surgery. The mean hospital stay was 18 days. Active movement of the leg was prescribed from the fifth day. The results were very good in 23 and poor in 2 patients. Complications such as wound infections and skin necrosis were not seen. Additional meniscal lesions could be diagnosed and treated better using this surgical technique. In addition, the limited incisions and consequently the avoidance of extensive arthrotomy allowed faster rehabilitation and a higher probability of healing the chondral tissue.

Pathological-anatomical study concerning the geometry and atherosclerosis of the carotid bifurcation.

Besides metabolic factors haemodynamic elements are important in the development of obliterating athero-sclerosis. Since the geometry of a bifurcation influences the local bloodflow, we hypothesise that non-optimal geometry of a bifurcation leads to flow-disturbances, which can be a factor in atherogenesis. To verify our hypothesis that there is a correlation between non-optimal geometry of a bifurcation and the presence of atherosclerotic lesions, we studied as a parameter for the geometry of a bifurcation the area ratio defined as: the sum of the cross-sectional areas of the distal arteries divided by the cross-sectional area of the proximal artery. In this study the area ratios of 100 carotid bifurcations were studied by post-mortem examination. The mean value calculated for 60 normal carotid bifurcations was 1.47, and the mean for 40 diseased bifurcations was 0.99. The last value is significantly less than the theoretical optimal area ratio of 1.16, which was found by Womersley and Hunt as the value at which a minimum reflexion of pressure waves and a minimum of blood-flow energy loss occurs at a bifurcation. We conclude that a non-optimal area ratio of a carotid bifurcation seems to be a factor in atherogenesis.

[Biliary ascariasis as complication after cholecystectomy for cholelithiasis]. / Biliaire ascariasis als complicatie na cholecystectomie wegens cholelithiasis.

A case history of a 39-year-old Turkish female with gallstones is described. Cholecystectomy and choledochotomy were performed. In the postoperative period, the patients was found to have an Ascaris lumbricoides infection. The epidemiology, complications and diagnostics are briefly reviewed.

Geometry of the aortic bifurcation measured by computed tomography.

Apart from metabolic risk factors haemodynamic disturbances play a role in atherogenesis. The haemodynamic factors depend among other things on the geometry of vessels including the aortic bifurcation. The geometry of the aortic bifurcation can be expressed by the diameter of the distal abdominal aorta, the area ratio of the bifurcation and the convergence of the aorta. Data on the geometry have been reported of both post-mortem and in-vivo investigations by angiography and echography. Because of the disadvantages of angiographic and echographic measurements, the aortic bifurcation has been assessed by CT-scanning in a series of 50 patients. The mean diameter of the distal aorta measured 15.9 mm for men and 13.0 mm for women. The calculated area ratio was 0.74 for men and 0.81 for women. These data are in agreement with the angiographic measurements. A convergence was found of 30.6 percent for men and 45.4 percent for women. There is a discrepancy between these values and those reported in the literature.

The diameter of the distal abdominal aorta and the aetiology of local atheroma.

In our patients it was found that small sized prostheses were usually implanted to replace obliterated aortic bifurcations. Consequently, the question was considered whether the haemodynamic processes involved in the lysis of the aortic wall at the bifurcation and in the succeeding atherosclerotic lesions were related to the small diameter of the aorta in these cases. In an extensive angiographic and ultrasonic study on men without atherosclerotic lesions, the diameter of the abdominal aorta was determined (control group). Aortic diameter appears to depend on age as well as body length. We also found a difference between the average diameters for women and for men. Of our patients who were operated on, over 35% had an aortic diameter below the 95% population lower boundary line of the control group, while for over 90%, the diameter was below the average of the control group. On analysis of our data the explanation for the aetiology of atheromatosis at the aortic bifurcation must be much more complicated than current hemodynamic theories suggest.

Case report: false aneurysm due to synovial sarcoma.

On the basis of a false aneurysm of the radial artery caused by a synovial sarcoma, the behavior and histology of this fairly rare tumor are discussed. There are no reports in the literature which record such a rapidly developing synovial sarcoma as that observed in the patient described here.