Forebrain projections of arcuate neurokinin B neurons demonstrated by anterograde tract-tracing and monosodium glutamate lesions in the rat.

Neurokinin B (NKB) and kisspeptin receptor signaling are essential components of the reproductive axis. A population of neurons resides within the arcuate nucleus of the rat that expresses NKB, kisspeptin, dynorphin, NK3 receptors and estrogen receptor alpha (ERalpha). Here we investigate the projections of these neurons using NKB-immunocytochemistry as a marker. First, the loss of NKB-immunoreactive (ir) somata and fibers was characterized after ablation of the arcuate nucleus by neonatal injections of monosodium glutamate. Second, biotinylated dextran amine was injected into the arcuate nucleus and anterogradely labeled NKB-ir fibers were identified using dual-labeled immunofluorescence. Four major projection pathways are described: (1) local projections within the arcuate nucleus bilaterally, (2) projections to the median eminence including the lateral palisade zone, (3) projections to a periventricular pathway extending rostrally to multiple hypothalamic nuclei, the septal region and BNST and dorsally to the dorsomedial nucleus and (4) Projections to a ventral hypothalamic tract to the lateral hypothalamus and medial forebrain bundle. The diverse projections provide evidence that NKB/kisspeptin/dynorphin neurons could integrate the reproductive axis with multiple homeostatic, behavioral and neuroendocrine processes. Interestingly, anterograde tract-tracing revealed NKB-ir axons originating from arcuate neurons terminating on other NKB-ir somata within the arcuate nucleus. Combined with previous studies, these experiments reveal a bilateral interconnected network of sex-steroid responsive neurons in the arcuate nucleus of the rat that express NKB, kisspeptin, dynorphin, NK3 receptors and ERalpha and project to GnRH terminals in the median eminence. This circuitry provides a mechanism for bilateral synchronization of arcuate NKB/kisspeptin/dynorphin neurons to modulate the pulsatile secretion of GnRH.

Successful external cardioversion of atrial fibrillation in patients referred to an electrophysiologist for internal cardioversion.

BACKGROUND: Internal cardioversion of atrial fibrillation with direct current energy has become an increasingly employed technique for patients who fail external cardioversion. HYPOTHESIS: The purpose of this study was to determine whether internal cardioversion could be avoided by careful attention to cardioversion technique in a group of patients referred specifically for internal cardioversion after failed external cardioversion by community cardiologists. METHODS: We performed external cardioversion utilizing two operators applying significant pressure to the thorax with up to 360 J prior to the planned internal cardioversion in 20 patients referred for internal cardioversion after failed attempts at external cardioversion. RESULTS: Sixteen patients (80%) were successfully cardioverted and avoided the risk, inconvenience, and cost of internal cardioversion. CONCLUSION: External cardioversion with significant anterior paddle pressure by two operators can decrease the need for internal cardioversion in a significant portion of patients referred to electrophysiologists for internal cardioversion and should be considered prior to an invasive procedure.

Effect of radiofrequency current on previously implanted pacemaker and defibrillator ventricular lead systems.

We compared the response of endocardial lead systems to radiofrequency (RF) current delivered during atrio-ventricular junction ablation (AVJA) for atrial fibrillation with uncontrolled ventricular rate in 107 patients. The mean age was 67 +/- 11 years and the mean ejection fraction 42 +/- 15%. Patients were divided into 3 groups based on the type of ventricular lead present at the time of ablation: a previously implanted defibrillator lead (group 3, n = 13), a previously implanted pacemaker lead (group 2, n = 46) or a temporary lead (group 1, n = 48), which was subsequently followed by a permanent lead implantation. During AVJA, a median of 5 RF applications (44 +/- 8 W) were given via 4-5-mm electrodes. All but 1 patient had right-sided lesions, while 6 patients also had left sided lesions. Ventricular pacing thresholds were evaluated immediately pre- and post-ablation at 24 hours and at 1 to 3 months. Increases in ventricular pacing voltage thresholds were noted in all 3 groups over time, with the greatest mean increase in group 3 patients: [table: see text]. A greater than 2-fold increase in pacing thresholds was observed only with previously implanted leads, usually within the first 48 hours. It occurred significantly more often in patients with group 3 (6/13 [46%]) compared to group 2 (6/46 [13%], odds ratio 7.6, P = 0.006). A progressive rise in pacing threshold required lead revision in 2/13 group 3 patients (15%) and 2/46 group 2 patients (4%). While RF current has only minor effects on pacing threshold in most patients with previously implanted ventricular lead systems, clinically important alterations requiring device reprogramming or lead revision may occur. Group 3 are significantly more vulnerable to RF current, though the mechanisms are unclear. Group 1 during AVJA, followed by permanent lead implantation appears advisable. Pts with a previously implanted group 3 who require AVJA should be monitored closely.

