Large diaphyseal-incorporating allograft prosthetic composites: when, how, and why : Treatment of advanced proximal humeral bone loss.

BACKGROUND: Proximal humeral bone loss in shoulder arthroplasty is a complex problem with a heterogeneous presentation. Different etiologies may contribute to varying degrees of severity in bone loss that dictate different treatment approaches. OBJECTIVES: The purpose of this is article is to describe our technique for treatment of proximal humeral bone loss with proximal humeral allograft prosthetic composites (APC) and identify factors that may predict when larger allografts may be necessary. MATERIALS AND METHODS: Ninety-nine patients were identified that had undergone reverse total shoulder arthroplasty with use of a proximal humeral allograft. Thirty-nine of these had large allografts that involved a significant portion of the diaphysis. Preoperative characteristics were examined to identify factors that may be associated with use of a larger diaphyseal-incorporating allograft. RESULTS: Well-fixed humeral stems could be treated with short metaphyseal allografts in 55 of 65 (85%) cases. Loose stems required longer diaphyseal-incorporating allografts in 28 of 31 (90%) cases, and these were commonly associated with periprosthetic fractures (n = 10), failed prior APC (n = 6), and infection (n = 5). Noncemented stems required diaphyseal grafts in 75% of cases, compared to cemented stems which required larger grafts in 34% of cases. CONCLUSIONS: Proximal humeral bone loss in the setting of revision shoulder arthroplasty can be successfully managed with a reverse total shoulder and proximal humeral allograft. Larger allografts are frequently required for loose humeral stems, and noncemented stems appear more likely to require larger allografts than cemented stems.

Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement.

OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis.

The purpose of this study was to compare the clinical and quantitative magnetic resonance imaging metrics of paediatric-onset multiple sclerosis to adult-onset multiple sclerosis. It was a prospective comparison of clinical and magnetic resonance imaging characteristics of two paediatric onset multiple sclerosis and two adult onset multiple sclerosis groups that were matched for disease duration. The paediatric-onset-C group consisted of children with paediatric-onset multiple sclerosis with mean disease duration of 2.7 years, whereas the paediatric onset-A group consisted of adults with mean disease duration of 20 years. The adult onset multiple sclerosis-1 and adult onset multiple sclerosis-2 groups were matched to the paediatric onset-C and paediatric onset-A groups. The brain magnetic resonance imaging measures included: T(1)-, T(2)- and gadolinium contrast-enhancing volumes and the T(2)-lesion volume relative magnetization transfer ratio, global and tissue specific white and grey matter brain atrophy and normal appearing grey and white matter magnetization transfer ratio. Regression analyses were employed for magnetic resonance imaging measures. The paediatric onset multiple sclerosis-C (n = 17) and adult onset multiple sclerosis-1 (n = 81) groups had mean disease duration values of 2.7 +/- standard deviation 2.0 and 2.6 +/- 1.1 years, respectively. The paediatric onset multiple sclerosis-A group (n = 33) and adult onset multiple sclerosis-2 group (n = 300) had mean disease durations of 20 +/- standard deviation 10.9 and 20 +/- 9.3 years, respectively. In regression analysis, the T(2)- lesion volume of the paediatric onset multiple sclerosis-C and adult onset multiple sclerosis-1 groups were similar but there was a trend toward higher T(1)- lesion volume (P = 0.028) in the paediatric onset group. The brain parenchymal fraction and grey matter fraction in the paediatric-onset multiple sclerosis-C group were higher than those for the adult onset multiple sclerosis-1 group (both P < 0.001). The frequency of progressive multiple sclerosis in the paediatric onset multiple sclerosis-A group (27.3%) trended lower (odds ratio = 0.43, P = 0.042) than that in the adult onset multiple sclerosis-2 group (46.3%). The Expanded Disability Status Scale (median; inter-quartile range) in the paediatric onset multiple sclerosis-A group (2.25; 2.5) trended lower (P = 0.058) compared with the adult onset multiple sclerosis-2 group (3.5; 4.0). There was a trend toward lower magnetization transfer ratio values in T(2)-lesions, normal appearing grey matter and normal appearing white matter and higher grey matter fraction in the paediatric onset multiple sclerosis-A group compared with the adult onset multiple sclerosis-2 group. There was no evidence for differences on T(2)-lesion volume, T(1)-lesion volume, brain parenchymal fraction or white matter fraction. Paediatric-onset multiple sclerosis is characterized by a significant disease burden both early and later in the disease course. Despite this, disability is slower to accrue in paediatric onset multiple sclerosis than adult onset multiple sclerosis.

