Lung nodules are reliably detectable on ultra-low-dose CT utilising model-based iterative reconstruction with radiation equivalent to plain radiography.

AIM: To determine if ultra-low-dose (ULD) computed tomography (CT) utilising model-based iterative reconstruction (MBIR) with radiation equivalent to plain radiography allows the detection of lung nodules. MATERIALS AND METHODS: Ninety-nine individuals undergoing surveillance of solid pulmonary nodules undertook a low-dose (LD) and ULD CT during the same sitting. Image pairs were read blinded, in random order, and independently by two experienced thoracic radiologists. With LD-CT as the reference standard, the number, size, and location of nodules was compared, and inter-rater agreement was established. RESULTS: There was very good inter-rater agreement with regards nodules ≥4mm for both the LD- (k=0.931) and ULD-CT (k=0.869). One hundred and ninety-nine nodules were reported on the LD-CT by both radiologists and 196 reported on the ULD-CT, with no nodules reported only on the ULD-CT. This gives a sensitivity of 98.5% and specificity of 100% for ULD-CT with MBIR. The effective dose of radiation was significantly different between the two scans (p<0.0001), 1.67 mSv for the LD-CT and 0.13 mSv for the ULD-CT. CONCLUSION: ULD-CT utilising MBIR and delivering radiation equivalent to plain radiography, allows detection of lung nodules with high sensitivity. The attendant 10-fold reduction in radiation may allow for dramatic reductions in cumulative radiation exposure.

Saddle nose deformity and septal perforation in granulomatosis with polyangiitis.

BACKGROUND: Patients who have granulomatosis with polyangiitis (GPA, syn. M. Wegener) often develop an external nose deformity which may have devastating psychological effects. Therefore, reconstruction of nasal deformities by rhinoplasty may become necessary to achieve a normal appearance. OBJECTIVE OF REVIEW: The aim of this systematic review was to investigate the efficacy and safety of surgical reconstruction in external nasal deformities and septal perforation in GPA patients. SEARCH STRATEGY: A systematic literature search with defined search terms was performed for scientific articles archived in the MEDLINE-Database up to 10 June 2016 (PubMed Advanced MEDLINE Search), describing management of cases or case series in GPA patients with saddle nose deformity and/or septal perforation. RESULTS: Eleven of 614 publications met the criteria for this analysis including 41 GPA patients undergoing external nasal reconstruction and/or septal reconstruction with a median follow-up of 2.6 years. Overall, saddle nose reconstruction in GPA patients is safe even if an increased rate of revision surgery has to be expected compared with individuals without GPA undergoing septorhinoplasty. Most implanted grafts were autografts of calvarial bone or costal cartilage. For septal perforation reconstruction, few studies were available. Therefore, based on the available data for surgical outcomes, it is impossible to make evidence-based recommendations. All included GPA patients had minimal or no local disease at the time of reconstructive surgery. Therefore, the relationship between disease activity and its impact on surgical outcomes remains unanswered. The potential impact of immune-modulating medications on increased complication rates and the impact of prophylactic antibiotics are unknown. CONCLUSIONS: This study systematically reviews the efficacy and safety of surgical reconstruction of external nasal deformities in GPA patients for the first time. Saddle nose reconstruction in GPA patients with minimal or no local disease is a safe procedure despite an increased rate of revision surgery. Further research is required regarding the impact of antibiotic prophylaxis, immune-modulating therapy, long-term outcomes and functional outcomes measured with subjective and objective parameters.

Disease burden, comorbidities and antecedents of chronic cough phenotypes in Australian adults.

BACKGROUND AND OBJECTIVES: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes. METHODS: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years. RESULTS: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV1/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough. CONCLUSIONS: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.

Neurotrophic actions of nonimmunosuppressive analogues of immunosuppressive drugs FK506, rapamycin and cyclosporin A.

