Experimental Results with 90Yttrium Beta-Particle Emitting Radioactive Stents in a Porcine Model of Restenosis

Background: Radioactive stents have been proposed as a means to prevent restenosis. The ideal radioisotope to deliver endovascular irradiation via a radioactive stent is unknown. Objectives: To evaluate the dose response effects of “high” dose rate irradiation delivered by a high energy, short half-life, beta-particle emitting ⁹⁰yttrium (⁹⁰Y) radioactive stent on neointimal formation in a porcine coronary model of restenosis. Methods: Fifty-two 0–16.0 μCi ⁹⁰y radioactive stents were implanted in the coronary arteries of 19 swine. Stents were oversized 10% to 20% greater than the baseline angiographic lumen diameter. After 28 days, quantitative histological analysis was completed to determine neointimal area and percent in-stent stenosis. Results: The mean vessel injury scores were similar for the control and each of the ⁹⁰Y radioactive stent groups. Neointimal area correlated with vessel injury for the control (r =0.54, P < 0.0001) stents. The percent in-stent stenosis was similar for the nonradioactive control and the 0.25, 0.5, 1.0, 1.25, 2.0, 8.0, and 16.0 μCi ⁹⁰Y radioactive stents. The neointimal area was greater for the 4.0 μCi (3.95 ± 1.16 mm²) and 8.0 μCi (3.55 ± 1.09 mm²) ⁹⁰Y stents as compared with the nonradioactive control stents (2.40 ± 7.72 mm², P ≤ 0.03). The increased neointimal area for the 4.0 μ⁹⁰Y stents resulted in significantly greater percent in-stent stenosis (55 ± 12) versus control nonradioactive stents (36 ± 18, P < 0.05). Conclusions: A radioactive stent manufactured with the short half-life beta-particle emitting radioisotope ⁹⁰Y, designed to deliver a higher dose rate at implant than a ³²P radioactive stent, is ineffective in reducing neointimal formation in the porcine coronary model of restenosis. Further study is required to define effective cumulative dose and dose rate delivery for radioactive stents.     

Approaches to the space-time modelling of infectious disease behaviour

A new approach to the space-time modelling of infectious diseasesis considered. A modulated heterogeneous Poisson process withintensity defined as a function of a two-dimensional susceptibilityfield is proposed. The model is fitted to a measles epidemicusing a proportional hazards approximation.     

Arrhythmogenic Effects of Quinidine on Catecholamine-Induced Delayed Afterdepolarizations in Canine Atrial Fibers

Arrhythmogenic Effects of Quinidine on Catecholamine-induced Delayed Afterdepolarizations. We studied the effects of quinidine and tetrodotoxin (TTX), two drugs that block Na⁺ channels, on delayed afterdepolarizations (DAD) caused by norepinepbrine in atrial fibers of the canine coronary sinus. At long stimulus cycle lengths of 10 seconds, quinidine increased the amplitude of the afterdepolarizations and caused triggered activity within 1–2 minutes. Simultaneously, action potential duration (APD) was lengthened but upstroke velocity was not decreased. Prolonged exposure to quinidine eventually decreased upstroke velocity but DAD amplitude remained larger than control and triggered activity was still induced more easily. The effects of quinidine to increase afterdepolarizations was partially related to its prolongation of the APD since shortening APD with repolarizing current decreased DAD amplitude. However, DAD amplitude remained larger than control indicating that quinidine caused triggering by other mechanisms as well. TTX, on the other hand, which blocks Na⁺ channels but shortens APD, decreased DAD amplitude and triggered activity. Part but not all of these effects resulted from the shortening of APD by TTX since prolongation of APD with depolarizing current only partially restored DAD amplitude. Anti-arrhythmic drugs, therefore, may have effects on DADs that partly result from changes in the APD. Quinidine may cause cardiac arrhythmias by virtue of its effects to potentiate triggered activity.     

Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal d-Trp or d-Tpi

In an attempt to produce more powerful (effective) bombesin/GRP receptor antagonists, the d forms of Trp or Trp analog (Tpi) were introduced at position 6 in two pseudononapeptides, Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin(6-14) and Leu¹³Ψ(CH₂NH)Phe¹⁴ -bombesin (6-14). These antagonists were tested for their ability to inhibit basal and gastrin releasing peptide (GRP) (14-27)-induced amylase release from rat pancreatic acini in a superfusion assay. They were also assessed for the inhibition of ¹²⁵I-Tyr⁴ -bombesin binding to Swiss 3T3 and small cell lung carcinoma cell line H-345 and the mitogenic response of Swiss 3T3 cells induced by GRP(14-27). The peptides, when given alone, did not stimulate amylase secretion, but were able to inhibit gastrin releasing peptide (14-27)-induced amylase release. All of the antagonists showed strong binding affinities for Swiss 3T3 and H-345 cells and suppressed the GRP(14-27)-induced increase of [³H]thymidine incorporation into DNA of Swiss 3T3 cells at nanomolar concentrations. Antagonist d -Tpi⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3095) was slightly more potent in these assays than d -Trp⁶,Leu¹³Ψ (CH₂NH)Leu¹⁴-bombesin (6-14)(RC-3125). Nevertheless, d -Trp⁶ Leu¹³Ψ (CH₂NH)Phe¹⁴-bombesin (6-14) showed the highest binding affinity for Swiss 3T3 and H345 cells and it was the most potent inhibitor of GRP(14-27)-induced amylase secretion. This antagonist RC-3420 was particularly effective in inhibiting the growth of Swiss 3T3 cells, exhibiting an IC₅₀ value less than 1 nm . Our work indicated that the substitution of d -Trp and d -Tpi at position 6 of the pseudononapeptide bombesin analogs (Ψ^13-14), in which the Met¹⁴ residue is replaced by Leu or Phe, results in potent bombesin/GRP antagonists with improved in vivo activity.     

