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Blood flow within the major arteries supplying the brain can be studied with transcranial Doppler sonography, a noninvasive, portable procedure. We describe the technique of examination, as well as indications in children and adults such as the investigation of intracranial stenosis, collateral pathways, vasospasm, cerebral emboli and arteriovenous malformations.
The proteoglycan decorin and its associated glycosaminoglycan (GAG), dermatan sulfate (DS), regulate collagen fibril formation, control fibril diameter, and have been suggested to contribute to the mechanical stability and material properties of connective tissues. The spatial distribution and orientation of DS within the tissue are relevant to these mechanical roles, but measurements of length and orientation from 2D transmission electron microscopy (TEM) are prone to errors from projection. The objectives of this study were to construct a 3D geometric model of DS GAGs and collagen fibrils, and to use the model to interpret TEM measurements of the spatial orientation and length of DS GAGs in the medial collateral ligament of the human knee. DS was distinguished from other sulfated GAGs by treating tissue with chondroitinase B, an enzyme that selectively degrades DS. An image processing pipeline was developed to analyze the TEM micrographs. The 3D model of collagen and GAGs quantified the projection error in the 2D TEM measurements. Model predictions of 3D GAG orientation were highly sensitive to the assumed GAG length distribution, with the baseline input distribution of 69+/-23 nm providing the best predictions of the angle measurements from TEM micrographs. The corresponding orientation distribution for DS GAGs was maximal at orientations orthogonal to the collagen fibrils, tapering to near zero with axial alignment. Sulfated GAGs that remained after chondroitinase B treatment were preferentially aligned along the collagen fibril. DS therefore appears more likely to bridge the interfibrillar gap than non-DS GAGs. In addition to providing quantitative data for DS GAG length and orientation in the human MCL, this study demonstrates how a 3D geometric model can be used to provide a priori information for interpretation of geometric measurements from 2D micrographs.
AIMS: We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty METHODS AND RESULTS: Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. CONCLUSION: These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.
Fendilin hydrochloride was tested in 9 normal anesthetized dogs and in 7 anesthetized dogs with acute coronary artery occlusion. The compound (1 mg/kg i.v.) caused a slight short lasting increase in coronary blood flow together with an increase in cardiac metabolic rate for oxygen of similar magnitude. There was no measurable effect on collateral conductance. No noteworthy effects on systemic hemodynamics were observed.
The mutual effects of components of excitatory postsynaptic potentials (EPSP) induced by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) were studied on living slices of rat hippocampus. Evoked responses were recorded in the radial layer (stratum radialis) in field CA1 after stimulation of collateral-commissural fibers. The contribution of the NMDA component to the total EPSP was altered by extracellular application of solutions containing different concentrations of magnesium. At low magnesium concentrations, when both components made significant contributions to EPSP, inhibition of one of the components by application of antagonists of the appropriate receptors led to increases in the area of the other component. Thus, the total magnitude of pharmacologically isolated components were significantly greater than the control response (for example, at 0.1 mM magnesium, the sum of the components was 340 +/- 120% of the control two-component EPSP (p < 0.01; N = 6). These results suggest that in controls, the AMPA and NMDA components of EPSP inhibit each other. The mutual inhibition of components may be an important factor affecting the conductivity and plastic properties of central glutamatergic synaptic pathways.
The effects of pentobarbital were studied on synaptic transmission in the rat hippocampal slice preparation. Low concentrations of pentobarbital (0.04 - 0.1 mM) produced an increase in the Schaffer collateral to CA 1 evoked EPSP and population field potential amplitudes. Higher concentrations of pentobarbital (0.2 - 1.0 mM) produced depression of field potential amplitudes. Pentobarbital altered synaptic transmission by affecting both pre- and post-synaptic functions. Analysis of input/output curves suggest the presynaptic site is most sensitive.
