Nerve conduction in children suffering Insulin Dependent Diabetes Mellitus

Objective: To determine the incidence of peripheral neuropathy in children suffering Insulin Dependent Diabetes Mellitus (IDDM) as well as to determine the relationship between other criteria of the disease and neuropathy.Methods : 40 children (17 males, mean age 11.9 years) suffering IDDM and receiving insulin therapy involving two injections a day and 30 healthy children (17 males, mean age 11.7 years) were included in the study. They were inquired about their demographical characteristics as well as the presence of neurological symptoms. Their detailed neurological examinations were conducted. Their glycemic control values (Hb A¹C) were recorded, and their nerve conduction studies were performed from right upper and lower extremities.Results : All nerve conduction values of children with IDDM were found to be significantly lower (p <0.0001) as compared to the control group. 60% of diabetic children (n=24) were found to suffer peripheral neuropathy. Statistically significant relationships were found between the glycemic control values and the peroneal, sural, tibial, ulnar and median nerve conduction velocities, and also between the duration of disease and the peroneal, sural, tibial and median nerve conduction velocities.Conclusion : The peripheral neuropathy is rather a frequently observed complication in diabetic children. The duration of disease and impaired glycemic control play an important role in the development of neuropathy. The introduction of new methods designed to ensure better glycemic control will reduce the incidence of the complication.     

Best practices in surgical abortion

Surgical abortion in the first trimester comprises the majority of voluntary pregnancy interruptions performed in the United States. The majority of these procedures are done in outpatient settings with the patient under local anesthesia. Appropriate volume of and deep injection of local anesthetic can reduce pain associated with the procedure. Waiting between administration of the paracervical block and initiating the procedure does not affect pain. Intravenous administration of sedation and analgesia improves patient satisfaction but does not significantly affect pain ratings. Antibiotic prophylaxis is warranted. Vasopressin is useful for prevention of hematometra and hemorrhage. Less evidence supports the routine use of ergots. Preoperative cervical priming reduces the risk of cervical injury and uterine perforation. Attention to operative technique can reduce the risk of incomplete abortion. Routine postoperative care at 2 or 3 weeks is timed to identify complications and to reinforce pregnancy and sexually transmitted disease prevention.     

Congenital heart block in neonatal lupus: the pediatric cardiologist's perspective

Clinical presentation. Congenital heart block (CHB) in the absence of major structural abnormalities is associated with maternal antibodies to Ro (SS-A) and La (SS-B). CHB is most commonly diagnosed between 18 and 24 wk of gestation, and may be first, second or third degree (complete). Mortality approaches ∼20%, and most surviving children require pacemakers. Affected infants may develop cardiomyopathy. Abnormalities in the skin, liver and blood of neonates are also associated with anti-Ro/La antibodies, and are usually self-limiting; these manifestations and CHB are collectively referred to as neonatal lupus syndromes (NLS).Investigation of pathogenesis. Recent studies demonstrate that Ro/La ribonucleoproteins appear on the surface of apoptotic fetal cardiocytes and are recognized by their cognate antibodies, promoting an inflammatory response. Mice immunized with Ro/La proteins have offspring with conduction abnormalities.In vitro, human serum and IgG with anti-Ro/La antibodies affect the conducting properties of isolated animal heart tissue.Diagnostic problems. If fetal bradycardia is identified, a 2-dimensional and M-mode fetal echocardiographic and Doppler ultrasound should be obtained to determine whether there is an atrial arrhythmia or atrioventricular (AV) block, and to what degree, and whether there are major structural abnormalities of the heart. The mother’s serum should be tested by ELISA for anti-Ro and/or anti-La antibodies.Therapeutic options. To date, only anecdotal and retrospective evidence guidesin utero therapy of CHB. A prospective trial is currently underway to evaluate the efficacy of maternal oral dexamethasone in treating newly identified first, second or third degree block. Established third-degree block appears to be irreversible. Dexamethasone and sympathomimetics may be of some benefit in treating hydrops fetalis. In pregnant women with anti-Ro/La antibodies, prophylactic therapy is not indicated but serial echocardiographic analysis is strongly recommended, with emphasis on the mechanical PR interval to identify a reversible block.Conclusion. CHB occurs in ∼1–5% of pregnancies in mothers with antiRo/La antibodies, independent of the mother’s disease status, and in ∼15–20% of pregnancies following the birth of a child with NLS. Treatment of CHB identifiedin utero is not established but guidelines are provided. Serial echocardiographic monitoring of high-risk pregnancies, using the mechanical PR interval to identify first degree block, may afford the earliest opportunities for therapeutic intervention     

Putative role of epithelial sodium channels (<Emphasis Type="Italic">ENaC</Emphasis>)in the afferent limb of cardio renal reflexes in rats

