Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated Vasorelaxation

Background: Calcitonin gene-related peptide (CGRP) is known to have an extremely potent and prolonged vasodilator effect on the coronary arteries. Studies have shown that CGRP increased coronary blood flow and alleviated reperfusion injury in vitro. It is still unknown, however, whether exogenous CGRP has a protective effect on the reperfusion heart associated with cardiopulmonary bypass (CPB). Methods: An in vivo porcine model of CPB was established. Twenty pigs, 10 controls and 10 CGRP used animals (CGRP group), were performed a median sternotomy followed by a standard CPB. All the hearts were arrested for 45 minutes. In the CGRP group, 1mg/kg CGRP was added into the cardioplegia, and another 1mg/kg was reperfused just before the aortic cross-clamp was removed. In both groups, myocardial microvascular perfusion, coronary arterial microvessel diameter and microvessel blood flow were detected by a laser doppler flowmeter and a contact microscope with TV monitor on five consecutive time perioperatively. Result: Myocardial microvascular perfusion was significantly higher and coronary arterial microvessel diameter was larger in the CGRP group on every point of time of reperfusion compared to those in the control group. In the CGRP group, microvessel blood flow also improved significantly than that in the control group during reperfusion. Conclusion: CGRP improves myocardial microcirculation during cardiac ischemia-reperfusion associated with CPB and could become a new, potent myocardial protector.     

Effects of the selective neutral endopeptidase inhibitor, retrothiorphan, on renal function and blood pressure in conscious normotensive Wistar and hypertensive DOCA-salt rats.

Atrial natriuretic peptide (ANP) is degraded by neutral endopeptidase (NEP) mainly in the proximal tubule of the kidneys. We studied the effects of retrothiorphan, a potent and highly specific NEP inhibitor on renal function and blood pressure (BP). A 25-mg/kg bolus injection (group bolus), or bolus injection plus infusion 25 mg/kg + 25 mg/kg/h (group infusion), was given to conscious normotensive Wistar and hypertensive DOCA-salt rats. Bolus and infusion produced increases in diuresis (110 +/- 15 vs. 103 +/- 15 vs. 42 +/- 9 microliters/min) and natriuresis (10.6 +/- 3.0 vs. 7.0 +/- 1.0 vs. 5.4 +/- 1.0 mumol/min) in normotensive rats, with a maximum change at 30 min. Change in kaliuresis was not significant. These renal effects were associated with nonsignificant increases in urinary cyclic GMP and ANP. Arterial pressure and heart rate (HR) were not affected. Bolus or infusion of retrothiorphan also induced increases in diuresis (92 +/- 16 vs. 124 +/- 13 vs. 38 +/- 6 microliters/min) and natriuresis (10.3 +/- 2.0 vs. 12.5 +/- 1.0 vs. 5.0 +/- 1.0 mumol/min) in DOCA-salt hypertensive rats, with a maximum change at 30 min. The changes in diuresis and natriuresis induced by retrothiorphan were correlated with a significant increase in urinary cyclic GMP excretion (r = 0.89, p < 0.001 and r = 0.91, p < 0.001). Urinary ANP did not change in controls but significantly increased in the treated rats; urinary immunoreactive bradykinin (BK) also tended to increase. Plasma ANP and hematocrit did not change after retrothiorphan, but plasma cyclic GMP increased significantly after infusion. Only infusion caused a decrease in arterial pressure in DOCA-salt rats (-20 mm Hg at 120 min). Renal clearance studies in DOCA-salt rats showed that retrothiorphan has a transient effect on renal hemodynamics, with increases in glomerular filtration and renal blood flow (RBF) and a decrease in renal vascular resistance (RVR). Its renal action was also tubular, with an increase in fractional sodium excretion. We also compared the effects of retrothiorphan in normotensive Brown-Norway kininogen-deficient rats (BN-Kat) and DOCA-salt hypertensive kininogen-deficient rats. The NEP inhibitor induced increases in diuresis and natriuresis in both groups, with increased urinary cyclic GMP. Urinary immunoreactive BK did not change significantly in normotensive or DOCA-salt hypertensive kininogen-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distal intramural spread of carcinoma of the rectum correlated with lymph nodal involvement

