Role of pylorus in mediating cholecystokinin-stimulated satiety in the Zucker rat

Obese Zucker rats are less responsive than their lean littermates to the effects of cholecystokinin-octapeptide on satiety and pancreatic growth and exocrine function. We hypothesized that the hyperphagia observed in obese Zucker rats may be caused by a decreased pyloric contractile response to cholecystokinin, resulting in an increased rate of gastric emptying, decreased postprandial gastric distention, and thus decreased satiety. Pyloric muscle strips from six obese Zucker rats and six lean littermates were mounted in separate tissue baths and isometric contraction was measured in response to acetylcholine and cholecystokinin-octapeptide. The dose-response curves for acetylcholine-and cholecystokinin-octapeptide-stimulated pyloric muscle contraction were similar for both the obese and the lean rats. (For cholecystokinin, D₅₀ obese=4.0±0.6 nM, D₅₀ lean=3.4±0.2 nM;P=0.16). We conclude that the decreased satiety response to cholecystokinin-octapeptide observed in obese Zucker rats is not secondary to a decreased pyloric responsiveness to cholecystokinin.This work was supported by NIH grant AM28303-03.     

Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography

Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.     

Direct intracavernous obliteration of high-flow carotid-cavernous fistulas

Four cases of high-flow carotid-cavernous sinus fistula (CCF), three of them posttraumatic and one spontaneous, have been treated by a direct surgical approach to the cavernous sinus. The CCF's were obliterated by the introduction into the cavernous sinus of muscle fragments and/or fibrin sealant. In the three cases with a preoperatively patent internal carotid artery (ICA), the CCF was occluded and the ICA flow preserved. One of these also had a posttraumatic false aneurysm that enclosed the two avulsed ends of a transected intracavernous ICA. This was treated by cervical ICA ligation following resolution of the CCF. A fourth patient, who had previously undergone an unsuccessful ICA trapping procedure elsewhere, also obtained a good result. The case histories and the surgical technique are presented. Direct intracavernous obliteration with muscle fragments and fibrin sealant fulfills the criteria for treatment of high-flow CCF's: occlusion of the arteriovenous fistula and preservation of the ICA circulation. While this surgical technique is a therapeutic option in some cases, it appears to have precise indications in others.     

Bladder dysfunction and neurosyphilis

Neurosyphilis today is a rare problem. We describe a man who presented with organic brain syndrome, psychosis and incontinence, and diagnosis was neurosyphilis with resultant bladder dysfunction. Urodynamic studies defined the voiding dysfunction as detrusor areflexia with a positive bethanechol test. This case reminds us of the necessity of obtaining a test for venereal disease to rule out neurosyphilis in patients with idiopathic voiding dysfunction.     

Localization of acetylcholine receptors and cholinesterase on nerve-contacted and noncontacted muscle cells grown in the presence of agents that block action potentials

The possible role of nerve activity in triggering changes in the localization of acetylcholine receptors (AChRs) and cholinesterase (ChE) on nerve-contacted Xenopus muscle cells has been assessed. The localization of these molecules was examined on nerve-contacted and noncontacted muscle cells in cultures of spinal cord and myotomal muscle derived from Xenopus embryos. Sites of high AChR density were revealed by staining with fluorescent alpha-bungarotoxin and sites of ChE localization were revealed histochemically. Localization of AChRs and ChE at sites of nerve-muscle contact occurred when the culture medium contained 1.2 micron tetrodotoxin (TTX), 1.2 micron TTX, 10 mM magnesium, and no calcium salts, 1.2 micron TTX and 2 mM manganese, or 106 mM potassium methyl sulfate instead of sodium chloride. The nerve-contacted muscle cells in each of these modified culture media also exhibited a reduced incidence of AChR and ChE patches away from the site of contact. It is concluded that the neural factor(s) that triggers the local and remote changes in AChR and ChE distribution can be supplied to the neurites and externalized in the absence of nerve impulses, and that the nerve and muscle cells can interact even when they are largely depolarized.     