Atypical atrial flutter originating in the right atrial free wall.

BACKGROUND: Data from experimental models of atrial flutter indicate that macro-reentrant circuits may be confined by anatomic and functional barriers remote from the tricuspid annulus-eustachian ridge atrial isthmus. Data characterizing the various forms of atypical atrial flutter in humans are limited. METHODS AND RESULTS: In 6 of 160 consecutive patients referred for ablation of counterclockwise and/or clockwise typical atrial flutter, an additional atypical atrial flutter was mapped to the right atrial free wall. Five patients had no prior cardiac surgery. Incisional atrial tachycardia was excluded in the remaining patient. High-density electroanatomic maps of the reentrant circuit were obtained in 3 patients. Radiofrequency energy application from a discrete midlateral right atrial central line of conduction block to the inferior vena cava terminated and prevented the reinduction of atypical atrial flutter in each patient. Atrial flutter has not recurred in any patient (follow-up, 18+/-17 months; range, 3 to 40 months). CONCLUSIONS: Atrial flutter can arise in the right atrial free wall. This form of atypical atrial flutter could account for spontaneous or inducible atrial flutter observed in patients referred for ablation and is eliminated with linear ablation directed at the inferolateral right atrium.

Frozen shoulder syndrome associated with subpectoral defibrillator implantation.

Pectoral implantation of transvenous non-thoracotomy internal cardioverter defibrillators (ICD) has resulted in very few complications whether placed subpectorally or subcutaneously. We report the case of a 68 year old man with a subpectorally implanted MINI-plus (Cardiac Pacemakers, Incorporated, St. Paul, Mn.) transvenous ICD who developed nearly instantaneous severe ipsilateral shoulder pain and immobilization. The symptoms progressed despite aggressive physical therapy. We elected to remove the device from the pectoral site and place it in a traditional abdominal position due to the severity, duration and refractoriness of his symptoms. This procedure utilized the chronic Endotak DSP (Model 0125, Cardiac Pacemakers, Incorporated) transvenous lead, a compatible Endotak DSP lead extender (Model 6952, Cardiac Pacemakers, Incorporated) and the above described ICD. Immediate relief of symptoms was accomplished by relocation of the device to an abdominal site. This intervention should be reserved for patients with severely debilitating symptoms. Prospective comparison of subpectoral and subcutaneous surgical approaches with respect to patient comfort and acceptance and complications may be warranted.

Retrograde fast pathway ablation for atrioventricular nodal reentry associated with markedly prolonged PR intervals.

Three patients with typical atrioventricular nodal reentrant tachycardia (AVNRT) and markedly prolonged PR intervals (>300 ms) without dual pathway physiology at baseline or during isoproterenol infusion underwent successful fast pathway ablation and remained asymptomatic without recurrent AVNRT, atrioventricular block, or symptomatic bradycardia for a mean of 19 months. In patients with recurrent AVNRT and markedly prolonged PR intervals, selective ablation of the retrograde fast pathway can eliminate AVNRT without further impairment of anterograde atrioventricular nodal function.

Atrial fibrillation after radiofrequency ablation of type I atrial flutter: time to onset, determinants, and clinical course.

BACKGROUND: The occurrence of atrial fibrillation after ablation of type I atrial flutter remains an important clinical problem. To gain further insight into the pathogenesis and significance of postablation atrial fibrillation, we examined the time to onset, determinants, and clinical course of atrial fibrillation after ablation of type I flutter in a large patient cohort. METHODS AND RESULTS: Of 110 consecutive patients with ablation of type I atrial flutter, atrial fibrillation was documented in 28 (25%) during a mean follow-up of 20.1+/-9.2 months (cumulative probability of 12% at 1 month, 23% at 1 year, and 30% at 2 years). Among 17 clinical and procedural variables, only a history of spontaneous atrial fibrillation (relative risk 3.9, 95% confidence intervals 1.8 to 8.8, P=0.001) and left ventricular ejection fraction <50% (relative risk 3.8, 95% confidence intervals 1.7 to 8.5, P=0.001) were significant and independent predictors of subsequent atrial fibrillation. The presence of both these characteristics identified a high-risk group with a 74% occurrence of atrial fibrillation. Patients with only 1 of these characteristics were at intermediate risk (20%), and those with neither characteristic were at lowest risk (10%). The determinants and clinical course of atrial fibrillation did not differ between an early (< or = 1 month) compared with a later onset. Atrial fibrillation was persistent and recurrent, requiring long-term therapy in 18 patients, including 12 of 19 (63%) with prior atrial fibrillation and left ventricular dysfunction. CONCLUSIONS: Atrial fibrillation after type I flutter ablation is primarily determined by the presence of a preexisting structural and electrophysiological substrate. These data should be considered in planning postablation management. The persistent risk of atrial fibrillation in this population also suggests a potentially important role for atrial fibrillation as a trigger rather than a consequence of type I atrial flutter.

