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Biomedical subjects

J L Robinson

Publications and source records attributed to J L Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1995

SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome.

Long QT syndrome (LQT) is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. We previously mapped three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene. Single strand conformation polymorphism and DNA sequence analyses reveal identical intragenic deletions of SCN5A in affected members of two unrelated LQT families. The deleted sequences reside in a region that is important for channel inactivation. These data suggest that mutations in SCN5A cause chromosome 3-linked LQT and indicate a likely cellular mechanism for this disorder.

Amino Acid Sequence↗
PubMed1995

Risk of cardiac events in family members of patients with long QT syndrome.

OBJECTIVES: This study sought to identify risk factors for cardiac events (syncope, aborted cardiac arrest or sudden cardiac death) in family members of patients with the long QT syndrome. BACKGROUND: Patients with the long QT syndrome are known to be at high risk for cardiac events. Whenever the first member of a family is identified as having the long QT syndrome (proband), there is concern regarding the likelihood of cardiac events in other family members. METHODS: A multivariate logistic regression model was used to evaluate the risk of cardiac events in 637 family members who were first- and second-degree relatives of 151 probands with the long QT syndrome and in a subset of 513 family members who were not receiving beta-adrenergic blocking agents. There were 293 first-degree (46%) and 344 second-degree relatives (54%) (293 men [46%], 344 women [54%]). Fifteen percent of the family members had a corrected QT interval (QTc) > 0.44 s, and relative tachycardia and bradycardia were observed in 12% and 25%, respectively. RESULTS: The risk of cardiac events occurring before age 40 in family members not taking beta-blockers was influenced by the QTc interval (odds ratio [OR] 1.18/0.01 increase in QTc value; 95% confidence interval [CI] 1.12 to 1.24), relative tachycardia (OR 2.21, 95% CI 0.97 to 5.02) or bradycardia (OR 2.24, 95% CI 1.10 to 4.56) and an interaction term combining gender and closeness of the relationship to the proband (OR for female first-degree relative 3.23 vs. all second-degree relatives, 95% CI 1.67-6.22). CONCLUSIONS: Female first-degree relatives of patients with the long QT syndrome have a higher risk of cardiac events than male first- or second-degree relatives, independent of recorded electrocardiographic findings. Not only bradycardia, but also tachycardia increases risk of cardiac events in family members of patients with the long QT syndrome.

Adolescent↗
PubMed1994

The stereospecific effects of isoflurane isomers in vivo.

The anesthetic potency of racemic isoflurane and the optically pure stereoisomers was examined in rats. The (+) isomer was 53% more potent than the (-) isomer (minimum alveolar concentration (MAC) = 1.06 +/- 0.07% vs. 1.62 +/- 0.02%, P < 0.05). MAC for racemic isoflurane was 1.32 +/- 0.03%. Both stereoisomers and the racemic isoflurane produced similar depression of arterial pressure. However, the (+) isomer blunted the cardiovascular response to a painful stimulus to a greater extent than did an equi-MAC dose of the (-) isomer. These are the first data to describe pharmacological differences between stereoisomers of a volatile anesthetic administered in vivo by the conventional route (inhaled) and measuring the clinically relevant index of anesthesia, MAC. These data are consistent with a receptor-mediated anesthetic mechanism by volatile anesthetics.

Anesthesia Recovery Period↗
PubMed1994

Wildlife as hosts for ticks (Acari) in Antigua, West Indies.

A survey was conducted to determine the status of wild mammals and birds as hosts for Amblyomma variegatum (F.) and other tick species in Antigua. Surveys of wild mammals and birds were conducted periodically from September 1988 through May 1991. Wild mammals surveyed included the small Indian mongoose (Herpestes auropunctatus Hodgson), Norway rat (Rattus norvegicus Berkenhout), and house mouse (Mus musculus L.), but only mongooses were surveyed intensively. Larvae and nymphs of A. variegatum, larvae of Boophilus microplus (Canestrini), and larvae of Ornithodoros puertoricensis (Fox) were recovered. The mean prevalences of infestation of mongooses by A. variegatum larvae and nymphs were 4.7 and 1.3%, respectively; maximums were 16.1 and 5.0%, respectively. The mean prevalence of infestation of mongooses by B. microplus was 3.2%. O. puertoricensis is reported from Antigua for the first time. The mean prevalence of infestation of mongooses by O. puertoricensis larvae was 41.2%, but seasonal prevalences ranged from 27.8 to 55.0%. Of 610 birds representing 16 species, three Carib grackles (Quiscalus lugubris Swainson) were each infested with one larva of A. variegatum.

