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Myocardial protection with calcium-channel blockers during ischaemia and reperfusion by PTCA.

The effects of calcium channel blockers on acute myocardial ischaemia have been evaluated over the past two decades. A number of experimental studies have demonstrated that calcium antagonists protect the myocardium when administered before or during PTCA. Intracoronary verapamil prior to the second inflation attenuates the severity of ischaemic ST-segment changes and anginal pain. Heart rate and blood pressure are not influenced by verapamil or placebo. Similarly, there are multiple clinical and biological data suggesting that intracoronary nifedipine, diltiazem or bepridil, and intracoronary or intravenous nicardipine might result in a reduced incidence of myocardial ischaemia during PTCA. The beneficial effect of these drugs can be explained by a direct cardioprotective effect or by an enhanced collateral flow and haemodynamic improvement. During early reperfusion in acute myocardial infarction (AMI) administration of calcium channel blockers or agents that inhibit calcium release from the sarcoplasmic reticulum can protect hearts from stunning and can decrease the no-reflow phenomenon. The most recent explanation relates this observation to decreased sensitivity of the myofibrils to calcium. Further clinical and experimental studies are necessary to clarify the protective role in reperfusion injury. To summarize, therefore, administration of calcium channel blockers can decrease ischaemia during elective PTCA and can reduce reperfusion injury during early PTCA in AMI.

Angioplasty, Balloon, Coronary↗

Glibenclamide antagonizes adenosine A1 receptor-mediated cardioprotection in stunned canine myocardium.

BACKGROUND: The main objective of the present study was to determine the role of adenosine in the development of myocardial stunning following multiple, brief periods of coronary artery occlusion as well as the subtype of adenosine receptor (A1 or A2) involved. A second objective was to determine if there was an interaction between the adenosine A1 receptor and the ATP-dependent K channel (KATP). METHODS AND RESULTS: The effects of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and agonist cyclopentyladenosine (CPA), the selective A2 receptor agonist CGS 21680, and the KATP channel blocker glibenclamide on myocardial stunning produced by repetitive coronary artery occlusions were studied in barbital-anesthetized dogs. Regional segment function was measured with sonomicrometry. Under control conditions, six 5-minute periods of coronary occlusion interspersed with 10-minute periods of reperfusion and ultimately followed by 2 hours of reperfusion produced regional segment dysfunction. Pretreatment with intravenous infusion of CPA (2.0 micrograms.kg-1.min-1) improved percent segment shortening throughout reperfusion, whereas pretreatment with DPCPX (1.0 mg/kg i.v. bolus) significantly worsened the recovery of postischemic contractile function. In contrast, neither DPCPX nor CPA had any effect on the recovery of contractile function when administered before the second coronary occlusion. Furthermore, pretreatment with CGS 21680 (0.2 micrograms.kg-1.min-1) did not affect the recovery of percent segment shortening. In addition, pretreatment with a low dose of glibenclamide (0.1 mg/kg) had no effect on percent segment shortening by itself but completely abolished the beneficial effect of CPA. Importantly, the effects of the various agents on percent segment shortening were independent of difference in systemic hemodynamics, collateral blood flow, or ischemic bed size. CONCLUSIONS: These results suggest that stimulation of myocardial adenosine A1 receptors, particularly when induced by the initial coronary artery occlusion, is cardioprotective during repetitive, brief periods of coronary artery occlusion and that these beneficial actions may be partially mediated via a glibenclamide-sensitive mechanism, possibly opening of myocardial KATP channels.

Adenosine↗

Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord.

