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PubMed2006

Selective fovea-related deprived activation in retinotopic and high-order visual cortex of human amblyopes.

Amblyopia is a visual disorder starting at early childhood and characterized by reduced visual acuity not of optical origin or due to any eye disease. One expression of such an anomalous early visual experience is abnormal foveal vision. In a previous fMRI study, faces that were presented to amblyopic eyes evoked little response compared to houses in high-order visual areas. Patients also demonstrated reduced recognition of facial expression, raising the possibility that these face-selective abnormalities are related to foveal vision deficit. Whether this deficit originates in low-level processing or is mediated by compromised activation in high-order visual areas is unresolved. In the present functional magnetic resonance imaging (fMRI) study, we explored the impact of amblyopia on the representation of object images presented in foveally biased central versus peripheral retinotopic eccentricities through manipulation of object size. Small and large pictures were correlated to visual acuities of 6/6 and 6/60, respectively. In low-level visual areas, the amblyopic eye showed significantly reduced activation for centrally placed, small pictures than the sound eye, while activation to large pictures was only slightly reduced. Similarly, in high-order visual areas, the amblyopic eye showed marked reduction in activation in the fusiform gyrus, with normal activation in the collateral sulcus. The center/periphery size-related amblyopic outcomes of this study support a "bottom-up" nature of the center-periphery effect observed in high-order visual areas. Taken together, these findings point to the regional extent and functional selectivity of fovea-related cortical reorganization that is related to abnormal visual development of one eye.

Adult↗
PubMed1998

Transient suppression of GABAA-receptor-mediated IPSPs after epileptiform burst discharges in CA1 pyramidal cells.

Epileptiform burst discharges were elicited in CA1 hippocampal pyramidal cells in the slice preparation by perfusion with Mg2+-free saline. Intracellular recordings revealed paroxysmal depolarization shifts (PDSs) that either occurred spontaneously or were evoked by stimulation of Schaffer collaterals. These bursts involved activation of N-methyl-D-aspartate receptors because burst discharges were reduced or abolished by -2-amino-5-phosphonovaleric acid. Bath application of carbachol caused an increase in spontaneous activity that was predominantly due to gamma-aminobutyric acid-A-receptor-mediated spontaneous inhibitory postsynaptic potentials (sIPSPs). A marked reduction in sIPSPs (31%) was observed after each epileptiform burst discharge, which subsequently recovered to preburst levels after approximately 4-20 s. This sIPSP suppression was not associated with any change in postsynaptic membrane conductance. A suppression of sIPSPs also was seen after burst discharges evoked by brief (100-200 ms) depolarizing current pulses. N-ethylmaleimide, which blocks pertussis-toxin-sensitive G proteins, significantly reduced the suppression of sIPSPs seen after a burst response. When increases in intracellular Ca2+ were buffered by intracellular injection of ethylene glycol bis(beta-aminoethyl)ether-N,N,N',N'-tetraacetic acid, the sIPSP suppression seen after a single spontaneous or evoked burst discharge was abolished. Although we cannot exclude other Ca2+-dependent mechanisms, this suppression of sIPSPs shared many of the characteristics of depolarization-induced suppression of inhibition (DSI) in that it involved activation of G proteins and was dependent on increases in intracellular calcium. These findings suggest that a DSI-like process may be activated by the endogenous burst firing of CA1 pyramidal neurons.

Action Potentials↗
PubMed1990

[The depressing effect of GABA on synaptic excitation in isolated rat hippocampal slices].

