Onset of vecuronium-induced neuromuscular block after a long priming interval

Purpose. We examined whether a new application of the priming principle, i.e., having the priming dose of vecuronium administered before the insertion of the epidural catheter, would hasten the onset of the neuromuscular block induced by the intubating dose of vecuronium. Methods. Forty-five adult female patients scheduled for general anesthesia combined with epidural anesthesia were studied. In group A (n = 15), the priming dose of vecuronium, 0.01 mg·kg⁻¹, was administered before insertion of the epidural catheter. The intubating dose of vecuronium, 0.09 mg·kg⁻¹, was given after the insertion of the epidural catheter. In group B (n = 15), the priming dose of vecuronium, 0.01 mg·kg⁻¹, was given 4 min before the intubating dose of vecuronium, 0.09 mg·kg⁻¹. In the control group (n = 15), no priming dose was given, and only the intubating dose of vecuronium, 0.10 mg·kg⁻¹, was administered. In all three groups, general anesthesia was induced with propofol 2.5 mg·kg⁻¹, and the trachea was intubated when T1/control value (control twitch height in response to train-of-four stimuli) was less than 0.1. Results. In group A, the priming dose was given 16 ± 3 min (mean ± SD) before the administration of the intubating dose. The times to onset of neuromuscular block in groups A and B, and the control group were: 145 ± 30, 184 ± 45, and 219 ± 23 s, respectively (P < 0.05 among the three groups). In all three groups, intubating conditions (graded on a four-point scale) were excellent (P = 0.59). Before the induction of anesthesia, symptoms of paralysis were observed in 5, 4, and 0 patients in groups A and B and the control group, respectively (P < 0.05 between group A or B vs control group). Conclusions. If the priming dose of vecuronium is given after a long priming interval (16 ± 3 min), the time to onset of the neuromuscular block caused by the intubating dose of vecuronium is markedly shorter than when the conventional priming interval of 4 min is employed. Received: March 5, 2001 / Accepted: October 4, 2001     

Patterns of X and Y optic nerve fibre terminations in the dorsal lateral geniculate nucleus of the cat

The distributions of X and Y optic nerve fibre terminals in the A and A₁ laminae of the dorsal lateral geniculate nucleus (LGNd) of the cat have been determined by a method that eliminates the Y fibres. A pressure-blocking technique was used in a sterile operation to produce anterograde degeneration in the Y fibres with minimal effect on the X fibres. Subsequently the Fink/Heimer technique was used to stain for degenerating fibres. This showed a strong peak of degeneration in the ventral regions of the laminae. Tritiated leucine was injected into one eye either of a normal cat or of one in which the optic nerve had been pressure-blocked at least one week previously. Subsequent examination of the LGNd by autoradiography showed a more uniform distribution of label in the laminae deprived of Y input (i.e. the pattern of distribution of X fibres). Subtraction of this distribution from that produced in a normal cat (i.e. X + Y input) gave the Y distribution. As in the degeneration studies, this revealed a peak of label in the most ventral part of each lamina but also showed a smaller peak in the most dorsal regions.     

高度近视合并原发性开角型青光眼的临床分析

目的 探讨高度近视合并原发性开角型青光眼（primary open-angle glaucoma,POAG)的早期诊断依据。方法 （1）将存档的21例（40只眼）高度近视合并POAG患者资料（A组）与随机抽取的21例（40只眼）中度近视合并POAG患者的资料（B组）及21例（42只眼）低度近视合并POAG患者的资料（C组）进行对照,比较初次就诊时3组患者间视野缺损,视网膜神经纤维层缺损（retinal nerve fibre layer defect,RNFLD),最高眼压值及最佳矫正视力等指标的差异;（2）观察A组患者的三维眼底照片,分析其临床特点。结果 （1）初诊时,A组患者中,重度视野缺损和RNFLD的比例明显高于B,C组,矫正视力低于B,C组;（2）高度近视患者视乳头,视网膜的特异性变化及视乳头周围病变等,直接干扰对青光眼的早期诊断;（3）散瞳检查或立体眼底拍片是提高青光眼检出率的重要手段。结论 认识高度近视本身及合并POAG时的临床特点,有利于提高临床医师对该病的警觉性及早期诊断水平。     

Physiologic-pharmacologic interpretation of the constants in the Hill equation for neuromuscular block: a hypothesis

Neuromuscular block (NMB) is simulated in pharmacodynamic models using the concentration of a muscle relaxant (MR) in the effect compartment and two constants, and IC50. No physiologic or pharmacologic interpretation is offered for either constant. We desired to explore whether the constants are properties of the muscle or the MR and to simulate NMB when the MR binds to two sites at a single receptor. Based on steady state conditions, we defined receptor occupancy using the equilibrium dissociation constants. Two concepts are introduced: threshold occupancy and occupancy at half-maximal NMB, Occ_NMB50. Threshold occupancy is defined as receptor occupancy at the motor end plate of a muscle fiber when the fiber fails to contract and Occ_NMB50 as the median threshold occupancy. NMB may be simulated as a function of either the concentration of the muscle relaxant or receptor occupancy. We suggest: (1) The distribution of threshold occupancies is an intrinsic property of a muscle and is characterized by two constants (_O and Occ_NMB50); (2) _O is numerically equal to the slope of the NMB vs. concentration curves and is independent of the equilibrium dissociation constants. IC50 is codetermined by Occ_NMB50 and by the equilibrium dissociation constants. (3) Binding of a muscle relaxant to the second binding site influences only the estimate of IC50 but not .     