One hundred and nineteen operative specimens of carcinoma of the rectum were prospectively studied to evaluate distant microscopic intramural spread with respect to gross tumoral margins and to determine if the degree of spread was related to involvement of the lymph nodes. Eighty-eight of the 119 specimens (74 per cent) did not have intramural extension distal to the gross distal margin of the tumor. Twenty-five (21 per cent) had intramural extension of less than 5 millimeters from the gross distal limit of the tumor. In these instances, tumoral spread was contiguous. In six (5 per cent), tumoral spread was found at more than 5 millimeters from the gross distal margin of the lesion. In all six specimens, the tumoral extension was separated from the gross lesion by undiseased tissue, the foci being located between 5 and 15 millimeters from the distal margin of the lesion. Lymph nodal involvement was found in 19 of 88 lesions without distal intramural spread, in 14 of 25 tumors with intramural spread of less than 5 millimeters and in five of six with intramural extension of 5 millimeters or more, respectively. The difference was statistically significant. With respect to the same three categories of distal extension, more than one lymph node was involved in 11 of 88 lesions, six of 25 and five of six, respectively. This difference was also statistically significant. In the six instances with distal intramural extension, results of immunohistochemical staining demonstrated the presence of tumoral embolism in both the blood and lymphatic vessels. In carcinoma of the rectum, lymph nodal involvement and its multiplicity are directly related to the extent of intramural spread.     

Anomalous origin of the right pulmonary artery from the ascending aorta: successful surgical repair

A case of isolated anomalous origin of the right pulmonary artery from the ascending aorta with severe pulmonary hypertension is reported. Surgical repair was achieved by anastomosis of the anomalous vessel to the pulmonary artery trunk using a continuous absorbable suture. Special emphasis is laid on the favorable postoperative evolution of the pulmonary hypertensive disease following the successful repair. The poor natural history of this uncommon congenital defect if untreated makes early corrective surgery imperative.     

Regional differences in surgical heart valve disease in Europe: comparison between northern and southern subsets of the EuroSCORE database

BACKGROUND AND AIMS OF THE STUDY: Although rates for coronary and valve surgery vary between northern and southern Europe, differences in the features of valve disease leading to surgery in Europe are poorly documented. The study aim was to compare demographics, risk factors, procedures and outcome in valve surgery between European regions, using the EuroSCORE database. METHODS: Between September and December 1995, information on 98 variables (risk factors, procedures and outcome) were collected on valve surgery patients in 128 European centers. Patients were allocated to two geographic subgroups (north, n = 1,990; south, n = 3,682). The distribution of variables was assessed. Subsequently, the impact of preoperative and operative risk factors on mortality was analyzed in both groups using a bivariate analysis. Risk-adjusted outcomes were then compared according to the EuroSCORE. RESULTS: Significant differences were identified for clinical features, risk factors and procedures. In northern Europe, surgery was performed on older patients with more severe coronary or associated disease, whilst in the south the cardiac status seemed more severely compromised. Degenerative aortic disease prevailed in the north (aortic valve replacement in 72.7% of cases), whilst in the south mitral surgery accounted for 46.1% of procedures. Despite differences in crude mortality (6.9% north versus 5.7% south), outcomes (when adjusted to risks) seemed comparable (observed-to-expected mortality ratio 0.90 for north versus 0.84 for south). The impact of individual risk factors on mortality was similar, except for atrial fibrillation. CONCLUSION: Despite large epidemiological differences between northern and southern Europe in terms of valve surgery, performances and outcomes were similar when individual risk factors and overall risk profiles were taken into account.     

Interobserver variation in parotid gland delineation: a study of its impact on intensity-modulated radiotherapy solutions with a systematic review of the literature

Objectives

This study evaluates the interobserver variation in parotid gland delineation and its impact on intensity-modulated radiotherapy (IMRT) solutions.

Methods

The CT volumetric data sets of 10 patients with oropharyngeal squamous cell carcinoma who had been treated with parotid-sparing IMRT were used. Four radiation oncologists and three radiologists delineated the parotid gland that had been spared using IMRT. The dose–volume histogram (DVH) for each study contour was calculated using the IMRT plan actually delivered for that patient. This was compared with the original DVH obtained when the plan was used clinically.

Results

70 study contours were analysed. The mean parotid dose achieved during the actual treatment was within 10% of 24 Gy for all cases. Using the study contours, the mean parotid dose obtained was within 10% of 24 Gy for only 53% of volumes by radiation oncologists and 55% of volumes by radiologists. The parotid DVHs of 46% of the study contours were sufficiently different from those used clinically, such that a different IMRT plan would have been produced.