The action of various gamma-aminobutyric (GABA) concentrations on the amplitude of population EPSPs (PEPSPs) recorded from dendrites was examined in hippocampal slices. GABA produced reversible dose-dependent diminishing of the amplitude of PEPSPs without features of desensitization. CA1 hippocampal PEPSPs were much more sensitive to GABA (threshold concentrations--3.10(-5)-2.10(-4)mol/l; IC50--5.10(-4)-1.10(-3) mol/l) the action of GABA on PEPSPs was not depressed by bicuculline, picrotoxin or penicillin. The inhibitory action of GABA on dendritic antidromic population spike (DAPS) (post-synaptic inhibitory effect) was greatly reduced by these drugs. Baclofen was more potent inhibitor of CA1 PEPSPs than GABA (threshold concentration--1.10(-6)mol/l; IC50--3.10(-6)mol/l), but even in high concentration it induced only slight reduction of DAPS amplitude. It is concluded that GABA inhibitory effects on CA1 hippocampal PEPSPs are caused in the main by its presynaptic action mediated by GABA(B)-receptors located probably on axon terminals of the Schaffer collaterals.

Animals↗
PubMed1997

Characterisation of novel human lung carcinoma cell lines selected for resistance to anti-neoplastic analogues of staurosporine.

The staurosporine analogues CGP 41251, UCN-01 and Ro 31-8220 are specific inhibitors of protein kinase C (PKC). CGP 41251 and UCN-01 exert anti-neoplastic activity against human tumours grown in rodents, and CGP 41251 reverses multidrug resistance. The hypothesis was tested that these agents can induce drug resistance and alter cellular levels of target kinases. Human-derived A549 lung carcinoma cells were exposed for 6 months to CGP 41251, UCN-01 or Ro 31-8220 at gradually increasing concentrations. Cells acquired resistance against these agents, 4.3-fold against CGP 41251 (A549/CGP cells), 4.0-fold against UCN-01 (A549/UCN cells) and 14-fold against Ro 31-8220 (A549/Ro cells). Cells were neither collaterally cross-resistant towards the PKC inhibitors nor resistant against the growth-inhibitory properties of 12-O-tetradecanoylphorbol-13-acetate. However, cross-resistance was observed in A549/CGP cells against staurosporine (13-fold) and in A549/Ro cells against doxorubicin (26-fold). All 3 cell types expressed multidrug resistance-associated protein, and A549/Ro cells expressed P-glycoprotein, as adjudged by Western blot analysis. Phorbol ester-stimulated PKC activity in these cells was decreased by between 57% and 96% compared to wild-type A549 cells. Levels of the PKC isoenzymes alpha and theta in all 3 resistant cell types and of PKC-epsilon in A549/UCN cells were concomitantly reduced. Cells regained drug sensitivity after culture in the absence of drug for 6 (A549/Ro cells), 5 (A549/CGP cells) and 1 (A549/UCN cells) months. Our results suggest the following features of this type of anti-signalling drug: (i) they can induce drug resistance, (ii) they may be potentially useful in combination because of the lack of cross-resistance between them and (iii) they can down-regulate PKC, which may have pharmacological or toxicological consequences.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Anatomy and magnetic resonance imaging of the posterolateral structures of the knee.

The purpose of the present study was to provide detailed information of the morphological and radiological characteristics of the posterolateral structures of the knee. Muscles and ligaments of the posterolateral part of the knee were studied by dissections of 50 adult cadaver knees and by Magnetic Resonance Imaging (MRI) before and after dissections for comparisons. Diverse morphological characteristics of the arcuate ligament were found. The fabellofibular ligament was present in 42.1% of the knees dissected, whereas the popliteofibular ligament was found in 37.5%. A ligamentous structure, which could be called the posterior tibial ligament, was found in 31.6% of the cases that originated from the lateral part of the capsule proximally and inserted distally on the mid portion of the proximal tibia. By comparing the cross sections and the dissections of the cadaver knees, the popliteus muscle, the arcuate ligament, the fibular collateral ligament, the popliteofibular ligament, and the fabellofibular ligament could be identified in MRI. Comprehensive understanding of the posterolateral anatomy of the knee and improved identification of the structures in MRI will help clinicians to make a more accurate and noninvasive diagnosis of posterolateral instability.

Adult↗
PubMedDate not supplied

CT evaluation of pararectal varices.