We show that the nonimmunosuppressive analogues of the immunosuppressive drugs FK506, rapamycin and cyclosporin A promote neurite outgrowth both in PC12 cells and sensory neuronal cultures of dorsal root ganglia with potencies resembling their immunosuppressive homologues. Neurotrophic potencies of the immunophilin ligands resemble their potencies in binding to and inhibiting the rotamase activity of FKBP-12 of cyclophilin. Since nonimmunosuppressive immunophilin ligands, which are devoid of calcineurin inhibitory activity, are equally neurotrophic, inhibition of calcineurin activity is not the mediator of the neurotrophic effects. The immunophilin ligands are neurotrophic in intact animals. FK506 and L-685,818 (the C18-hydroxy, C21-ethyl derivative of FK506) treatment of rats with crushed sciatic nerves enhances both functional and morphologic recovery. The striking potency of these agents, their bioavailability and the dissociation of neurotrophic from immunosuppressant actions argue for their therapeutic relevance in the treatment of neurodegenerative diseases.

Sleep influences on cardio-metabolic health in Indigenous populations.

Indigenous populations continue to be among the world's most marginalized population groups. Studies in Indigenous populations from high income countries (including the United States, Canada, Australia, and New Zealand) indicate increased risk of sleep disorders compared to non-Indigenous populations. Poor sleep, whether it be short sleep duration or fragmented sleep, is a well-established risk factor for cardio-metabolic diseases. Given the implications, targeted improvement of poor sleep may be beneficial for the health and well-being of Indigenous people. In this narrative review, we will: (1) discuss the effects of sleep on the cardio-metabolic processes; (2) examine sleep in Indigenous populations; (3) review the association between sleep and cardio-metabolic risk in Indigenous populations; and (4) review the potential role of sleep in cardiovascular disease risk detection and interventions to improve sleep and cardio-metabolic health in Indigenous people. In particular, this review highlights that the assessment of sleep quality and quantity may be a beneficial step toward identifying Indigenous people at risk of cardio-metabolic diseases and may represent a key intervention target to improve cardio-metabolic outcomes.

Regeneration of dopaminergic function in 6-hydroxydopamine-lesioned rats by neuroimmunophilin ligand treatment.

Nonimmunosuppressant immunophilin ligands have been found previously to stimulate neurite growth in culture and to promote regeneration of peripheral and central nerve fibers in vivo. To further characterize the effectiveness of these ligands, we have investigated the effect of the immunophilin ligand GPI-1046 in 6-hydroxydopamine (6-OHDA)-lesioned rats. In unlesioned rats, tetanic stimulation of the white matter induced long-term potentiation (LTP) of corticostriatal synaptic transmission as indicated by a 40-100% increase in the field potential amplitudes recorded in striatal brain slices. Unilateral microinjection of 6-OHDA into the substantia nigra resulted in a loss of corticostriatal LTP and in significant abnormality of motor behavior as assessed by amphetamine-induced ipsilateral rotations. Daily treatment of 6-OHDA-lesioned rats with GPI-1046 (10 mg/kg, s.c.) for 1 week reduced amphetamine-induced rotations by 75% and greatly restored the striatal tyrosine hydroxylase immunostaining. In addition, GPI-1046 almost completely restored corticostriatal LTP in 6-OHDA-lesioned animals. LTP in normal animals and that restored by GPI-1046 in lesioned animals were both blocked by the NMDA receptor antagonist APV, suggesting mediation by NMDA receptors. Both LTPs were sensitive to dopamine (DA) receptor antagonists. The nonselective DA receptor antagonist chlorpromazine and the selective D1-D5 receptor antagonist SCH23390 reduced the LTP by 90%. These results demonstrate that the immunophilin ligand GPI-1046 can reverse the abnormalities in the substantia nigra-striatal dopaminergic system that are caused by 6-OHDA, thus providing a potential therapeutic agent for Parkinson's disease.

Neural actions of immunophilin ligands.

Immunophilins, protein receptors for immunosuppressant drugs such as cyclosporin A and FK506, are enriched far more in the brain than in the immune system. Drug-immunophilin complexes bind to calcineurin, inhibiting its phosphatase activity and leading to immunosuppressant effects. The immunophilin FKBP-12 (FK506 binding protein, 12 kDa) forms a complex with the ryanodine and inositol (1,4,5) trisphosphate (IP3) receptors to regulate their physiological release of intracellular Ca2+. Here, Solomon Snyder and colleagues describe how non-immunosuppressant as well as immunosuppressant immunophilin ligands are neurotrophic for numerous classes of damaged neurones, both in culture systems and intact animals. Their ability to stimulate functional regrowth of damaged sciatic, cortical cholinergic, dopamine and 5-HT neurones may have therapeutic relevance.