The myths of emergency medical care access in the managed care era.

In this paper, we examine the perception that emergency care is unusually expensive. We discuss the myths that have fueled the ineffective and sometimes deleterious efforts to limit access to emergency care. We demonstrate the reasons why these efforts are seriously flawed and propose alternate strategies that aim to improve outcomes, including cooperative ventures between hospitals and managed care organizations. We challenge managed care organizations and healthcare providers to collaborate and lead the drive to improve the cost and clinical effectiveness of emergency care.

Adenosine-sensitive bundle branch reentry.

INTRODUCTION: Bundle branch reentry is an uncommon mechanism for ventricular tachycardia. More infrequently, both fascicles of the left bundle may provide the substrate for such macroreentrant bundle branch circuits, so-called interfascicular reentry. The effect of adenosine on bundle branch reentrant mechanisms of tachycardia is unknown. METHODS AND RESULTS: A 59-year-old man with no apparent structural heart disease and history of frequent symptomatic wide complex tachycardias was referred to our center for further electrophysiologic evaluation. During electrophysiologic study, a similar tachycardia was reproducibly initiated only during isoproterenol infusion, which had the characteristics of bundle branch reentry, possibly using a left interfascicular mechanism. Intravenous adenosine reproducibly terminated the tachycardia. Application of radiofrequency energy to the breakout site from the left posterior fascicle prevented subsequent tachycardia induction and rendered the patient free of spontaneous tachycardia during long-term follow-up. CONCLUSIONS: Patients with ventricular tachycardia involving a bundle branch reentrant circuit may be sensitive to adenosine. These results suggest that adenosine may not only inhibit catecholamine-mediated triggered activity but also some catecholamine-mediated reentrant ventricular arrhythmias.

Malpractice claims against emergency physicians in Massachusetts: 1975-1993.

This study reviewed 549 malpractice claims filed against emergency physicians in Massachusetts from 1975 through 1993, with a total of $39,168,891 of indemnity and expense spent on the 549 closed claims. High-risk diagnostic categories (chest pain, abdominal pain, wounds, fractures, pediatric fever/meningitis, epiglottitis, central nervous system bleeding, and abdominal aortic aneurysm) accounted for 63.75% of all closed claims and 64.23% of the total indemnity and expense spent on closed claims. Missed myocardial infarction (chest pain) claims accounted for 25.47% of the total cost of closed claims but only 10.38% of closed claims. The number of claims for missed myocardial infarction increased in the post-1988 closed claim group compared to the pre-1988 group; fractures and wounds were significantly less frequent in the post-1988 group. The frequency of high-risk claims decreased in the post-1988 group, largely because of the decline in fracture and wound claims. The category of missed myocardial infarction had a larger percentage of claims closed with indemnity payment than without indemnity payment. This parameter may serve as a marker for the overall seriousness of claims associated with a particular allegation, unlike the average cost per claim, which may be skewed by a few large awards.

Atraumatic rupture of utero-ovarian vessels during pregnancy: a lethal presentation of maternal shock.

Spontaneous rupture of utero-ovarian vessels during pregnancy is a rare cause of maternal and fetal loss. We report the case of a 30-year-old woman who presented to the emergency department in her third trimester with frank maternal shock. The prompt recognition of shock, correction of hypovolemia, and rapid surgical intervention by her obstetrician led to a favorable outcome for both mother and child.

Massachusetts emergency medicine closed malpractice claims: 1988-1990.