In the developing nervous system, patterned spontaneous activity affects a variety of developmental processes. Thus, it is important to identify the earliest time that such activity occurs and to characterize the underlying circuitry. In isolated mouse spinal cord-limb preparations, highly rhythmic spontaneous activity occurred as early as embryonic day 11 (E11)-E12, when many lumbosacral motoneurons were still migrating and extending their peripheral projections. This activity required both electrical and chemical transmission, and acetylcholine, rather than glutamate, provided the main excitatory drive. Our data are consistent with motoneurons themselves playing a critical role in generating such activity by making excitatory connections on each other and on GABAergic interneurons via dihydro-beta-erythroidine hydrobromide (DHbetaE)-insensitive nicotinic receptors. This resulted in the generation of local bursts. Consistent with these observations, E12-E12.5 mouse motoneurons retrogradely labeled by HRP were observed to have extensive axon collaterals that projected locally within the lateral motor column and to interneuron-containing regions dorsal and medial of the lateral motor column. Cholinergic axons, presumably from motoneurons, were also observed in the ventral and lateral funiculi. However, for local bursts to propagate throughout the cord, a second DHbetaE-sensitive cholinergic pathway that also involved glycinergic interneurons was required. This circuit characterization should facilitate the use of genetic mutations that alter specific subpopulations of interneurons or cholinergic transmission to determine how modifying different aspects of this early activity affects subsequent development of the spinal motor circuit.

Acetylcholine↗

Termination of afferent axons in macaque striate cortex.

We used horseradish peroxidase (HRP) to orthogradely label afferent axons in macaque striate cortex. Of the 38 axons that we recovered, nine were recorded intracellularly before being filled with HRP. Light microscope and computer reconstructions of filled processes reveal highly stereotyped patterns of arborization and suggest that there are at least five discrete populations of lateral geniculate nucleus (LGN) afferent axon: (1) those to layer 4C beta, which have extremely circumscribed, dense terminal fields (small branches of which occasionally intrude into 4C alpha) but which have not been shown to project to other laminae; (2) afferents to layer 4A, which in some cases send fine ascending collaterals into layer 2-3 and which do not, apparently, send collaterals to other laminae; (3) afferents to layer 1, which are fine, extend over large distances horizontally, and send collaterals to layer 6A; (4) afferents to the lower two-thirds of layer 4C alpha, which have few or no collaterals in layer 6; and (5) afferents to the upper half of layer 4C alpha, which have arborizing collaterals in layer 6B. Of the nine axons that were recorded intracellularly, those with projections to layer 4C beta (two axons) and to layer 1 (one axon) had color-selective properties, whereas those (six axons) which arborized in 4C alpha all had transient, broad band and highly contrast-sensitive receptive fields. These properties are consistent with derivations from somata in the parvocellular and magnocellular divisions of the LGN, respectively. Afferents to 4C alpha were found to cover approximately 6 times as much surface area as afferents to 4C beta. The preterminal trunks of all axons were found to follow tortuous paths through the neuropil--paths that may derive from axon segregation during development. The wide ranging, patchy distributions of single afferents in 4C alpha suggest that individual 4C alpha axons supply more than one ocular dominance stripe. In one case where the terminal arborization of a 4C alpha axon was mapped against the transneuronally determined pattern of ocular dominance, three separate patches of terminal boutons were indeed found to coincide with the bands of one eye.

Afferent Pathways↗

Sonographic signs in portal hypertension: a multivariate analysis.

A prospective case controlled study was conducted to evaluate the value of real time ultrasound in establishing the diagnosis and the etiology of portal hypertension. Patients attending the outpatient department of a tertiary care centre were included. There were 324 consecutive patients with portal hypertension due to cirrhosis (n = 229), non cirrhotic portal fibrosis (NCPF: n = 64) and extrahepatic portal venous obstruction (EHPVO: n = 31). During this period, 146 patients with dyspepsia, 35 with splenomegaly and 32 with ascites due to varied causes served as negative and positive controls. Real time ultrasonography using a 3.5 MHz linear array scanner was performed in a fasting state in all subjects. Portal and splenic vein diameter greater than 10 mm, splenomegaly, hepatic and splenic hilar collaterals were suggestive of portal hypertension. Non visualization of the portal vein which was replaced by a cavernoma had a diagnostic accuracy of 98% in EHPVO. Splenic infarcts and absence of ascites were features of non cirrhotic portal hypertension (NCPF and EHPVO). Sonography had an overall diagnostic accuracy of 80%. A stepwise logistic regression with multivariate analysis using discriminate function showed that collaterals at the hepatic and splenic hilum, hepatomegaly, ascites and splenic infarcts were independent markers to differentiate cirrhotic from noncirrhotic causes of portal hypertension. The discriminate equation generated had a mismatch of 9.8%. Correlations between the sonographic signs demonstrated that the variceal grade correlated positively with the presence of splenic hilar collaterals and the liver size inversely correlated with presence of ascites. It was concluded that real time ultrasonography is an accurate method to establish the presence and etiology of portal hypertension.