PURPOSE: This study was undertaken to determine the prevalence of pararectal varices on CT scan in patients with portal hypertension and to see if dilatation of the inferior mesenteric vein (IMV) or the presence of pararectal varices on CT correlates with rectal varices noted on colonoscopy. METHOD: We reviewed 83 consecutive CT scans of the abdomen and pelvis performed in patients with portal hypertension. The size and prevalence of pararectal varices were determined. Correlation with colonoscopic and endoscopic reports was performed. The diameter of the IMV was compared in those patients with pararectal varices with that in those patients without, as was the presence of esophageal varices. RESULTS: Twenty patients (24%) had CT evidence of pararectal varices, ranging from 5 to 11 mm in diameter (mean 7.8 mm). Colonoscopic correlation was available in 30 patients. Of these, 6 of 30 (20%) had pararectal varices on CT and no rectal varices on colonoscopy, 3 of 30 (10%) had pararectal varices on CT and rectal varices on colonoscopy, and 3 of 30 (10%) had no pararectal varices on CT but did have rectal varices on colonoscopy. Endoscopic correlation (available in 48 patients) demonstrated esophageal varices in 88% of patients with rectal or pararectal varices and in 66% of patients without rectal or pararectal varices (p = 0.170). The IMV was significantly larger in patients with pararectal varices (mean diameter 7.5 mm, SD 2.3) as compared with those without (mean diameter 5.8 mm, SD 2.0) (p = 0.014). However, in patients with colonoscopically proven rectal varices, only two of six (33%) had an IMV diameter of > or = 7 mm. CONCLUSION: Inclusion of the pelvis on CT scans of patients with portal hypertension can yield further information about the presence and extent of pararectal venous collaterals, which may be of particular importance in those patients requiring pelvic surgery. The presence of pararectal varices on CT and the diameter of the IMV do not correlate with the presence of rectal varices on colonoscopy. Decompression of portal hypertension by rectal and pararectal varices does not result in a decreased incidence of esophageal varices.

Adult↗
PubMed2002

Anatomy of stroke, Part II: volumetric characteristics with implications for the local architecture of the cerebral perfusion system.

BACKGROUND AND PURPOSE: The margin of a stroke is assumed to approximate a trace of the isobar of the perfusion threshold for infarction at the time that infarction occurred. Working from this hypothesis, we have analyzed stroke topography and volume in MR images obtained at a time remote from the stroke event. We have derived parameters from these images that may give information on local perfusion competence and microvascular architecture because they influenced the contour of stroke at the time infarction occurred. METHODS: MR images were obtained months after presumed embolic middle cerebral artery stroke in 21 subjects. Volumetric analyses of image data were undertaken with respect to the tissue shape of stroke and scaling ratios of anatomic partitions involved in stroke. RESULTS: For stroke confined to a single volume, the 3-dimensional form conforms to a parabola in which the height-to-width ratios are variable. The ratio for cortex is greater than that for underlying white matter. Scaling ratios indicate a close correlation between volume of cortex and radiata destroyed and total volume of stroke, but the relative proportions vary as a function of location within the M4 territory. CONCLUSIONS: Scaling ratios for cortex and radiata to stroke volume are consistent with vascular studies that depict a modular microvascular perfusion architecture for the cortex and underlying white matter. The stroke descriptors are inferred to be related to the competence of collateral perfusion at the time that stroke occurred. This inference may be tested by serial volumetric analysis of the perfusion-diffusion examination mismatch immediately and over the longer-term evolution of stroke.

Adult↗
PubMed1979

Inhibitory mechanisms influencing complex cell orientation selectivity and their modification at high resting discharge levels.

