Visualisation of the gastrin receptor within rat mucosa using a biotinylated gastrin antagonist

We have previously demonstrated that the peptide Boc-l -Trp-l -Leu-β-Ala is a potent and specific antagonist of pentagastrin-stimulated acid secretion in both the rat and the dog. Using conventional solution phase methodology, the analogue biotinyl-l -Trp-l -Leu-β-Ala was prepared in reasonable yield and purity and applied to cryostat sections of rat intestinal and other tissues. The sections were exposed to 5–10 μg of peptide and the bound analogue was visualised using streptavidin-fluorescein. The binding of the analogue was demonstrated in sections from fundus, duodenum, ileum, colon, and lung. However, the analogue failed to bind to tissue from the pancreas, heart, kidney, or liver. The binding of the probe was greatly reduced or completely inhibited by preincubation with Boc-l -Trp-l -Leu-β-Ala, pentagastrin, or gastrin 1–17. The distribution of the cells recognised by the probe was consistent with the distribution of histamine-containing enterochromaffin-like cells. The results of this study may have some bearing on current theories of the mechanism of gastrin-stimulated acid release.     

Hypothalamic Syndrome and Central Sleep Apnoea Associated with Toluene Exposure

We describe a young man who developed extensive hypothalamicdysfunction including diabetes insipidus, adipsia, hyperprolactinaemia,and poikiliothermia together with central sleep apnoea followingexposure to toluene.     

Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Surgical Treatment of Supraventricular Tachycardia: A Five-Year Experience

Two hundred and eight patients underwent operative therapy of supraventricular tachycardia between June 1984 and June 1986. There were 196 patients with Wolff-Parkinson-White syndrome, one with AV nodal reentry, two with atrial flutter, one with ectopic atrial tachycardia, three with paroxysmal sinus tachycardia, and five with atrial fibrillation. Map guided or direct surgery was performed in all patients except the three with atrial fibrillation. Direct surgery was generally successful with failures including one patient with Wolff-Parkinson-White syndrome, one with atrial flutter, and the three patients with paroxysmal sinus tachycardia. There was no mortality. Major complications were uncommon and included three resternotomies for bleeding, one chylopericardium. Six patients required reoperation.     

Physiologic Pacing: New Modalities and Pacing Sites

Right ventricular (RV) apical pacing impairs left ventricular function by inducing dyssynchronous contraction and relaxation. Chronic RV apical pacing is associated with an increased risk of atrial fibrillation, morbidity, and even mortality. These observations have raised questions regarding the appropriate pacing mode and site, leading to the introduction of algorithms and new pacing modes to reduce the ventricular pacing burden in dual chamber devices, and a shift of the pacing site away from the RV apex. However, further investigations are required to assess the long-term results of pacing from alternative sites in the right ventricle, because long-term results so far are equivocal. The potential benefit of prophylactic biventricular, monochamber left ventricular, and bifocal RV pacing should be explored in selected patients with a narrow QRS complex, especially those with impaired left ventricular function. His bundle pacing is a promising and evolving technique that requires improvements in lead technology.     

Internal Cardiac Defibrillation Threshold: Effects of Acute Ischemia

The influence of myocardial ischemia on defibrillation success was studied using two different lead orientations in halothane-anesthetized pigs. Ischemia was induced by ligating the left anterior descending artery in its distal third. Controls had loosely tied ligatures placed around the artery at the same site. Ventricular fibrillation was induced by electrical stimulation 30 minutes after coronary artery ligation. Defibrillation used a single truncated pulse of approximately 6 ms duration passed to either: a transvenous electrode catheter (Medtronic, 6880) with the cathode in the apex of the right ventricle and the anode in the superior vena cava-atrial junction region, or the cathode in the apex of the right ventricle and a mesh plaque on the epicardium of the basal lateral left ventricle as anode. Ten seconds after the onset of ventricular fibrillation, defibrillation was attempted with increasing incremental energies until defibrillation was achieved. Fibrillation episodes were repeated at 15-minute intervals until the minimum first shock was successful in defibrillating the animal (i.e., defibrillation threshold). The number of animals successfully defibrillated with a minimum energy above or below 30 J was not different between normal and ischemic animals for either electrode configuration (i.e., 3 out of 20 vs 1 out of 13 for the catheter and 5 out of 6 vs 6 out of 7 for the epicardial plaque, respectively). Also, the cumulative percent success as a function of defibrillation energy was similar in both the normal and ischemic groups. There was a significant reduction in the minimum energy necessary for defibrillation when passing current between the right ventricular apex and the left ventricular epicardial plaque. The present results indicate that, despite differences in lead orientations, acute ischemia in the anesthetized pig does not appear to influence defibrillation success.     

Arousal in obstructive sleep apnoea patients is associated with ECG RR and QT interval shortening and PR interval lengthening

Sudden cardiac death appears to be more prevalent during the normal sleeping hours in obstructive sleep apnoea (OSA) patients compared with the general population as well as to cardiovascular disease patients. The reasons for this remain unclear, but there are three likely main contributors to nocturnal death in OSA patients; cardiac arrhythmias, stroke/ruptured cerebral aneurism and myocardial infarction. Particularly marked cardiovascular system activation with arousal may play a role in initiating sudden adverse cardiovascular events in OSA. The purpose of this study was to investigate cardiac RR, QT and PR interval changes in the electrocardiogram (ECG) associated with spontaneous and respiratory-related arousals in OSA patients. A detailed observational study of ECG records obtained during conventional diagnostic sleep study with no further interventions was carried out in 20 patients (12 males, age 42.8 ± 2.1 years, body mass index 35.1 ± 1.9 kg m⁻², and respiratory disturbance index 51.8 ± 6.4 events/hour). RR and QT intervals showed significant shortening during arousals. RR interval shortening was found to be greater during respiratory arousals when compared to spontaneous arousals. PR interval showed a trend toward a greater prolongation during respiratory arousal. QT interval shortening was weakly correlated with arterial oxygen saturation levels preceding arousal. In conclusion, these data suggest that despite greater cardiac acceleration following respiratory versus spontaneous arousals from sleep, QT shortening and PR prolongation responses are similar independent of arousal type. These data support that arousals produce quite marked and differential cardiac conduction system activation in OSA and that the degree and pattern of activation may be partly influenced by the presence and severity of preceding respiratory events.