Orexins (OX), also called hypocretins, are bioactive peptides secreted from glucose-sensitive neurons in the lateral hypothalamus linking appetite, arousal and neuroendocrine-autonomic control. Here, OX-A was found to cause a slow-onset long-term potentiation of synaptic transmission (LTPOX) in the hippocampus of young adult mice. LTPOX was induced at Schaffer collateral-CA1 but not mossy fiber-CA3 synapses, and required transient sharp wave-concurrent population field-burst activity generated by the autoassociative CA3 network. Exogenous long theta-frequency stimulation of Schaffer collateral axons erased LTPOX in intact hippocampal slices but not mini slices devoid of the CA3 region. Pharmacological analysis revealed that LTPOX requires co-activation of ionotropic and metabotropic glutamatergic, GABAergic, as well as noradrenergic and cholinergic receptors. Together these data indicate that OX-A induces a state-dependent metaplasticity in the CA1 region associated with sharp-wave and theta rhythm activity as well as glutamatergic, GABAergic, aminergic, and cholinergic transmission. Thus, orexins not only regulate arousal threshold and body weight but also threshold and weight of synaptic connectivity, providing a molecular prerequisite for homeostatic and behavioral state-dependent control of neuronal plasticity and presumably memory functions.
Any technique that can detect nitrogen concentrations can screen for concealed explosives. However, such a technique would have to be insensitive to metal, both encasing and incidental. If images of the nitrogen concentrations could be captured, then, since form follows function, a robust screening technology could be developed. However these images would have to be sensitive to the surface densities at or below that of the nitrogen contained in buried anti-personnel mines or of the SEMTEX that brought down Pan Am 103, approximately 200 g. Although the ability to image in three-dimensions would somewhat reduce false positives, capturing collateral images of carbon and oxygen would virtually assure that nitrogenous non-explosive material like fertilizer, Melmac dinnerware, and salami could be eliminated. We are developing such an instrument, the Nitrogen Camera, which has met experimentally these criteria with the exception of providing oxygen images, which awaits the availability of a sufficiently energetic light source. Our Nitrogen Camera technique uses an electron accelerator to produce photonuclear reactions whose unique decays it registers. Clearly if our Nitrogen Camera is made mobile, it could be effective in detecting buried mines, either in an active battlefield situation or in the clearing of abandoned military munitions. Combat operations require that a swathe the width of an armored vehicle, 5 miles deep, be screened in an hour, which is within our camera's scanning speed. Detecting abandoned munitions is technically easier as it is free from the onerous speed requirement. We describe here our Nitrogen Camera and show its 180 pixel intensity images of elemental nitrogen in a 200 g mine simulant and in a 125 g stick of SEMTEX. We also report on our progress in creating a lorry transportable 70 MeV electron racetrack microtron, the principal enabling technology that will allow our Nitrogen Camera to be deployed in the field.
The effects of management of single forearm arterial injuries without other associated major muscular, vascular, or neurological trauma were studied. Ninety-six patients with acute injuries to either radial or ulnar arteries without obvious associated major injuries were evaluated. No patient had an ischemic hand secondary to arterial injury. The selection of operative treatment by arterial repair or ligation was by surgeon choice (50 injuries were ligated, and 46 were repaired). Six months to six years postoperative follow-up was done. The overall patency rate for all repaired vessels was 52% (24 cases). The collateral arteries appeared to be a factor causing the low patency rate. The remaining intact artery demonstrated a consistent increase in flow velocity. No subject had hand claudication; there were 51 cases (53%) of hand weakness, 27 incidents (28%) of parasthesia, and 14 incidents (15%) of cold sensitivity independent of patency of the damaged forearm vessel. In the absence of acute hand ischemia, ligation of a lacerated radial or ulnar artery is safe and cost effective.
