Von Willebrand factor abnormalities in IgA nephropathy

BACKGROUND: Plasma concentration of von Willebrand factor (vWF) has been used as an index of endothelial dysfunction. Increased release of vWF from endothelial cells has been reported in several conditions, and there is also evidence that dysfunctioning endothelial cells synthesize defective molecules. In fact, unusually large vWF multimers have been described and related to the pathogenesis of some microangiopathic diseases. Abnormal levels of vWF have been reported in primary glomerulitis, but this was no referred to histological diagnosis. Furthermore, no qualitative vWF analysis was performed in these glomerulopathies. Therefore the aim of our study was to analyse quantitatively and qualitatively vWF in patients with IgA (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN). METHODS: Fourteen IgAN patients, eight PGN patients, seven subjects with different glomerulonephritides, and 10 healthy controls formed the basis of this study. On peripheral venous blood collected in the presence of protease inhibitors, vWF parameters were investigated. vWF antigenic activity (vWF:Ag) was measured by electroimmunodiffusion. vWF subunits mobility was studied by crossed immunoelectrophoresis (CIE) and in some patients vWF multimeric analysis was performed by SDS- agarose gel electrophoresis. RESULTS: Mean vWF:Ag was significantly higher in PGN patients as compared to controls, while there was no significant difference between PGN and IgAN patients and between IgAN and controls. CIE revealed a pre-peak in 12 of 14 IgAN patients and a migration index which did not differ between controls, IgAN, and PGN subjects. No pre-peak was observed in PGN and in other glomerulonephritides. Analysis of plasma vWF multimeric pattern by SDS- agarose gel electrophoresis disclosed in four IgAN patients abnormally large vWF multimers that were not documented in PGN subjects. CONCLUSIONS: This study, by showing the presence of a pre-peak and of large vWF multimers in IgAN patients, suggests an altered postsecretory handling of the vWF in IgAN and possibly a different role of the vWF in IgAN in respect to PGN.      

Interleukin-7 receptor α (IL-7Rα) deficiency: cellular and molecular bases. Analysis of clinical, immunological, and molecular features in 16 novel patients

Summary: Analysis of gene‐targeted mice and patients with severe combined immunodeficiency due to mutations of the α chain of the interleukin‐7 receptor (IL‐7Rα) has shown important differences between mice and humans in the role played by IL‐7 in lymphoid development. More recently, it has been shown that IL‐7Rα is also shared by the receptor for another cytokine, thymic stromal lymphopoietin (TSLP). In this review, we discuss recent advances in IL‐7‐ and TSLP‐mediated signaling. We also report on the clinical and immunological features of 16 novel patients with IL‐7Rα deficiency and discuss the results of hematopoietic stem cell transplantation.     

Cross-reactivity of IgE-binding components between boiled Atlantic shrimp and German cockroach

IgE-antibody reactivity to boiled Atlantic shrimp ( Pandalus borealis ) and German cockroach ( Blattella germanica ) of sera from 89 patients, sensitive to one or the other, was investigated with an enzymatic immunoassay for specific IgE detection (CAP-FEIA System, Pharmacia, Sweden). IgE serum levels to both antishrimp and anticockroach allergens were found to be positive in 76 of the 89 (85.4%) tested sera. A positive anticockroach IgE was very rare in the absence of detectable antishrimp IgE (five of 89 sera). Linear regression analysis on antishrimp and anti-German cockroach IgE levels-log plot revealed correlation coefficient (r) of 0.73. Inhibition experiments showed that boiled Atlantic shrimp extract inhibited CAP with German cockroach, and vice versa. Immunoblotting showed the strongest IgE binding for both allergenic extracts between 30 and 43 kDa. By blot inhibition, the binding capacity of German cockroach was totally-abolished by Atlantic shrimp extract, while German cockroach extract only partially IgE binding to Atlantic shrimp. Cross-reactivity exists between shrimp, an important food allergen, and German cockroach, which has an increasing role in allergic asthma. It could be important to determine the clinical significance of cross-allergy to both allergens, in which exposures occur in different ways.     