Conclusion

Interobserver variation in parotid gland delineation is significant. Further studies are required to determine ways of improving the interobserver consistency in parotid gland definition.Permanent xerostomia is one of the most prevalent and debilitating long-term adverse effects of radiotherapy for head and neck squamous cell carcinoma (HNSCC) [1,2]. It has a negative impact on patients'' quality of life and oral health, and can lead to difficulties in chewing and swallowing [3-5]. It can also affect speech and taste, and predisposes these patients to dental caries, oral infections, mucosal ulcerations and osteoradionecrosis of the mandible [6]. The parotid glands are the largest of the salivary glands. In the stimulated state, they contribute more than two-thirds of the total salivary output. They are situated close to the Level II cervical lymph nodes, parapharyngeal space, tonsillar fossae and soft palate, and are likely to receive a significant dose when oropharyngeal cancers are treated with radiotherapy. Salivary flow from the parotid is affected by the radiation dose received and the volume of the gland irradiated. Several parameters of the parotid dose–volume–response relationship have been investigated. The one that seems to correlate best with long-term saliva production is the mean dose to the parotid [7-10]. An accepted target is to keep the mean dose below 24 Gy to preserve unstimulated salivary flow.Intensity-modulated radiotherapy (IMRT) delivers highly conformal radiation to the planning target volumes (PTVs), while sparing adjacent uninvolved organs at risk (OARs) such as the parotid glands. Prospective randomised trials and non-randomised clinical studies have shown IMRT to be superior to conventional two-dimensional radiotherapy in the preservation of long-term parotid function [11,12]. As a result, parotid-sparing IMRT has become the standard technique for delivering radiotherapy for oropharyngeal cancer.Accurate delineation of target volumes and OARs is essential for the success of IMRT. Interobserver variation in gross tumour volume (GTV) definition has been shown to be large and clinically significant for many tumour types, including HNSCC [13-17]. There is variation between individuals and groups such as oncologists and radiologists. Variation in parotid gland delineation can potentially offset the benefits of parotid-sparing IMRT.The objective of this study is to evaluate the interobserver variation in parotid gland delineation and to determine its impact on IMRT solutions.     

Echocardiographic diagnosis of a free and obstructive thrombus of the left atrium: a surgical emergency. Review of the literature apropos of a case

Thrombosis of the left atrium is frequent and often causes systemic embolism in patients with mitral valve regurgitation and major atrial dilatation. In contrast, free floating thrombi unconnected to the atrial wall are extremely rare and characterized by their great mobility and the risk they create of haemodynamic disturbances due to mitral valve obstruction. We report here one case of such a thrombus and compare our findings with those reported in the literature concerning 7 other cases diagnosed by echocardiography. The echocardiographic diagnosis of free floating thrombus is easier than that of adherent thrombus. The free floating thrombus may result from the release of an initially pedunculate thrombus, or it may form in the atrial cavity independent of the atrial wall. Its origin can only be determined at pathological examination. Emergency surgery is mandatory when faced with this situation at high risk of haemodynamic disturbances and embolism.     

Value of Naito's criteria in the surgical repair of tetralogy of Fallot

Naito suggested criteria for the optimal reconstruction of the right ventricular outflow tract in total correction of tetralogy of Fallot based on the minimum acceptable diameter of the pulmonary artery. The value of these criteria was assessed in 78 operated patients by haemodynamic measurements at surgery and 6 months after operation. Using these criteria, a ratio of right ventricular/left ventricular systolic pressure less than 0.60 was obtained with the creation of pulmonary regurgitation which was usually moderate. Long-term assessment of these results is required.     

Are drugs a risk factor of post-ERCP pancreatitis?

Background

Pancreatitis is the most severe complication of ERCP. The aim of this study was to assess whether the use of potentially pancreatotoxic drugs is a risk factor for post-ERCP pancreatitis.

Methods

Risk factors for post-ERCP pancreatitis and all drugs taken during the month before ERCP were recorded retrospectively in a database. Patients with other causes of acute pancreatitis or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis was defined as abdominal pain and/or vomiting associated with amylase/lipase plasma levels equal to or greater than twice the upper normal value.

Results

A total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included. Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were identified in a multivariate analysis: difficulty in cannulation (p<0.001), endoscopic sphincterotomy (p<0.005), and female gender (p = 0.02). Having taken potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis: odds ratio 3.7: 95% confidence intervals [1.1,12.4], p = 0.04.

Conclusions

Use of pancreatotoxic drugs before or during ERCP significantly increased the risk of post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before ERCP seems justified whenever possible.