STUDY PURPOSE: To describe the characteristics of malpractice claims against emergency physicians and to identify causes and potential preventability of such claims. POPULATION: Malpractice claims closed in 1988, 1989, and 1990 against emergency physicians insured by the Massachusetts Joint Underwriters Association were compared with claims closed from 1980 to 1987 as investigated in our previous study. METHODS: Retrospective review of malpractice claim files by board-certified emergency physicians. RESULTS: The average indemnity and expense per claim were higher in the current study population than in our previous study population (P = .05). Claims in eight high-risk diagnostic areas (chest pain, abdominal pain, fractures, wounds, pediatric fever/meningitis, subarachnoid hemorrhage, aortic aneurysm, and epiglottitis) accounted for 50.8% of claims in this study and 55.5% of total monetary losses. Four claims in this study were related to two instances of failure of an emergency department radiograph follow-up system. The evaluation of patients who were intoxicated contributed to major monetary losses, especially in cases of fractures and head injury. CONCLUSION: Emergency physicians must have a particular awareness of their great risk exposure for missed myocardial infarction. Addition of dictation or voice-activated record generation systems, departmental protocols for radiograph follow-ups, and holding and re-evaluation of the intoxicated patient will help provide systems supports for reducing the liability of individual emergency physicians.

Characterization of two genes encoding Bacillus thuringiensis insecticidal crystal proteins toxic to Coleoptera species.

Bacillus thuringiensis EG2838 and EG4961 are highly toxic to Colorado potato beetle larvae, and only strain EG4961 is toxic to southern corn rootworm larvae. To investigate the cause of the different insecticidal activities of EG2838 and EG4961, cryIII-type genes toxic to coleopterans were cloned from each strain. The cryIIIB gene, cloned as part of an 8.0-kb EcoRI fragment of EG2838 DNA, encoded a crystal protein (CryIIIB) of 74,237 Da. The cryIIIB2 gene, cloned as part of an 8.3-kb PstI-Asp718 fragment of EG4961 DNA, encoded a crystal protein (CryIIIB2) of 74,393 Da that was 94% identical to CryIIIB. Analysis of the transcriptional start sites showed that cryIIIB and cryIIIB2 were initiated from a conserved region located within 130 nucleotides upstream from the translation start sites of both genes. Although the CryIIIB and CryIIIB2 proteins were similar in sequence, they displayed distinct insecticidal activities: CryIIIB was one-third as toxic as CryIIIB2 to Colorado potato beetle larvae, and CryIIIB2, but not CryIIIB, was toxic to southern corn rootworm larvae. Genes encoding crystal proteins of approximately 32 and 31 kDa were located adjacent to the cryIIIB and cryIIIB2 genes, respectively. The 32- and 31-kDa crystal proteins failed to enhance the insecticidal activities of CryIIIB and CryIIIB2.

Pial venous pressure and acute hypertensive disruption of the blood-brain barrier in spontaneous and renal hypertension.

The purpose of this study was to determine whether changes in pial venous pressure during acute hypertension account for altered acute hypertensive disruption of the blood-brain barrier in chronic hypertension. We studied 13 normotensive WKY rats, 7 spontaneously hypertensive rats (SHR), and 9 two-kidney, one-clip renal hypertensive rats of the same age. Pial venous pressure (servonull technique) and clearance of fluorescein-labeled dextran from pial vessels (as an estimate of permeability of the blood-brain barrier) were measured before and during acute hypertension produced by i.v. infusion of phenylephrine. Experiments were performed in anesthetized rats (50 mg/kg sodium pentobarbital i.p.). Blood and artificial cerebrospinal fluid pO2, pCO2 and pH were within normal ranges throughout the experiment. The change, time to peak and peak pial venous pressures were the same in all groups. The peak arterial pressure after phenylephrine was greater in the hypertensive rats compared to WKY rats. The time to peak mean arterial pressure was the same in all groups of rats. Clearance of FITC dextran was the same in WKY versus renal hypertensive rats, but less in SHR versus WKY rats (P less than 0.05 by analysis of variance). We conclude that something other than an attenuation of the increase in pial venous pressure protects the blood-brain barrier of SHR against acute hypertensive disruption.

No rarefaction of cerebral arterioles in hypertensive rats.

A reduction in the density of small arterioles (rarefaction) has been reported in several vascular beds of the spontaneously hypertensive rat (SHR). There have been conflicting reports on the existence of rarefaction in the pial vasculature of SHR. In this study, we determined whether there was rarefaction of pial arterioles in several models of hypertension. We studied SHR; two-kidney, one-clip Goldblatt hypertensive rats; deoxycorticosterone-salt hypertensive rats; and Dahl salt-sensitive rats fed high salt diet. The two groups of normotensive controls were Wistar--Kyoto rats and Dahl salt-sensitive rats fed low salt diet. The duration of hypertension was about 2 months. Density of first-, second-, third-, and fourth-order arterioles was determined by counting the number of vessels from enlarge photographs. We also measured the lengths of segments of the arterioles. We did not observe any evidence of rarefaction of arterioles in the pial vasculature in any of the hypertensive groups of rats. We conclude that (i) rarefaction of arterioles does not occur in the pial microvasculature after approximately 2 months of hypertension and (ii) rarefaction of pial arterioles does not account for abnormalities in the cerebral circulation of hypertensive rats such as protection of the blood-brain barrier or changes in autoregulation of cerebral blood flow.

