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Biomedical subjects

M Dick

Publications and source records attributed to M Dick.

At least 37 records · Page 2Linked to original sources

A dose-response study of phenylephrine in critically ill, septic surgical patients.

OBJECTIVE: To determine the response of haemodynamic and oxygen-transport parameters to phenylephrine in a dose-response fashion in septic non-hypotensive, vasodilated surgical intensive care unit (ICU) patients. DESIGN: Prospective study. SETTING: Surgical ICU of a tertiary care, university medical centre. PATIENTS: Ten septic non-hypotensive, vasodilated surgical ICU patients. INTERVENTIONS: Routine ICU monitoring, including pulmonary and radial artery catheters. MEASUREMENTS: Haemodynamic and oxygen-transport measurements were taken at baseline and during-therapy. Phenylephrine was infused intravenously for 3 h at progressively increasing doses of 0.5, 1.0, 2.0, 3.0, 4.0, and 8.0 micrograms.kg-1.min-1 at 30-min intervals. Measurements were taken after each dose. RESULTS: Mean arterial pressure (MAP) and systemic vascular resistance (SVRI) increased linearly with phenylephrine dose. Cardiac index and pulmonary artery occlusion pressures did not change. Statistically significant changes were observed in heart rate, MAP, stroke index, and systemic and pulmonary vascular resistance. Eight patients had a clinically significant increase (> 15%) in oxygen consumption (VO2I). Oxygen delivery (D2OI) increased in only three patients. Serum lactate concentrations were unchanged or lower at the end of the study in all eight patients, who displayed a 15% increase in VO2I. CONCLUSIONS: Treatment with phenylephrine increased expected haemodynamic parameters in a linear fashion; however, clinical changes in VO2I occurred at variable doses. Dose-response trials are needed to determine the optimal dose of phenylephrine. Further study is needed to evaluate the clinical effects of phenylephrine in septic patients.

APACHE↗

Transhepatic access to the atrioventricular ring for delivery of radiofrequency energy.

INTRODUCTION: Transcatheter radiofrequency ablation is an effective, safe treatment of arrhythmias in children. However, despite technical advances, patients with obstructed venous access to the heart have not been candidates for this treatment. METHODS AND RESULTS: Two children (8.2 and 10.9 kg) with complex congenital heart disease, supraventricular tachycardia, and obstructed venous access underwent successful radiofrequency ablation of either a right (one patient) or left (one patient) accessory pathway using the transhepatic route to the heart. CONCLUSION: This experience underscores the usefulness of the transhepatic approach in small patients, in patients with limited venous access, and in patients with complex congenital heart disease.

Arterial Occlusive Diseases↗

The E1 protein is mandatory for pore formation by Semliki Forest virus spikes.

Insect cells (Aedes albopictus, clone C6/36) were infected with various variants of Semliki Forest virus including the wild type using the SFV replicon system. The variants included deletion mutants lacking one of the structural proteins and a mutant with a point mutation in p62 (SQL). The latter mutation results in a failure to process p62 to E2 and E3. After infection of the cells with different variant viruses and subsequent expression of viral proteins in the host cell plasma membrane low pH-induced pore formation was detected by measuring the efflux of a radiolabeled compound. The results of these experiments clearly showed that the E1 protein is mandatory for the acid-induced pore formation. A participation of the 6K or C-protein could be excluded. Furthermore, results obtained with the SQL mutant suggest that dissociation of the E1/E2 heterodimer and subsequent homooligomerization of E1 are required for pore formation.

Aedes↗

Gender comparisons of cognitive performances among vascular dementia, Alzheimer disease, and older adults without dementia.

BACKGROUND: We hypothesized that women with Alzheimer disease (AD) would perform worse on a test of semantic memory but not on tests of other cognitive domains. We did not expect that women without dementia would perform more poorly than men without dementia on the same task. OBJECTIVE: To explore the specificity of a semantic memory deficit among women with AD by exploring gender differences among a group of subjects with vascular dementia (VD). DESIGN: A case-control study in which differences between men and women were explored using regression models to control for the potentially confounding effects of age, education, duration of dementia, and severity of dementia. SETTING: Alzheimer's Disease Research Center Consortium of Los Angeles and Orange Counties, California. SUBJECTS: Volunteers, recruited from the community or clinic referrals, who met clinical criteria for AD (n = 159) or VD (n = 117) or met criteria for control status without dementia (n = 134). MAIN OUTCOME MEASURES: Five neuropsychological measures, commonly used in the diagnosis and assessment of dementia. RESULTS: Women with VD scored lower than men with VD on 3 tests. However, when controlling for potential confounds, the gender difference was maintained only for the semantic memory task. Women with AD showed a strong trend to perform worse than men with AD on the test of semantic memory only. No gender differences were found among subjects without dementia. CONCLUSIONS: Findings support the existence of a semantic memory deficit for women with AD and suggest that a similar deficit may exist among women with VD.

