The Cape Triage Score: a new triage system South Africa. Proposal from the Cape Triage Group

The Cape Triage Group (CTG) convened with the intention of producing a triage system for the Western Cape, and eventually South Africa. The group includes in-hospital and prehospital staff from varied backgrounds. The CTG triage protocol is termed the Cape Triage Score (CTG), and has been developed by a multi-disciplinary panel, through best available evidence and expert opinion. The CTS has been validated in several studies, and was launched across the Western Cape on 1 January 2006.     

Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis

The objective was to investigate the relationship between the presence of different types of antinuclear antibodies (ANA) in patients with systemic sclerosis (SSc) and the presence of clinical features. Sera from 230 patients with SSc were tested for the presence of ANA, including anticentromere antibodies (ab), antitopoisomerase I ab, anti- U1 RNP ab and antinucleolar ab, including anti-Th RNP, anti-U3 RNP and anti-U17 RNP. Clinical features were registered prospectively in a clinical database. Eighty-two per cent of the patients were women. The median age was 58 yr (45-67, quartiles) and median age at disease onset was 44 (30-55) yr. ANA were found in 86% of the patients (anticentromere: 34%; antitopoisomerase I: 14%; anti-U1 RNP: 6.5%; antinucleolar total: 16%; anti-Th RNP: 2.2%; anti-U3 RNP: 3.5%; anti- U17 RNP: 0%). Anticentromere ab were found to be related to a high prevalence of calcinosis, telangiectasia, digital ulcers, acrosclerosis, primary biliary cirrhosis, isolated reduction of pulmonary diffusing capacity, and a low prevalence of radiological evidence of pulmonary fibrosis. Antitopoisomerase I ab were associated with a high prevalence of digital joint deformity, distal osteolysis, radiological signs of pulmonary fibrosis, a low prevalence of calcinosis and late onset of disease. Anti-U1 RNP ab were related to a high prevalence of arthritis and myositis, a low prevalence of calcinosis, and early disease onset. The presence of antinucleolar ab, including anti-U3 RNP and anti-Th RNP, was not significantly related to any particular clinical features in this study; possibly due to the small number of patients with these ab. The presence of anticentromere, antitopoisomerase I and anti-U1 RNP ab in the serum was also found to have previously described clinical correlations in a group of Danish SSc patients.      

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.     

Immunoscintigraphy with a new indium-111-labeled monoclonal antibody (MAb 1A3) in patients with colorectal cancer

PURPOSE: This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N′-bis (2-hydroxybenzyl) 1 (4-bromoacetamidobenzyl) 1,2-ethylenediamine-N,N′-diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer. METHODS: Patients were injected with indium-111-N,N′-bis(2-hydroxybenzyl) 1 (4-bromoacetamidobenzyl) 1,2-ethylenediamine-N, N′-diacetic acid-monoclonal antibody 1A3 (1–50 mg, 1–5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy. RESULTS: At least one known tumor site was clearly defined by planar scintigraphy in 29 (76 percent) patients. Increased radioactivity was seen in 40 of 63 known tumor sites (37/43 abdominal-pelvic, 3/15 hepatic, and 0/5 pulmonary sites) without any apparent dose-related effects. Nineteen previously undetected sites were considered positive by imaging, and, of these, six were biopsy-proven tumor sites, four were probable tumor sites, three were definitely false positive sites, and six were probable false positive sites. Radioimmunoscintigraphy detected proven tumor in 15 of 16 patients with negative or equivocal computed tomography results. Of the 28 patients with rectosigmoid cancer, 25 (89 percent) had positive studies with 34 of 47 tumor sites showing definite uptake on the scintigrams. This included 3 of 9 hepatic metastases. The only adverse reaction occurred in one patient who developed transient hives. Human anti-mouse antibody responses occurred in approximately one-half of the patients injected with doses of 10 or 50 mg. CONCLUSION: This study shows that radioimmunoscintigraphy with this indium-111-labeled monoclonal antibody is safe, it can detect most nonhepatic abdominalpelvic tumors with a positive predictive value of 83 (44/ 53) percent, and it should prove to be useful, particularly in the diagnosis of recurrent rectal carcinoma.     

Learning From No-Fault Treatment Injury Claims to Improve the Safety of Older Patients

New Zealand’s treatment injury compensation claims data set provides an uncommon no-fault perspective of patient safety incidents. Analysis of primary care claims data confirmed medication as the leading threat to the safety of older patients in primary care and drew particular attention to the threat posed by antibiotics. For most injuries there was no suggestion of error. The no-fault perspective reveals the greatest threat to the safety of older patients in primary care to be, not error, but the risk posed by treatment itself. To improve patients’ safety, in addition to reducing error, clinicians need to reduce patients’ exposure to treatment risk, where appropriate.     

Diagnostic value of echocardiographic markers for diastolic dysfunction and heart failure with preserved ejection fraction

Heart Failure Reviews - This study aimed to evaluate the diagnostic performance of echocardiographic markers of heart failure with preserved ejection fraction (HFpEF) and left ventricular diastolic...     

Cloning and characterization of the gene encoding growth hormone in finback whale (Balaenoptera physalus)

In mammals growth hormone (GH) is generally a strongly conserved protein, reflecting a slow rate of molecular evolution. However, during primate and artiodactyl evolution episodes of rapid change occurred, so that the GHs of higher primates and ruminants differ markedly from those of other mammals. To extend knowledge of GH evolution in Cetartiodactyla (Artiodactyla plus Cetacea) we have previously characterized GH genes from several members of this group, including the common dolphin. Surprisingly the sequence deduced for dolphin GH differed at several residues from that described previously for another cetacean, finback whale. To investigate this anomaly we have now cloned and characterized the GH gene from finback whale. The overall organization of this gene is similar to that of dolphin, and the deduced amino acid sequence of finback whale GH differs from that of dolphin GH at only residue 47, and from that of pig GH at only residue 149. Phylogenetic analysis of the data provides further support for inclusion of Cetacea within the order Cetartiodactyla, as sister group of Hippopotamidae. The results support the idea that in Cetartiodactyla a burst of rapid evolution of GH occurred after the separation of the line leading to ruminants from other cetartiodactyls. Overall, the GH gene in cetaceans appears to be evolving more slowly than in most other cetartiodactyls.