Rendu–Osler–Weber syndrome presenting with pulmonary arteriovenous fistula

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu–Osler–Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5–15% of Rendu–Osler–Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49‐year‐old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X‐ray revealed a 5‐cm mass in the left lower lobe and after magnetic resonance examination, together with 3‐D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similiar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu–Osler–Weber syndrome presenting with a pulmonary arteriovenous fistula.     

Computed tomography diagnosis of tracheobronchopathia osteochondroplastica

Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease characterized by the presence of osseous and cartilaginous submucosal nodules projecting into the tracheobronchial tree. Most cases are asymptomatic and discovered incidentally at post‐mortem. We identified a case of TO on thoracic spiral CT and confirmed the diagnosis on bronchoscopy. This article reviews the imaging characteristics of TO, and shows the 3‐D virtual bronchoscopic and multiplanar reconstruction appearances of TO.     

Does Moral Case Deliberation Help Professionals in Care for the Homeless in Dealing with Their Dilemmas? A Mixed-Methods Responsive Study

Health care professionals often face moral dilemmas. Not dealing constructively with moral dilemmas can cause moral distress and can negatively affect the quality of care. Little research has been documented with methodologies meant to support professionals in care for the homeless in dealing with their dilemmas. Moral case deliberation (MCD) is a method for systematic reflection on moral dilemmas and is increasingly being used as ethics support for professionals in various health-care domains. This study deals with the question: What is the contribution of MCD in helping professionals in an institution for care for the homeless to deal with their moral dilemmas? A mixed-methods responsive evaluation design was used to answer the research question. Five teams of professionals from a Dutch care institution for the homeless participated in MCD three times. Professionals in care for the homeless value MCD positively. They report that MCD helped them to identify the moral dilemma/question, and that they learned from other people’s perspectives while reflecting and deliberating on the values at stake in the dilemma or moral question. They became aware of the moral dimension of moral dilemmas, of related norms and values, of other perspectives, and learned to formulate a moral standpoint. Some experienced the influence of MCD in the way they dealt with moral dilemmas in daily practice. Half of the professionals expect MCD will influence the way they deal with moral dilemmas in the future. Most of them were in favour of further implementation of MCD in their organization.     

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.     

Multicenter intercomparison assessment of consistency of left ventricular function from a gated cardiac SPECT phantom.

BACKGROUND: A multicenter intercomparison assessment was made of the variation in left ventricular (LV) volumes and ejection fractions (EFs) obtained from gated myocardial perfusion single photon emission computed tomography (SPECT) of the 3-dimensional AGATE (Amsterdam gated) cardiac phantom. METHODS AND RESULTS: The phantom was configured to produce 3 different standard end-systolic volume and end-diastolic volume combinations (50 mL and 120 mL, 90 mL and 160 mL, and 120 mL and 190 mL) with corresponding EF (58%, 44%, and 37%). Quantitative gated myocardial perfusion SPECT was performed with 39 SPECT systems in 35 departments. In the multicenter study, for all 3 filling conditions, a wide range of results was obtained. The EF was overestimated (by 1% to 15%), and both the end-systolic volume and end-diastolic volume were underestimated (by 1 to 65 mL). The extent of overestimation of EF was related to the extent of underestimation of the volumes and was independent of filling condition. The trend in error per center was comparable for all 3 filling conditions. Acquisition time per projection was the only independent predictor of the difference between measured and expected EF (P = .0001). CONCLUSIONS: Care should be taken before extrapolation of published and accepted cutoff values for LV EF and volumes in clinical decision making. Results should be validated in each center and monitored for accuracy and consistency over time.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.