Monocyte activation drives preservation of membrane thiols by promoting release of oxidised membrane moieties via extracellular vesicles.

The redox state of cellular exofacial molecules is reflected by the amount of available thiols. Furthermore, surface thiols can be considered as indicators of immune cell activation. One group of thiol containing proteins, peroxiredoxins, in particular, have been associated with inflammation. In this study, we assessed surface thiols of the U937 and Thp1 monocyte cell lines and primary monocytes in vitro upon inflammatory stimulation by irreversibly labelling the cells with a fluorescent derivative of maleimide. We also investigated exofacial thiols on circulating blood mononuclear cells in patients with rheumatoid arthritis and healthy controls. When analysing extracellular vesicles, we combined thiol labelling with the use of antibodies to specific CD markers to exclude extracellular vesicle mimicking signals from thiol containing protein aggregates. Furthermore, differential detergent lysis was applied to confirm the vesicular nature of the detected extracellular events in blood plasma. We found an increase in exofacial thiols on monocytes upon in vitro stimulation by LPS or TNF, both in primary monocytes and monocytic cell lines (p<0.0005). At the same time, newly released extracellular vesicles showed a decrease in their exofacial thiols compared with those from unstimulated cells (p<0.05). We also found a significant elevation of surface thiols on circulating monocytes in rheumatoid arthritis patients (p<0.05) and newly released extracellular vesicles of isolated CD14+ cells from rheumatoid arthritis patients had decreased thiol levels compared with healthy subjects (p<0.01). Exofacial peroxiredoxin 1 was demonstrated on the surface of primary and cultured monocytes, and the number of peroxiredoxin 1 positive extracellular vesicles was increased in rheumatoid arthritis blood plasma (p<0.05). Furthermore, an overoxidised form of peroxiredoxin was detected in extracellular vesicle-enriched preparations from blood plasma. Our data show that cell surface thiols play a protective role and reflect oxidative stress resistance state in activated immune cells. Furthermore, they support a role of extracellular vesicles in the redox regulation of human monocytes, possibly representing an antioxidant mechanism.

Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer.

BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.

The prognostic value of body protein in patients with lung cancer.

Lung cancer is a major cause of death in many countries. To improve the results of treatment, more individualized therapy is necessary; for this, it is necessary to identify new prognostic factors. In 21 patients with lung cancer (17 with non-small-cell lung cancer and 4 with small-cell lung cancer) that had received radiation treatment, the amount of body protein was estimated with in vivo neutron activation analysis. Patients in whom body protein decreased had recurrences of the disease earlier and a poorer survival than patients whose body protein increased. A clear relationship was seen between changes in the body's protein content and recurrence-free survival. To better evaluate the prognostic value of body protein content in patients with lung cancer, a larger number of patients and a longer follow-up period are needed.

Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial.

A randomised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate (MA) on the quality of life (QoL), appetite, weight and survival of patients with advanced, incurable, hormone-insensitive cancer. QoL was assessed at the start of treatment and at 4, 8 and 12 weeks, using the EORTC-QLQ-C30 instrument. 255 patients were randomised to 320 mg of MA daily or placebo for 12 weeks. 244 patients were assessable at baseline, 190 at 4 weeks (placebo 94; MA 96), 150 at 8 weeks (placebo 69; MA 81) and 112 at 12 weeks (placebo 55; MA 57). A beneficial effect of MA on appetite loss was observed at week 4 (P < 0.0001) and possibly at week 8 (P = 0.058). Further weight loss during treatment was significant only in the placebo group. In the first 8 weeks, changes in mean global QoL were small and similar in both groups. By 12 weeks the decrease in mean global QoL was more pronounced in the MA group (P = 0.028), which was related to a deterioration in physical function, while psychosocial function was not affected. Survival was not affected by MA, and side-effects were mild. The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity. However, MA does not appear to improve global QoL as measured by the EORTC QLQ-C30.

A 252Cf-based instrument for in vivo body protein monitoring in cancer patients.

A hospital-based facility for in vivo prompt gamma neutron activation analysis of nitrogen for body protein determination is described. The patient is laid on a movable couch and is scanned with a vertically collimated neutron beam from a 252Cf neutron source (the amount of Cf varying from 120 to 40 microg due to the physical decay) positioned below the patient. Four large NaI(Tl) detectors are used to measure the 10.8 MeV gamma-rays from nitrogen. To check the long-term stability of the system, a solid phantom simulating the geometry of the adult human trunk, having similar elemental composition as tissue, was constructed. Repeated phantom measurements over 6 months gave a reproducibility in nitrogen determination of 2.9% (1 SD). Duplicate patient measurements carried out within a week showed a reproducibility of 5% (1 SD). A calibration method for absolute protein measurements in patients is presented. Patients are normally measured for 40 min; giving a mean whole-body equivalent dose of 0.25 mSv. Results from measurements on 13 cancer patients are presented.

Body protein as a prognostic instrument for cancer patients?

Many cancer patients are affected by loss of appetite, weight loss and fatigue in the course of disease. These symptoms reduce the patients' quality of life, increase morbidity, and lessen tolerance to anti-tumor treatment. In some cases the symptoms are partly caused by various treatment modalities. The aim of this study was to investigate if radiotherapy affects the body weight and body protein of patients, and if changes in body protein have any clinical significance.

