SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
This study reports the practical problems involved in the use of a miniature Geiger counter to detect the site of bleeding into the intestine. The observations so far have been made in dogs but its possible application in man is proposed.
A technique is described for the electrophysiological investigation of motor-point muscle biopsies and the data from 13 biopsies are reported. It was not possible to demonstrate any influence of disease upon the resting potentials of individual biopsies, but resting potentials were in general lower than those reported for limb muscle in vivo. Miniature end-plate potentials (MEPPs) in clinically normal limb muscle were smaller and more frequent than those previously described in isolated intercostal muscle. In two biopsies from myasthenic patients very small amplitude MEPPs were recorded and, in one of these, MEPPs were also of very low frequency, possibly associated with the severity of the disease. The frequency and amplitude of MEPPs in muscular dystrophy and neurogenic disease have been reported and the possible significance of these findings is discussed.
An inflatable miniature cuff was used to apply local compression of 80 mm Hg or 30 mm Hg to a segment of rat sciatic nerve for time periods varying from two to eight hours. The endoneurial fluid pressure was measured by direct micropipette measurement techniques at one or 24 hours after removal of the cuff, and the nerves were subjected to histological analysis. Endoneurial oedema, associated with a four-fold increase in endoneurial fluid pressure, was observed after compression at 80 mm Hg for four hours, and a three-fold increase was found after compression at 30 or 80 mm Hg for eight hours. Such an increase in endoneurial fluid pressure may interfere with intrafascicular capillary flow, and thereby constitute an important pathophysiological mechanism in nerve compression injuries.
Preproduction and current models of the miniature Wright peak flow meter have been compared with the standard Wright peak flow meter on normal and abnormal subjects. Early problems in production appear to have been overcome, and the current model agrees to within 3% with the standard peak flow meter, which is as close as the agreement between two standard instruments. The new mini-meter may be enclosed in a case, making direct comparisons with other instruments possible.
Two miniature Shetland ponies showing clinical signs of Digitalis purpurea (foxglove) poisoning were examined. One animal died shortly afterwards, but the second was treated successfully with the anti-arrhythmic agent, phenytoin, and was discharged after 16 days.
Diagnostic imaging, including computed tomography, of a two-month-old foal with renal failure indicated that its right kidney was probably absent and that its left kidney was abnormal in shape. The foal was stabilised and released, but three days later its clinical signs recurred. Postmortem examination revealed renal hypoplasia and dysplasia, the first reported case of this condition in an American miniature horse.
Gastric myoelectrical and mechanical activity was recorded in miniature pigs using chronically implanted electrodes and strain gauge force transducers. Semiautomated methods were devised to obtain quantitative evaluations of the electrical and mechanical parameters measured in fasted and fed animals. The patterns of gastric myoelectrical activity in pigs were, on the whole, similar to the patterns described in dogs, including regular cyclic control activity and spike response activity associated with muscle contraction. However, several points were peculiar to the species studied: conduction velocity of pacesetter potentials increased only moderately in the antrum; tachygastria never occurred in the experiments; in response to a standard meal, the frequency of pacesetter potentials gradually increased; mechanical activity proceeded at its maximal force immediately after feeding and for a long period; no evidence of 'migrating electrical complexes' was found in the stomach during fasting. The 40-min period following administration of a test meal appeared especially suitable for pharmacological or physiological experiments in which inhibitory factors are to be tested on the stomach.