We investigated the role of extracellular ATP at astrocytes and inhibitory GABAergic interneurons in the stratum radiatum area of the mouse hippocampus. We show that exogenously applied ATP increased astrocyte intracellular Ca2+ levels and depolarized all calbindinand calretinin-positive interneurons in the stratum radiatum region of mouse hippocampus, leading to action potential firing and enhanced synaptic inhibition onto the postsynaptic targets of interneurons. Electrophysiological, pharmacological, and immunostaining studies suggested that the effect of ATP on interneurons was mediated by P2Y1 receptors, and that the depolarization of interneurons was caused by the concomitant reduction and activation of potassium and nonselective cationic conductances, respectively. Electrical stimulation of the Schaffer collaterals and perforant path, as well as local stimulation within the stratum radiatum, evoked increases in intracellular Ca2+ in astrocytes. Facilitation of GABAergic IPSCs onto interneurons also occurred during electrical stimulation. Both the stimulation-evoked increases in astrocyte Ca2+ levels and facilitation of GABAergic IPSCs were sensitive to antagonists of P2Y1 receptors and mimicked by exogenous P2Y1 receptor agonists, suggesting that endogenously released ATP can activate P2Y receptors on both astrocytes and interneurons. Overall, our data are consistent with the hypothesis that ATP released from neurons and astrocytes acts on P2Y1 receptors to excite interneurons, resulting in increased synaptic inhibition within intact hippocampal circuits.
Glass microelectrodes were inserted into motoneurons innervating pectoral fin muscles to record action and synaptic potentials, evoked by electrical stimulation of ventral and dorsal roots, and the medulla oblongata. Ventral root stimulation evoked a small depolarizing response which had properties compatible with those of the EPSP; its amplitude changes were graded, being increased by membrane hyperpolarization and decreased by high frequency repetitive stimulation. The latency of the response was sufficiently longer than that of the antidromic spike to allow for a monosynaptic delay. Stimulation of the dorsal root produced EPSPs with relatively long latencies, suggesting mediation by a polysynaptic pathway. EPSPs with short latencies were evoked by stimulation of the medulla oblongata, indicating the presence of a monosynaptic excitatory connection. Action potentials, recorded from peripheral nerve after stimulation of the medulla oblongata, were facilitated by conditioning volleys via ventral roots. This facilitation was blocked by dihydro-beta-erythroidine hydrobromide and atropine sulphate, indicating the cholinergic nature of the EPSP of ventral root origin. The conduction velocities of motor axons and of the ventral roots fibers responsible for production of EPSPs were about the same. The EPSP of ventral root origin had a slower rising time course and lesser sensitivity to shifts of membrane potential than the EPSP of medulla oblongata origin, suggesting that the sites of generation of the former EPSP were on the peripheral dendrites. From the above results, it was concluded that the EPSP of ventral root origin was mediated by recurrent axon collaterals of motoneurons.
Thermal damage of tissue is a major concern for all laser tissue repair techniques where the resulting strength of a repair is sensitive to slight alterations in tissue temperature as well as changes in the duration of exposure of the tissue to the laser beam. Too low of a temperature will prevent proper bonding between the surfaces while prolonged exposure of the tissue to the laser beam results in collateral thermal damage and decreased flexibility and strength of the repair. Temperature feedback systems that monitor the surface temperature of the repair site and adjust the laser irradiance accordingly increase the success rate of the technique. Knowledge of an optimal temperature for tissue soldering will also increase the reliability of the technique. The choice of solder material has been another challenge to the reproducibility of strong repairs. The emerging use of solder-doped polymer membranes as surgical adhesives offers numerous advantages over more traditional liquid and solid solders. Poly (L-lactic-co-glycolic acid) (PLGA), when used as a polymer scaffold, is porous enough to absorb serum albumin and can also be doped with various hemostatic and thrombogenic agents to aid tissue healing. An in vitro study was performed to correlate tissue temperature with the tensile strength of repairs formed using the solder-doped polymer membranes. Previous studies by our group indicate that a solder/tissue interface temperature of 65 degrees C is optimal. Using this parameter as a bench mark, laser irradiance was varied and the solder surface and solder/tissue interface temperatures were monitored by an IR temperature monitoring system, designed by the researchers, and a type K thermocouple, respectively.