Fluorenylalkanoic and benzoic acids as novel inhibitors of cell adhesion processes in leukocytes.

A series of fluoren-9-ylalkanoic and alkylbenzoic acids was prepared as simplified analogues of a previously reported series of antiinflammatory agents which act to inhibit neutrophil recruitment into inflamed tissue. The previous compounds ("leumedins") contained (alkoxycarbonyl)amino or benzoic acid moieties tethered to a fluorene ring. This functionality was replaced with simple structural elements. The new compounds were, in general, found to be more potent than the earlier series at inhibiting adherence of neutrophils to serum-coated wells or endothelial cells in vitro. Compound 9 was approximately 10-fold more potent than the previously reported FMOC-phenylalanine, of which it is an analogue. Similarly, compound 19 was superior in potency to its first generation progenitor, NPC 16570. The new compounds were shown to inhibit neutrophil adherence under conditions in which adherence is mediated by Mac-1 (CD11b/CD18) and LFA-1 (CD11a/CD18); they thus appear to target beta 2-integrins in their antiadhesion activity. These compounds provide a departure point for the further development of new cell adhesion inhibitors which should exhibit enhanced potency and a more selective mode of action.

The non-immunosuppressive immunophilin ligand GPI-1046 potently stimulates regenerating axon growth from adult mouse dorsal root ganglia cultured in Matrigel.

We used explant cultures of adult mouse dorsal root ganglia with spinal nerve attached growing in Matrigel to assess the effects of the non-immunosuppressive immunophilin ligand GPI-1046 [Snyder et al. (1998) TIPS 19, 21-26] on the growth rate of regenerating sensory axons and found a potent stimulation of axon growth. In these explant cultures, naked, unfasciculated axons emerge from the cut end of the spinal nerve and continue to grow in the Matrigel for up to eight days [Tonge et al. (1996) Neuroscience 73, 541-551]. Some axons are entirely smooth whilst others show prominent varicosities. Some of the former express the phosphorylated neurofilament epitope recognised by monoclonal antibody RT97, a marker for large calibre, myelinated axons, whilst the latter express calcitonin gene-related peptide, predominantly a marker for unmyelinated, and small diameter myelinated sensory axons. Many of the axons in these cultures also express the low-affinity neurotrophin receptor p75. GPI-1046 has been shown to have striking stimulatory effects on embryonic primary sensory axons growing in vitro and it was therefore of interest to see whether it could also enhance regenerating sensory axon growth from the adult ganglia in our cultures. GPI-1046 potently stimulated axon growth in our cultures in a dose-dependent manner. The stimulatory effect was not dependent on the class of sensory axon. These observations show that GPI-1046 is a potent stimulator of regenerating axons from adult, primary sensory neurones. The cellular site of action of GPI-1046 is unknown. To distinguish between a direct effect of the drug on neurones and an indirect effect we compared the effects of GPI-1046 on explant and dissociated cultures. In confirmation of previous results, we found that GPI-1046 potently stimulated axon outgrowth from explants of embryonic chick dorsal root ganglia. However, the drug was without effect on dissociated embryonic dorsal root ganglion neurones, suggesting that non-neuronal cells are important for axon growth stimulation.

Effects of colony stimulating factor-1 on human extravillous trophoblast growth and invasion.

