Serological Diagnosis of Tropical Canine Pancytopenia by Indirect Immunofluorescence

An indirect fluorescent-antibody test for detection and titration of antibodies to Ehrlichia canis, the causative agent of tropical canine pancytopenia, has been described. The organism propagated by an in vitro technique in canine blood monocytes served as an antigen in the test. The specificity of the test was revealed by absence of cross-reactivity between the antigen and sera from dogs infected with various common pathogens and specific sera against eight rickettsial species. The accuracy of the test was ascertained by isolation of the organism from reactor dogs located in and outside the United States. Histopathological examination of nine reactor dogs revealed plasmacytosis of meninges and kidneys in eight of them.     

The assessment and treatment of nerve dysfunction after trauma around the elbow

Nerve dysfunction after trauma around the elbow can lead to significant long-term pain and functional deficit. Fortunately, most of these injuries are neurapraxias that will recover spontaneously after conservative treatment. The necessity and time frame for surgical intervention for specific patterns of nerve dysfunction remains controversial. Often surgical exploration exacerbates rather than alleviates the presenting nerve problem. Distal humeral shaft fractures, elbow dislocations, Monteggia fracture-dislocations, supracondylar fractures in children, and proximal forearm trauma all have been associated with various types of nerve injuries with a variable degree of recovery. The early recognition of nerve dysfunction combined with appropriate treatment measures is the key to successful outcome.     

Cardiac Rhythm and Conduction Disturbances: What is the Role of Autoimmune Mechanisms?

The immunopathogenesis of cardiac rhythm and conduction disorders has been underestimated. Therefore, the aim of this review is to analyze the current data and controversial issues in this area. The incidence of autoantibodies to human conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies (ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to age-matched controls. The risk of acquiring an atrioventricular block was up to 3-fold in patients with anti-atrioventricular node antibodies (AAVNab) in comparison to controls. The incidence of anti His antibodies (AHISab) was low both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab) seemed to be an epiphenomenon and not a pathogenetic marker of conduction disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a possible prerequisite in the pathophysiology of the disease, although transplacental passage of various antibodies and immune complexes is widely recognized. The main autoantibodies detected both in children with congenital heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The cross-reactivity of laminin with anti-La antibodies could be important in the initiation of the autoimmune process. Autoantibodies against adrenoceptors and muscarinic cholinergic receptors of neonatal heart and human endogenous retrovirus-3 expressed in fetal cardiac tissue could also play a role in the pathogenesis of the congenital heart block. Of note, apoptosis could be one of the possible mechanisms of the progression of the congenital conduction disturbances to the complete heart block. In addition, evidence is compiling that cellular activation and cellular cytotoxicity specific for a given target tissue appears to be at least equally important in the pathogenesis of the disease as the humoral response. In conclusion, the immunopathogenesis of certain cardiac rhythm and conduction disorders is well established in sick sinus syndrome, congenital heart block, and connective tissue diseases. ASNab, AAVNab, anti-Ro/SS-A, and anti-La/SS-B antibodies can be regarded as diagnostic and prognostic markers.     

Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response

OBJECTIVE: A novel treatment option for diabetic patients is the enhancement of incretin hormone activity by inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4). This study was designed to establish a dose of the DPP-4-inhibitor vildagliptin (LAF237) that was effective in reducing HbA1c levels and was safe and well tolerated in patients with type 2 diabetes. PATIENTS AND METHODS: The study of 279 patients with type 2 diabetes consisted of a 4-week run-in phase where patients received placebo and a 12-week active treatment phase where they received one of the following dosages of vildagliptin: 25 mg twice daily, 25, 50 or 100 mg once daily (qd), or placebo. RESULTS: There was a statistically significant reduction in HbA1c levels in the vildagliptin 50 mg qd (p=0.003) and 100 mg qd groups (p=0.004) compared with the placebo group. The mean 4-h postprandial glucose level was significantly reduced from placebo in the vildagliptin 50 mg qd group (p = 0.012) and mean 4-h postprandial insulin was significantly increased from baseline vs. placebo in the vildagliptin 100 mg qd group (p=0.022). The assessment of beta-cell function (HOMA-B) was significantly increased in the vildagliptin 100 mg qd treatment group (p=0.007). The incidence of adverse events was similar in all treatment groups including placebo. CONCLUSIONS: Vildagliptin, at 50 and 100 mg qd, was effective in reducing HbA1c levels compared with placebo in patients with type 2 diabetes. Vildagliptin at dosages up to 100 mg qd appeared safe and well tolerated.     

Photodynamic antibacterial effect of graphene quantum dots

Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.     

Contractile reserve assessed by dobutamine test identifies super-responders to cardiac resynchronization therapy

Introduction

In this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker.

Material and methods

The study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation.

Results

A total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.

Conclusions

Contractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.     

Dissolution kinetics of paracetamol single crystals

The dissolution anisotropy of paracetamol crystals grown in the presence and absence of the molecularly similar additive, p-acetoxyacetanilide (PAA) was studied under controlled conditions using a single crystal dissolution method in undersaturated aqueous solutions. Linear dissolution rates were determined for all the major habit faces by measuring their movement (regression) with time in a flow cell using a microscope. The rates of dissolution of particular faces of the pure material were distinctly different in crystals of different morphology grown at different supersaturations. The dissolution rates of [001] and [110] faces of crystals grown in the presence of PAA (6.02% w/w in solution) are higher than those of pure paracetamol. The results correlate with the distribution of strain in the crystal and support the concept that integral strain increases the solubility and hence the dissolution rate of the material. The mechanism of the dissolution process at the [001], [201;] and [110] faces was defined using optical microscopy and X-ray topography. At all undersaturations above 1% the dissolution studies yielded well developed, structurally oriented, etch pits on both [001] and [201;] faces while on the [110] face rough shallow etch pits were observed. On all three faces, this etch-pitting was considerably more widespread than the dislocation content of the sector and probably reflects a 2-dimensional nucleation process rather than a dislocation controlled mechanism.