Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

The Effect of Aspirin on Recurrent Fetal Loss in Experimental Antiphospholipid Syndrome

PURPOSE: To evaluate the effect of aspirin treatment upon fetal loss in mice with experimental antiphospholipid syndrome (APLS). MATERIALS AND METHODS: Experimental APLS was induced in pregnant mice by passive transfer of mouse monoclonal anticardiolipin antibody. The mice were treated with high (100μg/d) or low (10μg/d) does of aspirin, using vitaminC(100μg/d or 10μg/d)as a control. The mice were assessed for the presence of lupus anticoagulants (prolonged aPTT), thrombocytopenia, degree of fetal resorption rate and mean embryo and placental weights. RESULTS: The mice with APLS had a higher fetal resorption rate(45.7± 12.2% vs 2.5 ± 0.4%, P<0.001), reduced placenta mean weight(104 ± 8 mgvs 169 ±7mg, P<0.001), prolonged aPTT (94± 14sec vs 39±4sec, P<0.001), and reduced mean platelet count(597± 186 ± 10³/mm³vs 847±51 ± 10³/mm³,P<0.001). The groupof mice with APLS, who were treated with low-dose aspirin, had a lower resorption rate (11.1 ±9.3% vs 45.7±12.2%, P<0.001), a higher placenta mean weight (178 ± 8 mg vs 104 ± 8 mg, P<0.001), a higher mean embryo weight (1042 ± 134 mg vs 721±91 mg, P<0.001), and a lower aPTT (58±15 sec vs 94±14 sec, P, <0.001). Micewho were treated with high-dose aspirin also had a lower resorption rate, although not as much as in the low-dose aspirin group (34.2 ± 12.7% vs 45.7 ± 12.2%, P<0.001). CONCLUSION: Aspirin, especially in low dose, has a protective effect against obstetrical complications associated with experimental APLS.     

Incidence of ICD Lead Related Complications During Long-Term Follow-Up: Comparison of Epicardial and Endocardial Electrode Systems

The aim of this study was to evaluate the longterm stability of epicardial and endocardial lead systems for third-generation cardioverter defibrillators (ICDs) and to assess the usefulness of diagnostic tools. One hundred forty patients with 61 epicardial (43.6%) and 79 nonthoracotomy systems (56.4%) were followed for 2 5 ± 19 months. A total of 18 (12.9%) lead related complications were documented. Complications of epicardial systems were detected in 10 patients (16.4%) during a follow-up time of 36 ± 8 months: crinkling of patch electrodes in 6 patients (9.8%), insulation breakage of sensing electrodes in 2 patients (3.3%), and adapter defect in 2 patients (3.3%). Eight of the patients (10.1%) with transvenous-subcutaneous systems had lead related complications during a 13 ± 6 months follow-up: fracture of the subcutaneous patch lead in 2 patients (2.5%), dislodgment of the right ventricular lead in 2 patients (2.5%), dislodgment of the superior vena cava lead in 2 patients (2.5%), insulation breakage of sensing electrodes in 1 patient (1.3%), and connector defect in 1 patient (1.3%). There was no significant difference in the incidence of lead related complications between epicardial and endocardial systems (P > 0.05). Fractures, dislodgments, and crinklings were documented within the first 8 ± 5 months by regular chest X ray. Defects of insulation, adapter, or connector were detected 22 ± 10 months after implantation and were associated with delivery of multiple inappropriate ICD therapies. An operative lead revision was indicated for 4 epicardial (6.6%) and 6 endocardial (7.6%) lead systems. Conclusions: Endocardial lead systems offer a similar long-term stability as compared to epicardial had systems. Chest X ray is the most useful tool to detect lead fracture, dislodgment. and patch crinkling. Marker recordings or real-time electrograms have not been helpful in this series to identify patients with suspected lead defects prior to the experience of inappropriate ICD discharges.     