Adult↗

The influence of collateral flow on the antegrade and retrograde distribution of cardioplegia in patients with an occluded right coronary artery.

BACKGROUND: The predictive value of electrocardiography (ECG) and coronary angiography for cardioplegia distribution in patients with an occluded right coronary artery was evaluated. METHODS: Coronary angiograms and ECGs were evaluated in 15 patients with right coronary artery occlusion. Prediction of antegrade cardioplegia distribution was based on ECG evidence of infarction and coronary collateral flow determined from the angiogram. Antegrade and retrograde delivery of cardioplegia was directly assessed in all patients by myocardial contrast echocardiography. Intraoperative transesophageal echocardiographic images of the right ventricular free wall, the apex, and the intraventricular septum were recorded while 4 ml of Albunex (Mallinckrodt Medical, St. Louis, MO) was injected into antegrade and retrograde cardioplegic catheters during cardioplegia delivery. The observed (myocardial contrast echocardiography) cardioplegia distribution was compared to the predicted cardioplegia distribution. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated. RESULTS: Eighty seven of 90 (97%) segments were analyzed. Angiography and ECG poorly predicted incomplete cardioplegia distribution. Electrocardiography was a better predictor of inadequate cardioplegia distribution to the right ventricle than was angiography. The negative predicted values of cardioplegia distribution ranged from 20 to 50% for the septum and right ventricle, respectively, with ECG criteria and from 0 to 33% for the septum and apex, respectively, with angiographic criteria. Antegrade cardioplegia delivery was distributed to the right ventricle in 31% of patients, despite 100% occlusion of the right coronary artery; whereas retrograde cardioplegia delivery to the right ventricle occurred 20% of the time. CONCLUSIONS: In the presence of 100% right coronary artery occlusion, retrograde cardioplegia delivery is not often observed and antegrade delivery of cardioplegia to the right ventricle is not easily predicted. The preoperative angiography and ECG are not predictive of coronary collateral circulation and therefore not predictive of cardioplegia distribution to the right ventricle.

Arterial Occlusive Diseases↗

Influence of paraesophageal venous collaterals on efficacy of endoscopic sclerotherapy for esophageal varices.

To determine the diagnostic accuracy of computer tomography in the detection of venous collaterals surrounding the esophagus in patients with portal hypertension, preoperative computer tomography interpretations of these veins in 15 patients who were candidates for the Sugiura procedure for treatment of esophageal varices were correlated with those of the intraoperative assessment. Laparotomy revealed severe paraesophageal varices in five patients; four of them were found to have paraesophageal varices in computer tomography films. The sensitivity and specificity of computer tomography in diagnosing severe paraesophageal varices were 80% and 100%, respectively. A second assessment was performed in 59 additional patients with esophageal variceal hemorrhage to investigate the influence of paraesophageal varices on the efficacy of endoscopic sclerotherapy in the treatment of varices. The patients were divided into two groups: Group A included 17 patients with and group B 42 patients without paraesophageal varices on presclerotherapy computer tomography. All patients underwent elective sclerotherapy after being deemed hemodynamically stable. Patients in group A required more treatment sessions, more sclerosant and longer periods to obliterate varices completely than did group B patients. Eight patients in group A and six in group B (57% vs. 16%, p < 0.05) had variceal recurrence after obliteration during mean follow-ups of 20.8 and 19.9 mo, respectively. The mean time elapsed before variceal reappearance was shorter for group A than for group B (4.1 +/- 3.3 vs. 11.8 +/- 2.7 mo, p < 0.05). Among patients who developed new varices, five patients in group A and one in group B experienced repeat bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Collateral Circulation↗

[Demonstration of reversible myocardial ischemia in necrotic akinetic areas using endocoronary ECG during angioplasty].