1. These experiments have investigated the contribution made by GABA-mediated inhibitory processes to the orientation tuning of complex cells in the cat's striate cortex. The GABA antagonist bicuculline has been ionophoretically applied to individual complex cells and the modifications produced in their orientation tuning documented. 2. In terms of the type of change produced in orientation tuning by the application of bicuculline, it seems that there are two categories of complex cells. 3. In one of these categories the orientation selectivity was eliminated during bicuculline application. The excitatory input to these cells would therefore appear to be non-orientation specific. Their orientation selectivity is presumably generated by a GABA-mediated inhibitory input. 4. In the other category of complex cells, although the orientation selectivity was decreased during bicuculline application, the cells retained a preference for a range of orientations that was generally centred around the original optimal orientation. It is suggested that for these cells the inhibitory input enhances the orientation tuning of an excitatory input that is already broadly orientation tuned. 5. Comparison of normal orientation tuning curves with those observed during the application of bicuculline provides a basis for estimating the orientation tuning of the GABA-mediated inhibitory input. In all cases, it is clear that at normal resting discharge levels, orientations either side of the optimal, and not those centred on the optimal, generate the most powerful inhibitory input. 6. These results would seem to be best explained by inhibitory interconnexions between cortical columns sensitive to different orientations. This type of lateral interaction between columns may serve to enhance the contrast in the orientation domain for the cortical representation of a specific stimulus orientation. 7. Increasing the resting discharge level of a complex cell, without blocking the action of GABA appeared to increase the gain of the inhibitory mechanisms acting on the cell. The normal excitatory responses to optimal or near optimal orientations were greatly reduced, or replaced by inhibitory responses, and non-optimal orientations produced only inhibitory responses. These inhibitory effects were blocked on the context of other observations in the literature. It is tentatively suggested that the interneurones providing the inhibitory drive to complex cells receive an input from recurrent collaterals of the recipient complex cells. Their other inputs would derive from neighbouring colums and from the afferent input to the parent column. The inputs from neighbouring columns would mediate the lateral inhibitory interactions in the orientation domain, and the recurrent collateral feed-back the decreased responsiveness at high resting discharge levels.

Animals↗
PubMed1982

Validity of monoamine oxidase in serum for diagnosis of liver cirrhosis: estimation of predictive values, sensitivities and specificities.

The validity of monoamine oxidase (EC 1.4.3.4) activity in serum for the diagnosis of fibroproliferative liver disorders was assessed by measuring the specificity, sensitivity and positive and negative predictive values of the enzyme. Enzyme activity was measured in sera of 567 patients including those with biochemically and/or histologically verified non-fibrotic liver diseases (n = 64), liver fibrosis (n = 45), and liver cirrhosis (n = 51). The fraction of liver cirrhotic subjects with pathologically elevated monoamine oxidase activity (greater than 630 U/1) was 0.61, whereas only 0.16 of the cases with liver fibrosis and 0.11 of those with non-fibrotic liver diseases had abnormally high enzyme activities. Among the various categories of diseases tested, significantly increased enzyme activities were confined to liver cirrhosis and chronic active hepatitis. For liver cirrhosis, sensitivities and specificities were calculated as functions of various cut-off (critical) values of monoamine oxidase activity in serum, and with respect to a reference population of healthy men and non-cirrhotic subjects. The predictive value of the positive test result (enzyme activity higher than 720 U/1) at a prevalence of liver cirrhosis of maximum 0.033 (estimated incidence of chronic liver diseases in West Germany) is 0.68 if tested against healthy persons and less than 0.30 if tested against patients with non-liver cirrhotic diseases. It is concluded that monoamine oxidase is probably not helpful in the early diagnosis of fibroproliferative liver dysfunctions but may provide a parameter of complications of cirrhosis, e.g. portal-systemic collateral circulation (portal hypertension).

Chronic Disease↗
PubMed1990

Intersubnuclear connections within the rat trigeminal brainstem complex.