Evidence against cholera toxin B subunit as a reliable tracer for sprouting of primary afferents following peripheral nerve injury

In order to investigate whether cholera toxin B subunit (CTb) is transported by unmyelinated primary afferents following nerve injury, we transected the sciatic nerves of six rats, and injected the transected nerves (and in three cases also the intact contralateral nerves) with CTb, 2 weeks later. The relationship between CTb and two neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was then examined in neurons in the ipsilateral L4 and L5 dorsal root ganglia, using immunofluorescence staining and confocal microscopy. We also immunostained sections of spinal cord and caudal medulla for CTb, NPY and VIP. Following nerve section, VIP immunoreactivity was increased in laminae I-II of the spinal cord while NPY immunoreactivity was increased in laminae III-IV of the spinal cord and in the gracile nucleus. On the contralateral side, CTb labelling was detected in laminae I and III-V of the dorsal horn of the L4 and L5 spinal segments, as well as in the gracile nucleus. CTb labelling was seen in the same areas on the lesioned side, but with a dramatic increase in lamina II. No VIP or NPY immunoreactivity was observed in L4 and L5 dorsal root ganglia on the side of the intact nerve, but on the lesioned side VIP was detected in many small neurons and NPY in numerous large neurons. In agreement with the report by Tong et al. [J. Comp. Neurol. 404 (1999) 143], we found that while CTb labelling in the dorsal root ganglion on the side of the intact nerve was mainly in large neurons, on the lesioned side CTb was present in dorsal root ganglion neurons of all sizes. The main finding of the present study was that almost all of the VIP- (96%) and NPY- (98%) positive neurons in the dorsal root ganglia on the lesioned side were also CTb-labelled. After nerve injury VIP is upregulated in fine afferents that terminate in laminae I and II, and most of these probably have unmyelinated axons. Since the cell bodies of these neurons were labelled with CTb that had been injected into the transected sciatic nerve, this suggests that many of these fine afferents, which do not normally transport CTb, are capable of doing so after injury.     

Subcellular localization of adenosine A(1) receptors in nerve terminals and synapses of the rat hippocampus

Adenosine is a neuromodulator in the CNS that mainly acts through pre- and postsynaptic A(1) receptors to inhibit the release of excitatory neurotransmitters and NMDA receptor function. This might result from a highly localized distribution of A(1) receptors in the active zone and postsynaptic density of CNS synapses that we now investigated in the rat hippocampus. The binding density of the selective A(1) receptor antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), was enriched in membranes from Percoll-purified nerve terminals (B(max)=1839+/-52 fM/mg protein) compared to total membranes from the hippocampus (B(max)=984+/-31 fM/mg protein), the same occurring with A(1) receptor immunoreactivity. [3H]DPCPX binding occurred mainly to the plasma membrane rather than to intracellular sites, since the binding of the membrane permeable A(1) receptor ligand [3H]DPCPX to intact hippocampal nerve terminals (B(max)=1901+/-192 fM/mg protein) was markedly reduced (B(max)=321+/-30 fM/mg protein) by the membrane impermeable adenosine receptor antagonist, 8-sulfophenyltheophilline (25 microM). Further subcellular fractionation of hippocampal nerve terminals revealed that A(1) receptor immunoreactivity was strategically located in the active zone of presynaptic nerve terminals, as expected to understand the efficiency of A(1) receptors to depress neurotransmitter release. A(1) Receptors were also present in nerve terminals outside the active zone in accordance with the existence of a presynaptic A(1) receptor reserve. Finally, A(1) receptor immunoreactivity was evident in the postsynaptic density together with NMDA receptor subunits 1, 2A and 2B and with N-and P/Q-type calcium channel immunoreactivity, emphasizing the importance of A(1) receptors in the control of dendritic integration.     