Colony stimulating factor (CSF)-1 has been localized in a variety of tissues and shown to influence proliferation and differentiation of numerous cell types. Messenger RNA and protein products of CSF-1 and its receptor (c-fms) have been identified in the human placenta and decidua. We examined whether CSF-1 and c-fms mRNA and protein are expressed by normal human first trimester invasive extravillous trophoblast (EVT) cells propagated in culture and whether CSF-1 influences proliferation and/or invasion of these cells. CSF-1 mRNA and protein expression was determined by RT-PCR and immunofluorescence microscopy. Proliferation was assessed by the cellular uptake of tritiated thymidine and invasion was evaluated by Matrigel invasion assay as well as Northern blot analysis of mRNA expression for invasion-associated enzymes and their inhibitors. Results revealed that normal invasive EVT cells in culture express both CSF-1 and c-fms mRNA and protein. Under serum-free conditions, exogenous CSF-1 greatly stimulated the proliferation of these cells. CSF-1 neutralizing and c-fms receptor blocking antibody (Ab) each abolished the growth stimulatory effects of CSF-1, indicating that CSF-1 and c-fms interaction was responsible for these effects. In fact, c-fms Ab alone reduced proliferation to below background levels. While exogenous CSF-1 failed to influence EVT cell invasiveness, Northern blot analysis of mRNA indicated a slight upregulation of the invasion-associated enzyme 72 kDa type IV collagenase as well as its natural inhibitor tissue inhibitor of metalloprotease (TIMP)-1, so that the balance between the two remained unaltered. These findings suggest that CSF-1 may represent an autocrine (and possibly paracrine) growth stimulatory factor for the invasive trophoblast cells in situ with no net effect on their invasiveness.

Systemic treatment with GPI 1046 improves spatial memory and reverses cholinergic neuron atrophy in the medial septal nucleus of aged mice.

Systemic treatment with GPI 1046, a non-immunosuppressive ligand of the immunophilin FKBP12 (FK-506-binding protein 12 kDa), has previously been shown to promote morphological recovery of the nigrostriatal dopaminergic projection after MPTP lesion in mice, and of lesioned sciatic nerve fibres after nerve crush in rats. In the present study, we investigated whether chronic systemic treatment with GPI 1046 could affect the decline of spatial learning and memory, and the atrophy of medial septal cholinergic neurons, associated with late senescence in C57 black mice. Three-month old (young) and 18-19-month old (aged) male C57BL/6N-Nia mice were first trained in a place learning task in the Morris water maze. Based on their performance relative to young controls, aged animals were then allocated to treatment groups (10 mg/kg GPI 1046, or vehicle). Retention of the spatial platform location was assessed after 3 weeks of dosing. We found that aged animals that had been dosed with GPI 1046 now performed at a significantly better level than their vehicle control group. Aged animals that had shown the greatest degree of impairment during training in the place learning task showed the greatest relative degree of improvement under treatment and were statistically indistinguishable from young, or aged unimpaired control animals. Cell volumes of cholinergic cells in the medial septal nucleus were assessed after an additional 10 months of dosing at 30 months of age, using stereological methods. We found that aged animals displayed a significant 34% decrease in volume of these cells relative to young controls. This atrophy was significantly reversed in aged GPI 1046-treated animals (13% shrinkage). We conclude that chronic systemic treatment with GPI 1046 positively affects memory mechanisms in the aged mouse, possibly by acting on the septohippocampal cholinergic system.

The small molecule FKBP ligand GPI 1046 induces partial striatal re-innervation after intranigral 6-hydroxydopamine lesion in rats.

Extensive unilateral striatal deafferentation was produced by intranigral 6-hydroxydopamine (6-OHDA) in rats. Beginning 60 days after 6-OHDA injection animals received a 14-day course of treatment with either the small molecule FKBP ligand GPI 1046 (10 mg/kg) or its vehicle alone. Striatal dopaminergic innervation density was determined from high power image analysis of striatal tyrosine hydroxylase (TH) immunohistochemistry. GPI 1046 treatment did not alter TH fiber density in the contralateral striatum but did produce significantly higher striatal TH fiber density in the ipsilateral caudate-putamen. This striatal re-innervation occurred in the absence of increased nigral sparing, and appears to reflect the GPI 1046 induced sprouting of residual TH+ fibers spared by the 6-OHDA lesion.

The superovulation of synchronous adult rats using follicle-stimulating hormone delivered by continuous infusion.

