(Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy.

UNLABELLED: As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. PATIENTS AND METHODS: In this study we examined the levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24 patients undergoing 1311 treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva(iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. RESULTS: 8-epi-PGF2alpha showed a significant 1311 dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha lower as compared to non-smokers. CONCLUSION: These results clearly demonstrate a dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8-epi-PGF2alpha) after 131I-therapy in the salivary glands.

Effect of black tea on (iso-)prostaglandins and platelet aggregation in healthy volunteers.

Flavonoids among others are found in tea. Many of them were shown to exhibit antioxidative action in vitro. We examined the effect of a 1-month consumption of 500 ml black tea containing 2.0 mg quercetin. While single tea consumption 2 h after finishing the intake did not affect any of the parameters (8-epi-PGF(2 alpha) in plasma and serum, 11-DH-TXB(2) and ADP-induced platelet aggregation) examined at all, 1-week consumption and even more than 1 month regular tea intake significantly decreased most of the parameters. The effect was somewhat more pronounced for females as compared with males, the values for 11-dehydro-thromboxane B(2) (11-DH-TXB(2)) and ADP-induced aggregation reached the level of significance in females only. These data show that regular daily black tea consumption for 1 month improves platelet function and decreases thromboxane and 8-epi-PGF(2 alpha) to a varying extent indicating a reduced in vivo oxidation injury.

Endovascular brachytherapy for prophylaxis against restenosis after long-segment femoropopliteal placement of stents: initial results.

PURPOSE: To evaluate the feasibility, safety, and effectiveness of endovascular brachytherapy for the prevention of restenosis after long-segment femoropopliteal percutaneous transluminal angioplasty (PTA) and stent implantation. MATERIALS AND METHODS: Thirty-three patients (23 men, 10 women; mean age, 66 years) with femoropopliteal lesions (mean treated length, 17 cm; range, 4-30 cm) underwent PTA and stent implantation followed by brachytherapy with a centering catheter. A dose of 14 Gy was delivered to the adventitia by using an iridium 192 source. Long-term pharmacotherapy with acetylsalicylic acid was combined with clopidogrel for 1 month. Follow-up examinations included measurement of the ankle-brachial index, color-coded duplex ultrasonography, and angiography. RESULTS: The overall 6-month recurrence rate was 30% (10 of 33 arteries). Seven patients developed sudden late thrombotic occlusion of the segment with the stent 3.5-6 months after stent implantation. Considering the overall results after successful local thrombolysis in six of these seven patients, only four (12%) of 33 arteries with a stent had in-stent restenosis caused by neointimal hyperplasia. CONCLUSION: The study results are promising concerning the possibility of reducing in-stent restenosis by means of brachytherapy after long-segment femoropopliteal placement of stents. The high incidence of late thrombotic occlusion requires optimization of the antithrombotic regimen.

Assessment of peripheral arterial vascular disease with radionuclide techniques.

Various radioisotopic imaging techniques for noninvasive detection of vessel stenosis and for functional investigation of reduced blood flow and follow-up have been developed during the last decade in peripheral vascular disease (PVD), with the aim of replacing invasive techniques and complementing standardized methods. Radionuclide assessment of PVD is divided into 2 major groups: imaging of perfusion and metabolic investigations. The measurement of arterial blood flow and muscle perfusion is intended to show the morphology, to evaluate the functional consequences of PVD, and to quantify the latter. The application of radiolabeled tracers was developed as a noninvasive alternative to angiography in morphologic imaging. Treadmill testing has been used to assess the functional effects of reduced blood flow in PVD where the onset of pain indicates the stage of disease, but the results can be confused by other symptoms. Scintigraphic measurement of muscle perfusion should detect insufficient nutritional blood flow in peripheral muscle and thus have a higher specificity for PVD than treadmill testing alone. Although there are very promising theoretical and experimental data in animals, the clinical use of radionuclide investigations is limited by different technical problems, such as methodologic differentiation between skin and muscle perfusion, the lack of controlled and prospective studies, and incomplete correlation with other standardized routine techniques. Among the great number of radioisotopic metabolic imaging techniques, only radiolabeled platelets and lipoproteins, to some extent, have shown a limited potential clinical use. Some other approaches seem to have a high potential from a theoretical point of view. They are limited, however, by a great number of problems. Correlation with sonographic or magnetic resonance imaging (MRI) findings may identify a potential metabolic value. Correlation with angiography reflecting the extent of the disease makes no sense. So far with PVD, neither radioisotopic perfusion studies nor metabolic imaging techniques are able to achieve a level of routine application or wider meaningful interpretation of the clinical condition of a specific patient. Competing techniques are easier to perform, less expensive, faster, more widely available, and do not carry the radiation burden. Positron emission tomography is still in its early stages of application, with great theoretical potential but at a high price. A great deal of work is still required to transform in vitro and experimental experience into more meaningful routine radioisotopic investigations in patients with PVD.