Abstract. Recent studies suggest a role of ion channels of the DEG/ENaC family for mechanosensation in different species and in baroreceptor reex control in rats. We tested the hypothesis that ENaC within the cardiac sensory network are mandatory for mechanosensation. Experiments were performed in male Sprague-Dawley rats, isolated nodose ganglion cells with cardiac afferents and isolated vagus nerves.Epicardial delivery of the amiloride analogue benzamil intended to specifically inhibit ENaC presumably located on cardiac sensory afferents indeed blunted the mechanosensitive (i. e., sympathoinhibition by intravenous volume loading [–32% and –42% in treated groups vs. –67% in controls; n = 7 each; p < 0.05]) as well as—though to a lesser extent—the 5-HT₃-mediated chemosensitive cardiorenal reex in vivo in a dose-dependent manner. Using patch clamp technique, however, it turned out that neither amiloride nor benzamil inuenced mechanically induced currents in ganglion nodosum cells in vitro, stimulated by hypoosmotic stress. The unspecific stretch activated ion channel blocker gadolinium completely abolished mechanically induced currents, indicating respective cells were mechanosensitive. In isolated vagus nerves benzamil impaired action potentials obtained by electrical stimulation (C-spike amplitude [–33%]; latency [+12%]; n = 8; p < 0.05).Our ndings at least cast doubt on ENaC exclusively playing a specific role as mechanotransducers within the cardiac sensory network. Other ion channels might be involved. Furthermore the observed ndings in vivo could also be due to unspecific disturbance of afferent signal conduction.     

Competition between acetylcholine and a nondepolarizing muscle relaxant for binding to the postsynaptic receptors at the motor end plate: simulation of twitch strength and neuromuscular block

The goal of the study was to simulate twitch strength and neuromuscular block produced by nondepolarizing muscle relaxants. Methods: In the proposed model, affinities of the two binding sites at a single postsynaptic receptor for acetylcholine (A) and the muscle relaxant (D) define the formation of three complexes with A only, three complexes with D only, and two complexes with both A and D. Twitch strength was postulated to be a function of the receptors with both binding sites occupied by A, and two constants. Neuromuscular block (NMB) was calculated from NMB=1-twitch. Results: Stimulus-induced release of A results in rapid, but transient, changes in the concentrations of free A, the eight complexes, and the unoccupied receptors. Muscle relaxants that display either a congruous or an inverse pattern of affinities for the binding sites relative to those of A produce NMB vs. [D] curves with slightly different slopes but markedly different estimates for IC50. Depending on the number of activated receptors at the end plates of muscle fibers, the simulations represent the distributions of contracting fibers in a whole muscle. Conclusion: Simulations of competition between A and D for binding to two sites at a receptor reveal that the potencies of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves depend on (1) the affinities of D for the two binding sites, (2) the orientation of the affinities relative to those of A, and (3) the affinities of A for the same two sites.     

Prospective randomised double-blind comparative study of rocuronium and pancuronium in adult patients scheduled for elective 'fast-track' cardiac surgery involving hypothermic cardiopulmonary bypass

The majority of cardiac anaesthetists in the UK use pancuronium for fast-track cardiac surgery. We compared the duration of action of pancuronium and rocuronium in patients undergoing fast-track hypothermic cardiopulmonary bypass and cardiac surgery. We determined whether patients would have had residual neuromuscular blockade at extubation. Twenty patients were randomly allocated to receive either pancuronium 0.1 mg x kg(-1) or rocuronium 1 mg x kg(-1). Neuromuscular function was assessed by acceleromyography; spontaneous recovery was evaluated by the train-of-four ratio measured at the adductor pollicis longus muscle. Median times to recover train-of-four ratio of 0.9 were 3 h 38 min for rocuronium and 7 h 52 min for pancuronium. The median difference in recovery times was 4 h 15 min (95% CI 2 h 30 min to 6 h 20 min; p = 0.0003 by Mann-Whitney test). None of the patients in the rocuronium group and seven of 10 patients in the pancuronium group had their extubations delayed because of residual neuromuscular blockade. Unless fast-track patients have neuromuscular function assessed before extubation, pancuronium should not be used.     

