Doppler ultrasound findings in healthy wrists and finger joints

OBJECTIVE: To evaluate the presence of flow by Doppler ultrasound (DUS) in the wrist and finger joints (carpometacarpal 1 (CMC1), metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints) of healthy controls. METHODS: Twenty seven healthy volunteers (15 women, 12 men; mean age 45 years, range 18-93) with a total of 324 joints were examined by DUS. The synovial vascularisation was determined by colour Doppler and the spectral Doppler resistive index (RI). Patients were only included if no synovitis was suspected at the clinical examination and the values for biochemical analysis were within the normal range. RESULTS: We found colour pixels in 15 of the 27 examined wrist scans and in 8 of these a measurable RI. In the CMC1 joint, colour pixels were found in 11 of the 27 scans and in 9 of these a measurable RI. For the MCP joints, colour pixels were found in 10 out of 135 scans and in 3 of these a measurable RI. The mean RI for all three types of joints was 0.85 and the mean pixel fraction varied from 0.05 to 0.08. Only one PIP joint scan was found to have colour pixels and a flow with an RI of 0.67. CONCLUSION: Synovial vascularisation may be detected in healthy subjects using DUS. Newer US machines have higher Doppler sensitivity, and it is necessary to be able to distinguish normal from pathological synovial flow.     

Specific immunoadsorption of pathogenic autoantibodies in pemphigus requires the entire ectodomains of desmogleins

Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are life‐threatening autoimmune blistering skin diseases. They are characterized by circulating autoantibodies which bind to the ectodomains of desmoglein (Dsg) 1 and Dsg3. These antibodies induce acantholysis in skin and mucous membranes. In severe cases of pemphigus, immunoadsorption is applied to remove total IgG from patient plasma using protein A or other ligands. To develop a specific adsorber for anti‐Dsg antibodies, epitope mapping studies of Dsg1 and Dsg3 ectodomains were conducted. Dsg variants were expressed on the surface of HEK‐293 cells and analysed for reactivity with pemphigus and control sera by indirect immunofluorescence technique. For Dsg1, a construct consisting of domain 1 directly fused to domain 5, seemed to be suitable for specific immunoadsorption of anti‐Dsg1 antibodies. The recognized epitopes were mainly conformation‐dependent. However, adsorption of pemphigus foliaceus IgG using this protein coupled to a Sepharose matrix did not completely remove pathogenicity from the sera, as proven by a keratinocyte dissociation assay. In contrast, full‐length Dsg1 and Dsg3 ectodomains were able to specifically adsorb anti‐Dsg antibodies and to efficiently eliminate pathogenicity. Therefore, the complete and correctly folded ectodomains of both desmogleins are required for therapeutic immunoadsorption.     

Influence of cigarette smoking on pemphigus – a systematic review and pooled analysis of the literature

Epidemiological evidence suggests that smoking cigarettes may be beneficial in pemphigus, but no systematic evaluation exists to corroborate this assumption. Therefore, a systematic literature review with pooled data analysis of the smoking status in patients with pemphigus was conducted. Electronic searches using PubMed from inception to November 2017 identified 13 reports meeting predetermined inclusion and exclusion criteria. Most were case–control studies partly reporting that pemphigus vulgaris and foliaceus occurred less frequently in current and former smokers. Studies also indicated that duration of smoking and number of cigarettes smoked were lower in patients with pemphigus than controls and that remission may be achieved sooner in those who smoke. However, although a generally low prevalence of smoking was demonstrated in patients with pemphigus, which was lower than in controls by pooled analysis, some investigations found no difference regarding the smoking status compared with non‐pemphigus subjects. One study demonstrated more severe mucosal involvement in non‐smoking patients with pemphigus, whereas another observed no difference in the rate of cutaneous or mucosal lesions between smokers and non‐smokers with pemphigus. This review indicates that smoking may be a possible protective factor in pemphigus, although some compromised study methodologies yet hinder any firm conclusion. Further investigations with a refined quality design are required to resolve the so far partly conflicting results in this area.     

Electrocardiographic markers of impaired left ventricular ejection performance in aortic stenosis

To determine whether the ECG would be useful in the prediction of impaired left ventricular ejection performance in aortic valve stenosis, the authors evaluated 121 patients according to (1) the time relationship of the R peak in V6 to the S peak in V2; and (2) the negative P wave terminal force in V1 (Morris index, n = 109). Left ventricular ejection fraction (LVEF) was significantly depressed in patients with the R peak in V6 later than the S peak in V2 (R peak delay in V6, n = 24), compared with those with the R peak in V6 preceding the S peak in V2 or with both peaks occurring simultaneously (n = 97) (LVEF 40.8 +/- 11.8% vs 69.9 +/- 13.3%, p = .000). LVEF less than 55% was present in 87.5% of patients with the R peak delay in V6 and in only 23.7% of those without this finding. The Morris Index was significantly greater in patients with LVEF less than 55% (n = 39) than in those with LVEF greater than or equal to 55% (n = 70) (Morris Index 0.063 +/- 0.035 msec vs 0.030 +/- 0.025 msec, p = .000). The R peak delay in V6 is a highly specific (96.1%), but less sensitive (47.7%), indicator of depressed LVEF, its positive predictive value and predictive accuracy being 87.5% and 78.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of Frank ECG measurements to the quantitative estimation of old anterior myocardial infarction

