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PubMed2006

Statistical combination schemes of repeated diagnostic test data.

RATIONALE AND OBJECTIVES: When diagnostic tests are repeated and combined, a number of schemes may be adopted. Guidelines for their interpretations are required. MATERIALS AND METHODS: Three combination schemes, "and" (A), "or" (O), and "majority" (M), are considered. To evaluate these schemes, dependency by specifying kappa values quantifying repeated test agreement was structured. In a pilot study, the combined accuracies of magnetic resonance imaging using six different pulse sequences of medial collateral ligaments of the elbows of 28 cadavers, with eight having lesions artificially created surgically, were examined. Images were evaluated simultaneously by using a five-point ordinal scale. For each pulse sequence, individuals for whom the diagnosis varied from once to three repetitions were considered. RESULTS: Scheme M improves diagnostic accuracy when sensitivity and specificity of a single test exceed 0.5, with maximal improvement at 0.79. Under scheme A, sensitivity decreases to 0.38-0.59. Under scheme O, sensitivity increases to 0.53-0.79. Scheme M yields a small improvement, reaching 0.50-0.71. Under scheme A, specificity increases to 0.95-0.98. Under scheme O, specificity decreases to 0.91-0.98. Scheme M also yields a small improvement, reaching 0.94-0.98. CONCLUSION: Scheme A is recommended for ruling in diagnoses, scheme O is recommended for ruling out diagnoses, and scheme M is neutral. Consequently, different schemes may be used to optimize the target diagnostic accuracy.

Algorithms↗
PubMed1999

Organization of olfactory and multimodal afferent neurons supplying the calyx and pedunculus of the cockroach mushroom bodies.

The mushroom bodies of neopteran insects are considered to be higher olfactory centers because their calyces receive abundant collaterals of projection neurons from the antennal lobes. However, intracellular recordings of mushroom body efferent neurons demonstrate that they respond to multimodal stimuli, implying that the mushroom bodies receive a variety of sensory cues. The present account describes new features of the organization of afferent neurons supplying the calyces of the cockroach Periplaneta americana. Afferent terminals segment the calyces into discrete zones, I, II, III, and IIIA, which receive afferents from 1) two discrete populations of sexually isomorphic olfactory glomeruli, 2) two types of male-specific olfactory glomeruli, 3) the optic lobes, and 4) multimodal interneurons that originate in protocerebral neuropils. In addition, intracellular recordings and dye fills show that at least four morphologically distinct GABAergic elements link many regions of the protocerebrum to the calyces. A new type of touch-sensitive centrifugal neuron has been identified terminating in the pedunculus. The dendrites of this afferent reside in satellite neuropil, beneath the mushroom body's medial lobe, which is supplied by collaterals from medial lobe efferent neurons and by terminals from the central complex. The role of this centrifugal cell in odorant sampling is considered. Golgi impregnation identifies other afferents in proximal regions of the calyx (zone IIIA) that also originate from satellite neuropils, suggesting major reafference from the medial lobes channeled through this region. The relevance of multimodal supply to the calyx in odorant discrimination is discussed as are comparisons between mushroom body organization in this phylogenetically basal neopteran and other taxa.

Animals↗
PubMed2002

Laser targeted photo-occlusion of rat choroidal neovascularization without collateral damage.

Laser targeted photo-occlusion (LTO) is a novel method being developed to treat choroidal neovascular membranes (CNV) in age-related and other macular degenerations. A photosensitive agent, encapsulated in heat-sensitive liposomes, is administered intravenously. A low power laser warms the targeted tissue and releases a bolus of photosensitizer. The photosensitizer is activated after it clears from the normal choriocapillaris but not from the CNV. Forty-five experimental CNV were induced in seven rats. Five weeks after LTO, complete occlusion was observed by laser targeted angiography (LTA) in 76% of treated CNV, and partial occlusion was found in the remaining 24%. The tissues outside the CNV but within the area treated by LTO showed no flow alteration and no dye leakage. All untreated CNV were patent on LTA at 5 weeks. Light microscopy and electron microscopy confirmed the results in treated and control lesions. Moreover, treated areas next to lesions showed normal photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris. These results indicate that LTO may improve current photodynamic therapy by alleviating the need for repeated treatments and by avoiding the long-term risks associated with damage to the RPE and occlusion of normal choriocapillaries.

Animals↗
PubMed1982

Effects of physical training on myocardial vascularity and perfusion.

Physical training is thought to be a stimulus for coronary vascular growth and coronary collateral development. This report is a summary of knowledge in the area. Studies in experimental animals with normal hearts indicate that physical training promotes increased myocardial capillary density and also causes enlargement of the surface coronary vessels. The physiologic effect of these changes on coronary vascular reserve and protection of segments of the heart against myocardial ischemia has not been established. Physically trained dogs and pigs do not appear to be protected against the effects of coronary occlusion, in that the ischemic area appears to be as large in trained animals as in untrained animals for any given coronary lesion. One study in physically trained rats appears to show protection against myocardial infarction, but whether this is related to coronary vascular changes has not been established. Experiments in dogs subjected to chronic narrowing or gradual occlusion demonstrate that physical training in these models does promote collateral blood flow as measured by retrograde flow in open-chest experiments. Studies using the microsphere technique in closed-chest animals confirms increased collateral flow to ischemic areas in some animals, but the magnitude of the increases appears to be small and varies greatly from animal to animal. Studies in athletes suggest that myocardial blood flow is lower at any submaximal level of training in athletes than in sedentary persons. Studies in patients with coronary artery disease have generally failed to show an increase in coronary blood flow or in perfusion of ischemic areas after physical training programs, but the techniques used might not have been sensitive enough to detect changes. The evidence in the experimental animals is sufficiently promising to indicate that the search should be continued to define physical training programs that will most stimulate myocardial vascularity and coronary collaterals in humans.

Animals↗
PubMed2003

Dopaminergic modulation of axon collaterals interconnecting spiny neurons of the rat striatum.

Dopamine is a critical modulator of striatal function; its absence produces Parkinson's disease. Most cellular actions of dopamine are still unknown. This work describes the presynaptic actions of dopaminergic receptor agonists on GABAergic transmission between neostriatal projection neurons. Axon collaterals interconnect projection neurons, the main axons of which project to other basal ganglia nuclei. Most if not all of these projecting axons pass through the globus pallidus. Thus, we lesioned the intrinsic neurons of the globus pallidus and stimulated neostriatal efferent axons antidromically with a bipolar electrode located in this nucleus. This maneuver revealed a bicuculline-sensitive synaptic current while recording in spiny cells. D1 receptor agonists facilitated whereas D2 receptor agonists depressed this synaptic current. In contrast, a bicuculline-sensitive synaptic current evoked by field stimulation inside the neostriatum was not consistently modulated, in agreement with previous studies. The data are discussed in light of the most recent experimental and modeling results. The conclusion was that inhibition of spiny cells by axon collaterals of other spiny cells is quantitatively important; however, to be functionally important, this inhibition might be conditioned to the synchronized firing of spiny neurons. Finally, dopamine exerts a potentially important role regulating the extent of lateral inhibition.

Animals↗
PubMed1985

Rat brain alpha 2-pre- and postsynaptic receptors are different or differently modulated?

