Board of Nursing decision puts patients at risk.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
D Beardsley
Publications and source records attributed to D Beardsley.
Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.
OBJECTIVE: To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN: Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered. RESULTS: Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported. CONCLUSION: rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.
Adolescent↗
International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies.
Platelet-associated and plasma autoantibodies against platelet glycoproteins (GP) have been demonstrated in patients with autoimmune thrombocytopenia (AITP) using various methods. Eight laboratories in seven countries participated in this international study to evaluate the interlaboratory agreement using glycoprotein-specific immunoassays for these autoantibodies. The participating laboratories received blind samples of frozen washed platelets and plasma from 22 normal donors and 22 AITP patients. Platelet-associated and plasma autoantibodies against GPIIb-IIIa and GPIb-IX were measured by MAIPA, immunobead assay or modified antigen capture assay. Of the control samples, 96.0% and 97.2% of all results for platelet-associated and plasma autoantibodies to GPIIb-IIIa/ GPIb-IX, respectively, were negative. The mean variation coefficient of the control samples of platelet-associated and plasma autoantibodies was 89.5% (range 11.1-272.9%) and 46.5% (range 21.0-78.0%), respectively. In 20/22 patient samples, platelet-associated autoantibodies to either glycoprotein were noted by at least two laboratories. The mean degree of agreement in these samples was 74.0%. There was a significant correlation in the individual antibody measurements between all laboratories (Kendall coefficient of concordance 0.60 and 0.38, P < 0.001; Spearman rank order test, range of correlation coefficient 52.3-94.0% and 42.2-85.0%, P < 0.05, for anti-GPIIb-IIIa and anti-GPIb-IX, respectively). In contrast, plasma autoantibodies to either glycoprotein were noted by at least two laboratories in only 13/22 patient samples. Moreover, the degree of agreement was poor (50.1%) and a significant correlation was noted between only six pairs of laboratories. We conclude that methods used in this study yield good interlaboratory agreement in measuring platelet-associated autoantibodies against GPIIb-IIIa and GPIb-IX. In contrast, poor agreement was found in detecting plasma autoantibodies to the same glycoproteins.
Autoantibodies↗
Hyperbaric dye solution distribution characteristics after pencil-point needle injection in a spinal cord model.
BACKGROUND: The flow-rate limiting and directional characteristics of caudally directed microcatheters, which lead to intrathecal maldistribution of hyperbaric 5% lidocaine, are believed to have contributed to at least 11 cases of cauda equina syndrome. The authors investigated the distribution characteristics of hyperbaric dye solutions via caudally directed side port needles at various rates of injection in a spinal cord model to determine the potential for maldistribution. METHODS: Using a digital video image processing technique, we injected a hyperbaric solution of phthalocyanine blue dye through caudally directed side-port needles into a supinely oriented transparent spinal canal model filled with simulated cerebrospinal fluid. Injections via commonly used spinal needles (24-gauge and 25-gauge Sprotte, and 25-gauge and 27-gauge Whitacre) were recorded using five injection rates (2, 4, 6, 8, and 16 ml/min). RESULTS: For all needles tested, injection rate had a significant effect on the peak dye concentration (P < 0.0001). Injection rates > or = 6 ml/min (2 ml/20 s) resulted in peak dye concentrations of less than 168 mg/1 (extrapolated concentration of 1% lidocaine). Injection via the 24-gauge Sprotte needle, which has a larger orifice area and internal diameter, resulted in significantly lower peak dye concentrations than via the smaller Whitacre needles tested (P < 0.05). CONCLUSIONS: Sacral maldistribution could be minimized by using injection rates > or = 6 ml/min (2 ml/20 s), for all of the side-port spinal needles used in this model study. When very slow injection rates (2 ml/min) are used, peak dye concentrations varied inversely and significantly with needle internal diameter and orifice area.
Anesthetics, Local↗
Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?
Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Does spinal anesthesia result in a more complete sympathetic block than that from epidural anesthesia?