Twenty scalar and vector measurements of the Frank ECG were compared between men categorized as having suffered nontransmural (n = 47) and transmural anterior myocardial infarction (n = 124), on the basis of clinical and angiocardiographic findings. Variables which showed significant differences of group means between cases with anterior wall hypokinesis and anterior wall akinesis and/or dyskinesis were submitted to linear discriminant-function analysis. The stepwise selection procedure of Rao's method demonstrated the three most decisive variables for differentiation to be: (1) the angular sum of dorsal displacement of the 5 initial QRS vectors obtained at 0.01 sec intervals (sum of negative azimuth angles); (2) the Q duration in lead Z (anterior force); and (3) the Q duration in lead X (rightward force). The classification routine can identify correctly 81% of the nontransmural and 79% of the transmural anterior infarctions. The high percentages of correctly classified nontransmural and transmural infarctions show significant diagnostic potential for patient management. From the results of discriminant-function analysis, it is apparent that the sum of negative azimuth angles derived from the dorsally directed vectors during the first half of QRS exceeds substantially the scalar variables in their contribution to differentiation of the two conditions.     

Anaerobic transformation of a technical brominated diphenyl ether mixture by super-reduced vitamin B12 and dicyanocobinamide

The anaerobic transformation of the technical octabromo diphenyl ether mixture, DE-79, was investigated by incubation with two super-reduced corrinoids, dicyanocobinamide and cyanocobalamin (vitamin B12). The transformation produced 33 brominated diphenyl ethers (BDEs), 23 of which could be assigned to known structures. Within 1 d, the hepta- to nona-BDEs in DE-79 were almost quantitatively transformed with dicyanocobinamide to lower-brominated homologs. Along with the decrease of high-brominated congeners, concentrations of some tetra- to hexabromo congeners initially increased, followed by a decreasing or constant concentration during longer incubations. Super-reduced cyanocobalamin also was able to transform BDE congeners of DE-79. Whereas the transformation rates of hepta- to nona-BDEs of DE-79 by both corrinoids were comparable, tri- to hexa-BDEs were susceptible to further transformation by super-reduced cyanocobalamin. Incubation of DE-79 with either corrinoid produced significant amounts of BDE 49. Because this congener is found in small quantities in both penta- and octabromo technical BDE mixtures, it may be a suitable indicator for reductive debromination of higher-brominated BDEs. Isolated BDE 196 was incubated as well with super-reduced dicyanocobalamine. After 1 d, 13 BDEs could be detected, with BDE 153, BDE 100, and BDE 99 dominating. After 7 d, only tetra-BDEs or lower-brominated BDEs were detectable. It could be shown that reductive debromination by super-reduced corrinoids is a possible source for lower-brominated BDEs (i.e., BDE 47, BDE 99, BDE 153, and BDE 154). The patterns observed with our bench-scale study design demonstrate that anaerobic transformation in the presence of reducing agents can help to explain the occurrence of environmentally relevant BDE congeners (e.g., BDE 47, BDE 99, and BDE 153).     

Left ventricular function-conduction impairment as reflected by the ECG in chronic aortic regurgitation

The study was conducted to ascertain that the ECG assists in the assessment of systolic dysfunction in chronic aortic regurgitation. Five variables were reviewed in 146 adults without bundle branch block who underwent angiocardiography: total 12-lead QRS amplitude, QRS duration, maximum R peak time in I, V5 or V6, maximum R peak time relative to S peak time of the maximum S in V1, V2 or V3, and maximum T wave amplitude and polarity in I, V6 or aVF. In order to define which of them could differentiate left ventricular ejection fraction (EF) ≥50% (n = 101) from EF <50% (n = 45) they were subjected to stepwise linear discriminant analysis. The maximum R peak time relative to S peak time emerged as the most promising variable. In predicting EF <50%, R peak time prolongation exceeding S peak time, i.e. R peak delay, yields reliable results, with specificity, positive and negative predictive value being 89.1%, 70.3% and 82.6%, respectively, and sensitivity being 57.8%. As given by the sample odds-ratio, R peak delay indicates an 11-fold increased risk of having EF <50%. R peak delay, a marker of left ventricular function-conduction impairment identifies patients who need valve replacement.     

Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients

Please cite this paper as: Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Experimental Dermatology 2010; 19: 458–463. Abstract: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are intraepidermal blistering skin diseases. PV is characterised by autoantibodies directed against desmoglein (Dsg) 3 and in patients with the mucocutaneous variant also against Dsg 1, whereas in PF, only Dsg 1 is targeted. Here, ectodomains of Dsg 3 and Dsg 1 were recombinantly expressed in a human cell line (HEK293) and applied as authentic solid phases in ELISA test systems. Autoantibodies against Dsg 3 and/or Dsg 1 could be detected in 71 (100%) of 71 PV sera and against Dsg 1 in 48 (96%) of 50 PF sera. Control sera showed reactivity with Dsg 3 and Dsg 1 in 0.2% and 0.7%, respectively, of 401 healthy blood donors and in 2.1% of 48 randomly selected patients with bullous pemphigoid. No reactivity with Dsg 1 and 3 was detected in 21 patients with linear IgA disease. For both pemphigus variants, a statistically significant correlation between clinical severity and autoantibody levels was observed as demonstrated for 10 PV and 5 PF patients. In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF.