The incidence, clinical presentation, pathophysiology, and possible treatment of two rare but clinically meaningful complications of tissue augmentation with Zyderm and Zyplast Collagen Implant are ...described. Abscesses as a manifestation of hypersensitivity to bovine collagen occur rarely (4 in 10,000 cases) and may persist for days to weeks. Periods of remission and exacerbation may occur from 1 month to more than 24 months. Localized tissue necrosis also occurs rarely (9 in 10,000 cases) after implantation and is probably the result of local vascular interruption and not hypersensitivity. The incidence varies greatly between the anatomic sites of implantation; more than half the reported cases involve the glabella. Evidence strongly suggests that the increased vulnerability of the glabellar region is due to its unique vascular distribution.
1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved ...to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-4-methyl-6-(methylamino)-1,3,5-triazin-2-yl-N-{4-bromo-2-(trifluoromethoxy)-phenylmethyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models.
Glucagon-like peptide-1 (GLP-1) and its mimetics reduce infarct size in the setting of acute myocardial ischemia/reperfusion (I/R) injury. However, the short serum half-life of GLP-1 and its mimetics ...may limit their therapeutic use in acute myocardial ischemia. Domain antibodies to serum albumin (AlbudAbs) have been developed to extend the serum half-life of short lived therapeutic proteins, peptides and small molecules. In this study, we compared the effect of a long acting GLP-1 agonist, DPP-IV resistant GLP-1 (7-36, A8G) fused to an AlbudAb (GAlbudAb), with the effect of the GLP-1 mimetic, exendin-4 (short half-life GLP-1 agonist) on infarct size following acute myocardial I/R injury.
Male Sprague-Dawley rats (8-week-old) were treated with vehicle, GAlbudAb or exendin-4. Myocardial ischemia was induced 2 h following the final dose for GAlbudAb and 30 min post the final dose for exendin-4. In a subgroup of animals, the final dose of exendin-4 was administered (1 μg/kg, SC, bid for 2 days) 6 h prior to myocardial ischemia when plasma exendin-4 was at its minimum concentration (C(min)). Myocardial infarct size, area at risk and cardiac function were determined 24 h after myocardial I/R injury.
GAlbudAb and exendin-4 significantly reduced myocardial infarct size by 28% and 23% respectively, compared to vehicle (both p < 0.01 vs. vehicle) after I/R injury. Moreover, both GAlbudAb and exendin-4 markedly improved post-ischemic cardiac contractile function. Body weight loss and reduced food intake consistent with the activation of GLP-1 receptors was observed in all treatment groups. However, exendin-4 failed to reduce infarct size when administered 6 h prior to myocardial ischemia, suggesting continuous activation of the GLP-1 receptors is needed for cardioprotection.
Cardioprotection provided by GAlbudAb, a long acting GLP-1 mimetic, following myocardial I/R injury was comparable in magnitude, but more sustained in duration than that produced by short-acting exendin-4. Very low plasma concentrations of exendin-4 failed to protect the heart from myocardial I/R injury, suggesting that sustained GLP-1 receptor activation plays an important role in providing cardioprotection in the setting of acute myocardial I/R injury. Long-acting GLP-1 agonists such as GAlbudAb may warrant additional evaluation as novel therapeutic agents to reduce myocardial I/R injury during acute coronary syndrome.
Background:
Questions have been raised about a possible relation between injectable collagen and polymyositis and dermatomyositis (PM/DM). Predictions of the prevalence of PM/DM have been based on ...anecdotal estimates of the duration of follow-up for the collagen-treated population.
Objective:
Our purpose was to study the duration of follow-up for a large sample of collagen-treated patients.
Methods:
Physicians in North America who purchased collagen implants during fiscal year 1988 were categorized according to collagen practice size; one third were randomly invited to participate in the study.
Results:
Review of 2622 patient records yielded an average duration of follow-up of 4 years.
Conclusion:
Five-year incidence rates were used to estimate the expected number of cases of PM/DM in the collagen-treated population. Through June 1993 the expected number was 30.2. The number of confirmed cases after treatment was seven, less than one fourth of the number of cases expected for a model of the collagen-treated population, matched for age, sex, and race.
Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid ...closed-loop algorithm with usual care over 6 months in this population.
In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299.
Of 147 people initially screened, 133 participants (mean age 13·0 years SD 2·8; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 –0·32 percentage points, −0·59 to −0·04; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% IQR 26–53), but consistently high with CamAPS FX (93% 88–96), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis.
The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX.
National Institute of Diabetes and Digestive and Kidney Diseases.
This report provides an overview of the safety and efficacy of flecainide for supraventricular tachyarrhythmias (SVT) based on a review of the world literature. This review provided 107 entries, but ...5 were review articles and 22 were articles not translated into English. The remaining 80 articles or published abstracts form the basis for this report. A total of 1,371 courses of therapy with intravenous or oral flecainide, or both, were represented. Efficacy was defined by each investigator. Intravenous flecainide was successful in terminating ongoing tachycardias in 81% of reported cases of atrioventricular (AV) nodal reentrant tachycardias, 88% of AV reentrant tachycardias and 100% of atrial tachycardias. Atrial fibrillation or flutter was terminated by intravenous flecainide in 62% of cases and arrhythmias associated with Wolff-Parkinson-White syndrome in 73%. Oral flecainide was successful in longer-term management of arrhythmia in 74 and 81% of patients with AV nodal and AV reentrant tachycardia, respectively, and in 83% with atrial tachycardia. Atrial flutter or fibrillation responded to oral drug in 61% of cases and arrhythmias related to Wolff-Parkinson-White syndrome in 61%. Adverse experiences were reported in studies totaling 695 patients (designated "at-risk patients"). They were not commented on in studies with the remaining 594 patients. Overall, a total of 6.9% of at-risk patients (3.7% of total patients) reported cardiac adverse experiences; 19% of at-risk patients (10% of total patients) reported at least 1 noncardiac adverse effect. Cardiac adverse events included worsened arrhythmias in 28, conduction disturbances in 15 and congestive heart failure in 5. The most frequent noncardiac adverse experiences were paresthesia and visual disturbance.
Sub-barrier Fusion of H 6 e with B 209 i Kolata, J. J.; Guimarães, V.; Peterson, D. ...
Physical review letters,
11/1998, Letnik:
81, Številka:
21
Journal Article
Three children had osteomyelitis due to Haemophilus influenzae type b. They were seen with signs and symptoms indistinguishable from infection caused by other organisms. One child was initially ...misdiagnosed as having septic arthritis because of failure to appreciate that Hemophilus may also cause bone infection. In the second patient osteomyelitis and arthritis developed during ampicillin sodium therapy for treatment of Hemophilus meningitis. His initial infection was caused by an ampicillin-sensitive isolate but his orthopedic infection subsequently responded to therapy only after changing to a regimen of chloramphenicol. In the third patient, bone scintigraphy was helpful in diagnosis since serial roentgenograms were not diagnostic of osteomyelitis. The anticapsular antibody responses of these patients were measured by radioimmune assay. The levels found were low but comparable to age-matched control children with H influenzae type b meningitis.
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