BACKGROUND: Spinal and epidural injection of local anesthetics are used to produce sympathetic block to diagnose and treat certain chronic pain syndromes. It is not clear whether either form of regional anesthesia produces a complete sympathetic block. Spinal anesthesia using tetracaine has been reported to produce a decrease in plasma catecholamine concentrations. This has not been demonstrated for epidural anesthesia in humans with level of anesthesia below C8. One possible explanation is that spinal anesthesia results in a more complete sympathetic block than epidural anesthesia. To examine this question, a cross-over study was performed in young, healthy volunteers. METHODS: Ten subjects underwent both spinal and epidural anesthesia with lidocaine (plain) on the same day with complete recovery between blocks. By random assignment, spinal anesthesia and epidural anesthesia were induced via lumbar injection. Before and 30 min after local anesthetic injection, a cold pressor test (CPT) was performed. Blood was obtained to determine epinephrine and norepinephrine plasma concentrations at four stages: (1) 20 min after placing peripheral catheters, (2) at the end of a 2-min CPT (before conduction block), (3) 30 min after injection of epidural or spinal lidocaine, and (4) at the end of a second CPT (during anesthesia). Mean arterial pressure, heart rate, noninvasive cardiac index, and analgesia to pin-prick were monitored. RESULTS: Neither spinal nor epidural anesthesia changed baseline resting values of catecholamines or any hemodynamic variable, except heart rate, which was slightly decreased during spinal anesthesia. Median level of analgesia was T4 during spinal and T3 during epidural anesthesia. CPT before conduction block reliably increased heart rate, mean arterial pressure, cardiac index, epinephrine, and norepinephrine. Conduction block attenuated the increase in response to CPT only in mean arterial pressure (spinal and epidural) and cardiac index (spinal only). Neither technique blocked the increase in heart rate, norepinephrine, or epinephrine to CPT. CONCLUSIONS: Spinal anesthesia did not result in a more complete attenuation of the sympathetic response to a CPT than did epidural anesthesia. In response to the CPT, spinal anesthesia blocked the increase in cardiac index, and epidural anesthesia resulted in a decrease in total peripheral resistance compared to the pre-anesthesia state. The differences between the techniques are not significant and are of uncertain clinical implications.
Adult↗
Does the choice of local anesthetic affect the catecholamine response to stress during epidural anesthesia?
BACKGROUND: Previous work has established that 2-chloroprocaine epidural anesthesia has no effect on circulating plasma epinephrine concentrations in young, healthy, resting volunteers, and results in a decrease in norepinephrine concentration only when a level of analgesia to pinprick of C-8 is reached. The current study was performed to evaluate the possibility that this finding is unique to 2-chloroprocaine. METHODS: Nine healthy volunteers were studied on three occasions at least 48 h apart; each received three local anesthetics (0.75% bupivacaine, 2% lidocaine, and 3% 2-chloroprocaine, all without epinephrine). After placement of lumbar epidural and central venous catheters, blood samples were drawn from the central venous catheter at the following stages: (1) 20 min after catheter placement (baseline), (2) during the first cold pressor test (CPT; hand held in an ice water bath for 90 s), (3) 20 min after reaching epidural analgesia to T-1 level of analgesia, and (4) during a second CPT (epidural analgesia to T-1). Monitoring consisted of noninvasive cardiac output (impedance), noninvasive blood pressure, and EKG. RESULTS: Extensive epidural block (stage 3) altered measured variables only minimally with respect to resting baseline state. During stage 2 (first CPT), mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), epinephrine, and norepinephrine increased. During stage 4 (second CPT), increases in HR and CI were not attenuated by any of the three local anesthetics. Increases in MAP were attenuated by epidural anesthesia with all three local anesthetics. Bupivacaine and 2-chloroprocaine epidural anesthesia significantly attenuated increases in plasma catecholamines, but lidocaine epidural anesthesia did not. CONCLUSIONS: Epidural anesthesia with all three local anesthetic agents tested resulted in an incomplete sympathectomy in the resting state in healthy young men, judged by plasma catecholamine concentrations and cardiovascular variables minimally changed from resting baseline. Lidocaine epidural anesthesia did not attenuate the catecholamine response to CPT, indicating decreased blockade of sympathetic efferent neural traffic compared with bupivacaine and chloroprocaine epidural anesthesia.
Adult↗
Ultra-deep blockade of Na+ channels by a quaternary ammonium ion: catalysis by a transition-intermediate state?
1. Individual Na+ channels from isolated guinea-pig ventricular heart cells were studied using the patch-clamp technique. To localize the selectivity region of the channels we investigated their blockade by a permanently charged quaternary ammonium ion (QX-314, 2-(triethylamino)-N-(2,6-dimethylphenyl)acetamide, 0-5 mM) that was applied to the cytoplasmic side of the channel. 2. Resolution of individual blocking events was enhanced by covalent removal of fast inactivation following brief internal exposure to the enzyme papain. The improved resolution reveals the existence of two distinct modalities of blockade: reduction of unitary current, and millisecond interruptions of current. 3. Both modes of internal block could be potentiated by lowering external Na+ concentration. This finding argues that the two corresponding sites of interaction are both located within the channel pore. 4. Analysis of the voltage dependence of block placed both binding sites deep within the pore, at 70% of the electric field from the cytoplasmic entrance. Combined with recent studies localizing block by external Cd2+, the present results argue that the selectivity region of Na+ channels is quite narrow (spanning about 10% of the electric field), and located near the external side of the channel. 5. The manner in which the two blocking processes interact, along with the physical proximity of their binding sites, leads us to propose that the block configuration responsible for the reduction in unitary current serves as a transition intermediate that catalyses formation of the discrete-block complex.
Animals↗
Hormonal responses to graded surgical stress.
We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.
Adult↗
Glucagon: endocrine effects and calcium involvement in cardiovascular actions in dogs.
Although the cardiovascular effects of glucagon are understood, its mechanism(s) of action remains unclear. We studied the effects of increasing doses of glucagon (0.001, 0.01, 0.1 mg/kg) on cardiovascular responses in dogs relative to concurrent measurements of circulating glucagon, cyclic AMP, glucose, norepinephrine, epinephrine, triiodothyronine, thyroxine, and cortisol levels. Glucagon-induced increases in plasma cyclic AMP, glucose, and catecholamine concentrations paralleled the heart rate response to glucagon administration. Further studies were conducted to evaluate the role of beta-adrenergic function as well as calcium in mediating glucagon's actions. The tachycardic effects of glucagon (0.01 mg/kg) were unaltered by prior beta-adrenergic receptor blockade with propranolol (3.5 mg/kg total dose). The calcium antagonist verapamil (0.2 mg/kg bolus then 7.5 micrograms/kg/min/infusion) prevented glucagon-induced increases in heart rate. However, the coadministration of glucagon (0.01 mg/kg) with calcium (1.0, 5.0, 10.0, or 50.0 mg/kg) did not alter glucagon's cardiovascular effects. These data indicate that glucagon is a potent tachycardiac agent that also elevates circulating endocrine-related substances. The antagonism of glucagon's tachycardiac effects by verapamil suggests that glucagon's action may be via glucagon-induced calcium movement through calcium channels, although extracellular calcium changes do not alter glucagon's effect. Furthermore, the persistence of glucagon's cardiovascular actions following beta-adrenergic blockade indicates the potential clinical utility of glucagon in reversing the adverse effects of beta-blocker overdoses, and its potential usefulness in treating circulatory shock in "beta-blocked" patients.
Animals↗
Studies of a familial platelet disorder.