Effects of different kinds of acute stress on nerve growth factor content in rat brain

Nerve growth factor (NGF) has several effects on the central nervous system; on the one hand NGF fosters survival and function of cholinergic neurons of the basal forebrain, on the other hand this protein is implicated in the stress response of the hypothalamic-pituitary-adrenocortical axis (HPAA). In this study we tested the influence of threatening and painful stress treatments in three different intensities as well as forced motoric activity on NGF content in different brain areas in adult rats. We found that threatening treatment with or without painful stimuli was followed by a significant decrease of NGF concentration in the amygdala (44.5%; P=0.03) and the frontal cortex (-45.5%; P=0.02). We also observed that after stress of forced motoric activity NGF content in the frontal cortex (-32%; P=0.01) and the hippocampus (-32%; P=0.006) was significantly reduced. Thus, NGF content in distinct brain regions is decreased, following different forms of acute stress. This might be relevant for the pathophysiological understanding of psychiatric diseases, such as depression, which are associated with stress.     

Peripheral nerve ischemia: apolipoprotein E deficiency results in impaired functional recovery and reduction of associated intraneural angiogenic response

Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects, reduced and delayed response to noxious thermal stimuli, abnormal morphology of unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this study, we show that, compared to wild-type mice, peripheral nerves of apoE KO mice have impaired ability to respond to ischemia, as demonstrated by measurement of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow, measured by laser Doppler, and intraneural angiogenesis after ischemia are significantly compromised in apoE-deficient mice. Finally, upregulation of the angiogenic cytokine vascular endothelial growth factor (VEGF), which physiologically occurs after ischemia in the peripheral nerve of wild-type mice, is severely impaired in apoE KO mice. Among the several neural defects that have already been described in mice lacking apoE, this is the first demonstration that functional recovery to ischemia is impaired in the peripheral nerves of these animals. This deficit is mirrored by the inability of upregulating VEGF and mounting an appropriate intraneural angiogenic response following injury. These findings provide new evidence of possible interdependent relationships between VEGF, angiogenesis, and nerve function and regeneration and may provide new important information on the role of apoE in the nervous system.     

Total length of nerve fibers in prefrontal and global white matter of chronic schizophrenics

It has been suggested that the dysfunction of the prefrontal cortex in schizophrenics is due to dysfunctional connections between the prefrontal cortex and more posterior structures. The present study uses a recent stereological method that allows quantitation of the myelinated nerve fibers in the brain white matter. As especially the prefrontal region is of interest in schizophrenics, the prefrontal white matter was quantitated separately. The total length of nerve fibers in post-mortem brains was estimated from eight male chronic schizophrenics and nine male controls (age-range: 40–81 years). Samples were taken systematically and randomly from both the entire white matter and selectively from the prefrontal white matter. The biopsies were rotated randomly before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at about 10,000× magnification and the fiber diameter of each counted fiber was measured to get the size distribution of the fibers. The schizophrenics had a total of 129,000 km myelinated fibers in the white matter and 25,700 km in the prefrontal white matter, which was non-significantly different from a total of 137,000 km in the entire white matter and 27,600 km in the prefrontal white matter in controls. The size distribution of the fibers in schizophrenics was within normal limits compared to controls. Our results do not show a larger loss of nerve fibers in neither the white matter globally or in the prefrontal white matter of schizophrenics.     

Characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT studies without significant coronary artery diameter stenoses

BACKGROUND: Single-photon emission computed tomography (SPECT) sestamibi (MIBI) is an excellent tool for detection of coronary artery disease (CAD), preoperative risk assessment, and follow-up management after coronary revascularization. While the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%, the specificity ranges between 53-100%. HYPOTHESIS: The study was undertaken to assess characteristics of patients with abnormal stress technetium Tc99m sestamibi SPECT (MIBI) studies without significant coronary artery diameter stenoses (< 50%). METHODS: Between January 1999 and November 2000, 270 consecutive patients were referred for coronary angiography due to reversible MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59 +/- 9 years), reversible MIBI uptake defects were assessed although coronary angiography showed no significant CAD. These patients were compared with age- and gender-matched patients with perfusion abnormalities (39% women, mean age 60 +/- 9 years), due to significant CAD (coronary artery stenosis > 50%). RESULTS: There were no significant differences between the two groups regarding body mass index, left bundle-branch block (LBBB), or method of stress test (dipyridamole in patients with LBBB or physical inactivity [n = 11] and exercise in all the others [n = 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior fascicular block (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with perfusion abnormalities with no significant CAD, whereas ST-segment depression during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p = 0.02) were significantly less common than in patients with abnormal MIBI perfusion studies and angiographically significant CAD. Sestamibi uptake defects during exercise were significantly smaller in patients without significant CAD than in matched controls with significant CAD (p < 0.0004). CONCLUSION: Of 270 consecutive patients, 41 (15%) referred to coronary angiography due to reversible MIBI uptake defects showed coronary artery stenoses < 50%. Twenty-six (10%) of these presented angiographically normal coronary arteries. The significantly higher proportion of left ventricular hypertrophy and LAFB in patients with reversible MIBI uptake defects without significant CAD suggest microvascular disease, angiographically underestimated CAD, and conduction abnormalities as underlying mechanisms.