Biomedical subjects
Publications and source records attributed to L Benson.
Angiotensin-converting enzyme inhibitors had no significant effect on cardiopulmonary exercise function in 14 patients who had undergone a Mustard operation for transposition of the great arteries. In some patients aerobic capacity improved and maximum systolic blood pressure decreased.
Noncompaction of the ventricular myocardium, sometimes referred to as "spongy myocardium", appears as excessive and prominent trabeculations and deep intratrabecular recesses within the ventricular wall, usually involving the left ventricle, although the right ventricle and interventricular septum can also be affected. It may occur with or without additional heart malformations. Roifman syndrome is a constellation of antibody deficiency, spondyloepiphyseal dysplasia, facial dysmorphism, growth retardation, and retinal dystrophy. We report a patient with Roifman syndrome who presented with noncompaction of the left ventricular myocardium. Our findings expand the spectrum of diseases associated with noncompaction. The recognition of noncompaction among patients with Roifman syndrome is important, as the immune deficiencies may be subtle and undiagnosed until adulthood. Thus, some patients may first present with cardiac failure.
OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.
OBJECTIVES: Endothelin-1 (ET-1) is a potent peripheral and coronary artery vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during cardiac arrest. The effect of ET-1 on return of spontaneous circulation (ROSC) following cardiac arrest has not been studied. Our hypothesis was that ET-1 does not improve ROSC from cardiac arrest when compared to placebo. METHODS: A total of 11 immature swine were used in this laboratory study. Animals were randomized to receive 300 microg ET-1 and standard dose epinephrine (SDE) or placebo and SDE during arrest. After a 10-min period of no-flow ventricular fibrillation (VF), CPR was performed for 3 min followed by ET-1/SDE or placebo/SDE administration. Following drug administration, standard ACLS was followed with SDE given every 3 min. Aortic pressure was monitored during resuscitation. ROSC was defined as any perfusing rhythm with a systolic pressure greater than 60 mmHg for 60 s. Animals received post-ROSC care as needed for 2 h post-ROSC. CPP and ROSC were analyzed using repeated measures ANOVA and Fischer's exact test respectively. P<0.05 was considered significant. RESULTS: Pre-arrest variables and CPP prior to ET-1 administration were not different between groups. Following ET-1 administration, CPP was significantly increased at all time points in ET-1/SDE versus placebo/SDE animals. ROSC was achieved in 1/5 (20%) ET-1/SDE versus 1/6 (16.7%) placebo/SDE animals (P>0.05). The resuscitated ET-1/SDE animal survived 6.5 min compared to 120 min for the resuscitated placebo/SDE animal. CONCLUSIONS: In our study, ET-1 administration during cardiac arrest increases CPP but does not improve ROSC.
We report a female child who had idiopathic renal magnesium wasting secondary to suspected Gitleman syndrome and cyclosporine A neurotoxicity after a heart transplant. The child had acute, progressive encephalopathy, intractable seizures, quadriparesis, and extensive, bilateral cortical involvement on neuroimaging. Two days after discontinuation of the cyclosporine, the child's condition improved dramatically, including an improved level of consciousness, and she became seizure free. By 6 weeks, she was fully ambulatory. Follow-up magnetic resonance imaging and electroencephalograms demonstrated significant improvement. This patient had drug-induced neurotoxicity, exacerbated by hypomagnesemia. Cyclosporine should be used cautiously in transplant patients with Gitelman syndrome or other acquired magnesium homeostasis disorders because of the possible increased risk of neurotoxicity. This report is the first case of a patient with both cyclosporine neurotoxicity and magnesium-wasting nephropathy.
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A phase III study was performed to compare the efficacy and safety of lamotrigine (Lamictal), desipramine (Norpramin), and placebo in the treatment of unipolar depression. Desipramine is extensively metabolized by cytochrome P450 2D6 (CYP2D6), and kinetics of this compound are altered in poor metabolizers. Genotyping was utilized to exclude poor metabolizers in order to increase subject safety and to eliminate the need to continuously monitor plasma desipramine levels. As part of screening, subjects were genotyped for the *3(A), *4(B), and *5(D) alleles, which identify approximately 95% of poor metabolizers. Extensive metabolizers were eligible for randomization to the lamotrigine, desipramine, or placebo arm. Follow-up genotyping for the *6(T) and *7(E) alleles was performed after study enrollment and was used to identify poor metabolizers who may have been incorrectly identified as extensive metabolizers upon initial three-allele screening. Of 628 subjects screened for *3(A), *4(B), *5(D) alleles, 590 (93.9%) were classified as extensive metabolizers. The remaining 38 (6.1%) subjects were poor metabolizers and excluded. Subsequent *6(T) and *7(E) testing revealed that two poor metabolizers had been enrolled, and the follow-up genotyping provided an explanation for the high desipramine plasma concentrations in one subject. No differences in phenotypic or allelic frequencies were found between the study population and literature populations. However, the frequency of poor metabolizers varied among clinical sites (0-15%). For a compound that is extensively metabolized by CYP2D6, prescreening subjects for *3(A), *4(B), *5(D), *6(T) and *7(E) alleles can increase subject safety and eliminate the need to continuously monitor drug plasma concentrations.
