Effects of the anticholinesterase edrophonium on spectral analysis of heart rate and blood pressure variability in humans.

Edrophonium, an anticholinesterase, exerts a biphasic effect on cardiovascular autonomic drive in humans (lower doses enhance; higher doses reduce). Twenty-five anesthetized, mechanically respired (10 breaths. min(-1), constant tidal volume) patients were given either saline (n = 10) or edrophonium (0.01-1.0 mg. kg(-1), n = 15) following surgery. ECG, radial arterial pressure, and respiratory rate were sampled at 250 Hz to obtain time series for consecutive R-R intervals (RRIs), and systolic (SBP) and diastolic blood pressure (DBP). A Wigner distribution was used for time frequency mapping of spectral powers at high (HFP, 0.15-0.5 Hz) and low (LFP, 0.0-0.05 Hz) frequency. Edrophonium produced a dose-dependent decrease in heart rate [baseline 66.8 +/- 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 +/- 1.4 beats per minute with 1.0 mg. kg(-1), P < 0.01]. HFP of the RRI increased at low doses (0.2-0.4 mg. kg(-1); maximum increase to 111.0 +/- 58.2% baseline; P < 0.01) but decreased (-49.5 +/- 35.5% baseline; P < 0.01) at higher (1.0 mg. kg(-1)) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to -26.2 +/- 7.5% baseline, P < 0.01, 1.0 mg. kg(-1)). LFP of SBP was also decreased (-46.3 +/- 10.9% baseline, P < 0.01, 1.0 mg. kg(-1)). Edrophonium may enhance (lower dose) or reduce (higher dose) cardiovascular autonomic drive in humans, as evidenced by the significant changes it evokes in HFP of the RRI (parasympathetic drive), and in the HFP and LFP of SBP (sympathetic drive). These observations may account for the modest autonomic side effects of edrophonium when this drug is used clinically.     

Distribution of GABAergic synaptic terminals on the dendrites of locust spiking local interneurones

Double-labelling and electron microscopy were used to assess the distribution of GABAergic synapses made onto the neurites of spiking local interneurones in the locust. The aims were to determine the sites of inputs mediating inhibition of the spiking local interneurones and to ascertain the relative abundance of such inputs. This information should allow us to understand better the integrative properties of these spiking local interneurones and the role of inhibition in shaping their receptive field properties or in fine tuning their spike-mediated outputs. Spiking interneurones in a midline population were labelled by intracellular injection of horseradish peroxidase after physiological characterisation. Colloidal gold immunocytochemistry was then used on ultrathin sections of these neurones with a polyclonal antibody raised against GABA. Most GABAergic (inhibitory) input synapses onto the interneurones are made on their ventral neurites, which also receive afferent (excitatory) inputs. These inhibitory inputs to the ventral neurites constitute 43% of the identifiable synapses. Relatively few GABAergic inputs were found onto the dorsal neurites, which are predominantly the sites of output synapses from these interneurones. These results suggest that much synaptic integration takes place in the ventral field of branches and that GABA-mediated presynaptic inhibitory control of spike-mediated outputs from the dorsal neurites is unlikely to occur. © 1993 Wiley-Liss, Inc.     

N-methyl-D,L-aspartate elicits hypothalamic gonadotropin-releasing hormone release in prepubertal male rhesus monkeys (Macaca mulatta)

