Elevated Heart Rate Following Heart Transplantation Is Associated With Increased Graft Vasculopathy and Mortality

Background

The effect of elevated heart rate (HR) on outcomes after heart transplantation (HT) has not been well established. The aim of this study was to assess predictors of elevated HR following HT and its impact on outcomes.

Biochemical, immunological, and in vivo functional characterization of B-domain-deleted factor VIII

Coagulation factor VIII (FVIII) is a cofactor in the intrinsic pathway of blood coagulation for which deficiency results in the bleeding disorder hemophilia A. FVIII contains a domain structure of A1-A2-B-A3- C1-C2 of which the B domain is dispensable for procoagulant activity in vitro. In this report, we compare the properties of B-domain-deleted FVIII (residues 760 through 1639, designated LA-VIII) to wildtype recombinant FVIII. In transfected Chinese hamster ovary (CHO) cells, LA- VIII was expressed at a 10- to 20-fold greater level compared with wildtype FVIII. The specific activity of purified LA-VIII was indistinguishable from wild-type recombinant FVIII and both exhibited similar thrombin activation coefficients. Wildtype recombinant-derived FVIII and LA-VIII also displayed similar timecourses of thrombin activation and heavy chain cleavage. However, compared with wildtype recombinant-derived FVIII, the light chain of LA-VIII was cleaved fivefold more rapidly by thrombin. Addition of purified von Willebrand factor (vWF) did not alter the kinetics of thrombin cleavage or activation of either wildtype recombinant-derived FVIII or LA-VIII. The immunogenicity of LA-VIII was compared with wildtype FVIII in a novel model of neonatal tolerance induction in mice. The results did not detect any immunologic differences between wildtype FVIII and LA-VIII, suggesting that LA-VIII does not contain significant new epitopes that are absent in wildtype FVIII. LA-VIII was tolerated well on infusion into FVIII-deficient dogs and was able to correct the cuticle bleeding time similar to wildtype recombinant factor VIII. In vivo, LA-VIII was bound to canine vWF and exhibited a half-life similar to wildtype recombinant FVIII. These studies support that B-domain-deleted FVIII may be efficacious in treatment of hemophilia A in humans.     

Is undifferentiated seronegative spondyloarthropathy a forme fruste of reactive arthritis?

Undifferentiated spondyloarthropathy (USpa) may either represent a forme fruste of other spondyloarthropathies like reactive arthritis or be a different disease entity. To study the link between USpa and reactive arthritis, we studied the presence of IgA antibodies to Yersinia enterocolitica, Salmonella typhimurium, Shigella flexneri, Campylobacter jejuni and Chlamydia trachomatis in sera from 14 patients with USpa (European Spondyloarthropathy Study Group criteria) using ELISA. Escherichia coli was used as a control antigen. An OD value of more than the mean +/- 2 S.D. of 51 blood donors was considered positive. Five patients had elevated IgA antibodies to S. flexneri, while two patients each had elevated antibody levels to S. typhimurium and Chlamydia. No patient had elevated antibodies to Y. enterocolitica, C. jejuni and E. coli. Among 51 normals, 1, 4, 3, 2 and 3 had elevated antibodies to S. flexneri, S. typhimurium, Y. enterocolitica, C. jejuni and E. coli, respectively. Nine of 14 patients with USpa had antibodies to one of the bacteria implicated in reactive arthritis: of these, antibodies to Shigella were the most frequent. Thus, a proportion of patients with USpa may in fact have reactive arthritis.      

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic. (Gastroenterology 1997 Dec;113(6):1823-7)     

The CASE survey: Patient and physician perceptions regarding asthma medication use and associated oropharyngeal symptoms

BACKGROUND:

Oropharyngeal (OP) symptoms are common in asthma patients using inhaled corticosteroids (ICSs) alone and in combination with a long-acting beta₂-agonist (LABA). Patterns of medication use, level of asthma control and association with OP symptoms are not often reported in a nonstudy setting.

OBJECTIVES:

To determine the prevalence of OP symptoms among adult asthma patients using ICSs alone and an ICS plus a LABA; to investigate the relationships between medication use, asthma control and OP symptoms; and to assess family physicians’ (FPs’) perceptions of the prevalence and management of OP symptoms.

METHODS:

A random telephone survey of 1003 asthma patients and 250 FPs treating asthma patients was conducted from February to March 2005 across Canada.

RESULTS:

Twenty-four per cent of patients experienced OP symptoms; 67% of them spoke to their FPs about the OP symptoms. Thirty-one per cent of patients who experienced OP symptoms stopped or reduced their dose of medication. OP symptoms were reported by 25% of patients using ICSs and 22% using an ICS plus a LABA. The incidence of OP symptoms was not affected by the choice of inhalation device (metered-dose inhaler versus dry powder inhaler) or the use of a spacer. Fifty-eight per cent of patients had uncontrolled asthma; patients achieving a lower level of general education were more likely to have poor control. Patients with uncontrolled asthma were more likely than those with controlled asthma to report OP symptoms (28% versus 18%, respectively; P<0.05). Eighty-nine per cent of FPs had patients who had reported OP symptoms to them. FPs estimated that 15% of their patients experienced OP symptoms and that compliance to treatment worsened in approximately 20% of them.

CONCLUSIONS:

The prevalence of OP symptoms in asthma patients using ICSs and an ICS plus a LABA is significant. OP symptoms were found to be associated with a reduced patient education level, with a likelihood of reducing or stopping medication, and with a less well-controlled asthma patient. While FPs recognized that a significant proportion of their asthma patients experience OP symptoms and that OP symptoms may affect compliance, they underestimated the prevalence of this problem.     

Concussion diagnoses among adults presenting to three Canadian emergency departments: Missed opportunities

Objectives

Patients with concussion commonly present to the emergency department (ED) for assessment. Misdiagnosis of concussion has been documented in children and likely impacts treatment and discharge instructions. This study aimed to examine diagnosis of concussion in a general adult population.

Worsening Renal Function in Patients With Acute Decompensated Heart Failure Treated With Ultrafiltration: Predictors and Outcomes

BackgroundUltrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF.Methods and ResultsBased on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17–13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48–48.42; P = .03), and E/E′ ≥15 (OR 3.78, 95% CI 1.26–17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate.ConclusionsWRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.