Use of autopsy results in the emergency department quality assurance plan.

Traditionally, the autopsy is viewed as the ultimate quality assurance indicator in clinical medicine, yet very few clinical departments actually incorporate autopsy results in their formal quality assurance plans. Consequently, to investigate how autopsy results can be included on our emergency department plan, the clinical and autopsy diagnoses of 244 patients were reviewed retrospectively and compared to identify conditions that were unapparent or misdiagnosed at the time of death. The study period was from January 1984 through June 1988. The average yearly ED census was 33,266. Differences between clinical and autopsy diagnoses were categorized as class 1, 2, 3, or 4 findings. Major unexpected findings (classes 1 and 2) were found in ten patients (4%); the most common missed diagnoses were aortic dissection 3 (1.2%) and pulmonary embolus 2 (0.8%). Minor unexpected findings (classes 3 and 4) were discovered in 14 patients (5.8%). The results clearly identify unexpected findings and point to the need for more aggressive evaluations of certain conditions. Systematic review of autopsy data as presented has led to meaningful changes and delivery of care to emergency patients. Autopsies are a vital source of outcome-based information that should be part of every ED's quality assurance and risk management plan.

Hypertension and cerebral arteries: relationship to disruption of the blood-brain barrier.

This study was performed to determine whether structural changes in cerebral arterioles could account for differences in susceptibility of the blood-brain barrier to acute hypertensive disruption between hypertensive and normotensive animals. We studied spontaneously hypertensive rats (SHR), 3 other models of hypertension and their normotensive controls. The age and duration of hypertension of the rats were matched to an earlier study showing that protection of the blood-brain barrier was usually found in rats with chronic hypertension. We measured the dimensions of fixed pial arterioles and minimal cerebrovascular resistance produced by bicuculline. Minimal cerebrovascular resistance was not different between the groups of animals. There were no differences in the area of the media of pial arterioles between any of the groups. In addition, we examined the possibility that sympathetic nerves might affect cerebrovascular resistance during bicuculline in SHR. The presence of sympathetic nerves in SHR, but not WKY, reduced the degree of cerebral vascular dilation during bicuculline. From these data we conclude that 1) structural changes in cerebral vessels do not account for protection of the blood-brain barrier in rats with a moderate duration of hypertension and 2) sympathetic nerves may have an exaggerated effect on cerebral vessels of SHR.

Chemotherapy-induced painful acral erythema in childhood: Burgdorf's reaction.

Painful acral erythema as a reaction to intensive chemotherapy has been increasingly recognized since 1982. It has not been reported in the pediatric literature. We report its occurrence in a 3-year-old boy who had received intensive chemotherapy for acute lymphoblastic leukemia.

Effect of chronic hypertension on acute hypertensive disruption of the blood-brain barrier in rats.

The effect of chronic hypertension on acute hypertensive disruption of the blood-brain barrier has been studied in only two models of hypertension, with inconsistent results. The purpose of this study was to reinvestigate whether chronic hypertension has a consistent effect on acute hypertensive disruption of the blood-brain barrier and to determine whether one of the previously studied models has an unusual response to chronic hypertension. We studied four rat models of chronic hypertension: spontaneously hypertensive rats (SHR), two-kidney, 1 clip Goldblatt rats (2K1C), rats treated with deoxycorticosterone acetate (DOCA) and NaCl, Dahl salt-sensitive rats fed a high salt diet, and two groups of normotensive controls: Wistar-Kyoto rats (WKY) and Dahl salt-sensitive rats fed a low salt diet. We caused acute hypertension in some rats with the use of bicuculline (1.2 mg/kg) and aortic occlusion. Rats without acute hypertension served as controls. Blood-brain barrier disruption was quantitated using the brain/blood ratio of 125I-labeled albumin. Acute hypertensive disruption was less in SHR, rats treated with DOCA-NaCl, and Dahl salt-sensitive rats fed a high salt diet, but not in 2K1C rats, as compared with normotensive controls. Acute hypertensive disruption was greater in Dahl salt-sensitive rats fed a low salt diet than in WKY. A series of control WKY, SHR, rats treated with DOCA-NaCl, 2K1C rats, and Dahl salt-sensitive rats fed low or high salt diets, but not subjected to acute hypertension, were also studied. Brain/blood 125I-albumin ratios were significantly less in these control rats not subjected to acute hypertension than in rats subjected to acute hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)