QT Prolongation and Monomorphic VT Caused by Pheochromocytoma

Introduction: Pheochromocytoma may present with ECG abnormalities as one of the few clues to the diagnosis.
Methods and Results: A 30-year-old woman presented with chest pain and a QTc of 525 ms. Four weeks later following a syncopal episode, her QTc was 660 ms. Short runs of monomorphic ventricular tachycardia were recorded. Investigations revealed an adrenal pheochromocytoma. Her QTc normalized after excision of the tumor. Comprehensive QT gene screening of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 was negative.
Conclusion: Pheochromocytoma may induce monomorphic VT and QT prolongation. The interaction of different catecholamines may have a compounding effect on cardiac repolarization.     

Inability of the Signal-Averaged Electrocardiogram to Determine Risk of Arrhythmia Recurrence in Patients with Implantable Cardioverter Defibrillators

Signal-averaged electrocardiography has been used to identify patients at risk for arrhythmic death after myocardial infarction. Since patients with implantable cardioverter defibrillators (ICDs) are at high risk for arrhythmic events, they should also be expected to have a high incidence of abnormal signal-averaged electrocardiograms (SAECGs). However, whether the SAECG can discriminate patients who will have arrhythmia recurrence and receive appropriate ICD shocks from those who will have no recurrence and no shocks is unknown. This study examines the usefulness of the SAECG to separate appropriate users from non-users of the ICD. Fifty patients with ICDs participated in this study. Those who received a shock preceded by symptoms, a shock without preceding symptoms but with electrocardiographic documentation of ventricular fibrillation or ventricular tachycardia, or a shock while asleep were classified as ICD users. All other patients were classified as nonusers. The SAECG was classified as normal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and if the total filtered QRS duration was less than 120 msec, the root-mean square voltage of the terminal 40 msec was greater than 25 muV, and the terminal low amplitude signal duration measured less than 38 msec. The SAECG was classified as abnormal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and any one of these three criteria were outside the "normal range." The SAECG was classified as indeterminate if the QRS duration on the standard 12-lead electrocardiogram was greater than 110 msec. For the entire group of 50 patients, 8 (16%), 12 (24%), and 30 (60%) had normal, abnormal, and indeterminate SAECGs, respectively. Of the 22 ICD users, 1 (5%), 5 (23%), and 16 (73%) patients had normal, abnormal, and indeterminate SAECGs, respectively. Of the 28 ICD nonusers, 7 (25%), 7 (25%), and 14 (50%) patients had normal, abnormal, and indeterminate SAECGs, respectively. ICD users had lower left ventricular ejection fractions (P = 0.0002), a higher incidence of ventricular tachycardia (P = 0.04), prior exposure to a greater number of antiarrhythmic drugs (P = 0.04), and a lower likelihood for survival (P = 0.02) compared to the ICD nonusers. There was no statistically significant difference between the ICD users and nonusers as stratified by SAECG classification regardless of whether or not the interminate studies were included or excluded from the analysis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nurse involvement in cardiac rehabilitation prior to hospital discharge

Summary

• ? Interviews were undertaken with 202 men admitted to five hospitals in northeast England following an uncomplicated first myocardial infarction. The likelihood of patients speaking to a nurse about recovery or seeing a physiotherapist, dietician or specialist rehabilitation nurse, varied considerably between hospitals.
• ? Whilst virtually all patients received written information concerning some aspect of life-style change or cardiac rehabilitation, the quality and range of information, particularly with regard to information about stress or anxiety, was frequently limited.
• ? Instructions about seeing a general practitioner following discharge were often vague; formal rehabilitation programmes, where they existed, excluded some patients.
• ? The study suggests that much patient education is dependent on the provision of written information alone, and that further evaluation of the effectiveness of self-help material supported by nursing input is desirable.

     

Verapamil or Adenosine for the Immediate Treatment of Supraventricular Tachycardia

A comparison of verapamil with adenosine for the immediate treatmentof supraventricular tachycardia was made from a retrospectivereview of 164 spontaneous episodes of paroxysmal tachycardiain 43 patients. Verapamil administered to 33 patients restoredsinus rhythm in 91 of 112 episodes (81 per cent). Hypotensionoccurred in 9 per cent of episodes. Adenosine terminated 94per cent of episodes of supraventricular tachycardia in 25 patients.The arrhythmia recurred shortly after adenosine restored sinusrhythm in 20 episodes. Transient side effects were common. Fifteenpatients were treated with both agents. Adenosine was successfulin all, but verapamil failed to restore sinus rhythm at leastonce in seven of the 15 patients. Early recurrence of tachycardiaoccurred in five of these after adenosine, but in only one afterverapamil. Verapamil and adenosine are both effective in the treatmentof supraventricular tachycardia; adenosine has the higher successrate and is safer, but transient symptoms are common and arrhythmiasmay recur.