Few reports in the literature validate the use of color Doppler imaging (CDI) for the evaluation of lower extremity arterial occlusive disease, particularly in the tibial and peroneal arteries. This prospective, blinded study compares CDI to arteriography to address the following questions: (1) how well does CDI visualize arterial segments, including those below the knee? and (2) can CDI alone accurately classify the degree of occlusive disease? Twenty-nine men undergoing arteriography before a lower extremity arterial reconstructive procedure were studied with a color ultrasound scanner from the level of the inguinal ligament to the ankle. Color images were examined for the presence or absence of triphasic flow, poststenotic turbulence, color bruits, and collateral vessels. Among 636 arterial segments adequately visualized by arteriography, > or = 90% were identified with color Doppler imaging, including the tibial and peroneal arteries. With color criteria only, specificity was > or = 92% for distinguishing < 50% from > = 50% lesions and > or = 93% for differentiating patent from occluded arteries. Sensitivity for detecting an occlusion was > or = 97% in the superficial femoral (SFA) and popliteal arteries and 83% in the tibial vessels. For identifying a > or = 50% stenosis, sensitivity was > or = 85% in the SFA and popliteal arteries but only 79% and 86% in the posterior and anterior tibial arteries, respectively. CDI reliably identifies vessel location from the level of the groin to the ankle. For the detection of occlusions, CDI is an accurate screening tool in the SFA and popliteal arteries but is less accurate in the tibial vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Effects of volatile anesthetic agents on N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic transmission have not been well characterized. The authors compared effects produced by halothane and isoflurane on electrophysiologic properties of NMDA and non-NMDA receptor-mediated synaptic responses in slices from the rat hippocampus. METHODS: Field excitatory postsynaptic potentials (fEPSPs) in the CA1 area were recorded with extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. NMDA or non-NMDA receptor-mediated fEPSPs were pharmacologically isolated using selective antagonists. Clinically relevant concentrations of halothane or isoflurane were applied to slices in an artificial cerebrospinal fluid perfusate. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic agents. RESULTS: Clinically relevant concentrations of halothane (1.2 vol% approximately 0.35 mM) depressed fEPSP amplitudes mediated by NMDA receptors and non-NMDA receptors to a similar degree (mean +/- SD: 63.3 +/- 14.0% of control, n = 5; 60.2 +/- 7.3% of control, n = 7, respectively). In contrast, isoflurane (1.4 vol% approximately 0.50 mM) preferentially depressed fEPSP amplitudes mediated by NMDA receptors (44.0 +/- 7.4% of control, n = 6, P < 0.001) compared with those for non-NMDA receptors (68.7 +/- 5.4% of control n = 6), indicating a selective, additional postsynaptic effect. Paired pulse facilitation of fEPSPs was increased significantly by both anesthetic agents from 1.37 +/- 0.13 to 1.91 +/- 0.25 (n = 5, P < 0.05 for halothane) and from 1.44 +/- 0.04 to 1.64 +/- 0.08 (n = 5, P < 0.01 for isoflurane), suggesting that presynaptic mechanisms are also involved in fEPSP depression produced by the anesthetic agents. Neither rise times nor decay times of fEPSPs were changed in the presence of the anesthetic agents. CONCLUSIONS: These results indicate that fEPSPs mediated by postsynaptic NMDA receptors are more sensitive to clinically relevant concentrations of isoflurane than are non-NMDA receptor-mediated responses, but this selective effect was not observed for halothane. Both agents also appeared to depress release of glutamate from nerve terminals via presynaptic actions.