OBJECTIVE: To review the outcomes of transcatheter closure of atrial septal defects using the Cardio-Seal implant. DESIGN: A prospective interventional study. SETTING: Tertiary referral centre. PATIENTS: The first 50 patients (median age 9.7 years) who underwent attempted percutaneous occlusion. INTERVENTIONS: Procedures were done under general anaesthesia and transoesophageal guidance between December 1996 and July 1998. MAIN OUTCOME MEASURES: Success of deployment, complications, and assessment of right ventricular end diastolic diameter, septal wall motion, and occlusion status by echocardiography. RESULTS: The median balloon stretched diameter was 14 mm. Multiple atrial septal defects were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19 (38%). In four patients (8%), a second device was implanted after removal of an initially malpositioned first implant. There were no significant immediate complications. All patients except one were discharged within 24 hours. At the latest follow up (mean 9.9 months) a small shunt was present in 23 patients (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion abnormalities normalised in all but one patient. No predictors for a residual shunt were identified. Supporting arm fractures were detected in seven patients (14%) and protrusion of one arm through the defect in 16 (32%), the latter being more common in those with smaller anterosuperior rims. No untoward effects resulted from arm fractures or protrusion. There were no complications during follow up, although five patients (10%) experienced transient headaches. CONCLUSIONS: The implantation of the Cardio-Seal device corrects the haemodynamic disturbances secondary to the right ventricular volume overload, with good early outcome.
Familial hypertrophic ventricular cardiomyopathy has been demonstrated to be associated with a number of mitochondrial DNA (mtDNA) mutations. A fibroblast cell line carrying a mutation in its mtDNA at position 9997 in the gene encoding tRNA glycine was obtained from a patient with hypertrophic cardiomyopathy. To demonstrate that the etiology of this disease was a result of the mtDNA mutation, cybrid clones were constructed by fusion of enucleated patient skin fibroblasts to rho0 osteosarcoma cells. Clones carrying high levels of mutant mtDNA showed predominantly cytochrome c oxidase and complex I deficiency, as well as an elevated lactate/pyruvate (L/P) ratio, a biochemical marker characteristic of respiratory chain deficiencies. Pulse-labeling experiments demonstrated a strong negative correlation between the levels of newly synthesized mtDNA-encoded polypeptides and glycine content. These data suggest that the T9997C mutation in mtDNA is causative of respiratory chain dysfunction when present at high levels of heteroplasmy.
Subjects screened a set of jobs, retaining those for which they wished to apply and rejecting those that were no longer under consideration. In Experiment 1, subjects who indicated the jobs for which they would apply/not apply screened out fewer jobs than those with instructions to reject/not reject or those with instructions simply to screen (control). There were no differences between the reject and control conditions. Experiment 2 used a design similar to that of Experiment 1, but subjects were made accountable for their screening judgments. The reject-apply discrepancy remained, but the accountability manipulation made the subjects more stringent in their screening compared to those who were not accountable for their judgments. In Experiment 3, subjects were told to consider either the regret resulting from retaining a bad option (regret bad) or the regret from rejecting a good option (regret good). Subjects in the regret bad condition rejected more jobs than did subjects in the regret good condition, but not more than subjects in the control condition. As predicted by image theory, the normal screening process appears to be to screen out the bad options rather than screen in the good options. This is demonstrated by screening in the control condition being similar to screening under the reject instructions (Experiment 1) and under regret bad instructions (Experiment 3), since these conditions were shown to focus attention on the bad options. Copyright 1999 Academic Press.