Animals↗
PubMed1994

Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families.

BACKGROUND: The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity). METHODS AND RESULTS: Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QTc) were determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at theta = 0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at theta = 0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P < .0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P < .001). CONCLUSIONS: In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P < .001) demonstrated for this disorder.

Base Sequence↗
PubMed1994

The influence of the AGSM, PBG, and anti-G suit inflation on thoracic hemodynamics during +Gz in swine.

With the advent of pressure breathing for +Gz (head-to-foot inertial loading) protection (PBG) and the development of improved extended coverage anti-G suits (ECGS) it has become important to expand our knowledge of the cardiopulmonary physiologic interrelationships of pressure breathing, anti-G suit protection, and the anti-G straining maneuver (AGSM). Although high levels of pressure breathing have been previously investigated, there was continuing concern within the aeromedical community regarding the introduction of COMBAT EDGE, a PBG system. Some of the concerns were: barotrauma, pneumothorax, air embolism, excessive transmural vascular pressures, possible cardiac valvular damage, and possible overdilation of the right ventricle from a surge in venous return following +Gz. This study describes the experimental preparation and results of a hemodynamic investigation to address some of these concerns using chronically instrumented miniature swine (MS).

Animals↗
PubMed1994

Analysis of HLA and disease susceptibility: chromosome 6 genes and sex influence long-QT phenotype.

The long-QT (LQT) syndrome is a genetically complex disorder that is characterized by syncope and fatal ventricular arrhythmias. LQT syndrome, as defined by a prolonged electrocardiographic QT interval, has a higher incidence in females than in males and does not exhibit Mendelian transmission patterns in all families. Among those families that are nearly consistent with Mendelian transmission, linkage between a locus for LQT syndrome and the H-ras-1 locus on the short arm of chromosome 11 has been reported in some families but not in others. Earlier analyses suggesting that LQT syndrome might be caused by a gene in the HLA region of chromosome 6 were not confirmed by standard linkage analyses. Here, we present an analysis of HLA haplotype sharing among affected pedigree members, showing an excess of haplotype sharing in a previously published Japanese pedigree and possibly also in 15 families of European descent. The haplotypes shared by affected individuals derive from both affected and unaffected parents. In an analysis of independent (unrelated) HLA haplotypes, we also found a nonrandom distribution of HLA-DR genes in LQT syndrome patients compared with controls, suggesting an association between the LQT phenotype and specific HLA-DR genes. Our data indicate that DR2 has a protective effect and, particularly in males, that DR7 may increase susceptibility to the LQT syndrome. Thus, LQT syndrome may be influenced by genes on chromosomes 11 and 6, possibly with a sex-specific effect. These results provide a model for an effect of HLA-region genes inherited from either parent on the expression of an illness that may be determined principally by alleles at loci not linked to HLA.

Chromosomes, Human, Pair 6↗
PubMed1993

Low incidence of citrullinemia carriers among dairy cattle of the United States.

Bovine citrullinemia is an autosomal recessive disorder that is lethal in the early postnatal period. Dairy bulls from the US were screened for citrullinemia genotype with a mutation-specific assay of semen or leukocyte DNA. One heterozygote was detected among 367 US Holstein bulls tested, corresponding to an incidence of .3%; DNA sequencing showed that this bull (bull C) was heterozygous for the translation-termination mutation described as the cause of bovine citrullinemia. Tests on daughters of bull C revealed that 26 were heterozygous and 25 were homozygous normal, confirming that the condition is autosomal recessive and that bull C was heterozygous. Although bull C was among 273 bulls tested from the top 400 bulls based on Type-Production Index as of July 1990, he was not among the 90 tested from the top 100. He has fewer than 2000 offspring registered with the Holstein Association of America and has few sons in AI. Furthermore, he was culled for other reasons before his citrullinemia status was known. Accordingly, the incidence of citrullinemia carriers is low among US Holsteins, and the impact of the one carrier found on the future of the breed is expected to be minor. No carriers were found among 102 US Guernsey bulls and 53 US Jersey bulls tested.