The estrous cycles of adult female rats were synchronized with an LHRH agonist on the morning of Day -4 (Day 0 = day of mating). On Day -2, animals received s.c. implants of continuous-infusion osmotic minipumps containing different doses of an FSH preparation (Folltropin) in combination with hCG at various ratios of hCG:FSH or were given single injections of eCG in doses ranging from 15 IU to 60 IU. Rats infused with the optimal dose (3.4 U/day) of FSH ovulated 44.1 +/- 5.4 oocytes/rat while rats treated with the most effective dose (60 IU) of eCG ovulated only 20.5 +/- 4.3 oocytes/rat on the morning of Day 1. The inclusion of hCG in pumps at ratios from 0.188:1 to 0.75:1 (hCG:FSH) had no significant effect on ovulation rate. The importance of synchronization of estrus in successful superovulation was demonstrated by the finding that only 70% of the unsynchronized animals ovulated (29.1 +/- 4.8 oocytes/rat) whereas 95% of the synchronized animals ovulated (51.0 +/- 3.6 oocytes/rat). Oocyte viabilities were assessed by determining fertilization rates and embryonic development in vivo following mating with fertile males. In rats superovulated by use of the FSH regimen, 92% (39.0 +/- 4.1) of the recovered embryos were 1-cell zygotes on Day 1, 89% (36.3 +/- 5.6) were at the 2-cell embryo stage of development on Day 2, and 88% (28.8 +/- 2.2) were at the morula and blastocyst stages on Day 5 following mating on Day 0. The high ovulation rates and oocyte viability in rats receiving infusions of Folltropin following estrus synchronization offer a reliable method for superovulation of adult rats.

Uterine vascular permeability after uterine stimulation to rats differentially sensitized for the decidual cell reaction.

Uterine vascular permeability (VP) was assessed after unilateral intrauterine injection of sesame oil to rats given either optimal sensitization for the decidual cell reaction or one of several forms of suboptimal sensitization. The study was intended to determine the relationship between changes in uterine VP and imminent endometrial decidualization. Uterine VP was estimated by the rate at which the uterine volume of distribution of i.v. injected 125I-labeled albumin approached the uterine extracellular fluid volume (ECFV). When ideal sensitization was provided, uterine VP was significantly greater in stimulated than nonstimulated horns at 4, 8, 16, and 32 h after stimulation (p < 0.05). Maximum VP in stimulated horns occurred at 8 h, with the time for the 125I-labeled albumin volume to reach half the uterine ECFV (t1/2) estimated to be 30 min. Different types of sensitization resulted in different levels of uterine VP in stimulated and nonstimulated horns, with maximal VP occurring in stimulated horns of rats that had previously received optimal sensitization for decidualization. We conclude that endometrial decidualization is preceded by significant increases in uterine VP and that optimal sensitization promotes an optimal VP response.

Uterine extracellular fluid volume and blood flow after artificial uterine stimulation to rats differentially sensitized for the decidual cell reaction.

Uterine extracellular fluid volume (ECFV) and blood flow (BF) were assessed after unilateral intrauterine injection of sesame oil to rats given either ideal sensitization for the decidual cell reaction or one of several forms of non-ideal sensitization. The study was intended to determine how changes in uterine ECFV and BF might contribute to the Evans blue dye reaction that can be elicited during early decidualization. Uterine ECFV was determined by the uterine volume of distribution of 51Cr-EDTA after its i.v. injection; BF was determined by the radioactive microsphere technique. ECFV was significantly greater in oil-injected than in control horns by 8 h after deciduogenic stimulation, reaching a maximum of 0.63 +/- 0.06 microliter/mg (p < 0.05) in oil-injected horns at 16 h. Ideal temporal sensitization and sensitization with estrogen both were essential to obtain the significantly increased ECFV in stimulated horns. Although absolute uterine BF increased to oil-injected horns, the increase matched uterine weight gains, making relative uterine BF similar for both horns (3-4 microliters/min/mg) at all times after unilateral deciduogenic stimulation. Ideal sensitization did not significantly alter the relative uterine BF. The increase in ECFV occurs at a similar time and requires the same ideal sensitization as the stimulation-induced increase in endometrial vascular permeability described previously, suggesting that these events are under similar control. We suggest that enzymatic changes to the uterine extracellular matrix may contribute to the Evans blue reaction by creating a larger compartment into which protein-dye complexes may diffuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Uterine vascular changes after unilateral intrauterine infusion of indomethacin and prostaglandin E2 to rats sensitized for the decidual cell reaction.