Prior intracellular recording and labeling experiments have documented local-circuit and projection neurons in the spinal trigeminal (V) nucleus with axons that arborize in more rostral and caudal spinal trigeminal subnuclei and nucleus principalis. Anterograde tracing studies were therefore carried out to assess the origin, extent, distribution, and morphology of such intersubnuclear axons in the rat trigeminal brainstem nuclear complex (TBNC). Phaseolus vulgaris leucoagglutinin (PHA-L) was used as the anterograde marker because of its high sensitivity and the morphological detail provided. Injections restricted to TBNC subnucleus caudalis resulted in dense terminal labeling in each of the more rostral ipsilateral subnuclei. Subnucleus interpolaris projected ipsilaterally and heavily to magnocellular portions of subnucleus caudalis, as well as subnucleus oralis and nucleus principalis. Nucleus principalis, on the other hand, had only a sparse projection to each of the caudal ipsilateral subnuclei. Intersubnuclear axons most frequently traveled in the deep bundles within the TBNC, the V spinal tract, and the reticular formation. They gave rise to a number of circumscribed, highly branched arbors with many boutons of the terminal and en passant types. Retrograde single- or multiple-labeling experiments assessed the cells giving rise to TBNC intersubnuclear collaterals. Horseradish peroxidase (HRP) and/or fluorescent tracer injections into the thalamus, colliculus, cerebellum, nucleus principalis, and/or subnucleus caudalis revealed large numbers of neurons in subnuclei caudalis, interpolaris, and oralis projecting to the region of nucleus principalis. Cells projecting to more caudal spinal trigeminal regions were most numerous in subnuclei interpolaris and oralis. Some cells in lamina V of subnucleus caudalis and in subnuclei interpolaris and oralis projected to thalamus and/or colliculus, as well as other TBNC subnuclei. Such collateral projections were rare in nucleus principalis and more superficial laminae of subnucleus caudalis. TBNC cells labeled by cerebellar injections were not double-labeled by tracer injections into the thalamus, colliculus, or TBNC. These findings lend generality to currently available data obtained with intracellular recording and HRP labeling methods, and suggest that most intersubnuclear axons originate in TBNC local-circuit neurons, though some originate in cells that project to midbrain and/or diencephalon.

Animals↗
PubMed1998

1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association.

OBJECTIVE: To revise and expand the 1992 edition of the clinical practice guidelines for the management of diabetes in Canada incorporating recent advances in diagnosis and outpatient management of diabetes mellitus and to identify and assess the evidence supporting these recommendations. OPTIONS: All aspects of ambulatory diabetes care, including organization, responsibilities, classification, diagnosis, management of metabolic disorders, and methods for screening, prevention and treatment of complications in all forms of diabetes were reviewed, revised as required and expressed as a set of recommendations. OUTCOMES: Reclassification of types of diabetes based on pathogenesis; increased sensitivity of diagnostic criteria; recommendations for screening for diabetes; improved delivery of care; recommendations for tighter metabolic control; and optimal methods for screening, prevention and treatment of complications of diabetes. EVIDENCE: All recommendations were developed using a justifiable and reproducible process involving an explicit method for the citation and evaluation of the supporting evidence. VALUES: All recommendations were reviewed by an expert committee that included people with diabetes, family physicians, dietitians, nurses, diabetologists, as well as other subspecialists and methodologists from across Canada. BENEFITS, HARM AND COSTS: More aggressive screening strategies and more sensitive testing and diagnostic procedures will allow earlier detection and management of diabetes. Cost-effectiveness analyses suggest that this will lead to savings in health care costs relating to diabetes care by reducing the incidence of complications of diabetes. Similarly, tighter metabolic control in most people with diabetes, through intensive diabetes management, seeks to reduce the incidence of complications and, hence, their associated social and economic burdens. RECOMMENDATIONS: This document contains numerous detailed recommendations pertaining to all aspects of ambulatory diabetes care, ranging from service delivery to prevention and treatment of diabetes-related complications. The terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" should be replaced by the terms "type 1" and "type 2" diabetes. Testing for diabetes using fasting plasma glucose (FPG) level should be performed every 3 years in those over 45 years of age. More frequent or earlier testing should be considered for people with additional specific risk factors for diabetes. The FPG level at which diabetes is diagnosed should be reduced from 7.8 to 7.0 mmol/L to improve the sensitivity of the main diagnostic criterion and reduce the number of missed diagnoses. Depending on the type of diabetes and the therapy required to achieve euglycemia, people with diabetes should generally strive for close metabolic control to achieve optimal glucose levels. This entails receiving appropriate diabetes education through a diabetes health care team, diligent self-monitoring of blood glucose, attention to lifestyle and adjustments in diet and physical activity, and the appropriate and stepwise use of oral agents and insulin therapies needed to maintain glycemic control. Also highlighted is the need for appropriate surveillance programs for complications and management options. VALIDATION: All recommendations were graded according to the strength of the evidence and consensus of all relevant stakeholders. Collateral efforts of the American Diabetes Association and the World Health Organization and the input of international experts were also considered throughout the revision process.