Caisson disease of bone

Caisson disease of bone, which may affect compressed air workers and divers, is characterized by regions of bone and marrow necrosis that may lead to secondary osteoarthrosis of the hip and shoulder joints. A review of the pathologic, radiologic, and clinical aspects demonstrated uncertainties in the exact etiology. Early diagnosis is often not possible because of the delayed appearance of radiologic abnormalities. Research into these two aspects of this condition was carried out by the Medical Research Council Decompression Sickness Research Team in Newcastle upon Tyne over a ten-year period (1972 to 1982). Because no suitable animal model exists for the study of this condition, bone and marrow necrosis was produced by embolism of bone blood vessels with glass microspheres. With this model, it was shown that the presence of bone and marrow necrosis could be detected by bone scintigraphy using 99mTc-MDP and by measuring changes in serum ferritin concentration at a much earlier stage than was possible by radiography. However, only the former method has proved useful in clinical practice. Investigations into the etiology of caisson disease of bone have shown evidence for an increase in marrow fat cell size resulting from hyperoxia. This phenomenon may play a role in the production and localization of gas bubble emboli, which are thought to be the cause of the bone and marrow necrosis.     

Neuronal activity evoked by chronically implanted intracortical microelectrodes

The averaged evoked compound action potentials (AECAPs) were recorded from the ipsilateral pyramidal tract of awake, unrestrained cats before, during, and after continuous electrical stimulation of the cerebral cortex via chronically implanted activated iridium or platinum-30% iridium (Pt30%Ir) microelectrodes. After stimulating 24 h at 20 pulses per second (pps), using charge-balanced, 200-microseconds pulse pairs of 40 to 80 microA (400 to 800 microC/cm2, 8 to 16 nC/phase (ph), 2 to 4 A/cm2), there was a transient elevation of the threshold of the early (direct) and of the alte (transynaptic) components of the AECAP. After cessation of continuous stimulation at 80 microA, the threshold of the early component of the AECAP remained elevated for as long as 24 h and the late component as long as 4 days, indicating significant but reversible depression of the electrical excitability of cortical neurons close to the microelectrodes. In three cats stimulated 23 h/day for 1 week, the AECAP also recovered to their prestimulus threshold. In contrast, pulsing for 24 h at 320 microA (3200 microC/cm2, 64 nC/ph, 16 A/cm2) produced marked elevation of the threshold of the AECAPs which was not reversed by 7 to 12 days after termination of intracortical stimulation. The electrical excitability of neurons adjacent to (unpulsed) microelectrodes 2 mm from the pulsed electrode was not affected. The observations reported here, in conjunction with the histologic results reported in the companion paper, indicate that both the Pt30%Ir and the iridium microelectrodes can be operated safely at currents to at least 80 microA, charge/ph of 16 A/cm2, and a charge density of 800 microC/cm2 X ph. However, on the basis of the electrophysiologic criteria, both types appear to be unsafe when pulsed at 320 microA (64 nC/ph, 3200 microC/cm2 X ph, 16 A/cm2).     

The transcranial Doppler in the adult. Preliminary results in 31 patients

Non-invasive transcranial Doppler US investigation in adult patients was first described by Aaslid et al. (1982). The apparatus consists in a 2 MHz bidirectional pulsed Doppler with spectrum analyser. Middle and anterior cerebral arteries were insonated by transtemporal exploration, basilar artery by occipital foramen. The criteria of identification were: position and angulation of the probe, direction of the flow, depth of sample volume. The authors present a first series of 31 patients, all with cervical CW Doppler and B-mode Echo. The percentage of identification was: MCA 72%; ACA 69%; BA 54%. Some clinical cases are illustrated. The interest of the method is emphasized in spite of constraints depending on probe position and anatomical variability of the circle of Willis: ambulatory and non-invasive methods; assessment of intracranial blood flow in various conditions: cerebral ischemia and infarction, intracerebral angioma; complementarity with other non-invasive and non-expensive techniques: EEG and cervical US investigation.