The presence of ischaemic myocardial tissues in necrotic territories and the usefulness of revascularizing these territories are controversial matters. We have determined the existence of this phenomenon by the per-angioplastic intracoronary ECG method, and we have compared the sensitivities of intracoronary ECG and surface ECG. Intracoronary EVG is achieved by using the mobile teflon-coated guide wire of coronary angioplasty as a unipolar epicardial electrode. Being epicardial and localized, the electrode explores a limited area of the myocardium, distal to the artery being dilated and momentarily occluded by the balloon during inflations. The study involved 12 patients (mean age 53.7 years) who presented with the following criteria of admission: transmural myocardial infarction, presence of a Q wave on two leads, akinetic segment at ventriculography and coronary stenosis or occlusion amenable to angioplasty. Patients with collateral circulation between the larger epicardial vessels were excluded. Intracoronary ECG recordings were taken before, during and after inflations. In 9 out of 12 patients the ST segments was elevated by 1.3 mV on average between inflations (S.D. 3.14 mV) and by 4.8 mV (S.D. 3.99 mV) during inflations. These high standard deviations were due to major inter- and intra-individual variations of ST. The difference was significant (p less than 0.05) at variance analysis. No variation of ST was observed in 3 patients. Only one of the 12 patients had elevated ST on both surface ECG and intracoronary ECG tracings. Thus, intracoronary ECG is a sensitive method to evaluate myocardial ischaemia during coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Projections of the tectospinal tract to the upper cervical spinal cord of the cat: a study with the anterograde tracer PHA-L.

The goal of the present experiments was to re-examine the spinal projections of neurons in the superior colliculus (SC) of the cat by taking advantage of the high sensitivity of the anterograde tracer, phaseolus vulgaris leucoagglutinin (PHA-L). In seven experiments, multiple injections of PHA-L into different regions of the SC labelled a total of 172 axons in the predorsal bundle; yet only 11 tectospinal tract (TST) axons were found in the upper cervical spinal cord. Collaterals emerging from these axons were rare and arose exclusively from TST axons with a diameter of less than 1 micron. Individual collaterals had different termination zones: some terminated in the lateral part of lamina V and VI after taking a dorsolateral course through lamina VII and VIII; others terminated in the medial part of lamina VII. One collateral terminated within lamina IX and the ventral part of lamina VIII. The combined termination of all collaterals was densest in lamina VII and dorsal lamina VIII. A small number of boutons were also found in the lateral parts of laminae V and VI, and in lamina IX and immediately adjacent regions in lamina VIII. Compared to axons belonging to other spinal descending systems, individual TST axons give rise to much simpler intraspinal collaterals with relatively few boutons. This feature, together with the relative paucity of TST axons, suggests that direct connections from the SC to neurons in the upper cervical spinal cord are sparse. Furthermore, our results are consistent with electrophysiological studies that show that few, if any, neck motoneurons receive monosynaptic connections from TST neurons. Projections to neck motoneurons must therefore involve a relay, either through other descending pathways, such as the reticulospinal system, or via local segmental interneurons.

Animals↗

Responses of Renshaw cells coupled with hindlimb extensor motoneurons to sinusoidal stimulation of labyrinth receptors in the decerebrate cat.

Contraction of ipsilateral limb extensors during side-down roll tilt of the head, leading to selective stimulation of labyrinth receptors, is attributed to an increased discharge of excitatory vestibulospinal (VS) neurons (alpha-responses) and a decreased discharge of medullary inhibitory reticulospinal (RS) neurons (beta-responses), both of which act on ipsilateral extensor motoneurons. Experiments were performed in decerebrate cats, with the de-efferented gastrocnemius-soleus (GS) muscle fixed at a constant length, to find out whether Renshaw (R) cells linked with GS motoneurons responded to labyrinth stimulation elicited by head rotation, while the neck had been bilaterally deafferented. We hoped in this way to clarify the role and the mechanism by which these inhibitory interneurons act on limb extensor motoneurons during the vestibular reflexes. 72.7% of the R-cells, disynaptically excited by group I volleys elicited by single shock stimulation of the GS nerve, weakly responded to head rotation at frequencies of 0.026-0.15 Hz and at a peak amplitude of 10 degrees. For the frequency of head rotation of 0.026 Hz, +/- 10 degrees C, most of the GS R-cells increased their firing rate during side-down head displacement (alpha-responses); some responses were related to head position, but others showed some phase lead or lag with respect to head position. The gain of the first harmonic of these unit responses was very low and corresponded on the average to 0.084 +/- 0.062, S.D. imp./s/deg, while the sensitivity corresponded to 2.14 +/- 2.35, S.D.%/deg (base frequency, 6.85 +/- 5.97, S.D. imp./s). These responses were attributed to the activity of VS neurons, the increased discharge of which during side-down head rotation exerts a weak excitatory influence on a limited number of GS motoneurons and, through their recurrent collaterals, on the related R-cells. The modulation of the firing rate of R-cells coupled with the GS motoneurons increased linearly by increasing the peak amplitude of displacement from 5 degrees to 20 degrees at the frequency of 0.026 Hz, so that the response gain remained almost unchanged. An increase in frequency of head rotation from 0.026 to 0.32 Hz at a fixed amplitude of 10 degrees, thus changing the maximal angular acceleration from 0.26 degrees/s2 to 41.7 degrees/s2, reversed the response pattern of R-cells reported above. The resulting beta-responses, which also showed some phase lead or lag with respect to head position, were attributed to vestibular activation of RS neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Color-coded Doppler evaluation of cholecystic varices in portal hypertension.

A 11-year-old white girl presented with a diagnosis of thrombosis of the portal vein after newborn septicemia. Duplex sonography revealed significant narrowing of the portal vein and its right and left branches. A Doppler signal could only be obtained in certain short segments of the portal vein and indicated hepatopetal flow. Color-coded Doppler sonography showed extensive varicose veins in the gallbladder with a bigger draining vessel running to the porta hepatis. Documentation of varices like those in the gallbladder wall confirms the diagnosis of portal hypertension and may increase the sensitivity of Doppler sonography. Color mapping has the potential to detect unexpected flow and to analyze blood flow to better advantage.

Child↗

Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan.

Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action. Topotecan (TPT), a hydrophilic derivative of camptothecin, is currently undergoing phase II clinical trials in small-cell lung cancer (SCLC). Human SCLC OC-NYH cells were made more than 6-fold resistant to topotecan by stepwise drug exposure and resistance was stable for 70 passages without drug. NYH/TPT cells had half the topoisomerase I level and activity of wild-type cells. However, no difference in camptothecin or topotecan inhibition of topoisomerase I-mediated DNA relaxation was found, indicating that the enzyme itself was unchanged in the resistant cell. In NYH/TPT cells, topoisomerase II alpha and beta levels were increased approximately 2-fold. Accordingly, the topoisomerase II-directed drug etoposide (VP-16) induced an increased number of DNA single-strand breaks in NYH/TPT cells. However, sensitivity to different topoisomerase II-targeting agents in NYH/TPT cells varied from increased to decreased, indicating a role for as yet unidentified factors acting on the pathway to cell death after topoisomerase II-induced DNA damage has occurred. Of 20 anti-cancer agents tested, only hydroxyurea showed marked collateral hypersensitivity in NYH/TPT cells.

Antigens, Neoplasm↗

Quantitative contrast echocardiographic assessment of collateral derived myocardial perfusion during elective coronary angioplasty.

OBJECTIVE: To determine whether myocardial contrast echocardiography can be used to quantify collateral derived myocardial flow in humans. METHODS: In 25 patients undergoing coronary angioplasty, a collateral flow index (CFI) was determined using intracoronary wedge pressure distal to the stenosis to be dilated, with simultaneous mean aortic pressure measurements. During balloon occlusion, echo contrast was injected into both main coronary arteries simultaneously. Echocardiography of the collateral receiving myocardial area was performed. The time course of myocardial contrast enhancement in images acquired at end diastole was quantified by measuring pixel intensities (256 grey units) within a region of interest. Perfusion variables, such as background subtracted peak pixel intensity and contrast transit rate, were obtained from a fitted gamma variate curve. RESULTS: 16 patients had a left anterior descending coronary artery stenosis, four had a left circumflex coronary artery stenosis, and five had a right coronary artery stenosis. The mean (SD) CFI was 19 (12)% (range 0-47%). Mean contrast transit rate was 11 (8) seconds. In 17 patients, a significant collateral contrast effect was observed (defined as peak pixel intensity more than the mean + 2 SD of background). Peak pixel intensity was linearly related to CFI in patients with a significant contrast effect (p = 0.002, r = 0.69) as well as in all patients (p = 0.0003, r = 0.66). CONCLUSIONS: Collateral derived perfusion of myocardial areas at risk can be demonstrated using intracoronary echo contrast injections. The peak echo contrast effect is directly related to the magnitude of collateral flow.

