Design and synthesis of 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity

A series of 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives was designed, synthesized, and screened for their phosphodiesterase (PDE 4B) inhibitory activity and bronchodilation ability. Compound 7e showed 41.80% PDE 4B inhibition at 10 µM. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC₅₀ values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC₅₀ = 425 µM). Molecular docking at the PDE 4B active site revealed a binding mode and docking scores comparable to those of a reference ligand, consistent with their PDE 4B inhibition activity.     

Fatigue resistance and microleakage of CAD/CAM ceramic and composite molar crowns

Purpose: The aim of this study was to determine effect of compressive cyclic loading on fatigue resistance and microleakage of monolithic CAD/CAM molar ceramic and composite crowns. Materials and Methods: Thirty‐two extracted molars were prepared to receive CEREC crowns according to manufacturer's guidelines using a special paralleling device (Parallel‐A‐Prep). Sixteen feldspathic ceramic crowns (VITABLOCS Mark II) (VMII) and 16 resin‐composite crowns (Paradigm‐MZ100 blocks) (PMZ) were milled using a CEREC‐3D machine. Eight crowns of each group were cemented to their respective teeth using self‐etching resin cement (Panavia‐F‐2.0) (PAN), and eight were cemented using self‐adhesive resin cement (RelyX‐Unicem‐Clicker) (RXU). Following storage for 1 week in water, specimens were subjected to uniaxial compressive cyclic loading in an Instron testing machine at 12 Hz for 1,000,000 cycles. Load was applied at the central fossa, and the cycle range was 60–600 N. Specimens were then subjected to microleakage testing. Data were statistically analyzed using factorial ANOVA and Post Hoc (Tukey HSD) tests. Results: All composite crowns survived compressive cyclic loading without fracture, while three ceramic crowns from the subgroup cemented with RXU developed surface cracks at the center of occlusal surfaces, extending laterally. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other three subgroups (p < 0.05). Conclusions: After 1,000,000 cycles of compressive cyclic loading, PMZ composite molar crowns were more fatigue‐resistant than VMII ceramic crowns. Cement type had a significant effect on fatigue resistance of the ceramic crowns but not the composite ones. Microleakage scores of ceramic crowns cemented with PAN were significantly lower than those of the other subgroups (p < 0.05).     

MDCT to guide transcatheter aortic valve replacement and mitral valve repair

Percutaneous management of valvular heart disease is becoming a reality, with multicenter trials supporting minimally invasive procedures for both aortic and mitral valve disease. Historically, the treatment of choice has been aortic valve replacement with conventional surgery for patients with severe aortic stenosis, as the prognosis of untreated patients is poor, particularly if the patient is symptomatic. Transcatheter aortic valve replacement is now available as a minimally invasive option to treat select high-risk patients with severe aortic stenosis. At present more than 30,000 procedures have been performed worldwide, mostly confined to patients at high surgical risk. The short- and medium-term outcomes have been promising.     

Hollow screws: a diagnostic tool for intracranial empyema

Background

Subdural (SDE) and epidural empyema (EDE) are life-threatening intracranial infections. They require immediate diagnosis and treatment. However, in some cases, magnet resonance imaging (MRI) is not able to contribute to diagnosis; therefore, surgical exploration is indicated. Hollow screws used for decompression of chronic subdural haematoma (cSDH) are valuable tools for minimally invasive biopsy in awake patients when SDE and EDE are suspected.

Methods

Between 2006 and 2010, eight patients in our department underwent biopsy of a suspected SDE or EDE using hollow screws. In these cases, MRI or computed tomography (CT) were not able to provide sufficient diagnostic security to indicate primary craniotomy. Diagnostic and therapeutic efficacy was evaluated on preoperative and postoperative imaging. The focus was on qualitative parameters, such as contrast enhancement or impaired diffusion on diffusion-weighted images (DWI).

Results

The application of the hollow screw under local anaesthesia permitted an exact diagnosis in all cases. In one case, the suspected diagnosis of cSDH could be refuted by diagnostic puncture. In four cases of uncertain diagnosis, the application of the hollow screw revealed a cSDH. Seven of eight patients previously received neurosurgical treatment; three of those cases were SDE or EDE and four were cSDH. Cases of SDE and EDE needed further craniotomy after diagnostic puncture, whereas patients with cSDH were sufficiently treated by hollow screws.

Conclusions

Given their comparably wide diameter, hollow screws allow a sufficient sample size and, therefore, lead to precise diagnosis of SDE and EDE without significant operative risks or strains for the patient.     

