Significance of endothelial dysfunction in sleep‐related breathing disorder

The endothelium functions not only as a semi‐selective barrier between body tissue and circulation; it also plays an active role in the maintenance of a healthy vasculature. Endothelial dysfunction is increasingly found to play a pivotal role in the pathogenesis of atherosclerosis. Impaired endothelium‐dependent vasodilation, as a marker of endothelial dysfunction, predates and predicts cardiovascular disease. Endothelial dysfunction is thought to result from oxidative stress, inflammatory gene activation and cytokine cascade, as well as impairment of endothelial repair mechanisms. In the context of sleep‐related breathing disorders, obstructive sleep apnoea (OSA) is postulated to contribute independently to cardiovascular morbidity and mortality. Thus, endothelial dysfunction is an important target of research in vascular pathogenesis and also serves as an intermediary outcome indicator in clinical trials evaluating cardiovascular sequelae in OSA. Basic or translational studies have identified cellular and molecular mechanisms of potential relevance to endothelial dysfunction in OSA, while epidemiological or clinical studies have shown endothelial dysfunction attributable to sleep‐disordered breathing, which could improve with effective treatment of OSA. Endothelial dysfunction is poised to serve as a call for timely intervention with possibility of halting or even reverting vascular injury in sleep‐related breathing disorders. Much remains to be explored about the complex pathways of endothelial dysfunction and its clinical manifestations in subjects with OSA, which are likely to involve multiple contributing factors. Evidence‐based information will allow us to construct the framework for guiding individualized clinical management and public health strategies for OSA, as well as cardiometabolic diseases.     

Peritoneo-Venous Shunting for Ascites

A new minor surgical procedure for ascites has been devised wherein a specially designated one way pressure activated valve is implanted to create a permanent peritoneo-venous shunt. The normally closed valves opens only when the peritoneal pressure rises 3-5 cm higher than the intrathoracic venous pressure thus preventing backflow of blood and closing the valve should the venous pressure rise from the over-infusion of ascitic fluid. The procedure has been performed on 45 patients but nine were terminal at the time of surgery. Prolonged relief of ascites occurred in 28 of 37 cases.     

A point mutation in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene in a case of acute myeloid leukemia results in the overexpression of a novel G-CSF-R isoform

A novel human granulocyte colony-stimulating factor (G-CSF) receptor isoform, designated SD, has been identified in which the distal C- terminal cytoplasmic region, previously shown to be essential for maturation signalling, is substituted by an altered C-terminus. The SD receptor has a high affinity for G-CSF and retains the membrane- proximal cytoplasmic region known to be sufficient for proliferative signalling. Nonetheless, the SD isoform lacks the ability to transduce growth signals in murine BAF3 cells and, in contrast to the wild-type G- CSF receptor, is scarcely capable of activating JAK2 kinase. Expression of SD receptor was found to be low in normal granulocytes, but was significantly increased in a patient with acute myeloid leukemia (AML). The leukemic cells of this patient harbour a point mutation in the SD splice donor site of the G-CSF receptor gene. These findings provide the first evidence that mutations in the G-CSF receptor gene can occur in certain cases of clinical de novo AML. The possible contribution of defective G-CSF receptor signalling to leukemogenesis is discussed.     

How many different headaches do you have?

Patients with migraine attending a specialist clinic often have more than one type of headache. One hundred and two patients attending the City of London Migraine Clinic for the first time were asked: "What type(s) of headache do you think you have?" A separate diagnosis was made by the doctor, who was blinded to the self-diagnosis. On clinic diagnosis, 27 (26.5%) patients were found to have migraine plus an additional non-migraine headache. When compared with the self-diagnosis, 15 (56%) of these had correctly self-diagnosed two types of headache. Many migraineurs can distinguish migraine from non-migraine headaches when they have both.     

Preimplantation diagnosis of non-deletion Duchenne muscular dystrophy (DMD) by linkage polymerase chain reaction analysis

The use of preimplantation diagnosis for sex determination and detection of exon deletion means that unaffected babies can be born to parents suffering from Duchenne muscular dystrophy (DMD). However, those who do not have exon deletion should also be considered for further investigation. A new method, known as linkage analysis, has been developed to diagnose the presence of non-deletion DMD in preimplantation embryos. Linkage analysis uses informative intragenic and flanking markers to track the chromosome bearing the mutated gene. The present study reports the analysis of two polymorphic sites, in blastomeres biopsied from embryos from a female carrier of DMD. A single male embryo was obtained who had inherited alternate maternal alleles to the woman's affected surviving son, and this embryo was transferred.      

Recovery and systems transformation for schizophrenia.

The Recovery Movement, initiated in the 1990s by mental health consumer groups and leaders, has emerged as a major force in the mental health field. This movement has been gaining strength and promises to impact mental health service delivery through innovations in care that other models of care have not offered. Recent efforts to conceptualize and study recovery empirically have bolstered the movement from a scientific standpoint. This article reviews the growing literature regarding recovery, offers a conceptual framework for understanding recovery, and discusses a specific manner in which systems transformation has begun to occur.     

How useful is glucose detection in diagnosing cerebrospinal fluid leak? The rational use of CT and Beta-2 transferrin assay in detection of cerebrospinal fluid fistula

BACKGROUND: This report describes the sensitivity and specificity of glucose detection using Glucostix test strips and computed tomography (CT) of the skull base for confirming cerebrospinal fluid (CSF) fistulae in patients with persistent rhinorrhoea or otorrhoea, and comparing them with the beta-2 transferrin assay as the gold standard for CSF detection. METHODS: Fluid samples from the nose were collected from 18 patients with suspected CSF fistulae. The samples were assayed for beta-2 transferrin using the Western blotting and immunostaining technique. CT (5mm axial slice) of the skull base was performed for evidence of skull base fracture. The glucose levels and Glucostix results were compared. RESULTS: Out of the 18 samples, 15 were positive for beta-2 transferrin adn the leaks were validated surgically in 10 patients. Give leaks healed spontaneously with conservative management. Glucostix tests produced three false positive results from blood and nasal mucus contaminated fluid. Glucostix failed to detect another three CSF leaks resulting from false negative tests because of low CSF glucose levels. The Glucostix glucose test was nonspecific and insensitive compared with the beta-2 transferrin assay. CT failed to detect three of the 15 beta-2 transferrin-positive leaks but there were no false positive results. CT produced six negative results, of which three were false negatives. CONCLUSIONS: Glucose detection using Glucostix test strips is not recommended as a confirmatory test due to its lack of specificity and sensitivity. In the presence of a skull bas fracture on CT and a clinical CSF leak, there is no need for a further confirmatory test. In cases where a confirmatory test is needed, the beta-2 transferrin assay is the test of choice because of its high sensitivity and specificity.