Apolipoprotein E ε4-positive multiple sclerosis patients develop more gray-matter and whole-brain atrophy: a 15-year disease history model based on a 4-year longitudinal study.

Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4- year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.

DDT residues in marine phytoplankton: increase from 1955 to 1969.

Phytoplankton samples collected in Monterey Bay, California, from 1955 to 1969 contained compounds identified as p,p'-DDT, p,p'-DDD, and p,p'-DDE. Total concentrations of these compounds were approximately three times greater in the later samples. Lower concentrations throughout the period were associated with higher densities of standing crop.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics.

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study.

BACKGROUND: There is growing evidence for the concept of multiple sclerosis (MS) as an inflammatory neurodegenerative disease, with a different pattern of atrophy evolution in grey matter (GM) and white matter (WM) tissue compartments. OBJECTIVE: We aimed to investigate the evolution of different MRI measures in early relapsing-remitting patients with MS and in normal controls (NCs) over 2 years. We also evaluated the progression of these MRI measures in a subset of patients who were followed for up to 5 years. METHODS: Included in this study were 147 patients who participated in the combination ASA (Avonex Steroids Azathioprine) study and completed full treatment, clinical and MRI assessment at 0, 12 and 24 months. A subgroup of 66 patients was followed for 36 months, 51 patients for 48 months and 43 patients for 60 months. Mean age at baseline was 30.7 years, mean disease duration was 5.5 years, mean EDSS was 1.8 and mean annualised relapse rate before study entry was 1.7. MRI scans were performed on a 1.5T scanner every 2 months for the first 2 years and thereafter once yearly for up to 5 years. In addition to the MS group, 27 NCs were examined at months 0, 12 and 24 using the same MRI protocol. Percentage brain volume change (PBVC), GM volume (GMV), WM volume (WMV) and peripheral grey volume (PGV) were measured annually using SIENA/X software. T2-hyperintense lesion volume (LV), lateral ventricle volume (LVV) and third ventricle width (3VW) were also assessed annually. RESULTS: Over the period of 0-24 months, patients with MS lost significantly more GMV (-2.6% vs -0.72%, p<0.001), PGV (-2.4% vs -1.03%, p<0.001) and PBVC (-1.2% vs -0.22%, p<0.001), and increased in LVV (+16.6% vs +0.55%, p<0.003) and 3VW (+9.3% vs 0%, p = 0.003), when compared with NCs. Within-person change in MRI measures for patients with MS over 5 years was -4.2% for PBVC, -6.2% for GMV, -5.8% for PGV, -0.5% for WMV (all p<0.001), +68.7 for LVV (p<0.001), +4% for 3VW (p<0.001) and +42% for T2-LV (p<0.001). CONCLUSIONS: Our study confirmed a different pattern of GM, WM and central atrophy progression over 2 years between patients with MS and NCs. The study showed a different evolution of tissue compartment atrophy measures in patients with MS, with faster decline in cortical and deep GM regions, as well as periventricular WM regions, over a 5-year period.

Managed delay for coronary artery bypass graft surgery: the experience at one Canadian center.

OBJECTIVES: This study sought to assess the impact of delaying coronary artery bypass surgery at one Canadian academic tertiary referral center. BACKGROUND: Universal access to medical services in Canada comes at the expense of waiting lists whose impact has been incompletely assessed. METHODS: A prospective, observational study of all residents of Nova Scotia and Prince Edward Island accepted for bypass surgery between 1 April 1992 and 31 October 1992 was undertaken to determine 1) whether triage guidelines were being followed; and 2) the incidence of cardiac death, nonfatal myocardial infarction and worsening symptoms associated with delayed operation. The analysis had 90% power to detect a mortality rate of > or = 3% (alpha 0.05). RESULTS: Of 423 patients referred, 35% were triaged as urgent, 9.7% as semiurgent A, 39% as semiurgent B and 16.3% as elective, with no age or gender bias identified. Operation occurred at < or = 1 week in 25%, < or = 1 month in 47%, and >6 months in 1.4%. There were no nonfatal myocardial infarctions, but five cardiac deaths occurred (1.2%). Of 275 patients not initially classified as urgent, 12.4% required reclassification to higher priorities because of worsening symptoms; none had perioperative myocardial infarction or died. One in four patients queued longer than target waiting times. Only 4% of patients considered prioritization on the basis of medical need unfair, but 64% experienced at least moderate anxiety. CONCLUSION: This triage system equitably stratified patients to a queue. Deaths were rare and could not be attributed to the triage process. Patients with worsening clinical status were safely accommodated with earlier waiting times, but concerns remain regarding excessive waiting times and patient anxiety.

Impact of clinical history and electrophysiologic characterization of accessory pathways on management strategies to reduce sudden death among children with Wolff-Parkinson-White syndrome.

OBJECTIVES: This study sought to determine whether the clinical and electrophysiologic criteria developed in adults also identify children with Wolff-Parkinson-White syndrome at risk for sudden death. BACKGROUND: In adults with Wolff-Parkinson-White syndrome, a shortest RR interval <220 ms during atrial fibrillation is a sensitive marker for sudden death. However, because reliance on the shortest RR interval has a low positive predictive value, the clinical history has assumed a pivotal role in assessing risk. This approach has not been evaluated in children. METHODS: We retrospectively evaluated 60 children

Effect of the right ventricular isolation procedure on ventricular vulnerability to fibrillation.

A certain critical mass of myocardium is believed to be necessary to initiate ventricular fibrillation. The right ventricular isolation procedure, employed clinically to confine ventricular tachyarrhythmias to the right ventricle, decreases the ventricular mass available for fibrillation by isolating the ventricles from each other. The effect of this procedure on ventricular fibrillation thresholds is unknown. Left and right ventricular fibrillation thresholds were measured before and after right ventricular isolation in 10 adult mongrel dogs utilizing a single 5 ms stimulus of increasing current strength applied to the epicardium during the vulnerable period. There were no significant differences in heart rate, aortic blood pressure, left atrial pressure, temperature, arterial blood gases or regional myocardial blood flow between the study periods. In 9 of the 10 dogs, the isolated right ventricle could not sustain ventricular fibrillation despite the utilization of stimulus strengths of up to 80 mA. In the 10th dog, the right ventricular fibrillation threshold increased 150%, from 20 to 50 mA. The left ventricular fibrillation threshold markedly increased in every dog, with an average increase from 23 +/- 2 to 40 +/- 4 mA (p less than 0.0005). To determine whether time, cardiopulmonary bypass or the right ventricular incision could cause similar changes in ventricular fibrillation threshold, five different dogs underwent the entire experimental protocol except for incomplete isolation of the right ventricle. There were no significant changes in ventricular fibrillation thresholds in these dogs. Thus, in the canine model, right ventricular isolation can prevent the occurrence of sustained fibrillation in the isolated right ventricle and can significantly increase the left ventricular fibrillation threshold.

Hemodynamic importance of systolic ventricular interaction, augmented right atrial contractility and atrioventricular synchrony in acute right ventricular dysfunction.

To delineate the determinants of right ventricular performance with acute right ventricular dysfunction, surgical electrical isolation of the right ventricular free wall was produced in 13 dogs. During atrioventricular (AV) pacing, hemodynamic and wall motion measurements were normal. When not paced, the right ventricular free wall became asystolic, resulting in a depressed and bifid right ventricular systolic pressure (33 +/- 5 to 18 +/- 4 mm Hg) and decreased left ventricular systolic pressure (100 +/- 18 to 80 +/- 18 mm Hg) and stroke volume (14 +/- 4 to 10.3 +/- 3.5 ml) (all p less than 0.05). Ultrasound demonstrated right ventricular free wall dyskinesia, increased right ventricular end-diastolic size (155 +/- 13% of control), but decreased left ventricular size (69 +/- 11% of control) (both p less than 0.05). Right atrial pressure increased (5.8 +/- 2.5 to 7.6 +/- 2.8 mm Hg, p less than 0.05) with an augmented A wave and blunted Y descent, indicating pandiastolic right ventricular dysfunction. The septum demonstrated reversed curvature in diastole and bulged paradoxically into the right ventricle during early systole, generating the initial peak of right ventricular pressure and reducing its volume. Later, posterior septal motion coincided with maximal left ventricular pressure and the second peak of the right ventricular waveform. Left ventricular pacing alone led to further decreases in right ventricular systolic pressure and size, left ventricular systolic pressure and stroke volume. The previously augmented A wave was replaced by a prominent V wave. Therefore, when contractility of its free wall is acutely depressed, right ventricular performance is dependent on left ventricular-septal contractile contributions transmitted by the septum.(ABSTRACT TRUNCATED AT 250 WORDS)

Right atrial ischemia exacerbates hemodynamic compromise associated with experimental right ventricular dysfunction.