Embryotoxicity Study of Monomeric 4,4'-Methylenediphenyl Diisocyanate (MDI) Aerosol after Inhalation Exposure in Wistar Rats

One of the uses of MDI is as an alternative to formaldehydein the manufacture of furniture, its main route of exposureto humans being by inhalation. There have been no previous studieson the potential prenatal toxic effects of this compound. Toclose this gap in information, gravid Wistar rats, Crl:(WI)BR,were exposed by whole-body inhalation to clean air (control)and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per dayfrom Days 6 to 15 post conception (p.c). Rats were killed onDay 20 p.c. and the following results were obtained: Treatmentcaused a dose-dependent decrease in food consumption in allsubstance-treated groups during exposure, returning to normalvalues after cessation of treatment. The lung weights in thehigh-dose group were significantly increased compared to thesham-treated control animals. Treatment did not influence anyother maternal and/or fetal parameters investigated (maternalweight gain, number of corpora lutea, implantation sites, pre–and postimplantation loss, fetal and placental weights, grossand visceral anomalies, degree of ossification), although aslight but significant increase in litters with fetuses displayingasymmetric sternebra(e) was observed after treatment with thehighest dose of 9 mg/m³. Although the relevance of an increaseof this minor anomaly in doses which cause toxic effects indams (reduced food consumption, increased lung weights) is limitedand the number observed is within the limits of biological variability,a substance-induced effect in the high-dose group cannot beexcluded with certainty. Consequently, a no embryotoxic effectlevel of 3 mg/m³ was determined.     

Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2We investigated the effects of captopril (2×25 mg day⁻¹), or ASA (1×100 mg day⁻¹), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α), and PGE₂ were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3− and cyclic GMP as indicators. 3Urinary 2,3-dinor-6-keto-PGF_1α excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB₂ excretion was inhibited by >80% by ASA alone or in combination with captopril (each P<0.05), but was not affected by captopril alone. Urinary PGE₂ excretion was not significantly changed by either of the treatments. Urinary NO3− and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB₂ excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.     

Scientifically Based Rationale and Protocol for Use of Modern Indirect Resin Inlays and Onlays

The desire to place esthetically pleasing, conservative, functionally stable, posterior restorative materials has steadily increased over the past 20 years. The creation of successful dentin bonding adhesives and appropriate resin luting cements has paved the way for the development of a myriad of indirect resin-based restorative materials. These materials have been specifically designed to overcome the negative attributes of their porcelain counterparts, and to simplify fabrication, insertion, and post-delivery adjustments. Possibly like no other product before, these restorative materials have met with instant clinical acceptance by many practitioners, and concern exists that these materials have not been sufficiently studied to warrant such widespread acceptance. This article presents an overview of the history and development of resin-based, esthetic, indirect systems, and offers the clinician a review of the literature supporting their role in posterior restorative dentistry. Additionally, a scientifically based protocol for preparation, impressing, provisionalization, and subsequent cementation and adjustment of indirect laboratory-processed resin inlays and onlays is presented.
CLINICAL SIGNIFICANCE
This article reviews the history of indirect laboratory-processed resin restorations, reviews available literature supporting their use, and presents a scientifically based protocol for their placement and use as a viable alternative for conservative reconstruction of posterior teeth.     

IS INTRAOPERATIVE ELECTROSTIMULATION OF ERECTILE NERVES POSSIBLE?

PURPOSE: We improved intraoperative conditions to achieve better corpora cavernosal response to stimulation of the erectile nerves. MATERIALS AND METHODS: A total of 18 men undergoing nerve sparing retropubic prostatectomy were evaluated with intraoperative stimulation for identification of the erectile nerves. Intracavernosal pressure was measured directly or via electromyography of the corpora cavernosa. Different kinds of anesthesia were used with or without urapidil. RESULTS: Intracavernosal pressure was recorded in all patients. Use of isoflurane based anesthesia blocked change, and total intravenous anesthesia with propofol resulted in a measurable change in intracavernosal pressure during electrostimulation. However, local urapidil, a potent alpha-blocking agent, doubled or tripled intracavernosal pressure. Electromyography of the corpora cavernosa demonstrated no measurable change. CONCLUSIONS: Intraoperative electrostimulation of erectile nerves requires special anesthesia as well as local blocking of alpha-receptors. The functional anatomy of the erectile nerves is variable.