In order to get better characterization of alpha 2-pre- and postsynaptic noradrenergic receptors in the rat brain, we investigated the alpha 2-receptor changes which take place during a 12-day treatment with the alpha 2-antagonists yohimbine (4 mg/kg) and mianserin (10 mg/kg). These treatments caused a significant increase in the sensitivity of hypothalamic synaptosomes to the inhibitory action of the noradrenergic agonist clonidine on the 3H-noradrenaline release elicited by K depolarization. Frontal cortex alpha 2-autoreceptors were not affected by drug treatments. However, the 3H-p-aminoclonidine (3H-PAC) binding to membranes from hypothalamus or frontal cortex from treated animals was the same as in controls. Changes in neural firing, elicited by the alpha 2-antagonists on noradrenergic neurons, could explain our results. The presynaptic autoreceptors may thus become hypersensitive to counteract the enhanced neurotransmitter release in the hypothalamus, where the noradrenaline is accumulated at the synaptic cleft. In the frontal cortex, where it seems that only 5% of the noradrenergic terminals make synaptic contacts with postsynaptic elements, the alpha 2-autoreceptors are less sensitive to an enhanced neurotransmitter release. Alternatively, they have scarce functional importance because the noradrenaline release is effectively modulated by the inhibitory recurrent locus coeruleus collaterals. At the postsynaptic level, the receptor down-regulation might be prevented by chronic presence of the antagonist drug. Thus the different behavior between pre- and postysynaptic alpha 2-receptors and between alpha 2-receptors of different brain areas may be ascribed to a different modulation rather than to different molecular arrangements.

Adrenergic alpha-Agonists↗
PubMed1994

Pressure distribution in the knee joint. Influence of flexion with and without ligament dissection.

Biomechanical factors influencing the patterns of pressure distribution at the articular surface and the subchondral bone are suggested to be most important in the pathogenesis of osteoarthritis and osteochondritis dissecans at the knee joint. Besides this, chronic joint instability is another important factor under discussion in the etiology of osteoarthritis of the knee. The patterns of pressure distribution on the femoral condyles of weight-bearing knee joints were investigated in a biostatic cadaver model. The pressure on the femoral condyles was evaluated using pressure-sensitive films with the knee in different physiological joint positions (extension, 15 degrees and 30 degrees flexion) with and without division of either the medial collateral ligament (MCL), the lateral collateral ligament (LCL), the MCL and the anterior cruciate ligament (ACL), or the LCL and the ACL. Results showed that the location of the contact area and peak pressure depended on the joint position and stage of ligament division. Without ligament division the maximum peak pressure was always observed on the medial condyle. Only after MCL and combined MCL + ACL division did the lateral condyle show in extension a higher peak pressure than the medial condyle. Division of the LCL and LCL + ACL resulted in an increase in peak pressure on the medial condyle, particularly in flexion. The highest peak pressure of all was measured in the 30 degrees flexion position on the medial condyle after division of the LCL. The lowest at all was found on the lateral condyle in 15 degrees flexion after LCL division. Additional ACL division resulted in only minor further changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1992

[The value of sonographic diagnosis of the injured knee joint in trauma-surgical practice].

In a period of two years (January 1990 to December 1991) 136 knee joints were examined by ultrasound and arthroscopy. 40 out of 42 arthroscopically proven lesions of the anterior cruciate ligament were detected by ultrasound. The sensitivity therefore was 95.24%. We found three cases of ruptures of the posterior cruciate ligament, which were not detected clinically. 16 cases of ruptured medial collateral ligaments and 27 cases of elongations of the same ligament were diagnosed. Ultrasound examination of the knee and especially of the cruciate ligaments showed to be an accurate tool in order to obtain additional information on an injured knee even if clinical examination is difficult or impossible. Sonography is able to exclude lesions of the cruciate ligaments precisely. Therefore it helps to restrict the necessity of acute or early arthroscopy of knee joints.

Anterior Cruciate Ligament↗
PubMed1996

Influence of age on the clearance of K+ from the extracellular space of rat hippocampal slices.

We examined the hypotheses that aging alters the capacity of brain tissue to regulate extracellular K+ activity (K+o), and that age-related decreases in glucose metabolism may underlie these alterations. Hippocampal slices from young adult (6-9 months old), middle-aged (16-19 months old), and aged (26-29 months old) Fischer 344 rats were exposed to physiological solutions containing 5-20 mM glucose maintained at 36-37 degrees C. Schaffer collaterals in each slice were stimulated at 40 Hz for 2 s, and the resulting changes in K+o were recorded with K+o-sensitive microelectrodes placed in stratum pyramidale of hippocampal subfield CA1. We found that K+ clearance from the extracellular space of hippocampal slices was significantly slowed in the middle-aged group compared with the young adult group in physiological solutions containing 5 and 10 mM glucose. Age-related differences in K+o clearance disappeared in 20 mM glucose. Also, the rate of K+o clearance was modified by glucose concentration. These results suggest that K+ transport rates are modified by age, and that age-related alterations in glucose metabolism may be involved.

