Examination of the dermal lymphatics in psoriasis⋆

In recent years, research on the aetiology of psoriasis has focused on immune aetiopathogenesis. However, in the last few years, research on the immunoloogical changes in psoriasis has failed to mention the lymphatics. Also, studies emphasizing the importance of the dermal lymphatics have neglected the lymphatic changes seen in psoriasis. Therefore, we decided to put this matter back on the agenda. Skin biopsies from 20 patients with psoriasis vulgaris were examined lymphatically by light microscopy using the orcein stain. We found a considerable increase in both number and dilatation in the lymphatics of psoriatic plaques, compared with both the clinically uninvolved skin of the psoriatic patients and also the skin of the control group.     

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Despite its long history, there has been very little systematic study of figure skating. Successful skaters and coaches have passed on ideas, traditions, and opinions to their followers with the idea that what once produced good results must be the correct approach. Skaters are significantly shorter, lighter, and leaner than their sedentary counterparts and have a rather low percent body fat. Their cardiovascular fitness levels are 50% to 60% higher than those of sedentary people of the same age, but far less than those of endurance athletes.     

Characterization and solubilization of vasoactive intestinal peptide receptors from rat lung membranes

Receptors for vasoactive intestinal peptide (VIP) were characterized in rat lung membranes by binding and covalent cross-linking of [125I]VIP using ethylene glycolbis-(succinimidylsuccinate). Binding studies indicated the presence of two classes of binding sites for VIP in rat lung membranes: 0.28 +/- 0.11 pmol/mg protein high affinity receptors (Kd = 79.2 +/- 26.4 pM) and 3.3 +/- 0.9 pmol/mg protein lower affinity receptors (Kd = 4.8 +/- 2.1 nM). Furthermore, binding of [125I]VIP to rat lung receptors was inhibited by micromolar concentrations of GTP analogs, guanosine-5'-O-(3-thiotriphosphate) GTP gamma S), and guanylylimidodiphosphate, suggesting that VIP receptors in rat lung membranes were tightly coupled to the guanine nucleotide regulatory protein (Ns). Scatchard analysis of VIP binding in the presence of GTP gamma S revealed selective inhibition of binding to high affinity sites. A 58K band was specifically labeled when membranes covalently labeled with [125I]VIP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. The apparent size of this species was not altered when sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis was carried out in the absence of reducing agent. Unlabeled VIP inhibited the labeling, with an IC50 of about 1 nM. A related peptide, GH-releasing factor-(1-40)OH, exhibited a much lower binding affinity, and two unrelated peptides, insulin and atrial natriuretic factor, did not inhibit labeling of the 58K species, even at micromolar concentrations. Labeling of the 58K species was inhibited in a GTP gamma S-dependent manner, suggesting the involvement of this species in the coupling to Ns. These data collectively indicated that the 58K species was a VIP-binding unit of VIP receptors in rat lung membranes. Several nondenaturing detergents were tested for extraction of labeled receptors from the membrane; the best extraction was obtained using 1% n-octyl-beta-D-glucopyranoside.     

Ventricular arrhythmias in patients with COPD are associated with QT dispersion

STUDY OBJECTIVE: QT dispersion (QTd) and late potentials derived from signal-averaged ECG (SAECG) have been proposed as noninvasive predictors of cardiac arrhythmias that occur in patients with COPD. In this study, we aimed to investigate QTd and SAECG in patients with COPD. DESIGN: Cross-sectional study. SETTING: Teaching chest disease hospital and cardiology center in a university hospital. PATIENTS: Thirty patients with COPD (28 men and 2 women; mean +/- SD age, 60 +/- 9 years) and 31 age- and sex-matched control subjects (28 men and 3 women; mean age, 57 +/- 7 years) were included. Measurements and results: Respiratory function tests, arterial blood gas analyses, echocardiographic examinations, rhythm Holter recordings, and heart rate variability (HRV) analyses were performed in addition to the measurements of QT intervals and SAECG. Patients with COPD had higher rate of ventricular premature beats (VPBs) as compared to control subjects (924 +/- 493 beats vs 35 +/- 23 beats, p = 0.009). Eight patients with COPD (27%) had nonsustained runs of ventricular tachycardia (VT). QTd rates were significantly increased in patients with COPD as compared to control subjects (57.7 +/- 9.9 ms vs 37.5 +/- 8.2 ms, p < 0.001). On comparing patients with COPD with and without runs of VT, patients with VT had longer QTd (67 +/- 10 ms vs 55 +/- 8 ms, p = 0.001). However no difference in any HRV and late potential parameters were found between patients with COPD with and without runs of VT. VPB rates were strongly correlated with QTd in patients with COPD (r = 0.61, p < 0.001). On SAECG analysis, patients with COPD had significantly increased total QRS duration as compared to control subjects. Nine of the 30 patients with COPD (30%) had positive late potentials. However, QTd and VPB rates were also similar between patients with COPD with and without late potentials. CONCLUSIONS: The development of ventricular arrhythmia in patients with COPD was associated with increased QTd. Increased QTd may be associated with autonomic changes seen in patients with COPD.     

Effect of diurnal variability of heart rate on development of arrhythmia in patients with chronic obstructive pulmonary disease

We examined the possible effect of diurnal variability of heart rate on the development of arrhythmias in patients with chronic obstructive pulmonary disease (COPD). Forty-one COPD patients (M/F: 39/2, mean age: 59+/-8.5 years) and 32 (M/F: 27/5, mean age: 57+/-11 years) healthy controls were included. Twenty-four hour ECG recordings were analyzed for atrial fibrillation (AF) or ventricular premature beats (VPB), and circadian changes in heart rate variability (HRV) were assessed by dividing the 24-h period into day-time (08:00-24:00 h) and night-time (24:00-08:00 h) periods. Night-time total (TP), low frequency (LF) and high frequency (HF) powers were similarly lower from day-time parameters in AF(-) COPD patients (HF 3.91+/-1 vs. 4.43+/-1.04 ms(2), P=0.001) and controls (HF 3.95+/-0.72 vs. 4.82+/-0.66 ms(2), P<0.001). The LF/HF ratios were also significantly reduced in the same patient groups (AF(-) COPD 1.35+/-0.21 vs. 1.27+/-0.19, P=0.04, controls 1.43+/-0.14 vs. 1.24+/-0.09, P<0.001). Night-time TP and LF were increased, HF unchanged and LF/HF significantly increased (1.11+/-0.25 vs. 1.19+/-0.27, P<0.05) in AF(+) COPD patients. Frequency of VPB was correlated with corrected QT dispersion (QTc(d)) (r=0.52, P=0.001) and the day-time/night-time HF ratio (r=0.43, P=0.02). Patients with QTc(d)>or=60 ms did not have the expected increase in night-time HF and had a statistically insignificant increase in LF/HF ratio. In COPD patients with QTc(d)<60 ms, circadian changes in HRV parameters were parallel with the controls. We concluded that COPD patients with arrhythmia had circadian HRV disturbances such as unchanged night-time parasympathetic tone and disturbed sympatho-vagal balance in favor of the sympathetic system all day long, which may explain the increased frequency of arrhythmia.     

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy—based on creatinine level, proteinuria and disease activity—was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.