Coxibs and heart disease: what we have learned and what else we need to know.

Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2) inhibitors has swung from a domination of drug sales to serious disputes about their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that have emerged, drawing conclusions about their cardiovascular safety has been complicated by conflicting results, underpowered clinical trials, and the lack of a placebo group and use of post hoc analyses in many trials. Nonetheless, certain conclusions can be made with reasonable accuracy. This review addresses the controversy in 3 segments. It begins with a discussion of the several mechanisms proposed to explain how selective COX2 inhibition impacts the cardiovascular system. This is followed by a recount of the several clinical studies that delved into the cardiovascular outcomes associated with COX2 inhibitors. Finally, answers to key questions are provided to assist the clinician in devising a systematic approach to the risk-benefit analysis of COX2 inhibitors in actual practice.     

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.Abbreviations BS blood sample - CD count density - dP/dt change in pressure over time - [¹²³I] 123-iodine - K_m affinity constant - MIBG metaiodobenzylguanidine - MB_q mega Bequerel - SPECT single photon emission computerized tomography - V_m capacity constant     

Radiation doses deriving from patients undergoing 111In-DTPA-d-Phe-1-octreotide scintigraphy

The purpose of this study was to estimate the radiation doses to nursing staff, other patients, accompanying persons and family members deriving from patients undergoing ¹¹¹In-DTPA-d-Phe-1-octreotide (¹¹¹In-OCT) scintigraphy. Dose rates were measured from 16 patients who had received an intravenous injection of 140±40 MBq ¹¹¹In-OCT. The measurements were performed at three different distances (0.5, 1 and 2 m) at 10–20 min, 5–7 h and 24 h (and in some cases, up to 48 h) after administration of ¹¹¹In-OCT. The effective half-lives of the biexponential decrease of the dose rates were estimated to be 2.94±0.27 h (T ₁) and 65.17±0.58 h (T ₂). The calculated maximum dose to other persons in the waiting area was 27.2 μSv, to family members 61.5 μSv, to nursing staff in a ward 24.1 μSv and to neighbouring patients in the ward 69.5 μSv. Our results clearly demonstrate that the calculated maximum radiation exposure to accompanying persons, personnel, family members and other patients is well below the maximum annual dose limit for non-professionally exposed persons. Received 20 May and in revised form 9 July 1997     

Exercise: the best therapy for intermittent claudication?

The prophylactic value of physical activity for arteriosclerotic diseases is generally accepted. Regular exercise is also the most effective therapy for intermittent claudication although drug treatment is more popular in general practice. Recent findings show that exercise and drug treatments complement each other.     

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Sympathetic reinnervation after heart transplantation, assessed by iodine-123 metaiodobenzylguanidine imaging, and heart rate variability.

OBJECTIVE: Complete allograft denervation occurs during heart transplantation. Partial ventricular sympathetic reinnervation may develop one year or later after transplantation and can be measured with iodine-123-meta-iodobenziylguanidine (MIBG) uptake. Aim of this study was to assess sinus node sympathetic reinnervation measured with heart rate variability and ventricular sympathetic reinnervation evaluated with MIBG. METHODS: Twelve patients and 14 healthy controls were included. In patients, MIBG scintigraphy with early and late imaging was performed. Heart to mediastinum ratio (HMR) was calculated and patients were divided in groups with (HMR>1.3) and without left ventricular reinnervation (HMR<1.3). Bipolar ECG with high sampling rate and resolution was recorded over 8.5 min in supine position and in upright position after 10 min interval. R-R intervals in time domain and heart rate variability in frequency domain through spectral power analysis of R-R intervals were analysed to evaluate sinus node reinnervation. Spectral power in low frequency range (0.04-0.15 Hz) above 4.5 ms(2) was considered as sinus node sympathetic reinnervation. RESULTS: Six (50%) patients had evidence of left ventricular sympathetic reinnervation on scintigraphy. Sinus node sympathetic reinnervation based on heart rate variability was detected in 6 (50%) patients in supine, and in 4 (33%) patients in upright body position. Four patients groups were discerned: (1) with ventricular and sinus node sympathetic reinnervation, (2) with sinus node sympathetic reinnervation, (3) with ventricular sympathetic reinnervation and (4) without atrial or ventricular sympathetic reinnervation. Ventricular reinnervation process was time dependent and sinus node reinnervation was not. CONCLUSIONS: Simultaneous ventricular sympathetic reinnervation assessed by MIBG and sinus node sympathetic reinnervation assessed by heart rate variability in supine as in upright position were detected only in two patients (17%). The results of our study show that eventual sinus node sympathetic reinnervation and left ventricular sympathetic reinnervation do not occur simultaneously.     

Esophagus atresia after cervical spine surgery: case report and literature review

We report on a case of esophageal atresia following cervical spine surgery. A swallowing examination was performed using fibre-optic endoscopy and videofluoroscopy. There was scar tissue fixation of the larynx and esophagus to the cervical spine. Operative mobilization of the larynx and esophagus and formation of a sliding layer using a platysma-fascia flap was done. The PEG and tracheal cannula were removed; oral nutrition was initiated after 3 months. Swallowing disorders following operations on the upper cervical spine should be investigated. Careful preparation that preserves the layers should be carried out. Fixation of tissues as a result of scarring should be treated with a sliding layer.     

Tumorigenicity study in Syrian hamsters fed areca nut together with nitrite

In order to evaluate the effect of concurrent administrationof areca nut and sodium nitrite, a long-term feeding study wasconducted with 120 Syrian hamsters. The animals were dividedinto four treatment groups, each consisting of 15 males and15 females, and received 2 g/kg diet of sodium nitrite (groupI), 20 g/kg diet of powdered areca nut (group II), 2 g/kg dietof sodium nitrite plus 20 g/kg diet of areca nut (group III)or powdered diet only (group IV) throughout their lifetime.Urine samples from all groups were analysed for N-nitrosonipecoticacid (NNIP), a major urinary metabolite of areca-nut-derivednitrosamines. NNIP was only detected in the urine of hamstersfed nitrite plus areca nut (concentration: 1.9±0.9 ng/mlurine), indicating that areca nut alkaloids underwent in vivonitrosation to form arecanut-specific nitrosamines. The totaltumour response was not significantly elevated in groups IIand III. Hamsters of group III had a markedly, but also insignificantlyhigher frequency of malignant tumours than those of the othergroups, with a statistically significant increase in malignantlymphomas in the males. Although limited by the low number ofanimals per group, these results indicate that exposure to nitritetogether with areca nut constituents appears to enhance therisk of developing malignancies.