Lidocaine versus ropivacaine for continuous interscalene brachial plexus block after open shoulder surgery

BACKGROUND: This study compared the postoperative infusion of 1% lidocaine and 0.2% ropivacaine for continuous interscalene analgesia in patients undergoing open shoulder surgery. METHODS: Forty patients undergoing open shoulder surgery received an interscalene brachial plexus block with 30 ml of either 1.5% lidocaine (n = 20) or 0.5% ropivacaine (n = 20), followed by a continuous patient-controlled interscalene analgesia with 1% lidocaine or 0.2% ropivacaine, respectively. A blinded observer recorded the quality of analgesia and recovery of motor function during the first 24 h of infusion. RESULTS: Onset of the block occurred after 7.5 (5-40) min with lidocaine and 30 (10-60) min with ropivacaine (P = 0.0005). Postoperative pain intensity was higher with lidocaine than ropivacaine for the first 8 h of infusion. The ratio between boluses given and demanded from the pump was 0.5 (0.13-0.7) with lidocaine and 0.7 (0.4-1.0) with ropivacaine (P = 0.005). Rescue IV tramadol was required during the first 24 h of infusion by 16 patients of the lidocaine group (84%) and eight patients of the ropivacaine group (46%) (P = 0.05). At the 16 h and 24 h observation times a larger proportion of patients receiving ropivacaine had complete regression of motor block (70% and 95%) than patients receiving lidocaine (50% and 55%) (P = 0.05 and P = 0.013, respectively). CONCLUSIONS: Although 1% lidocaine can be effectively used for postoperative patient-controlled interscalene analgesia, 0.2% ropivacaine provides better pain relief and motor function.     

Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia

A wide range of drugs has been shown to prolong the QT interval of the electrocardiogram by blocking the pore-forming subunit of the rapidly activating delayed rectifier K+ channel, HERG (ether-à-go-go-related gene), sometimes leading to life-threatening arrhythmia. In this paper we describe cloning, sequence, and expression of the zebrafish orthologue of HERG, Zerg. Further, we studied effects of Zerg inhibition in zebrafish embryos caused by drugs or by an antisense approach. Zerg is expressed specifically in both heart chambers of zebrafish embryos, is composed of six transmembrane domains, and shows an especially high degree of amino acid conservation in the S6 and pore domain (99% identity). Several QT-prolonging drugs added to the bathing medium elicited bradycardia and arrhythmia in zebrafish embryos. The arrhythmia induced ranged from an atrioventricular 2:1 block, the ventricle beating half as often as the atrium, to more severe irregular arrhythmia with higher concentrations of the drugs. These effects were highly specific, reproducible, and rapid, e.g., 10 microM astemizole caused a 2:1 heartbeat within a minute after addition of the compound in all the embryos studied. Morpholino antisense oligonucleotides targeting Zerg were injected into zebrafish embryos and elicited similar dose-sensitive and specific arrhythmia as the QT-prolonging drugs, suggesting an evolutionarily conserved role for Erg in regulating heartbeat rate and rhythm. Further, we identified a mutation in the Per-Arnt-Sim domain of the Zerg channel in the breakdance mutant, also characterized by a 2:1 atrioventricular block. In conclusion, the zebrafish could be a tractable model organism for the study of Erg function and modulation but might also have a value in the field of cardiovascular pharmacology, e.g., as an early preclinical model for testing drugs under development for potential QT prolongation.     

Effects of an extracellular metal chelator on neurovascular function in diabetic rats

Abstract Aims/hypothesis. Increased oxidative stress has been causally linked to diabetic neurovascular complications, which are attenuated by antioxidants. There are several possible sources of reactive oxygen species in diabetes. Our aim was to assess the contribution of free radicals, produced by transition metal catalysed reactions, to early neuropathic changes. To this end, we examined, firstly, the effects of an extracellular high molecular weight chelator, hydroxyethyl starch-deferoxamine, which is expected to be confined to vascular space, on nerve perfusion and conduction deficits in diabetic rats and, secondly, the action of a single chelator dose. Methods. Diabetes was induced by streptozotocin. In vivo measurements comprised sciatic nerve motor conduction velocity and endoneurial perfusion, monitored by hydrogen clearance microelectrode polarography. Results. We found that 8 weeks of diabetes reduced sciatic blood flow and conduction velocity by 48.3 % and 19.9 % respectively. Two weeks of intravenous treatment corrected these deficits. Starch vehicle was ineffective. The time-course of action of a single hydroxyethyl starch-deferoxamine injection was examined in diabetic rats. There was a rapid increase in nerve blood flow on day 1, which remained within the non-diabetic range for 9 days before declining to the diabetic level at day 27. In contrast, conduction velocity changes were slower, reaching the non-diabetic range at day 6 and declining to the diabetic level at day 27. Conclusion/interpretation. Extracellular transition metal catalysed reactions play a major role in the neurovascular deficits of experimental diabetes. Given the long-lasting effect of a single treatment, extracellular metal chelator therapy could be suitable for further assessment in clinical trials. [Diabetologia (2001) 44: 621–628] Received: 30 October 2000 and in revised form: 12 January 2001