To determine the importance of right atrial function with acute right ventricular dysfunction, sequential right ventricular and right atrial ischemia were induced in 15 dogs. Right ventricular ischemia resulted in right ventricular free wall dyskinesia, right ventricular dilation by ultrasound, elevated right ventricular filling pressure and paradoxic septal motion. There were decrements in right ventricular systolic pressure (28.9 +/- 5.5 to 25.5 +/- 4.6 mm Hg) (p less than 0.05 for these and all subsequent values) and stroke work (5.66 +/- 0.94 to 2.66 +/- 0.62 g.m/m2), resulting in reductions in left ventricular preload, systolic pressure (123 +/- 11 to 97 +/- 12 mm Hg) and stroke volume (24.2 +/- 4.3 to 19.1 +/- 5.2 ml). Right atrial contractility was augmented, as indicated by increases in peak A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.22 +/- 0.02 to 1.46 +/- 0.3) and right atrial stroke work (0.11 +/- 0.02 to 0.25 +/- 0.05 g.m/m2). Right atrial ischemia depressed right atrial contraction, as indicated by decreased A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.46 +/- 0.3 to 1.04 +/- 0.2) and stroke work (0.25 +/- 0.05 to 0.04 +/- 0.01 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of distant potentials on unipolar electrograms in an animal model utilizing the right ventricular isolation procedure.

The effects of distant potentials on local epicardial unipolar electrograms were examined utilizing a model that enabled both ventricles to be paced independently in five dogs. The right ventricular isolation procedure electrically isolates the right from the left ventricle. Right ventricular electrograms were separated into their local (right ventricular) and distant (left ventricular) components by altering the left-right ventricular pacing interval. Waveform configuration, peak to peak amplitude, magnitude of the slope and timing of the fastest downstroke were carefully evaluated at each electrode site, both with and without the presence of distant left ventricular potentials. Except for the timing of the fastest downstroke, all of these variables were significantly altered by distant potentials. Although the slope of the fastest downstroke was significantly affected by distant potentials, it remained a sensitive indicator of local versus distant activation. All electrograms of local right ventricular activation had a slope magnitude greater than 2.5 mV/2 ms whereas none of the right ventricular electrograms containing only distant left ventricular activity had a magnitude greater than 2.5 mV/2 ms. Computer-generated electrograms were calculated by digitally summing the recorded local right and distant left ventricular components. The simulated electrograms correlated well with the recorded electrograms during synchronous ventricular pacing. Thus, the configuration, amplitude and slope of unipolar electrodes were profoundly influenced by distant potentials. The timing of the fastest downstroke is largely independent of the effect of distant potentials and most closely represents local activation. The magnitude of the slope of the recorded electrogram accurately distinguishes local from distant activation.

Importance of left ventricular function and systolic ventricular interaction to right ventricular performance during acute right heart ischemia.

To determine whether modulation of systolic ventricular interaction influences right ventricular performance during right heart ischemia, the effects of septal ischemia and inotropic stimulation were studied in 15 dogs in an open chest preparation. Right coronary branch occlusions led to right ventricular dilation and free wall dyskinesia, reversed septal curvature and reduced left ventricular diastolic volume. In systole, the septum thickened but bulged paradoxically into the right ventricle generating an active but depressed right ventricular systolic pressure (28.9 +/- 5.5 to 22.1 +/- 4.5 mm Hg), with associated decreases in right ventricular stroke work (5.66 +/- 0.94 to 1.92 +/- 0.53 g.m/m2) and left ventricular systolic pressure (123 +/- 11 to 80 +/- 10 mm Hg). Septal ischemia induced systolic septal thinning, left ventricular dilation and decreased left ventricular systolic pressure (80 +/- 10 to 55 +/- 10 mm Hg) and stroke work. Although the extent of paradoxic septal displacement increased, there were further decrements in right ventricular systolic pressure (22.1 +/- 4.5 to 18.7 +/- 4.3 mm Hg) and stroke work (1.92 +/- 0.53 to 0.7 +/- 0.2 g.m/m2). Dopamine infusion augmented left ventricular free wall contraction and increased left ventricular systolic pressure (55 +/- 10 to 172 +/- 17 mm Hg) and stroke work. Although systolic septal thinning persisted, the extent of paradoxic septal displacement increased strikingly and, despite continued right ventricular free wall dyskinesia, right ventricular systolic pressure increased (18.7 +/- 4.3 to 39.6 +/- 6.2 mm Hg) as did right ventricular stroke work (0.7 +/- 0.2 to 7 +/- 1.6 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