UNLABELLED: The feasibility of non-invasive assessment of coronary flow reserve (CFR) in the left anterior descending artery (LAD) using echo-enhanced high-resolution transthoracic color Doppler echocardiography (TTCD) was investigated. The results were compared with the degree of coronary diameter-stenosis obtained during cardiac catheterization. CFR has proven to be useful in the selection of patients undergoing invasive treatment of coronary artery disease and in estimating their prognosis. However, CFR could only be determined in everyday practice invasively during catheterization procedures. Recent development of high-resolution TTCD allows transthoracic visualization of distal LAD and supra-apical intramyocardial perforator branches, and non-invasive measurement of CFR. CFR was determined by measuring the ratio of pulsed-wave Doppler time velocity integral during adenosine-induced hyperemia (140 micrograms/kg/min i.v.) to baseline value. If Doppler signal of LAD flow was insufficiently at basal condition, an echo enhancer (Levovist) was used. 45 patients were examined by TTCD (7 MHz B-mode, 5 MHz color Doppler, 3.5 MHz PW Doppler) after coronary angiography had been performed. Group I consisted of 15 patients without heart disease, Group II of 15 patients with 40 to 70% isolated LAD diameter stenosis, and Group III of 15 patients with > 70% LAD diameter stenosis. Peripheral LAD coronary flow at baseline condition was assessed in 40 patients (88%) using TTCD. CFR could be quantified in 36/45 patients (80%), in 18 patients without echo enhancer, and in 18 patients with echo-enhancing agent. In 9/45 patients CFR could not be assessed. CFR in Group I was 3.13 +/- 0.57, in Group II 2.23 +/- 0.20 (vs Group I p < 0.01) and in Group III 1.64 +/- 0.30 (vs Group II p < 0.02). CONCLUSION: CFR of LAD can be determined in 80% of patients by the synergistic use of high-resolution TTCD combined with intravenous given ultrasound echo-enhancing agent.
Parenting interventions for substance-abusing adults have been broadly based on two approaches, one emphasizing parental control as a means to managing children's behavior and the second emphasizing parental warmth and sensitivity as means to fostering children's psychological development. In this investigation, we examined associations of parental control and parental warmth, respectively, with children's behavioral and psychological adjustment in a sample of 98 women enrolled in methadone maintenance and their school-aged and adolescent children. Using collateral data collected during the baseline phase of a randomized clinical trial (Luthar, S. S., Suchman, N. E., & Altomare, M. [in press]. Relational Psychotherapy Mothers Group: A randomized clinical trial for substance abusing mothers [in preparation]), we tested predictions that (a) parental control would be more strongly associated with children's behavioral adjustment and (b) parental warmth would be more strongly associated with children's psychological adjustment. Both predictions were generally confirmed, although some crossover among parenting and child dimensions was also evident. Results support the theoretical stance that parental limit setting and autonomy support, as well as nurturance and involvement, are important factors, respectively, in children's behavioral and psychological adjustment.
BACKGROUND: Serum Troponin I is used routinely as an adjunct to EKG for the diagnosis of myocardial infarction (MI); however, a correlation between marker level and infarct size has yet to be documented in vivo. We report findings from a chronic coronary artery ligation model in the canine (n = 12) in which peak Troponin I is related to infarct size as determined by high-resolution cardiac magnetic resonance imaging. METHODS: All animals underwent a left anterior thoracotomy to allow for ligation of the left anterior descending artery. Evidence of myocardial infarction, including EKG changes, elevated Troponin I, along with visual reduction in perfusion and wall motion, was noted in all animals. Thirty days after surgical intervention, cine MRI and contrast-enhanced MRI were performed. Dedicated analysis software was used to quantify global infarction size, LV function and to map regions of MI to a 3D model of the left ventricle. RESULTS: A linear relationship between infarct extent and peak Troponin I level exists (r = 0.98, P < 0.0001). In addition, we observed a negative trend between infarct extent, peak Troponin I, and ejection fraction. CONCLUSION: The findings of this study indicate that Troponin I and cardiac magnetic resonance imaging provide a more accurate estimation of infarct size than was previously reported using markers with less sensitivity and imaging modalities of lower spatial resolution and viability imaging capability.
Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.