Aging↗
PubMed2004

Bypassing V1: a direct geniculate input to area MT.

Thalamic nuclei are thought to funnel sensory information to the brain's primary cortical areas, which in turn transmit signals afresh to higher cortical areas. Here we describe a direct projection in the macaque monkey from the lateral geniculate nucleus (LGN) to the motion-selective middle temporal area (MTor V5), a cortical area not previously considered 'primary'. The constituent neurons are mostly koniocellular, send virtually no collateral axons to primary visual cortex (V1) and equal about 10% of the V1 population innervating MT. This pathway could explain the persistence of motion sensitivity in subjects following injury to V1, suggesting more generally that residual perception after damage in a primary area may arise from sparse thalamic input to 'secondary' cortical areas.

Animals↗
PubMed1999

Adenosine: a sensitive indicator of cerebral ischemia during carotid endarterectomy.

BACKGROUND: For the human brain, there are no data available concerning the significance of adenosine and its metabolites as biochemical indicators of cerebral ischemia. Since adenosine may counteract key pathogenetic mechanisms during cerebral ischemia, its sensitivity and specificity as a marker of cerebral ischemia was investigated in relation to hypoxanthine and lactate. METHODS: Arterial and jugular venous concentration changes of adenosine, hypoxanthine, and lactate were studied in 41 patients undergoing carotid endarterectomy. Cerebral tissue oxygenation was monitored continuously by somatosensory-evoked potentials. A carotid artery shunt (n = 6) was placed only after complete loss of somatosensory-evoked potentials. RESULTS: Before carotid artery clamping jugular venous concentrations of adenosine, hypoxanthine, and lactate in subsequently shunted patients were 229+/-88 nM, 1105+/-116 nM, and 0.85+/-0.52 mM, respectively (mean +/- SD). In patients who required shunting, carotid artery clamping induced a significant increase in jugular venous adenosine (389+/-114 nM) and jugular venous hypoxanthine (1444+/-168 nM). In contrast, the increase in jugular venous lactate (0.91+/-0.48 mM) did not reach statistical significance. Focal cerebral ischemia was indicated by jugular venous adenosine with a sensitivity and specificity of 0.83 and 0.71, respectively. CONCLUSIONS: Carotid artery clamping induced significant increases in jugular venous adenosine and hypoxanthine in patients with inadequate collateral blood flow. In addition, focal cerebral ischemia was reflected by changes in adenosine concentrations.

Adenosine↗
PubMed1992

Validation of a telephone version of the mini-mental state examination.

OBJECTIVE: To assess the construct validity of a telephone-administered version of the Mini-Mental State Examination (MMSE). DESIGN: Validity testing by comparing a telephone version of the MMSE administered first to a face-to-face evaluation done several days later. SETTING: Outpatient geriatric assessment center. SUBJECTS: 100 of 175 consecutive referrals. MAIN OUTCOME MEASURES: MMSE and a brief neuropsychological screening test (BNPS) face-to-face and a telephone version of the MMSE as part of the Adult Lifestyles and Function Interview (ALFI-MMSE). RESULTS: Test scores of the two MMSE versions correlated strongly for all subjects (Pearson's r = 0.85, P = 0.001) and remained significant for the cognitively intact (P = 0.02) and questionably (P = 0.002), mildly (P = 0.0001), and moderately (P = 0.003) demented. Comparison of the two versions' equivalent 22 items revealed no significant difference for scores of all subjects (P = 0.07) but with a trend toward higher scores in the original version. Diminished hearing, reported either by the subject (P = 0.003) or by the collateral source (P = 0.02) was associated with lower scores on the telephone version. Five individual test items were biased by the route of test administration. Sensitivity and specificity relative to the BNPS were 67% and 100% for the ALFI-MMSE and 68% and 100% for the MMSE, respectively. CONCLUSION: The scores on the ALFI-MMSE correlated strongly with the scores of the original version given face-to-face in subjects undergoing geriatric assessment. The results indicate that the ALFI-MMSE could be a useful and economical tool to screen for cognitive impairment.

