Subcellular Phototoxicity of Photofrin-II and Lutetium Texaphyrin in Cells In Vitro

. Three cell types including bovine pulmonary artery endothelium cells (CPAE), rat kangaroo kidney cells (PTK₂), and human larynx epidermoid carcinoma cells (Hep-2) were used to study subcellular localisation and phototoxicity of Photofrin-II and lutetium texaphyrin (Lu Tex). Cells were examined for fluorescence after administration of the photosensitisers. Subcellular regions were exposed with a laser microbeam system that used an argon ion laser pumped dye laser generating a 630 nm for Photofrin-II and 730 nm for Lu Tex. Fluorescence detection suggests that the Photofrin-II is bound primarily to the mitochondria with some diffuse fluorescence in the rest of the cytoplasm. The fluorescence in Lu Tex treated cells appears to be localised to the lysosomes. The percentage of damaged cells following light exposure to the different subcellular regions after Photofrin-II or Lu Tex treatment demonstrates that the nuclear region was the most sensitive target followed by the perinuclear region and peripheral cytoplasm region. Paper received 27 January 1998; accepted after revision 21 August 1998.     

Unimpinged and impinged anterior cruciate ligament grafts: MR signal intensity measurements

Regionalized magnetic resonance (MR) signal intensities were quantitatively measured in impinged and unimpinged anterior cruciate ligament (ACL) grafts. Images were obtained with a 1.5-T imager, and signal intensity was measured in the proximal, middle, and distal thirds of the graft. In 15 unimpinged ACL grafts, the signal intensity remained low and did not vary during the 1st year of graft implantation (45 images). In contrast, 17 impinged ACL grafts showed an increase in signal intensity in the distal two-thirds of the graft that persisted 1-3 years after implantation (P less than .001). Unimpinged grafts were placed in tibial tunnels posterior and parallel to the slope of the intercondylar roof. Reconstructions with anterior tibial tunnels resulted in graft impingement that caused increases in graft signal intensity. This increase demonstrates a clear association between surgical technique and the subsequent MR appearance of the graft.     

Assessment of antiarrhythmic drug efficacy in the treatment of supraventricular arrhythmias

Few guidelines exist for judging the efficacy of antiarrhythmic drugs in patients with supraventricular arrhythmias. Useful definitions concerning the frequency and duration of supraventricular arrhythmias are offered, and complete and partial efficacy criteria are outlined for noninvasive electrocardiographic and invasive electrophysiologic techniques. Several open label, double-blind, parallel and crossover study designs are suggested for efficacy studies concerning the termination and prevention of supraventricular tachycardia. These recommendations are useful for designing new drug trials needed to evaluate properly the efficacy of antiarrhythmic agents in the treatment of various supraventricular arrhythmias.     

Effect of induced hypotension on serum concentrations of atropine after intramuscular administration

The serum concentrations of atropine after a single intramuscular injection of 0.01 mg/kg were determined by radioimmunoassay in nine general surgical patients during and after a combination anaesthesia and compared with those of 13 neurosurgical patients operated on during induced hypotensive anaesthesia (sodium nitroprusside plus trimetaphan). Surprisingly, comparable serum levels were found in both patient groups. We conclude that this kind of induced hypotension cannot be used as a model of drug absorption in such clinical situations as cardiac failure, haemorrhage or anaphylactic drug reactions.     

Enhanced Predictive Power of Quantitative TWA during Routine Exercise Testing in the Finnish Cardiovascular Study

Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD).
Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 μV. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA ≥ 20 μV predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 μV, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ≥50 μV, with 90 μV TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ≥60 μV indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 μV (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ≥60 μV during exercise, with maximum HR of 4.6 at 60 μV (P = 0.002), but was not predicted during pre- or postexercise.
Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise.     

Fibronectin in synovial fluid and tissue in rheumatoid arthritis

Fibronectin is a glycoprotein found in body fluids, loose connective tissue matrix and in basement membranes. Fibronectin in rheumatoid arthritis synovial fluid was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis. Fibronectin isolated from rheumatoid synovial fluid by affinity chromatography on gelatin--Sepharose had a polypeptide pattern similar to that of plasma fibronectin in SDS--polyacrylamide gel electrophoresis. In fifty-one patients with rheumatoid arthritis and related diseases fibronectin concentrations is synovial fluid were 445 +/- 103 micrograms/ml (mean +/- SD) and within normal range, 335 +/- 52 micrograms/ml, in plasma. Immunofluorescence staining showed a prominent increase of fibronectin in the proliferating synovial connective tissue in rheumatoid arthritis as compared to normal synovial membrane. The results suggest an increased local production of fibronectin in rheumatoid synovial tissue.