Canada↗
PubMed1998

Coronary artery injection technique: a quantitative in vivo investigation using modern catheters.

To date, there have been no quantitative in vivo assessments of contrast volumes and injection rates using modern high flow catheters during coronary angiography. Contrast volumes (n = 554), injection durations (n = 563), and injection rates (n = 498) were collected during 88 cardiac catheterizations. With increasing cathetersize (6, 7, and 8 French), injection volume increased (P < 0.0001), duration decreased (P < 0.0001), and rate increased (P < 0.0001). Compared with injections into the right coronary artery, left coronary artery injections were larger (7.1 +/- 0.1 cc vs. 4.8 +/- 0.1 cc, p < 0.0001), longer (3.6 +/- 0.05 sec vs 3.0 +/- 0.07 sec, P < 0.0001) and faster (2.1 +/- 0.04 cc/sec vs. 1.7 +/- 0.06 cc/sec, P < 0.0001). Patients with a significant stenosis in the left main or proximal right coronary artery received less contrast (P < 0.0001) more slowly (P < 0.0001) over a similar duration of injection (P = NS). When collaterals arose from the injected artery, angiographers injected more contrast (P < 0.001) over a longer period (P < 0.0001) more slowly (P < 0.0001). Catheter size and the injected vessel's location and anatomy significantly affect coronary catheterization injection technique.

Angioplasty, Balloon, Coronary↗
PubMed1997

2D time-of-flight MR angiography using concatenated saturation bands for determining direction of flow in the intracranial vessels.

We prospectively studied 15 patients to assess 2D time-of-flight (TOF) magnetic resonance angiography (MRA) with concatenated saturation bands for determining the direction of intracranial blood flow. This MRA sequence was compared to T2-weighted spin-echo MRI, 3D-TOF MRA, and intra-arterial angiography (IAA) as regards demonstration of vessels and determination of the direction of flow in the circle of Willis and its branches. The 2D-TOF MRA sequence demonstrated flow in 98.5% vessel segments identified on IAA, 3D-TOF demonstrating 92% and spin-echo images 77%. The direction of flow shown on the 2D-TOF sequence was correct in 94% when compared to conventional angiography, the remaining six segments not demonstrating flow. In ten patients, the flow abnormalities demonstrated by this MRA technique provided clinical information similar to that of conventional angiography in nine, but it was incomplete in three, and misleading in one. Slow retrograde flow in ophthalmic artery collaterals and differentiation of arteries and veins presented some problems. 2D-TOF MRA with concatenated saturation bands provides flow direction information using widely available, easily applicable TOF techniques, and can be a useful adjunct to MRI and MRA if information on flow direction is needed.

Arteries↗
PubMed1999

Chronic intermittent ethanol exposure alters CA1 synaptic transmission in rat hippocampal slices.