Muscle fibers from diaphragms of old (14 to 24 months) and young adult (1 to 2 months) inbred (strain C57BL/6) mice were voltage clamped at -140 mV with two microelectrodes near the neuromuscular junction. Miniature endplate currents (MEPCs) were digitized so that peak amplitudes and rise times could be determined. MEPC amplitude distributions from old mice varied greatly between fibers from the same diaphragm, and the mean MEPC amplitude (2.1 +/- 0.83 nA, mean +/- SD) was smaller than in young mice (5.2 +/- 0.59 nA). In old mice, some (50%) amplitude distributions were bell shaped, composed of mainly bell-MEPCs with a 2- to 5-nA mode, whereas others (30%) were skewed with a 0.5- to 2-nA mode, and some (20%) showed two peaks, representing both skew- and bell-MEPC classes. MEPC rise-time distributions from old mice varied between fibers, although they all had similar modes. Some (30%) were bell shaped (similar to those in young mice) with a mode between 0.5 and 1 ms (coefficient of variation, 40%), but most distributions were skewed. Endplates with smaller mean MEPC amplitudes showed a longer mean rise time, and for a given junction, MEPC amplitudes were correlated positively to the corresponding rise times. This observation, together with analyses of the rising phases, indicates that MEPCs with long rise times were not generated at remote sites. We discuss our results with regard to the hypothesis of a dynamic formation of transmitter packets, and we attribute long rise time, skew-MEPCs to a prolonged release process. During aging, the state of release that generates the skew-MEPC class appears more dominant than the state generating the bell-MEPC class.
Coronary collateral blood flow was measured in 7 miniature pigs, exercise trained (ET) for 10 mo by running about 35 km/wk, and in 10 sedentary control pigs (SC). In acute, open-chest preparations, radiolabeled (85SR, 141CE, or 51Cr) microspheres, 15 +/- 5 micron in diameter, were injected into the left atrium during each of three conditions: control (C), total occlusion of the left circumflex artery (TO), and TO plus mechanically elevated aortic pressure (TOP). Blood flow to the circumflex bed during control condition in ET and SC was 0.36 +/- 0.07 (SE) and 0.43 +/- 0.10 ml.g-1.min-1, respectively. During TO, circumflex flow in ET and SC fell to 0.05 +/- 0.01 and 0.06 +/- 0.01 ml.g-1.min-1, respectively. In the presence of TOP, left circumflex flow in ET and SC rose to 0.11 +/- 0.04 and 0.11 +/- 0.02 ml.g-1.min-1, respectively. Blood flow to the tissue bed of the left anterior descendens was the same in both groups of pigs under all conditions. Thus, 10 mo of endurance exercise training seems to have no effect on the development of coronary collaterals in the left ventricles of pig hearts.
The relationship between phasic systolic and diastolic coronary blood flow and its transmural distribution has been studied in 29 Yucatan miniature pigs at rest and during heavy exercise, with and without adenosine infusion (1.5 mg . kg-1 . min-1) and with and without a subtotal coronary artery occlusion. Altered factors that affected coronary flow included vascular resistance, perfusion pressure, myocardial oxygen demand, and extra-vascular pressure. The data indicate that, at rest, endomural perfusion is significantly dependent on diastolic blood flow. However, the ability of the myocardial vessels to autoregulate during systole as well as during diastole was clearly shown with the use of adenosine infusion. This ability to regulate flow intrinsically appeared to transcend the endocardial dependency on diastolic perfusion under certain stressful conditions, e.g., during heavy exercise, when the diastolic duration was significantly reduced. Systolic transmural perfusion may then become a significant factor in meeting the blood flow demands of the myocardium. However, due to gradients in vascular resistance, perfusion pressure, and oxygen demand, the coronary reserve of the epicardium appears to be greater than that of the endocardium under any condition.
An implantable device for continuous measurement of regional myocardial radioisotope activity was designed and validated. The probe consists of a 2-mm3 cadmium telluride crystal surrounded by lead foil housed in a 4.5-mm outer diameter steel cylinder. Activity in serial dilutions of thallium-201 measured by this miniature gamma detector correlated well with activity measured in the well counter (r = 0.99). In vivo probe measurements of regional myocardial thallium-201 activity in a canine model were compared with activity in punch biopsies, again with excellent correlation (r = 0.90). The crystal was mounted on a modified arterial clamp, which was inserted into the left ventricle through, the apex and situated on the endocardial surface of the anterior or posterior wall. It was thus possible to measure regional isotope activity without excessive background from the blood pool and opposite heart wall. The probe was found best suited for monitoring activities of isotopes with energies between 60 and 250 keV. With a pair of these devices, dynamic studies of the myocardial kinetics of radioisotopes such as thallium-201 in normal and ischemic myocardium are now possible.