OBJECTIVES: The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. BACKGROUND: Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. METHODS: The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. RESULTS: The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. CONCLUSIONS: Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Spontaneous atrial flutter in a chronic canine model of the modified Fontan operation.

OBJECTIVES: This study sought to 1) establish whether the atrial flutter (AFL) inducible acutely occurs spontaneously in a chronic canine model, and 2) characterize any reentrant circuits present chronically. BACKGROUND: We previously demonstrated, in an acute canine model of the modified Fontan operation, that the lateral tunnel suture line creates a sufficient electrophysiologic substrate for AFL. METHODS: Using cardiopulmonary bypass, a suture line was placed through a right atriotomy in adult dogs (n = 7) to simulate the lateral tunnel of the Fontan operation. Holter recordings were made preoperatively, on the first postoperative day and 2, 4 and 6 weeks postoperatively. At 6 to 8 weeks, through bilateral ventriculotomies, 253-point unipolar atrial electrodes were inserted. AFL was induced using atrial burst pacing, and endocardial activation sequence maps were created. RESULTS: Preoperatively, all dogs were in sinus rhythm. Spontaneous AFL occurred in all dogs postoperatively, with a mean (+/-SD) cycle length of 192 +/- 22 ms. At 6 weeks postoperatively, of six dogs that survived, four had intermittent AFL, and two had incessant AFL. At reoperation, sustained AFL was inducible in six of six dogs, with a mean cycle length of 194 +/- 17 ms. Activation sequence maps demonstrated conduction block at the lateral tunnel suture line, which facilitated unidirectional conduction critical for propagation of the reentrant circuit. The AFL circuit was similar to that observed acutely. CONCLUSIONS: In a chronic canine model of the modified Fontan operation, the lateral tunnel suture line alone, in the absence of atrial stretch or hypertension, provides an electrophysiologic substrate that promotes spontaneous AFL. This model may be useful for evaluating various forms of treatment and prevention of AFL after the Fontan operation.

Pericardiocentesis guided by a pulse generator.

This study was performed to compare pericardiocentesis guided by a pacing current applied through the pericardiocentesis needle with the traditional method of monitoring ST segment elevation from the needle tip electrogram. ST segment elevation was measured at 3 mm from the epicardium, after epicardial contact, after epicardial penetration and again at 3 mm from the epicardium after epicardial penetration. Two millivolts of ST segment elevation gave the highest combined positive (86%) and negative (79%) predictive value for epicardial contact by the pericardiocentesis needle between the two groups with the largest difference: 3 mm from the epicardium before contact and after epicardial penetration. Therefore, ST segment monitoring cannot reliably determine the point of epicardial contact. To determine the optimal stimulus strength for pulse generator-guided pericardiocentesis, pacing studies were performed using 2, 4, 6, 8 and 10 mA unipolar stimulus strengths. The pacing studies were performed both with and without a hemodynamically significant pericardial effusion to determine if increased pericardial pressure altered the pacing threshold. A 4 mA unipolar cathodal stimulus was chosen because it captured the ventricle only with direct contact of the epicardium. Ten dogs were instrumented and cardiac tamponade produced so that a subxiphoid approach to the epicardium with the pacing needle electrode could be attempted. During pericardiocentesis, needle tip electrograms were recorded, alternating with pacing attempts using a 4 mA unipolar stimulus. In all 10 dogs, the effusion was entered and epicardium was contacted as indicated by capture. No myocardial perforation or coronary artery or venous injuries were produced. These findings support the use of a pulse generator to guide pericardiocentesis.

Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries.