In higher primates, the protracted delay from infancy to puberty results from an interruption in hypothalamic GnRH release. To determine whether the quiescent hypothalamic GnRH neurons of the prepubertal macaque are capable of discharging the decapeptide in response to a generalized neural depolarization, an excitatory amino acid analog, N-methyl-D,L-aspartate (NMA), was administered systemically to orchidectomized rhesus monkeys between 13 and 20 months of age. GnRH secretion was estimated indirectly by monitoring changes in circulating LH concentrations after the responsivity of pituitary gonadotropes to GnRH had been greatly facilitated by the chronic intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every hour). The iv bolus administration of increasing doses of NMA (1.5, 4.8, and 15.0 mg/kg BW), 10-14 h after termination of the priming infusion of GnRH, elicited distinct discharges of LH, with magnitudes directly related to the amount of the excitant injected. Administration of a higher dose of NMA (48 mg/kg BW), however, failed to induce further LH release. The finding that pretreatment with a long-acting and potent GnRH receptor antagonist [( AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10] GnRH-HOAc) abolished the LH-releasing activity of NMA provides compelling evidence for the view that the action of the neural excitant to induce gonadotropin release was exerted at a suprapituitary level. The additional observation that an N-methyl-D-aspartate receptor antagonist (D,L-2-amino-5-phosphono-valeric acid) blocked the NMA-induced release of GnRH suggests that the amino acid analog interacted with the N-methyl-D-aspartate receptor on neurons that synthesize and/or control the release of the hypothalamic hormone. Most interestingly, three sequential GnRH discharges, with a period and an amplitude apparently similar to those generated by the hypothalamus of the adult, were elicited from the brain of prepubertal monkeys by the sequential administration of three injections of NMA at hourly intervals. Taken together these findings demonstrate that the apparent dormancy of hypothalamic GnRH neurons, which is characteristic of prepubertal development in higher primates and underlies the protracted delay in the onset of puberty in these species, may be readily terminated by application of a generalized neural excitation. Plasma FSH, PRL, GH, and cortisol concentrations were also monitored during the course of some of these experiments, and release of each of these four hormones was observed after the iv injection of NMA (15 mg/kg BW).     

Brachial Plexus Nerve Block Exhibits Prolonged Duration in the Elderly

Background: Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery.

Methods: Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval.

Results: Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min]vs. 150 min [range, 105-160 min];P < 0.05) and motor (357 min [range, 270-475 min]vs. 150 min [range, 90-210 min];P < 0.05) blockade. Duration of complete sensory block was significantly correlated with age ([rho] = 0.56;P < 0.05).     

The Tempofilter®: A Multicenter Study of a New Temporary Caval Filter Implantable for up to Six Weeks

multicenter study was conducted to evaluate a new temporary caval filter (TempofilterT) designed to be implanted for up to 6 weeks. A total of 66 patients with a mean age of 51.8 years were enrolled in the study. All had documented high risk of pulmonary embolism: severe deep venous thrombosis in 89.5% of cases and previous symptomatic pulmonary embolism in 65% of cases. Filter placement was performed in association with a surgical or obstetrical procedure in 68.5% of cases. The indication for filter placement was contraindication to or failure of anticoagulant therapy in 85% of the cases. The mean duration of implantation was 29.9 days. Pulmonary embolism was not observed during the implantation period. Partial thrombosis of the filter was observed in 15% of cases due to trapping of clots by the filter. Thrombosis did not hinder filter removal when attempted. Filter-related complications were minor. Filter migration occurred in only 7.5% of cases. Migration never led to complications and did not hinder filter removal. In all cases migration was due to specific, preventable causes. The results of this study show that the TempofilterT is not only safe and easy to use but also effective in preventing pulmonary embolism. A significantly longer maximum implantation time is a major advantage of the TempofilterT over conventional temporary filters. We believe that this filter can be used for temporary protection against the risk of pulmonary embolism particularly in young patients and in a surgical setting. (Ann Vasc Surg 1997;11:520–528.)     

Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.     

Effects of ami-25 on liver vessels and tumors on T1-weighted turbo-field-echo images: Implications for tumor characterization

This study was devoted to tumor differentiation in liver MR T1-weighted imaging with superparamagnetic iron oxide (SPIO). Twenty-one patients with 40 liver lesions were studied at 1.5 T. Before and at least 45 minutes after SPIO administration, turbo-field-echo (TFE) T1-weighted, TFE T1 × T2*-weighted (MXT), and fat-suppressed turbo-spin-echo T2-weighted images were acquired. A quantitative analysis was performed blindly. On TFE T1-weighted images, the signal enhancement was ?33% ± 12 for the liver, ?24% ± 2 for adenomas and focal nodular hyperplasia, +60% ± 33 for the hemangiomas; metastases and cyst enhancement were not significant. After SPIO on TFE T1-weighted images, the hemangioma-to-liver signal ratio (149% ± 18) was definitely higher than the mean metastasis-to-liver signal ratio (90% ± 16). This T1-related differentiation ability lacked dramatically on TFE MXT images and, in one case, was reduced on post-SPIO TFE T1-weighted images by a long imaging delay after SPIO administration (2 hours).