A method for constructing miniaturized Doppler blood flow probes is presented. Since these probes weigh less than 100 mg and have crystal heads less than 0.5 mm in size, they are suitable for chronic placement on vessels as small as 200 micron. The probes are positioned under the vessel and rotated to optimize the Doppler signal. While held in that position, the crystal head is attached to the adventitia of the vessel with cyanoacrylate glue. A cuff holding the vessel and probe in the chosen position is then formed in situ by the application of a drop of silicone polymer. Data are presented showing the linearity of a flow probe response with the volume blood flow at rates as low as 14 microliter/min. With the use of the uterine artery of the conscious, unrestrained rat as an example, the probe was demonstrated to detect a dynamic change in flow.
In order to obtain a nore reliable picture of transmitter release, spontaneous synaptic activity was studied in vivo in the rat soleus neuromuscular junction. The in vivo miniature end-plate potential (MEPP) recordings were compared with those obtained in vitro and, in both circumstances, MEPP frequency was measured at external potassiumconcentrations ranging from 5 to 15 mM. The influence of external potassium loading on intra- and extracellular potassium concentration also estimated by measuring the muscle ionic composition and water distribution at normal and high plasma potassium concentrations. The MEPP frequencies recorded in vivo were consistently lower than those observed in vitro for all external potassium concentrations studied (P less than0.01). These data suggest that better experimental conditions are maintained in thein vivo preparations, since the intracellular potassium increase that follows the external potassium loading can only partially justify the observed differnce and other factors, such as anesthetic effects, etc, may be ruled out.
Ion transport and the electric profile of distal airways of sheep lungs were studied in a miniature polypropylene chamber with a 1-mm aperture. Small airways with an inner diameter < 1 mm were isolated, opened longitudinally, and then mounted as a flat sheet onto the 1-mm aperture where it was glued and secured with an O-ring. Both sides of the tissue were bathed with identical physiological solutions at 37 degrees C and oxygenated. Pooled data from 27 distal airways showed an inner airway diameter of 854 +/- 22 (SE) microm and a transepithelial potential difference (PD) of 1.86 +/- 0.29 mV, lumen negative. Short-circuit current (I(sc)) was 25 +/- 3.5 microA/cm(2), tissue resistance was 96 +/- 14 Omega, and conductance was 15.2 +/- 1.7 mS/cm(2). At baseline, amiloride-sensitive Na transport accounted for 51% of I(sc) (change in I(sc) = 9.7 +/- 2.6 microA/cm(2); n = 8 airways), corresponding to 0.36 microeq. cm(-2). h(-1). Treatment with 0.1 mM bumetanide did not reduce the I(sc) (n = 5 airways). Exposure to 1 microM Ca ionophore A-23187 raised the I(sc) by 9 microA/cm(2) (47%; P < 0.03; n = 6 airways). The latter effect was blunted by bumetanide. Carbachol at 1 microM provoked a biphasic response, an initial rapid rise in I(sc) followed by a decline (n = 3 airways). There was no significant increase in PD or I(sc) in response to isoproterenol or dibutyryl cAMP. The data suggest that Na absorption constitutes at least 50% of baseline transport activity. Cl or other anion secretion such as HCO(3) appears to be present and could be stimulated by raising intracellular Ca.
This study validates the accuracy of miniature ultrasonic transit-time flow probes for measuring renal blood flow (RBF) in the rat. Probes for 1-mm and 2-mm vessels were calibrated ex vivo using excised arteries at varying flow rates and hematocrit (Hct). Correlation between measured and true flow rates for the 2-mm probe were identical (r = 1.0) at both normal and subnormal Hct values. Correlation for the 1-mm probe was high (r = 0.994) at normal Hct, but varied at both high flow rates and subnormal Hct values. In vivo correlation of RBF measurements using the 1-mm probe with the clearance and extraction of p-aminohippuric acid showed a high correlation (r = 0.84; n = 72, P < 0.0001) over a wide range of flow rates (0.5-21 ml/min) and Hct (36-74%). Zero flow levels remained steady, averaging -0.2 +/- 0.2 ml/min during occlusion in the living animal and -0.1 +/- 0.3 ml/min after exsanguination. This study shows that the ultrasonic transit-time flowmeter (1-mm and 2-mm probes) is a reasonably accurate and reliable method with which to measure RBF in the anesthetized, acute-instrumented rat.