Hydrolysis of adenine nucleotides in platelets from patients with acute myocardial infarction

ObjectivesTo investigate the rate of ATP, ADP and AMP hydrolysis on the surface of platelets from acute myocardial infarction (AMI) patients.Design and methodsTwenty-five patients diagnosed with AMI, through clinical criteria, electrocardiographic changes and increase of cardiac biomarkers, as well as 25 healthy patients were selected. The hydrolysis of ATP, ADP and AMP was verified in isolated platelets of these patients.ResultsThe results demonstrated that an increase in ATP (54%) and ADP (45%) hydrolysis occurred in AMI patients when compared to the control group. The hydrolysis of AMP also increased by 46% in AMI patients probably leading to an enhancement in the adenosine level.ConclusionsOur results suggest an increase in nucleotide hydrolysis in platelets from AMI patients, which could be related to a compensatory organic response to thrombotic events that occur in AMI.     

Serological screening confirms the re-emergence of canine leishmaniosis in urban and rural areas in Governador Valadares,Vale do Rio Doce,Minas Gerais,Brazil

This study performed clinical, serological and parasitological assessments in dogs from Vale do Rio Doce, in Minas Gerais State, Brazil, a region considered as a ‘controlled endemic’ area for canine visceral leishmaniosis (CVL). Nevertheless, there are signs that CVL in dogs may be re-emerging as a programme to control the disease was interrupted in the 1990s. The majority of the animals examined presented various symptoms associated with CVL. The enzyme-linked immunosorbent assay test indicated 13.7 and 12.4% of positivity of dogs from the urban and rural areas, respectively. According to indirect immunofluorescence assay test and TRALd tests, 18.2 and 42.2% of dogs in the rural area were seropositive, respectively. Parasitism in seropositive dogs was confirmed by in vitro tissue culture. Sand flies of the genus Lutzomyia, which are able to transmit both cutaneous and visceral leishmaniosis, were found in the area. The results provide a strong evidence of the re-emergence of CVL in this region.     

Cardiopulmonary exercise testing is more accurate than ECG-stress testing in diagnosing myocardial ischemia in subjects with chest pain

Background

Cardiopulmonary exercise stress testing (CPET) is used to grade the severity of heart failure and to assess its prognosis. However it is unknown whether CPET may improve diagnostic accuracy of standard ECG stress testing to identify or exclude obstructive coronary artery disease (O-CAD) in patients with chest pain.

Methods

We prospectively studied 1265 consecutive subjects (55 ± 8 years, 156 women) who were evaluated with ECG stress testing (ET) for chest pain. No one had a documented O-CAD. All patients performed an incremental CPET with ECG recordings on an electronically braked cycle ergometer.

Results

Of 1265 patients, 73 had a positive CPET and 1192 had a negative CPET. Seventy-three patients with a positive CPET and 71 patients with a negative CPET agreed to undergo nuclear SPECT imaging and coronary angiography. Follow-up lasted 48 ± 7 months. As compared with ET, sensitivity, specificity, PPV and NPV were all improved significantly (ET: 48%, 55%, 33%, 95%; CPET: 88%, 98%, 73%, 99%, respectively, P < 0.001). Patients with both peak VO₂ > 91% of predicted VO₂ max and absence of VO₂-related signs of myocardial ischemia had no evidence of O-CAD in 100% of cases. Cardiac events occurred in 32 patients with a positive CPET and 8 patients with a negative CPET (log rank 18.2, P < 0.0001).

Conclusions

In patients with chest pain, CPET showed a better diagnostic and predictive accuracy than traditional ET to detect/exclude myocardial ischemia. Its use should be encouraged among physicians as a first line diagnostic tool in clinical practice.