We investigated the neuroadaptive changes in synaptic transmission in the CA1 region of the hippocampus as a result of chronic intermittent ethanol exposure. Male Wistar rats were exposed daily (14 h) to ethanol vapors (blood alcohol levels = 150-200 mg%) for 12-14 days, and synaptic field potentials elicited by Schaffer collateral stimulation were compared in hippocampal slices from control and chronic ethanol-treated rats. Excitatory postsynaptic responses of slices were recorded under three conditions: (i) normal physiological saline; (ii) continued presence of 33 mM (150 mg%) ethanol (chronic ethanol-treated rats only); (iii) acute exposure to 33 mM ethanol. When recorded in ethanol-free physiological saline, the mean amplitude of the dendritic synaptic potential and the somatic population spike were significantly smaller in slices from chronic ethanol-treated rats compared to slices from control rats. Under conditions of continuous ethanol exposure, somatic and dendritic synaptic responses of slices taken from chronic ethanol-treated rats were further depressed, suggesting that neural pathways in area CA1 remained sensitive to ethanol. Acute application of ethanol led to a more pronounced reduction of the mean somatic population spike amplitude in slices from chronic ethanol-treated rats than in slices from control rats. However, dendritic synaptic responses were unaffected by acute ethanol in slices from both control and chronic ethanol-treated rats. In addition, we examined the involvement of presynaptic mechanisms in the effects of chronic intermittent ethanol using paired-pulse protocols. When recorded in the continued presence of ethanol, slices from chronic ethanol-treated rats exhibited a significant reduction in paired-pulse facilitation of the dendritic synaptic response compared to slices from control rats, indicating a presynaptic component to the neuroadaptive effects of chronic intermittent ethanol exposure. Conversely, acute ethanol exposure resulted in an enhancement of paired-pulse facilitation of the dendritic synaptic response, an effect that was similar in slices from both control and chronic ethanol-treated rats. Paired-pulse facilitation of the somatic population spike amplitude was not altered by chronic ethanol treatment. However, acute ethanol exposure significantly enhanced paired-pulse facilitation of the somatic population spike in slices from chronic ethanol-treated rats. This effect of acute ethanol was not observed in slices from control rats. Paired-pulse inhibition was not significantly altered in slices from chronic ethanol-treated rats, suggesting that GABAergic inhibitory mechanisms were not involved in the neuroadaptive effects of chronic intermittent ethanol exposure. We suggest that chronic intermittent ethanol exposure can induce multiple neuroadaptive changes in synaptic transmission of CA1 pyramidal neurons that are detectable at both the pre- and postsynaptic levels. Alterations in paired-pulse facilitation indicate presynaptic changes involving the release of the excitatory neurotransmitter glutamate, whereas changes in dendritic synaptic responses suggest postsynaptic changes in the responsiveness of neurons to synaptic input. Moreover, differential effects of chronic ethanol treatment on synaptic responses recorded in the dendrites versus the somatic region implicate additional effects of ethanol on somatically located mechanisms of CA1 pyramidal neurons. Furthermore, we suggest that complete tolerance to ethanol does not occur in the CA1 region of the hippocampus following chronic intermittent ethanol exposure.

Alcoholism↗
PubMed1992

Left ventricular aneurysm and prognosis in patients with first acute transmural anterior myocardial infarction and isolated left anterior descending artery disease.

To determine the clinical and angiographic factors responsible for left ventricular aneurysm formation and the prognosis of patients with aneurysm, 79 patients with a first acute transmural anterior myocardial infarction and angiographically documented isolated left anterior descending artery disease were retrospectively evaluated. Presence of large infarct size and left ventricular volumes, reduced left ventricular function, and evidence of clinical functional impairment were more common in patients with aneurysm (n = 31) than in those without (n = 48). Patients with aneurysm often had total occlusion of the proximal left anterior descending artery without collateral vessels on angiography. During a mean follow-up of 53 months, 10 patients with and three without aneurysm died (P less than 0.01). Compared to survivors with or without aneurysm, the nonsurvivors were older, had significantly larger infarct size and left ventricular volumes and poor systolic function. The incidence of total occlusion of the left anterior descending artery without collaterals was higher in nonsurvivors. In patients with aneurysm, stepwise multivariate analysis revealed that left ventricular ejection fraction and the status of left anterior descending artery obstruction and collaterals were independent predictors of mortality. The study indicates that in patients with a first acute transmural anterior myocardial infarction and isolated anterior descending artery disease, left ventricular aneurysm often results from a large infarct caused by total occlusion of the proximal left anterior descending artery without collateral supply to the infarct region. The reduced survival rate for patients with aneurysm is primarily related to severe global left ventricular dysfunction which may be determined by assessing the residual flow to the infarct region.