Uterine extracellular fluid volume (ECFV), vascular permeability (VP), and blood flow (BF) were assessed after unilateral infusion of PBS, 0.05 mM indomethacin (IM), or IM plus 1 mg/ml prostaglandin (PG) E2 (PGE2) into uteri of rats sensitized for decidualization. The study was intended to determine the importance of PGE2 in mediating uterine vascular changes during early decidualization. Uterine ECFV was assessed by the uterine volume of distribution of 51Cr-EDTA, and uterine VP by the rate of change of the uterine volume of distribution of 125I-albumin, after i.v. injection of the respective tracers. Uterine BF was determined by the radioactive microsphere technique. ECFV and VP were significantly higher in infused than in control horns after both 10 and 20 h of PBS infusion (p < 0.05). Infusion of IM abolished these vascular changes while coinfusion of PGE2 with IM returned ECFV and VP to levels not significantly different from those associated with PBS infusion. Infusion of PBS resulted in proportionate increases in both uterine weight and total uterine BF for infused horns (p < 0.05) whereas neither of these variables changed after infusion of IM. Infusion of IM+PGE2 resulted in significantly reduced tissue BF (in microliter/min/mg) to infused horns because increases in uterine weights were not matched by proportionate increases in total BF. We conclude that PGs are essential for the increases in uterine VP and ECFV that precede endometrial decidualization and that PGE2 is sufficient to accomplish these vascular changes. Whereas PGs appear necessary for the increases in total uterine BF that maintain constant tissue BF during early decidualization, PGE2 alone does not appear to serve this function.(ABSTRACT TRUNCATED AT 250 WORDS)

Early identification of sites of embryo implantation in rats by means of gadolinium-enhanced MR imaging.

To determine if magnetic resonance (MR) imaging techniques can be used to examine sites of embryo implantation in intact rats, pregnant animals were imaged with gadopentetate dimeglumine-enhanced MR imaging approximately 10 hours after initiation of implantation on day 5 of pregnancy. T1-weighted, three-dimensional SPGR (spoiled gradient-recalled acquisition in the steady state) sequences were used to image the volume of abdomen containing the uterine horns before and after injection of gadopentetate dimeglumine into a femoral venous catheter. While unenhanced images provided little detail in uterine tissue, analysis of the gadolinium-enhanced abdominal images with interactive vascular imaging allowed easy identification of sites of embryo implantation along both uterine horns in four of four pregnant rats. These punctate patterns of enhancement match those of macroscopic bluing after injection of Evans blue dye. Similar gadolinium-enhanced MR imaging of nonpregnant rats produced only a slight, generalized enhancement of entire uterine horns. The authors conclude that local increases in extracellular fluid volume, vascular permeability, and blood flow in the uterus may all contribute to the gadolinium enhancement of the implantation sites. They propose that this approach can be used in experimental settings to provide information regarding embryo implantation unaccessible with traditional approaches. In clinical settings, gadolinium-enhanced MR imaging may be used to examine potential causes of infertility, including luteal phase defects.

Obstructive sleep apnoea and cardiovascular disease.

Obstructive sleep apnoea (OSA) leads to both acute and chronic physiological effects on the cardiovascular system. There is now a large amount of evidence showing that OSA is independently associated with a wide spectrum of clinical cardiovascular disease (CVD). Evidence for a causative effect of OSA is strongest for hypertension, but is weaker for other cardiovascular disorders. Large prospective trials are ongoing and when results become available the link between OSA and CVD is likely to be strengthened. Treatment of OSA with continuous positive airway pressure has been shown to improve blood pressure, particularly in those with hypertension, and also left ventricular ejection fraction in those with congestive heart failure. Given the high prevalence of OSA in the community and its effects on the cardiovascular system, symptoms of this disorder should be sought in patients being investigated or treated for CVD.