Impact of type of thrombolytic agent on in-hospital outcomes in ST-segment elevation myocardial infarction patients in the Middle East

Little is known about the impact of thrombolytic agents on in-hospital outcomes in the Middle East. The objective of this study was to evaluate the impact of thrombolytic agents on in-hospital outcomes in ST-segment elevation myocardial infarction (STEMI) patients in six Middle Eastern countries. Gulf Registry of Acute Coronary Events was a prospective, multinational, multicentre, observational survey of consecutive acute coronary syndrome patients admitted to 65 hospitals in 2006 and 2007. Out of 1,765 STEMI patients admitted to hospitals within 12 h of symptoms onset, 25, 43, and 30% were treated with streptokinase, reteplase, and tenecteplase, respectively. Median age of the study cohort was 50 (45–59) years and majority were males (89%). The overall median symptom onset-to-presentation and median door-to-needle times were 130 min (65–240) and 45 min (30–75), respectively. Streptokinase patients had worse GRACE risk scores compared to patients who received fibrin specific thrombolytics. Academic hospitals and cardiologists as admitting physicians were associated with the use of fibrin specific thrombolytics. After significant covariate adjustment, both reteplase [odds ratio (OR), 0.38; 95% CI: 0.18–0.79; P = 0.009] and tenecteplase (OR, 0.30; 95% CI: 0.12–0.77; P = 0.012) were associated with lower all-cause in-hospital mortality compared with streptokinase. No significant differences in other in-hospital outcomes were noted between the thrombolytic agents. In conclusion, in light of the study’s limitations, fibrin specific agents, reteplase and tenecteplase, were associated with lower all-cause in-hospital mortality compared to the non-specific fibrin agent, streptokinase. However, the type of thrombolytic agent used did not influence other in-hospital outcomes.     

High-sensitivity C-reactive protein (hs-CRP) in systemic lupus erythematosus patients without cardiac involvement; relation to disease activity,damage and intima-media thickness

Aim of the workTo assess the high sensitivity C-reactive protein (hs-CRP level) in systemic lupus erythematosus (SLE) patients without cardiac involvement and find its relation with clinical and laboratory findings, disease activity, damage index and intima-media thickness (IMT).Patients and methodsForty-five female SLE patients were recruited in the present study without any cardiac involvement. History taking, examination and laboratory investigations were performed for patients. Disease activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage by the Systemic Lupus International Collaborating Clinics (SLICC) index. Thirty age matched female healthy subjects were considered as a control group. hs-CRP was measured quantitatively by microplate immunoenzymometric assay and the IMT measured by ultrasonography.ResultsThe hs-CRP in the patients was significantly higher (4.84 ± 3.91 mg/l) compared to the control (1.74 ± 0.61 mg/l) (p < 0.001). The IMT in the patients was significantly increased (0.72 ± 0.37 mm) compared to the control (0.54 ± 0.15 mm) (p 0.004). There was no difference in the level of hs-CRP according to the presence or absence of clinical manifestations. However, it was significantly higher in those with positive DNA (5.71 ± 4.36 mg/L) compared to those with negative results (3.12 ± 1.97 mg/L) (p 0.009). There was a significant correlation of the hs-CRP level with the IMT (r 0.49, p 0.001) and SLEDAI (r 0.67, p < 0.001).ConclusionsThese findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of future cardiac events. Measuring hs-CRP may be useful as a marker of disease activity, increased IMT and subclinical atherosclerosis in SLE especially those with positive ds-DNA.     

Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia with high defibrillation threshold requiring subcutaneous shocking coil implantation

Cardiac involvement in patients with sarcoidosis has been reported in up to 25-39% of patients and is responsible for up to 85% of deaths attributed to the disease, often due to sudden cardiac death. An established diagnosis of cardiac sarcoidosis (CS) portends an ominous prognosis, with an estimated five year-survival of 44%. We report a case that was initially diagnosed as arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), but extra-cardiac biopsies later on were consistent with sarcoidosis and a final diagnosis of CS was made. The patient received an implantable cardioverter defibrillator (ICD) with a subcutaneous lead array implant for high defibrillation threshold (DFT). Exclusive right ventricular (RV) involvement is atypical for CS. The predominant RV involvement based on echocardiogram, cardiac magnetic resonance imaging (MRI) and right precordial electrocardiogram changes can lead to misdiagnosis as ARVD/C based on the modified task force criteria. Cardiac sarcoidosis is an under-diagnosed disease and the delay in its diagnosis and appropriate therapy can lead to a fatal outcome. High defibrillation thresholds have not been previously reported in patients with CS, but given the natural progression of the disease and the limitations in current pharmacotherapy, implanters who diagnose and treat such patients must be prepared to deal with this issue.     

Post-remission retinal microvascular and choroidal thickness changes in eyes with Behḉet’s disease posterior uveitis: an OCTA longitudinal study

International Ophthalmology - To investigate the retinal microvascular and choroidal thickness changes in eyes with active Beh?et’s disease posterior uveitis and post-remission. A...