Adult↗
PubMed1992

Intracoronary gallopamil during percutaneous transluminal coronary angioplasty.

The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA.

Adult↗
PubMed1994

[Selective occlusion of subretinal neovascularization with photodynamic therapy].

Conventional photocoagulation of subretinal membranes induces a non-selective thermal necrosis of retinal and choroidal layers with extensive collateral damage. Hence, this modality is of limited value for the treatment of lesions close to or underneath the fovea. Photodynamic therapy uses systemic administration of a primarily non-toxic photosensitizer with localized light activation of the dye by subthermal light intensities. It provides intraluminal vascular occlusion by means of localized endothelial damage. Enhanced selectivity for neovascularization is achieved by the use of carrier molecules with increased receptor density on proliferating endothelial cells, e.g. low-density lipoproteins (LDL). Benzoporphyrin derivative (BPD), currently in phase I clinical trials, was complexed with LDL. BPD-LDL was used for photodynamic occlusion of the choriocapillary layer in the rabbit model. Subretinal photothrombosis and collateral damage to neural retina, retinal pigment epithelium, Bruch's membrane and large choroidal vessels were documented by ophthalmoscopy, angiography and light and electron microscopic histology. Homogenous vascular occlusion without retinal destruction was induced with light doses as low as 10 J/cm2. Selective neovascular occlusion by photodynamic therapy may allow occlusion of subretinal membranes while preserving retinal integrity and visual function.

Animals↗
PubMed1997

Effects of acute, chronic ethanol and withdrawal on dorsal raphe neurons: electrophysiological studies.

The effect of a single intravenous administration of ethanol (0.25-1.0 g/kg) on the spontaneous activity of putative serotonin neurons of the dorsal raphe nucleus was studied in unanesthetized rats. Ethanol produced a slight but progressive decline in neuronal activity in 67% (six of nine) of all neurons tested. The remaining 33% (three of nine) were unresponsive. Upon withdrawal of chronic ethanol treatment (1-5 g/kg every 6 h for six consecutive days, 12 h from last ethanol administration), the mean firine rate of dorsal raphe neurons was found to be significantly reduced, by about 30% (n=71), as compared with the control group (n=83), whereas the cells/track index was unaltered. Under these conditions, ethanol administration further reduced firing rate in 67% (four of six) of all the neurons tested. In the remaining 33% (two of six), no response was observed. At 72 h after the last ethanol administration, the mean firing rate of dorsal raphe neurons was found to be within control values (n=90). Further, to evaluate the functional status of the autoreceptors under control conditions and after withdrawal from chronic ethanol, the selective serotonin-1A receptor agonist 8-hydroxy-(2-di-n-propylamino)tetralin was administered intravenously in cumulative doses (1-16 microg/kg) and dose-response curves were generated for both groups. Autoreceptor sensitivity of dorsal raphe neurons was found to be not statistically different in control and ethanol withdrawn rats (n=6 for both groups) as indexed by a similar potency displayed by 8-hydroxy-(2-di-n-propylamino)tetralin in reducing the spontaneous activity of dorsal raphe neurons. The results indicate that, in spite of the widespread use of serotonin transmission potentiating agents in the treatment of alcoholism, neither acute nor withdrawal from chronic ethanol administration produces drastic effects on dorsal raphe neurons. However, the inhibition of dorsal raphe neuronal activity after acute ethanol may be due to the reported ability of ethanol to increase serotonin release from terminal areas. This increased serotonin tone could, at the level of recurrent axon collaterals in the dorsal raphe nucleus, reduce the spontaneous activity of the cells. On the other hand, a similar reduction in spontaneous activity after withdrawal from ethanol correlates well with the reduction in serotonin levels observed under these conditions in microdialysis studies.

8-Hydroxy-2-(di-n-propylamino)tetralin↗