Aged↗

Dynorphin exerts both postsynaptic and presynaptic effects in the Globus pallidus of the rat.

The opioids contained in striato-pallidal axons are thought to play a significant role in motor control. We examined post- and presynaptic effects of the kappa (kappa)-receptor agonist dynorphin A (1-13) (DYN13) on the globus pallidus (GP) neurons in rat brain slice preparations using the whole cell recording method. DYN13 hyperpolarized and decreased the input resistance of approximately one-quarter of neurons examined. All of these DYN13-sensitive neurons had medium-sized somata, large aspiny dendrites and generated repetitive firing without strong accommodation. The hyperpolarization was blocked by barium and was independent of TTX and intracellular chloride levels. The hyperpolarization was also selectively blocked by the kappa-antagonist nor-binaltorphimine dihydrochloride but not by the mu- or delta-antagonists. These data suggested that DYN13 activates barium-sensitive potassium currents in some GP neurons. Low- and high-intensity stimulation of the neostriatum (Str) evoked long- and short-latency GABAergic responses, respectively. Previous data suggested that the long- and the short-latency responses were due to activation of the striato-pallidal axons and the local collaterals of pallido-striatal axons, respectively. DYN13 diminished the amplitude of both the short- and long-latency GABAergic responses in all the neurons tested. The effects of DYN13 on GABAergic postsynaptic responses were also selectively blocked by a kappa-antagonist. To investigate whether the effects were pre- or postsynaptic, the effects of DYN13 on spontaneous inhibitory postsynaptic potentials (IPSPs) and TTX-independent miniature-inhibitory postsynaptic currents (IPSCs) were examined. DYN13 decreased the frequency, but not the amplitude, of spontaneous IPSCs and calcium-dependent miniature-IPSCs. However, DYN13 did not alter the cadmium-insensitive miniature-IPSCs. These results suggested that DYN13 suppressed GABA release from presynaptic terminals. This possibility was tested using a paired-stimulation test. DYN13 reduced the probability of evoking IPSCs to the first stimulation and greatly increased the success probability to the second stimulus. The amplitude of successfully evoked IPSCs was not changed with DYN13. DYN13 did not affect the excitatory postsynaptic potentials (EPSPs) or the response to iontophoretically applied GABA and glutamate. Together, these results suggest that DYN released from striato-pallidal axons controls the activity of GP neurons 1) by directly hyperpolarizing a population of neurons and 2) by presynaptically inhibiting GABA release from striato-pallidal and intrapallidal terminals.

Animals↗

The medial crosssover toe: a cadaveric dissection.

UNLABELLED: The development of a medial crossover second toe (second toe crossing over the first toe) is not a rare clinical condition. It often occurs in the setting of hallux valgus, although not exclusively so. The resulting displacement of the second toe can cause pain in shoes, with surgical correction being problematic. The pathologic anatomy of this condition has not been fully described. In an effort to better understand it, dissection of a cadaveric specimen with a full crossover toe is presented. The dissection revealed findings not previously documented. They include medial displacement of the flexor tendons and plantar plate along with deformity of the plate itself. These changes are in addition to contracture of the medial collateral ligaments and the previously described rupture of the lateral collateral ligaments. Both the plantar plate and the collateral ligaments, the two major static soft tissue stabilizers of the lesser MP joint, were found to be significantly involved. Pull on the flexor tendons only accentuated the malalignment of the toe. CLINICAL SIGNIFICANCE: The extensive soft tissue changes explain the difficulty in achieving a successful long term correction of a full medial crossover toe with a soft tissue procedure. With attenuation of the plantar plate and medial displacement of the flexor tendons, there is an imbalance of muscle forces across the MP joint. This muscle imbalance would not be corrected by release of the medial collateral ligament, dorsal capsular release or extensor tendon lengthening. Reconstruction of the collateral ligament is at risk for incomplete correction since it is unlikely to resolve deformity in the plate if already present.

