Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.     

Red cell abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis.

Of 52 patients receiving a mean dose of 2.5g sulphasalazine/day as maintenance therapy for ulcerative colitis, 35 were found to have one or more drug-induced red cell abnormalities, which were not found in 50 normal controls or in 10 colitics not receiving sulphasalazine. Twenty-three of the treated patients had contracted red cells, an abnormality that is thought to result in mild haemolysis. Red cell contraction was related to the dose of sulphasalazine (P smaller than 0.01), the serum total sulphapyridine level (P smaller than 0.001), and acetylator status. Eleven of the treated patients had a macrocytosis, 21 had elevated levels of methaemoglobin, and one had Heinz bodies. A dose of 1.5 g sulphasalazine/day was not associated with red cell contraction, and is suggested as a safer maintenance dose for the asymptomatic colitic.     

Induction of rainbow trout MH class I and accessory proteins by viral haemorrhagic septicaemia virus

Major histocompatibility (MH) class I receptors are glycoproteins which play a critical role during responses to intracellular pathogens by presenting endogenous peptides to cytotoxic T cell lymphocytes (CD8+). To date, little is known about MH class I regulation at the protein level during viral infections in fish. In this study, we characterised the MH class I pathway response to polyinosinic–polycytidylic acid (poly I:C) and upon infection with viral haemorrhagic septicemia virus (VHSV) genotype IVa using the rainbow trout monocyte/macrophage cell line RTS11. A 14-day challenge with VHSV IVa at 14 °C demonstrated enhanced expression of the class I heavy chain, β2 microglobulin (β2M) and tapasin, while the expression of other accessory molecules ERp57 and calreticulin remained unchanged. However, when infection occurred at 2 °C no change in expression levels of any of these molecules was observed. β2M accumulated in the media of RTS11 over time, however the β2M concentrations were 2 fold higher in cultures infected with VHSV 14 days post infection. Strikingly, when cells were maintained at 2 °C the secretion of β2M was significantly reduced in both infected and non-infected cultures. These results indicate that VHSV infection alters the kinetics of β2M release as well as the expression of MH class I and suggests that cellular immunity against VHSV can be compromised at low temperatures which may increase host susceptibility to this virus during the winter.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Ultrasound-Induced Mild Hyperthermia as a Novel Approach to Increase Drug Uptake in Brain Microvessel Endothelial Cells

Purpose. Drug delivery to the central nervous system (CNS) is limited by the blood-brain barrier (BBB). Thus, a noninvasive and reversible method to enhance BBB permeation of drugs is highly desirable. In the present work, we studied if ultrasound-induced mild hyperthermia (USHT, 0.4 watts (W)/cm² at 41°C) can enhance drug absorption in BBB endothelial cells, and we elucidated the mechanism of USHT on cellular accumulation. Methods. To accomplish these aims, we studied the effects of hyperthermia (41°C), USHT, P-glycoprotein (P-gp) modulator (PSC 833), and combination of USHT and PSC 833 on accumulation of P-gp substrate (R123) and non-P-gp substrates (sucrose, 2-deoxyglucose, and antipyrine) in monolayers of primary bovine brain microvessel endothelial cells (BBMEC). Results. USHT, through its thermal effect, produces a significant (relative to controls; no USHT) and comparable increase in R123 accumulation with PSC 833. We also demonstrate that USHT increases permeability of hydrophobic (R123 and [¹⁴C]-antipyrine) and not hydrophilic molecules ([¹⁴C]-sucrose and 2-[³H]-deoxy-d-glucose). The enhanced permeability is reversible and size dependent, as USHT produces a much larger effect on cellular accumulation of [¹⁴C]-antitpyrine (molecular weight of 188 D) than that of R123 (molecular weight of 380.8 D). Although USHT increases membrane permeability, it did not affect P-gp activity or the activity of glucose transporters. Conclusions. Our results point to the potential use of USHT as a reversible and noninvasive approach to increase BBB permeation of hydrophobic drugs, including P-gp-recognized substrates.