OBJECTIVES: We assessed the use and effects of acute intravenous and later oral atenolol treatment in a prospectively planned post hoc analysis of the GUSTO-I dataset. BACKGROUND: Early intravenous beta blockade is generally recommended after myocardial infarction, especially for patients with tachycardia and/or hypertension and those without heart failure. METHODS: Besides one of four thrombolytic strategies, patients without hypotension, bradycardia or signs of heart failure were to receive atenolol 5 mg intravenously as soon as possible, another 5 mg intravenously 10 min later and 50 to 100 mg orally daily during hospitalization. We compared the 30-day mortality of patients given no atenolol (n=10,073), any atenolol (n=30,771), any intravenous atenolol (n=18,200), only oral atenolol (n=12,545) and both intravenous and oral drug (n=16,406), after controlling for baseline differences and for early deaths (before oral atenolol could be given). RESULTS: Patients given any atenolol had a lower baseline risk than those not given atenolol. Adjusted 30-day mortality was significantly lower in atenolol-treated patients, but patients treated with intravenous and oral atenolol treatment vs. oral treatment alone were more likely to die (odds ratio, 1.3; 95% confidence interval, 1.0 to 1.5; p=0.02). Subgroups had similar rates of stroke, intracranial hemorrhage and reinfarction, but intravenous atenolol use was associated with more heart failure, shock, recurrent ischemia and pacemaker use than oral atenolol use. CONCLUSIONS: Although atenolol appears to improve outcomes after thrombolysis for myocardial infarction, early intravenous atenolol seems of limited value. The best approach for most patients may be to begin oral atenolol once stable.

Structure, organization and regulation of a rat cysteine proteinase inhibitor-encoding gene.

During postnatal development, submandibular glands of rats produce the secretory protein, cystatin S (CysS), which belongs to family 2 of the mammalian cysteine proteinase inhibitor superfamily. While the rat CysS gene is not expressed in the salivary glands of adult rats, it can be induced by isoproterenol (IPR), which acts via beta-adrenergic receptor/adenylate cyclase/cyclic AMP (cAMP) mechanisms. In addition, IPR-induction of CysS mRNA in submandibular glands is more pronounced in females than in males, at both prepuberal and mature ages. These results suggest that sex hormones may participate in the regulation of the rat CysS gene via estrogen-responsive elements (ERE), and IPR induction of this gene supports the hypothesis that cAMP-responsive elements (CRE) may also play a role in regulating CysS gene expression. We have isolated, sequenced and characterized the complete gene. The CysS gene contains three exons interrupted by two intervening sequences, with consensus splice junctions. The transcription start point is 73 nucleotides upstream from the start codon which is surrounded by a typical Kozak sequence. CCAAT and TATA boxes are present in the 5'-flanking region of the CysS gene. This region also contains several possible regulatory elements that resemble those of other eukaryotic genes, i.e., ERE, CRE, and glucocorticoid-responsive elements. The first intron sequence contains other potential CRE highly homologous to those found in the IPR-inducible mouse and hamster proline-rich-protein-encoding genes.

The complete nucleotide sequence of the ilvGMEDA cluster of Escherichia coli K-12.

The ilvGMEDA gene cluster of Escherichia coli K-12 has been the focus of intensive genetic and biochemical analysis for the past 30 years. Genetic regulation of the ilvGMEDA cluster involves attenuation, internal promoters, internal Rho-dependent termination sites, a site of polarity in the ilvG pseudogene of the wild-type organism, and autoregulation by the ilvA gene product, the biosynthetic L-threonine deaminase. We have now completed the nucleotide sequence of the 6600-bp cluster and have analyzed it, along with the ilvYC, ilvBN, and ilvIH genes, for codon frequencies and possible evolutionary relationships. The isoleucine content of each of the gene products of the ilvGMEDA cluster is quite similar (less than a two-fold variation), thus excluding one possible interpretation of the isoleucine-specific downstream amplification phenomenon. There is no evidence for retrograde evolution in the cluster since no significant homologies are detectable among genes that catalyze sequential reactions of the pathway. A highly significant homology does exist, however, between the threonine deaminases of yeast mitochondria and E. coli. The sequence at the boundary of the ilvA and ilvD genes is TAATAATG, so that the second TAA stop codon of ilvD overlaps the ATG initiation codon of ilvA.