Aged↗
PubMed1984

P1 bacteriophage and tellurite sensitivity in Klebsiella pneumoniae and Escherichia coli.

Klebsiella pneumoniae and Escherichia coli respond inversely toward P1 bacteriophage or TeO3(-2). Klebsiella pneumoniae is resistant to both antagonists and E. coli is sensitive. However, P1 cmts lysogens (P1 cmts resistant) of K. pneumoniae became sensitive to tellurite and when cured from P1 cmts regained resistance. Escherichia coli spontaneous mutants selected for resistance to either P1 or TeO3(-2) were collaterally resistant to the other. As well, TeO3(-3) enhanced the adsorption of P1 vir to both E. coli and K. pneumoniae. Several outer membrane proteins were enhanced in the K. pneumoniae lysogens and were reduced in E. coli lysogens; one of which was the same molecular weight (77 000) in both bacteria. When partially purified it enhanced the plaque efficiency of P1 vir. Lipopolysaccharide (LPS) from E. coli C600 inactivated P1 vir, but neither the P1 lysogens nor LPS derived from the lysogens inactivated P1 vir. Escherichia coli P1 lysogens produced only heptose-deficient LPS. It is suggested that both LPS and outer membrane protein(s) comprise the P1 receptor. TeO3(-2) may interact with one or both components.

Adsorption↗
PubMed1987

Voltage-dependence of glycine-activated Cl- channels: a potentiometer for inhibition?

Single- and double-electrode voltage-clamp techniques have been employed in situ to analyze Mauthner cell inhibitory synaptic responses produced both by activation of the recurrent collateral network and by direct intracellular stimulation of single presynaptic interneurons. The results demonstrate that the synaptically evoked glycinergic postsynaptic currents exhibit a striking voltage sensitivity. Specifically, the time constant of the decay of the synaptic conductance is increased by depolarization and decreased by hyperpolarization. This parameter is exponentially related to membrane potential, changing e-fold for a 45 mV potential shift, regardless of the degree of intracellular chloride loading or the magnitude of the underlying synaptic conductance. In addition, the amplitude of this inhibitory conductance change is decreased by membrane hyperpolarizations of 15 mV or more. Computer modeling demonstrates that the voltage dependence of the kinetics of the synaptic response may serve to enhance the magnitude and duration of inhibitory responses appreciably in the face of increased excitation.

Animals↗
PubMed2001

Cerebrovascular reserve in patients with carotid occlusive disease assessed by stable xenon-enhanced ct cerebral blood flow and transcranial Doppler.

BACKGROUND AND PURPOSE: Cerebrovascular reserve (CVR) by both transcranial Doppler ultrasonography (TCD) and quantitative cerebral blood flow (CBF) can identify subgroups of patients at increased risk for stroke. A direct comparison of CVR measurements obtained with both technologies in patients with cerebrovascular occlusive disease is lacking. METHODS: CVRs before and after acetazolamide administration (1 g IV) were measured by TCD insonation of the middle cerebral artery (MCA) and CBF obtained with stable xenon CT (Xe/CT) in 38 patients with carotid occlusive disease. Sensitivity/specificity calculations were based on 2 Xe/CT MCA values: an average over 4 levels and the level with the lowest percent change in CBF. Compromised CVR was defined as no reactivity or a decrease in reactivity. RESULTS: Using the analysis of the systolic TCD, we found that velocity changes compared with the average Xe/CT MCA CVR showed a sensitivity of 33%, specificity of 90.6%, positive predictive value of 54.5%, and negative predictive value of 80%. The sensitivity of TCD compared with the lowest Xe/CT CBF CVR was 35.5%, specificity and positive predictive values were 100%, and negative predictive value was 66.7%. The index of validity was between 72% and 76%. CONCLUSIONS: TCD is much less sensitive than Xe/CT CBF in identifying patients with compromised CVR. This may be a result of the inability of TCD to identify patients with compromised reserves when their MCA blood flow comes from collateral sources. The lack of correlation between TCD and Xe/CT CBF for identifying patients with compromised CVR should be considered when stroke risk assessments are made by TCD.