Aged↗

Use of the His/RVA electrode catheter in children.

Comprehensive electrophysiologic study with radiofrequency ablation requires a number of intracardiac catheters. To reduce the number of catheters placed in children, the authors evaluated a series of customized catheters that combined the functions of two catheters. The customized 6F catheter contains eight electrodes placed in pairs at 4, 5, 6, 7, or 8 cm from the tip for recording the His electrogram and at the tip for right ventricular pacing. The amplitude of the bundle of His potential recorded through the His right ventricular apex (RVA) catheter (n = 63) and the ventricular pacing threshold (in mA) (n = 48) were measured and compared to the maximal bundle of His potential recorded with a 6F hexapolar catheter in 24 and 13 other patients, respectively. The relationship between the distance from the distal electrode pair at the tip and the third electrode from the tip (the His/RVA distance) and patient size was analyzed in 42 patients. Following the initial study in the 90 patients, the selection of the optimal His/RVA catheter for 19 patients was determined by examining the regression plots derived from the first group of 90 patients. The measured His/RVA distance was then determined by noting the His/RVA distance of the catheter used. Regression analysis was then used to evaluate the fit between the predicted His/RVA distance based on weight, height, or body surface area (BSA) and the observed His/RVA distance. The maximal bundle of His electrogram measured in the two groups using the His/RVA catheter was compared. To evaluate catheter stability during the study, the amplitude of the maximal His potential was measured in the 19 patients at the onset, midpoint, and end of the study. The maximal His potential recorded through the octapolar catheter (0.21 mV) was significantly (P < .04) greater than that recorded through the hexapolar catheter (0.10 mV). The mean ventricular threshold measured through the octapolar catheter (0.44 mA) was significantly (P < .001) less than that measured through the hexapolar catheter (1.13 mA). There was a significant (P < .0001) correlation between BSA, weight, and height and the His/RVA distance. There was no significant difference in the mean maximal amplitude of the His potential (0.21 +/- 0.31 mV vs 0.15 +/- 0.12 mV) recorded through the His/RVA catheter between the two groups. The His/RVA distance estimated by weight, when plotted against the measured distance, demonstrated a good correlation (r = .84) between the expected His/RVA distance based on the subject's weight and that actually observed. In 18 of 19 subjects, the first catheter based on the patient's weight (in kilograms) predicted the appropriate and only catheter used. There was no significant difference in the mean maximal bundle of His electrogram recorded at the beginning of the study (0.15 +/- 0.12 mV), midway into the study (0.15 +/- 0.11 mV), and at the end (0.13 +/- 0.13 mV); however, there was extensive variation within individuals and over time. These data support the recording of a stable, high-quality bundle of His electrogram and RVA pacing through a single catheter system and, hence, have important, practical implications for invasive electrophysiologic studies in children.

Adolescent↗

Vision in dementia: contrast effects.

Contrast sensitivity has been shown to be affected in Alzheimer's disease (Ad). We investigated low contrast acuity and contrast sensitivity using clinical test charts in this patient population. Additionally, we tested patients with vascular dementia (vd) and mixed dementia (md), (Alzheimer' with vascular dementia). Contrast sensitivity was assessed using the Vistech VCTS 6500 test chart. Low contrast acuity was measured using the Regan charts at four contrast levels (96%, 50%, 25% and 11%). The patient population consisted of 19 Ad patients, 9 vd patients and 10 md patients. Reduction in acuity was found with contrast level in all cases. Regression lines were fit to the data and statistical analysis was performed. We did not find a statistically significant difference between the Ad and vd or md groups. We did, however, find a difference between the vd and md groups. We did find reduction in contrast sensitivity at all spatial frequencies when compared to the elderly normal. Correspondingly, we found a significant difference in acuity when compared with normal data at the four contrast levels tested. Acuity is reduced with contrast in all patient groups. Our contrast sensitivity results are similar to those reported in the literature. This study points out the importance of using simple clinical test charts and further underscores the idea that there is a primary visual deficit in Ad.

Aged↗

KVLQT1 mutations in three families with familial or sporadic long QT syndrome.

Congenital long QT syndrome (LQTS) is a heterogeneous group of heritable disorders characterized by prolongation of the QT interval on the electrocardiogram, ventricular arrhythmias and sudden death. At least four genes can, when mutated, produce this phenotype. Of these genes, the recently identified KVLQT1 potassium channel is thought to be the one most commonly responsible. In this study, we used single strand conformational polymorphism (SSCP) analysis to screen two large and nine small LQTS families for mutations of the KVLQT1 potassium channel gene. We identified a novel missense mutation in two unrelated families which substitutes a serine for a conserved glycine in the putative pore region of the KVLQT1 channel. In a third family, a new alanine to valine mutation at a CpG dinucleotide resulted in the spontaneous occurrence of the long QT syndrome in monozygotic twin offspring of unaffected parents. Mutations at this same nucleotide have been observed in eight of the 19 LQTS families determined to have KVLQT1 mutations, suggesting this is a mutational hot spot. Both of these mutations alter the amino acid sequence in, or adjacent to, the pore of the channel and many diminish the channel's ability to conduct a repolarizing potassium current. To date, all KVLQT1 mutations determined to cause the LQTS are missense mutations. These data confirm the role of KVLQT1 in the LQTS and suggest that mutant KVLQT1 proteins may exert a dominant negative effect on repolarizing potassium currents by forming multimers with normal potassium channel protein subunits, dramatically reducing the number of fully-functional KVLQT1 channels.

Amino Acid Sequence↗

The molecular genetics of the congenital long QT syndromes.

During the past half decade, significant insight into the clinical electrocardiographic, and genetic features of the congenital long QT syndromes has emerged. Based on this foundation, recent linkage analysis studies have demonstrated the genetic heterogeneity of the Romano-Ward long QT syndrome and led to the discovery of two of the four (or more) responsible genes. Further functional characterization of these two genes, the HERG potassium channel and the SCN5A voltage-gated cardiac sodium channel, as well as the identification and characterization of the other long QT syndrome genes, may allow improved diagnosis and therapy for these disorders. Furthermore, the increased understanding of myocardial repolarization that is gained from characterization of these genes may lead to improved treatment for other ventricular arrhythmias, including those related to potassium-channel blockade, central nervous system insult, and, possibly, myocardial infarction.

Animals↗

Developmental regulation of expression and activity of multiple forms of the Drosophila RAC protein kinase.

We have characterized the Drosophila homologue of the proto-oncogenic RAC protein kinase (DRAC-PK). The DRAC-PK gene gives rise to two transcripts with the same coding potential, generated by the use of two different polyadenylation signals. Each transcript encodes two polypeptides because of the presence of a weaker initiator ACG codon, upstream from the major AUG, such that the larger protein contains an N-terminal extension. Like the human isoforms, DRAC-PKs possess a novel signaling region, the pleckstrin homology domain. DRAC-PK proteins have a similar expression pattern, being regulated both maternally and zygotically, and are expressed throughout Drosophila development. Antisera specific for recombinant DRAC-PK and for its C terminus detected two polypeptides of 66 and 85 kDa in Drosophila extracts. The antirecombinant antisera also recognized a polypeptide of 120 kDa from Drosophila, which apparently shared an epitope related to DRAC-PK sequences. The role of p120 appears to be restricted compared with that of DRAC-PK, since it was not detected in larvae or adult flies. There was no spatial restriction of DRAC-PK expression during embryogenesis, suggesting that localized activation might be a regulatory mechanism for its function. DRAC-PK possesses an intrinsic kinase activity that is approximately 8-fold higher in adult flies than in 0-3-h embryos undergoing rapid mitotic cycles.

Amino Acid Sequence↗

Catheter interruption of atrioventricular conduction using radiofrequency energy in a patient with transposition of the great arteries.

Percutaneous catheter mapping and radiofrequency ablation of the AV node-His bundle system (with subsequent transvenous endocardial ventricular pacing) were performed on an 18-year-old woman with transposition of the great arteries and intact ventricular septum and chronic arrhythmias 15 years following a Mustard operation. Exclusion of the AV conduction tissue from the systemic venous circulation by the complex anatomy and the Mustard repair was circumvented by a retrograde approach across the aortic valve to the morphological right ventricle yielding access to the AV node-His bundle system.

Adolescent↗

Peritoneal migration of an abdominally implanted epicardial pacemaker: a cause of intestinal obstruction.

We report the case of a 10-year-old child with an abdominally implanted epicardial pacemaker that eroded through the peritoneum and migrated to an intraperitoneal location, resulting in partial and then complete intestinal obstruction. This potentially life-threatening complication should be considered when a patient with an abdominally implanted pacemaker presents with abdominal pain.

Child↗

The use of radiofrequency energy in pediatric cardiology.

The use of radiofrequency energy for the treatment of supraventricular tachycardia in pediatric patients has gained widespread acceptance, especially for tachyarrhythmias associated with palpitations, dizziness, presyncope or syncope, cardiomyopathy, and cardiac arrest. Ablation of the substrate supporting atrioventricular reentry, atrioventricular node reentry, and automatic atrial tachycardia yields a 90%-98% success rate with low incidence (< 1%) of complications and adverse side-effects. Ablation of intra-atrial reentry, including atrial flutter and fibrillation, appears to be promising and would be a significant advance in the management of patients following extensive atrial surgery for congenital heart disease. Radiofrequency energy is also used to treat various forms of idiopathic ventricular tachycardia. Finally, radiofrequency energy has been extended to control the ventricular rate associated with malignant atrial tachycardia by either modification or ablation of the atrioventricular node, and subsequent pacemaker implant. Long-term outcome of radiofrequency ablation is unknown, but the short-to-intermediate (1-5 yrs) outcome is excellent, with low recurrence rate of the tachycardia, no proarrhythmic effect, and excellent clinical state.

Catheter Ablation↗

Haemophilus influenzae type B invasive disease in urban and rural children: immunization patterns and prevalence of disease.

To examine the impact of the introduction of Haemophilus influenzae type b (Hib) conjugate vaccine, we reviewed the incidence of Hib invasive disease in the state of Florida from 1984 to 1992. We analyzed the incidence of disease in two populations of children, one residing in an urban area and the other in a rural area. This study was designed to compare incidence rates prior to and following the introduction of Hib vaccine for children. Our data show a > 80% decrease in the incidence of Hib invasive disease in the state of Florida and a similar decrease in both the urban and rural populations examined. Analysis of the data revealed that the majority of children contracting Haemophilus influenzae type b invasive disease in both populations were either not immunized or were only partially immunized.

Child, Preschool↗

Usefulness of the bidirectional Glenn procedure as staged reconstruction for the functional single ventricle.

The bidirectional Glenn operation may be particularly useful as an intermediate procedure before Fontan correction in high-risk patients. From October 1989 through February 1992, 50 patients 1 to 60 months old (median 12) have undergone a bidirectional Glenn operation. Diagnoses included hypoplastic left heart syndrome in 21 patients, pulmonary atresia with intact ventricular septum in 10, tricuspid valve atresia in 9, other complex univentricular heart defects in 9, and Ebstein's anomaly in 1. Mean pulmonary vascular resistance was 2.2 +/- 0.2 Wood U (range 0.5 to 7.3) and mean pulmonary artery area Nakata index was 318 +/- mm2/m2 (range 80 to 821). Additional procedures were performed in 17 patients, including pulmonary artery reconstruction in 15 (29%) and bilateral caval anastomoses in 5 (10%). There were 4 hospital deaths (8%). Two deaths resulted from myocardial infarction in patients with pulmonary atresia with intact ventricular septum and sinusoids and 1 from severe pulmonary vascular disease in a patient with hypoplastic left heart syndrome. There was 1 late death from pneumonia. Actuarial survival is 92 +/- 4% at 1 month and beyond, with a mean follow-up of 13.4 +/- 1 months. Risk factor analysis showed that pulmonary vascular resistance > 3 Wood U and pulmonary artery distortion were associated with increased mortality. Twelve patients have undergone a Fontan procedure at a mean duration after bidirectional Glenn of 18 months with 1 death (8%). The bidirectional Glenn procedure provides excellent palliation in high-risk patients and appears useful as a staging procedure before Fontan correction.

Anastomosis, Surgical↗