X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses.</p> <p>Methods</p> <p>The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed.</p> <p>Results</p> <p>2 patients previously diagnosed with CVID associated with virtual absence of CD19⁺B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. <b>Patient 1</b>, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). <b>Patient 2</b>, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA</p> <p>Conclusion</p> <p>These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19⁺B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.</p

Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and Applications

Hydrogels have been shown to be very useful in the field of drug delivery due to their high biocompatibility and ability to sustain delivery. Therefore, the tuning of their properties should be the focus of study to optimise their potential. Hydrogels have been generally limited to the delivery of hydrophilic drugs. However, as many of the new drugs coming to market are hydrophobic in nature, new approaches for integrating hydrophobic drugs into hydrogels should be developed. This article discusses the possible new ways to incorporate hydrophobic drugs within hydrogel structures that have been developed through research. This review describes hydrogel-based systems for hydrophobic compound delivery included in the literature. The section covers all the main types of hydrogels, including physical hydrogels and chemical hydrogels. Additionally, reported applications of these hydrogels are described in the subsequent sections

Inflammatory Aspects of Sleep Apnea and Their Cardiovascular Consequences

Obstructive sleep apnea (OSA) is a common medical condition that occurs in a considerable percentage of the population. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA is a risk factor for the development of hypertension. It is established that OSA may be implicated in stroke and transient ischemic attacks. OSA is associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with pre-existing pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified as important in the development of atherosclerosis. OSA is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease

Mechanical Aortic Valve Thrombosis with Heart Failure Successfully Treated with Oral Anticoagulation: A Case Report

Muhannad Ababneh,1 Abdullah Al-Kasasbeh,1 Emad Algorani2 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Muhannad Ababneh, Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan, Tel +9622 799964654, Email [email protected]: The use of anticoagulation is mandatory for prevention of prosthetic valve thrombosis (PVT) worldwide, regardless of the valve type or position in the heart. In case a thrombosis causes symptomatic dysfunction, treatment usually includes the use of thrombolytic therapy or surgery. We report a case of PVT involving a patient with a mechanical aortic valve which was treated entirely with the use of anticoagulation therapy (warfarin).Case Presentation: A 58-year-old man had an aortic valve replacement using a Carbomedics® mechanical valve due to severe aortic stenosis as a result of a calcific bicuspid native aortic valve. He was commenced on warfarin after surgery which was continued thereafter. He presented to our hospital after three years with shortness of breath at rest. On clinical examination, his condition was poor with a New York Heart Association functional classification of IV. He was in sinus rhythm and had an enlarged heart shadow on chest X-ray. Transesophageal echocardiography (TEE) revealed aortic valve regurgitation with vegetations on the anterior valve leaflet causing reduced hemi leaflet motility and a mean pressure gradient of 50 mmHg. Cinefluoroscopy revealed a dysfunctional mechanical valve leaflet. Surgery was at high risk of mortality due to the patient’s clinical status and he was continued on warfarin therapy with close monitoring. Cinefluoroscopy and echocardiography done six months later revealed complete dissolution of thrombus and a normally functioning mechanical aortic valve.Conclusion: Only a few cases of symptomatic, thrombotic mechanical aortic valve were entirely treated with anticoagulation only. Our patient is one such case who had resolution of symptoms and improvement on NYHA functional classification (IV to I).Keywords: prosthetic valve thrombosis, PVT, anticoagulation, mechanical aortic valve, PVT managemen

Associations of Alcohol Consumption and Chronic Diseases With Sleep Apnea Among US Adults

Background: Sleep apnea (SA) is a common sleep disorder among US adults. Associations of SA with alcohol consumption and some chronic diseases have been inconsistent. Objectives: This study aimed to estimate prevalence of SA and examine its associations with potential factors including alcohol consumption, asthma, diabetes, and hypertension. Patients and Methods: This was a cross-sectional study on 823 adults with SA and 38,638 controls from the 2011 National Survey on Drug Use and Health Data. Weighted univariate and multiple logistic regression analyses were used to examine the associations of SA with the potential factors. Results: The prevalence of SA was higher in males (4.01%) than in females (2.61%), while the prevalence increased with age (0.86%, 3.50%, and 4.47% for age groups of 18-25, 26-64, and ? 65, respectively). Univariate analysis revealed that all factors except for income and education were associated with SA (P \u3c 0.05). In multivariable analyses, participants who were current and past alcohol consumers had significantly higher odds of having SA (OR = 1.52, 95% CI = 1.03-2.23; OR = 1.65, 95% CI = 1.09-2.49, respectively) than non-alcohol drinker. Furthermore, asthma (OR = 2.77, 95% CI = 2.04-3.75), diabetes (OR = 2.89, 95% CI = 2.19-3.83), and hypertension (OR = 2.42, 95% CI = 1.91-3.07) were significantly associated with SA. Conclusions: Age, alcohol consumption, asthma, diabetes, and hypertension, were positively associated with SA. More efforts should be directed to promoting screening for SA and finding possible treatments for SA among these vulnerable groups