Transgenic/knockout mice with pre-defined mutations have become increasingly popular in biomedical research as models of human diseases. In some instances, the resulting mutation may cause cardiorespiratory distress in the neonatal or adult animals and may necessitate resuscitation. Here we describe the design and testing of a miniature and versatile ventilator that can deliver varying ventilatory support modes, including conventional mechanical ventilation and high-frequency ventilation, to animals as small as the newborn mouse. With a double-piston body chamber design, the device circumvents the problem of air leakage and obviates the need for invasive procedures such as endotracheal intubation, which are particularly important in ventilating small animals. Preliminary tests on newborn mice as early as postnatal day O demonstrated satisfactory restoration of pulmonary ventilation and the prevention of respiratory failure in mutant mice that are prone to respiratory depression. This device may prove useful in the postnatal management of transgenic/knockout mice with genetically inflicted respiratory disorders.
Corticosteroid hormones are released in high amounts after stress and bind to intracellular receptors in the brain, which in activated form function as transcription factors. We here tested the effect of a high dose of corticosterone on AMPA-receptor-mediated transmission in the CA1 hippocampal area, which is enriched in corticosteroid receptors. To focus on slow gene-mediated effects of the hormone, excitatory postsynaptic currents were measured at least 1 h after a brief application of 100 nM corticosterone to slices from adrenally intact adult mice. The amplitude but not frequency of miniature postsynaptic excitatory currents was found to be significantly enhanced. These effects were mimicked by 100 nM RU 28362, a selective agonist for intracellular glucocorticoid receptors. Evoked AMPA responses at the single cell were significantly enhanced when measured 2-4 h after application of 100 nM corticosterone, but not at earlier moments nor with a longer delay. In summary, the present results show that activation of hippocampal glucocorticoid receptors induces a slow enhancement of AMPA-receptor-mediated responses, at the single-cell level.
In vitro differentiated embryonic stem (ES) cells have been proposed as potential donor cells for cell replacement therapies of neurodegenerative diseases. The functional synaptic integration of such cells appears conceivable because ES cell-derived neurons are well known to establish excitatory and inhibitory synapses. However, long-term synaptic plasticity, a prerequisite of memory formation, has not yet been demonstrated at these synapses. After in vitro differentiation and purification by immunoisolation, we co-cultured ES cell-derived neurons with neocortical explants, which strongly innervated the ES cell-derived target neurons. ES cell-derived neurons exhibited action potential firing similar to primary cultured neocortical neurons. The formation of glutamatergic synapses was indicated by AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA mEPSCs). In addition, a N-methyl-D-aspartate receptor-mediated, D-2-amino-5-phosphonopentanoic acid-sensitive mEPSC component was observed. We first studied activity-dependent homeostatic plasticity (synaptic scaling) of mEPSCs at glutamatergic synapses. Chronic blockade of action potential activity by TTX resulted in an increase in the amplitudes of AMPA mEPSCs. This indicates that ES cell-derived neurons are capable of a homeostatic regulation of postsynaptic AMPA receptors. In addition, we investigated neurotrophin-induced synaptic plasticity of mEPSCs at glutamatergic synapses. Chronic addition of brain-derived neurotrophic factor (BDNF; 100 ng/ml) to the culture medium resulted in an increase in both the frequency and the amplitudes of AMPA mEPSCs. These results suggest that BDNF induces the formation and/or the functional maturation of presynaptic release sites in parallel with an upregulation of postsynaptic AMPA receptors. Thus BDNF represents a potential co-factor that could improve functional synaptic integration of ES cell-derived neurons into neocortical networks.