At least 22 members of a large kindred have a bleeding tendency resulting from an autosomal dominant disorder of platelet production and function. Phenotypic manifestations include mild to moderate thrombocytopenia, bleeding time prolongation, and abnormal platelet aggregation. Platelet survival time is normal. The platelet disorder in this family appears to differ from known hereditary thrombocytopenic or thrombocytopathic syndromes and may represent a new genetic disease. Six family members reportedly developed hematologic neoplasms: acute monocytic leukemia nine years after treatment for congenital neuroblastoma; lymphosarcoma at age 10 years; myeloid leukemia at age 23 years; acute myelocytic leukemia at age 62 years; leukemia of unknown type at age 48 years; and lymphocytic lymphoma at age 52 years.
Adolescent↗
Sympathetic block during spinal anesthesia in volunteers using lidocaine, tetracaine, and bupivacaine.
BACKGROUND AND OBJECTIVES: Spinal anesthesia to high thoracic dermatomes is alleged to result in almost complete block of all sympathetic efferent nerves. To examine the degree of sympathectomy during spinal anesthesia, the sympathetic response to a cold pressor test (CPT) applied to unblocked dermatomes before and during spinal anesthesia was measured with use of three different local anesthetics. METHODS: Twelve healthy volunteers were studied in a randomized and double-blind fashion on three separate occasions. In random order, each volunteer received approximately equipotent spinal doses of tetracaine 15 mg, bupivacaine 15 mg, and lidocaine 100 mg in hyperbaric solutions. Prior to and 30 minutes after spinal injection of local anesthetic, a CPT was applied for 2 minutes, and changes from baseline resting conditions in five physiologic variables were measured. RESULTS: The CPT 1 given before anesthetic administration resulted in an increase in heart rate, mean arterial pressure, cardiac index, and plasma concentrations of norepinephrine and epinephrine. Spinal anesthesia to a median level of T3 resulted in a decrease in mean arterial pressure by 10-12% but did not significantly decrease the other variables. Spinal anesthesia did not change the increase in heart rate or cardiac index in response to the second CPT, but the increase in mean arterial pressure was attenuated compared to the CPT before anesthesia. No increase in norepinephrine or epinephrine concentration was observed during the CPT given during spinal anesthesia. There was no significant relationship between level of analgesia and sympathetic response to stress. CONCLUSIONS: Spinal anesthesia with hyperbaric solutions of tetracaine 15 mg, bupivacaine 15 mg, and lidocaine 100 mg attenuated sympathetic function but did not produce complete sympathectomy. The effects were independent of the local anesthetic used.
Adult↗
Differential epidural block. Does the choice of local anesthetic matter?
BACKGROUND AND OBJECTIVES: It is well established that spinal anesthesia results in a differential block to the sensations of pinprick and cold temperature discrimination. However, the existence of differential block during epidural anesthesia has not always been accepted. Recently, it has been shown that lumbar epidural anesthesia with chloroprocaine and lidocaine produces a differential block to pinprick and cold sensation. The purpose of this study was to determine if the choice of local anesthetic used for epidural anesthesia has any influence on the relative levels of anesthesia, analgesia, and cold sensation. METHODS: The authors studied nine healthy subjects; each was studied three times and received one of three local anesthetics (0.75% bupivacaine, 2% lidocaine, and 3% chloroprocaine) via an epidural catheter placed into the second or third lumbar epidural space. The authors tested the following modalities compared to an unblocked dermatome: anesthesia, loss of sensation to pinprick; analgesia, loss of an equally sharp sensation to pinprick; and cold sensation, loss of cold sensation to alcohol. RESULTS: Twenty minutes after injection of the local anesthetic, zones of differential sensory block existed for all three agents tested. Anesthesia and analgesia were the most caudad and cephalad, respectively, while loss-to-cold sensation was found to be between these two levels. There was no significant difference in the dermatomal level achieved among the three local anesthetics tested. Sensory testing data observed 10 minutes later showed that no significant change had occurred. CONCLUSIONS: This study reaffirms the existence of differential sensory block during epidural anesthesia and establishes that the observed differential block appears to be independent of the local anesthetic used.
Adult↗