OBJECTIVES: To evaluate the early results and effectiveness of left ventricular outflow tract enlargement with aortic allograft or pulmonary autograft in children with complex left ventricular outflow tract obstruction. METHOD: The records of 30 children who underwent aortic root enlargement and replacement with either an aortic allograft (22 patients) or pulmonary autograft (8 patients) between January 1987 and June 1997 were reviewed. The predominant diagnosis was complex left ventricular outflow tract obstruction (n = 19), associated with aortic incompetence in 11 children. Before root enlargement, 27 children underwent surgical valvotomy (14 patients), balloon dilatation (10 patients), or both interventions (3 patients). Mean age at root enlargement was 5.4 +/- 3.5 years (range, 2 days-16 years). Most of the children (27 patients) underwent a Konno aortoventriculoplasty. Concomitant septal myectomy was performed in 4 children, mitral valve procedure in 5 children, and endocardial fibroelastosis resection in 1 child. RESULTS: Five children (17%) died in hospital. Four of these were infants less than 2 months old. All had acute aortic incompetence as the result of recent intervention necessitating urgent operation. The fifth child, aged 10 years, died of myocardial failure 2 weeks after the operation. During the follow-up period (mean length, 4.1 +/- 2.8 years), sudden death occurred in 1 child 3 months after the operation. Follow-up echocardiograms (obtained for 23 of the surviving 24 children within 3 +/- 2.3 years) showed a left ventricular outflow tract gradient reduced from a mean of 65 to 11 mm Hg (P =.001); Z value increased from a mean of -0.5 to 4.1 (P <. 001), and aortic incompetence was trivial or mild except in 2 children. CONCLUSION: Urgent aortic root enlargement in decompensating neonates carries higher mortality rates. In older children, the early results of root enlargement and implantation of allograft or autograft are good.
This research examined the process through which justice evaluations are formed. Using image theory's screening process we hypothesized that a rejection threshold exists with regard to violations of just treatment (e.g., laying off an employee without notice). If the number of violations exceeds the decision-maker's threshold, a negative justice evaluation results. Nonviolations (e.g., providing laid-off employees with a generous severance package) were hypothesized to only influence justice evaluations when violations do not exceed the threshold. Three studies compared the impact of justice violations and nonviolations on fairness evaluations. We also examined differences in fairness evaluations operationalized as judgments vs decisions. Results indicated that when making judgments about fairness, both violations and nonviolations are equally important. However, when one has to decide on a course of action based on considerations of fairness, nonviolations are only considered if fewer than three violations have been encountered. These results identify important distinctions between judgment and decisions and have implication for research examining outcomes of justice evaluations. Copyright 1998 Academic Press.
An adolescent girl was seen with acute heart failure 6 days after the onset of a viral illness and otitis media treated with cefaclor. An endomyocardial biopsy specimen revealed active myocarditis with an eosinophilic infiltrate typical of hypersensitivity myocarditis. The patient showed dramatic improvement within 48 hours after withdrawal of the drug and administration of corticosteroids and immunoglobulin.
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In the present study we describe conditions that permit the characterization of noncovalent protein-substrate complexes in aqueous solution by microspray electrospray ionization-mass spectrometry (ESI-MS), using a heated transfer capillary at low temperature (45 degrees C). Specifically, we examined the binding of calmodulin to two polypeptides; the calmodulin-binding domain of calmodulin-dependent protein kinase II (CamK-II) and melittin. Calmodulin, a well known calcium-binding protein, binds to a number of small amphipathic peptides in a calcium-dependent manner. Our results directly show that both peptides form equimolar complexes with calmodulin only in the presence of calcium. The stoichiometry necessary for the formation of each complex was 1:1:4 for calmodulin:peptide (melittin or CamK-II):Ca2+, respectively. Furthermore, it is demonstrated that the detection of the complex in ESI-MS is source temperature dependent.
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OBJECTIVES: This study was undertaken to investigate the long-term outcome of balloon angioplasty for recurrent coarctation of the aorta in a large series of patients. BACKGROUND: Balloon angioplasty has become the standard treatment for residual or recurrent aortic coarctation. Despite the widespread use of this treatment modality, there are few data outlining the long-term outcome of a large patient cohort. METHODS: Clinical, echocardiographic, hemodynamic and angiographic data on 90 consecutive patients who underwent balloon angioplasty between January 1984 and January 1996 were reviewed. RESULTS: Mean systolic pressure gradients were reduced from 31 +/- 21 to 8 +/- 9 mm Hg after dilation (p = 0.0001). The mean diameter of the stenotic site, measured in the frontal and lateral views, increased by 38% and 35%, respectively (p = 0.001). Neurologic events occurred in two patients, with one death. An aortic tear occurred in one patient, requiring surgical intervention. Optimal results were defined as a postprocedure gradient < 20 mm Hg and were obtained acutely in 88% of patients. At long-term follow-up (12 years), 53 (72%) of 74 patients with an early optimal result remained free from reintervention. Transverse arch hypoplasia, defined as an arch dimension < 2 SD below the mean for age, was the primary predictor of the need for reintervention. CONCLUSIONS: Although the majority of patients undergoing percutaneous balloon angioplasty for recoarctation of the aorta will achieve long-term benefit, the need for further surgical intervention in those with transverse arch hypoplasia remains high.