Acetazolamide↗
PubMed1998

[Diagnosis of myocardial vitality using contrast echocardiography--ready for routine clinical use?].

The most benefit from the evaluation of myocardial viability in coronary artery disease is expected in patients with reduced left ventricular function. There is increasing evidence that the outcome of this patient group is better after revascularization if viable myocardium was present before as compared to patients without pre-reperfusion myocardial viability. Therefore, diagnostic tools for the detection of viable myocardium are of enormous therapeutic and economic relevance. The contrast echocardiographic demonstration of myocardial microvascular integrity has been demonstrated to be a corollary of myocellular viability in the experimental and clinical setting. In animal models of reperfusion in acute myocardial infarction, it could be demonstrated that myocardial echocontrast defects, however, only accurately estimate the extent of microvascular damage and the amount of viable tissue after reactive hyperemia has abated. In patients, immediately after reperfusion of the infarct-related artery in acute myocardial infarction, myocardial areas of no reflow could be detected using contrast echocardiography. It has been shown that these myocardial segments exhibit significantly reduced recovery of regional contractile function weeks after reperfusion. In contrast, regions with myocardial microvascular integrity as defined by contrast echocardiography recover function to a significantly higher degree. Furthermore, in patients with remote myocardial infarction, myocardial opacification by contrast echocardiography indicates myocardial collateral perfusion with preserved tissue viability and a high probability of functional recovery after reperfusion. In patients with chronic coronary artery disease and reduced left ventricular ejection fraction, functional recovery could be predicted by myocardial contrast echocardiography with a very high sensitivity in several studies. The lower specificity of the technique may be due to the fact that recovery of contractile function after reperfusion may not be expected in all segments at rest (which was used as the gold standard for viability evaluation in these studies) but rather during physical or pharmacological stress. Therefore, post-reperfusion demonstration of contractile reserve might be a more adequate criterion for the assessment of diagnostic accuracy of myocardial contrast echocardiography for pre-reperfusion viability detection. So far, for the evaluation of myocardial viability, myocardial contrast echocardiography has been exclusively performed using intracoronary injection of echo contrast media; based on the evidence from various studies, this technique is ready for routine clinical application; the place of venous myocardial contrast echocardiography for this purpose, which is an extremely promising technique, however, remains to be defined.

Collateral Circulation↗
PubMed1995

Identification of collaterally perfused areas following focal cerebral ischemia in the rat by comparison of gradient echo and diffusion-weighted MRI.

Diffusion-weighted (DW) and gradient echo (GE) magnetic resonance images were acquired before and after occlusion of the middle cerebral artery (MCA) in the rat. Upon occlusion, an increase in DW imaging signal intensity was observed in a core area within the MCA territory, most likely reflecting cytotoxic edema. The signal from GE images, which is sensitive to changes in the absolute amount of deoxyhemoglobin, decreased following ischemia within a region that extended beyond the core area observed with DW imaging. This hypointensity is attributed to increases in blood volume and/or oxygen extraction fraction, which result from a decrease in perfusion pressure in the collaterally perfused area. The evolution of the GE imaging signal intensity from different regions was studied for 3.5 h following the occlusion. In the core area, the GE imaging signal returned towards baseline values after approximately 1-2 h, while it remained stable in the surrounding area. This feature may reflect a decrease in hematocrit due to microcirculatory defect and/or a decrease in the oxygen extraction fraction due to ongoing infarction of the tissue and may indicate that tissue recovery is severely compromised. The combined use of DW and GE imaging offers great promise for the noninvasive identification of specific pathological events with high spatial resolution.

Animals↗