Phase II study of gemcitabine in combination with cisplatin in patients with locally advanced and/or metastatic pancreatic cancer.

The present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy with gemcitabine and cisplatin in patients with locally advanced or metastatic carcinoma of the pancreas. Sixteen patients received six courses of an i.v. cytotoxic regimen consisting of gemcitabine (1000 mg/m2, days 1, 8 and 15) and cisplatin (35 mg/m2, days 1, 8 and 15) administered in 28-day intervals. Complete remission (CR) occurred in one patient (6%), partial remission (PR) in four patients (25%) and stable disease in seven patients (44%), whereas four patients (25%) developed progressive disease resulting in an overall response rate of 31%. Mean duration of responses (CR+PR) was 3.6 (range 0.7-8.5) months and mean time to progression was 7.4 (range 3.8-12.6) months. After a mean observation period of 11.5 months the overall survival was 9.6 months with 12 patients (75%) still being alive, which compares favorably with historical data of the administration of gemcitabine alone. The performance status improved in three (19%) and stabilized in eight (50%) out of 16 patients for 4 weeks or longer. Treatment-associated toxicity included alopecia of WHO grade III in all cases, leukopenia of WHO grades I and II in 10 patients (63%), grade III in five patients (31%), and thrombocytopenia grades I and II in four patients (25%), and grades III and IV in 10 patients (63%). We conclude that the administered dosage and schedule of gemcitabine and cisplatin in patients with locally advanced or metastatic cancer of the pancreas constitutes an active cytotoxic regimen associated with moderate toxicity.

Defective antigen presentation resulting from impaired expression of costimulatory molecules in breast cancer.

Previous experiments from our laboratory have shown that immune mechanisms aiming at the destruction of tumour cells including the recognition of target cells and their elimination via the expression of intercellular adhesion molecule-1 (ICAM-1; CD54), the production of tumour necrosis factor-alpha (TNF-alpha) by monocytes and appropriate function of lymphocyte subpopulations were defective in breast cancer. Previous observations were extended to assess expression levels and regulatory mechanisms of costimulatory molecules CD54, CD80 and CD86 on monocytes derived from patients with early breast cancer (EBC). In addition, antigen presentation by antigen-presenting cells (APC) was analyzed within this context. We report that monocytes derived from patients with EBC exhibited significantly decreased expression levels of CD54 (p = 0.0002), CD80 (p = 0.009) and CD 86 (p = 0.002) compared with monocytes derived from healthy females. Simultaneously, lipopolysaccharide (LPS)-induced TNF-alpha production of monocytes was found to be defective in patients with EBC. Finally, T-cell proliferation in response to tetanus toxoid (TT) was significantly decreased in patients with EBC compared with healthy control females (p < 0.0001). Furthermore, T-cell proliferation in response to TT-pulsed APC derived from healthy controls was significantly inhibited in the presence of anti-CD54 and/or anti-CD80 antibodies in a dose-dependent manner, thus corroborating the necessity of the presence of CD54 and CD80 as costimulatory molecules in the present setting. We conclude that monocytes derived from patients with EBC showed a simultaneous defect of expression of CD54 and its regulation via TNF-alpha, CD80 and CD86 as well as T-cell proliferation following exposure to TT-pulsed APC. Based upon these findings, it is speculated that defects in costimulatory molecule expression might contribute to tolerance of the immune system towards the presence of malignant cells in patients with EBC.