[Experience with partial removable dentures anchored by the Vigano attachment]. / Tapasztalataink a Vigano-féle finommechanikai eszközzel elhorgonyzott részleges lemezes fogpótlásokkal.

In 1993 the Vigano attachment appeared in Hungarian commercial turnover. On the basis of 20 cases observed during one year it can be stated, that the use is simple for dental technicians, the fitting effect is good, requires small place, insertion and removal is easy for elderly and handicapped patients; it is aesthetically satisfying and the design ensures minimum likelihood of repairs.

[Anchoring of partial dentures using OT-CAP precision attachments]. / Részleges lemezes pótlások elhorgonyzása OT-CAP finommechanikai rögzítöeszközökkel.

The authors have examined a precision attachment recently invented in Hungary. They are reporting about the experience gained during clinical examination of dentures made in different classes on the basis of the Fábián and Fejérdy classification of partial edentulousness.

[Aerobic conditions and the dynamics of the methyl red reaction in Klebsielleae]. / Conditionarea aeroba si dinamica reactiei rosului de methyl la Klebsielleae.

The development of the methyl red reaction (MR) in Klebsielleae, analyzed during a 4-day thermostatting, showed important pH-variations. Two steps are distinguished during the reaction dynamics: the former of acidification, common to all Enterobacteriaceae and the latter of alkaline reversion, specific to Enterobacter, Klebsiella, Serratia and other MR germs. The processes determining the alkaline reversion are conditioned by the presence of large amounts of air/oxygen (aerobic processes). In this situation, the lack of oxygen and maintenance of a relative degree of anaerobiosis block realkalinization (media covered with paraffin oil) whereas the large aeration stimulates it (optimum ratio between the large contact surface and a small volume of medium). Alkaline reversion cannot be explained by the more or less intense process of glucose fermentation but by degradations of nitrogenized substances with formation of amines, ammonia, and other basic compounds. That is why the analysis of the reaction mechanism of methyl red has to consider the characteristics of the catabolism of the nitrogenized substances and the intense realkalinization capacity of the culture medium proper to Klebsielleae but poorly expressed and non efficient in Enterobacteriaceae.

[Postoperative lymph node scintigraphy in patients with malignant melanoma]. / Postoperatív nyirokcsomó-szcintigráfiás vizsgálatok lymphadenectomizált melanoma malignumban szenvedö betegeken.

Completeness of regional lymph node dissection was controlled in 23 patients with melanoma malignum. For that purpose 3--6 weeks after block-dissection lymph node scintigraphy was performed, by administration of intercostal and interdigital radiopharmacutical. Blockdissection was considered as complete, when neither after intercostal, nor after interdigital administration, any lymph nodes were delineated. On the basis of investigations until now, postoperative lymph node scintigraphy proves to be suitable, held to be a non-invasive method for controlling completeness of blockdissection.

Bone-scintigraphic examinations in patients treated with retinoids: a prospective study.

Possible early side-effects of retinoid treatment on bones were studied with the aid of bone-scintigraphy. Isotretinoin treatment (1.0 mg/kg daily for 4 months) was given to 18 patients with acne. Fifteen patients with psoriasis received etretinate treatment (0.7-1.0 mg/kg/day) for 4 months. In the group treated with isotretinoin, pathological uptake of radiolabel was found in three cases, while in the group treated with etretinate, no bone changes attributable to treatment were found. During isotretinoin treatment, a decrease in growth-plate activity was observed. Bone-scintigraphy is considered to be a suitable method for early screening for bone changes occurring in retinoid treatment.

Acitretin treatment of severe psoriasis.

Fourteen male patients suffering from severe psoriasis were treated with 30 to 50 mg/day acitretin during 12 weeks. At the end of the treatment, 6 patients were in remission and 7 showed a marked improvement of the disease. One patient did not show any change. All patients experienced the usual retinoid side effects.

[Scintigraphic studies of the lymph nodes in patients with melanoma following lymph node excision]. / Lymphknoten-Szintigraphische Untersuchungen bei Lymphadenektomisierten Melanom-Patienten.

We report on 20 patients suffering from malignant melanoma, who had undergone regional lymph node dissection. In order to make certain that all the lymph nodes had been completely removed, we performed lymphoscintigraphy 3 to 6 weeks after block dissection with the help of a radiopharmacon intercostally or interdigitally applied. We judged the removal to be complete, if neither intercostal nor interdigital application led to any evidence of regional lymph nodes. On the basis of our experiences so far, we consider postoperative lymphoscintigraphy a suitable non-invasive method to check the completeness of block dissection.

Spermatological investigations in patients treated with etretinate and isotretinoin.

Possible side effects of the retinoids etretinate and isotretinoin on the germinal epithelium were examined. 15 men received etretinate and 13 isotretinoin. After 16 weeks of treatment at therapeutic doses, no changes were observed in fundamental spermatological parameters. On the basis of examinations and data in the literature, we hold the opinion that retinoid treatment is to be considered safe from the andrological viewpoint.