Cadaver↗

Cortical blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage: three-dimensional N-isopropyl-p-[(123)I]iodoamphetamine single photon emission CT findings.

BACKGROUND AND PURPOSE: The relationship between regional cerebral blood flow (rCBF) during cerebral vasospasm after subarachnoid hemorrhage (SAH) and angiographic vasospasm and the value of rCBF in predicting vasospasm and the prognosis are not fully delineated. Our aim was to investigate the changes in extent of vasospasm-induced decreased cortical rCBF on three-dimensional (3D) displays of single photon emission CT (SPECT) findings. The clinical usefulness of these assessments was analyzed. METHODS: In 58 cases of SAH, SPECT and digital subtraction angiography were performed on the same day, 5-9 days after SAH or within 24 hours after the onset of delayed ischemic neurologic deficit (DIND). Cerebral blood flow data were assessed by measuring the area of decreased cortical rCBF on 3D SPECT images. RESULTS: The area of decreased cortical rCBF on the 3D images was significantly increased in cases with DIND (P <.001), in cases with a large infarction due to vasospasm (P =.006), and in cases with a poor prognosis after vasospasm (P =.045). These increases were also related to the type of angiographic vasospasm; the greatest decrease in cortical rCBF occurred in the combined type (combination of the peripheral and proximal types) of vasospasm, followed by cases with the peripheral type, proximal type, and no angiographic vasospasm. In cases with DIND, patchy decreased cortical rCBF areas were seen before the onset of DIND. CONCLUSION: Combined-type vasospasm leads to reductions in CBF greater than those due to isolated peripheral or proximal vasospasm. Two-dimensional and mean-hemispheric CBF analyses are less sensitive for this change than is 3D SPECT.

Adult↗

Effects of polyamines on synaptic transmission, with special attention to the glutamatergic system.

Effects of synthetic philanthotoxin-4.3.3 (PTX-4.3.3) and of its eleven structural analogues on glutamatergic transmission in the insect muscle, nicotinic transmission in the insect CNS and glutamatergic transmission in the mammalian CNS, are described. Compared with the insect muscle, the insect CNS is about 100 times less sensitive for most of these toxins and the mammalian CNS about 1000 times less reactive. In general, the relative activities of the analogues are comparable except for one toxin: dideaza-PTX-12, which is hardly active in insects and is the most active blocker of synaptic transmission from the Schaffer collaterals to pyramidal cells in the rat hippocampal slices. Dideaza-PTX-12 is also the most active inhibitor of glutamate uptake. It is concluded that the latter compound may be a prototype of a new class of neuroactive drugs affecting the glutamatergic transmission in the mammalian CNS.

Animals↗

Recordings from slices indicate that octopus cells of the cochlear nucleus detect coincident firing of auditory nerve fibers with temporal precision.

Acoustic information in auditory nerve discharges is integrated in the cochlear nuclei, and ascends through several parallel pathways to higher centers. Octopus cells of the posteroventral cochlear nucleus form a pathway known to carry information in the timing of action potentials. Octopus cells have dendrites oriented to receive converging input from many auditory nerve fibers. In all 34 intracellular recordings from anatomically identified octopus cells in slices, shocks to the auditory nerve evoked brief, consistent, graded EPSPs. EPSPs were about 1 msec in duration. At all but the lowest shock strengths, the delays between shocks and the peaks of resultant EPSPs had SDs of 0.02 msec. Polysynaptic excitation, perhaps arising from the axon collaterals of octopus cells, was observed. No detectable glycinergic or GABAergic inhibition was evoked with shocks. The input resistances were low, around 10 M omega, voltage changes were rapid, with time constants of about 1 msec, and action potentials were small. The low input resistance resulted in part from a Cs(+)-sensitive conductance. In the presence of 10 or 15 mM extracellular Cs+ the time constants increased 20-fold in the hyperpolarizing voltage range. As several subthreshold inputs were required to produce suprathreshold responses, octopus cells detect the coincident firing of auditory nerve fibers. Under physiological conditions the low input resistance and resulting short time constant limit the time over which temporal summation of excitation from auditory nerve fibers can occur and thus provide temporal precision to electrical signaling.

Action Potentials↗