Animals↗
PubMed1992

Identification of the homozygous recessive genotype for the deficiency of uridine monophosphate synthase in 35-day bovine embryos.

Holstein-Friesian cattle heterozygous for the deficiency of uridine monophosphate (UMP) synthase have half-normal activity of UMP synthase. The homozygous recessive genotype would result in little or no activity, has not been observed among live animals and apparently leads to embryonic mortality at approximately Day 40 of gestation. Activity of UMP synthase averaged 2.74 +/- 0.61 units/mg protein for 19 obligatory normal embryos (from normal x normal matings). Activity for 18 embryos from heterozygote x heterozygote matings yielded three non-overlapping groups as follows: (i) five presumed normals with greater than two-thirds normal activity, (ii) ten apparent heterozygotes with one-third to two-thirds normal activity and (iii) three putative homozygous recessive embryos with less than one-third normal activity. The distribution among these groups was consistent with the 1:2:1 ratio expected for autosomal inheritance. Conception of embryos homozygous recessive for this disorder was demonstrated.

Animals↗
PubMed1991

Hospital-based case management for medically fragile infants: program design.

A hospital-based multidisciplinary team is demonstrating services for medically fragile infants which facilitate transition from the hospital to the community and home. The team provides education and counseling for communities and families to overcome barriers to services. With individualized case management, the team facilitates family access to the community services they need in infant health, infant development and family functioning. The team plans the infant's discharge from the hospital and collaborates on the initial Individualized Family Service Plan (IFSP) with the family and local community providers. The initial IFSP details potential outcomes in the areas of infant health, infant development and family functioning for the first year the infant is home. Systematic home visits with the team's nurse or developmental consultant, the family and the local provider continue the education and counseling process during the infant's first year of life. This describes the educational aspect of case management services for medically fragile infants.

Aftercare↗
PubMed1991

Hospital-based case management for medically fragile infants: results of a randomized trial.

A recent federal law has expanded the eligibility for multidisciplinary evaluation and assessment of infants suspected of developmental delay. At the same time, modern neonatal care has increased infant survival. These two developments have created a need for family education regarding the need for health and developmental intervention, as well as counseling to maintain family participation in these services. This study compares the education and counseling services of a hospital-based case management team with the traditional discharge and follow-up services of a neonatal intensive care unit (NICU). Subjects were the 10% most medically severe infants discharged from a neonatal intensive care unit over a 16-month period. Preliminary data suggests a significantly greater number of families accessed community-based, coordinated, comprehensive health and developmental services when they received case management services. The data suggest that hospital professionals generally refer the most medically severe 3% of this group for services under a traditional model. However, the additional 7% referred under the transition model showed greater developmental benefits from the services during the first 6 months of life. These data support current federal initiatives for early intervention services which are family-centered, community-based and coordinated.

Aftercare↗
PubMed1991

Effect of insect control on the occurrence and distribution of streptothricosis lesions on cattle.

Trials were set up to ascertain whether the observed occurrence of streptothricosis lesions at dorsal sites on cattle in Antigua was related to the feeding activity of flies. Animals in two herds were treated with insecticide while a third herd served as an untreated control group. There was no significant difference in the occurrence or distribution of lesions on animals in all the three herds over a two month observation period except that a higher proportion of animals in one of the treated herds was affected at the end of the study.

Actinomycetales Infections↗
PubMed1991

Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome.

BACKGROUND: From the international long QT syndrome (LQTS) study, 30 patients with corrected QT interval (QTc) of more than 0.44 second 1/2 were identified who had permanent pacemakers implanted for management of recurrent syncope or aborted cardiac arrest. METHODS AND RESULTS: Pacemakers were implanted on average 7 years after the onset of the first syncopal episode. Most of the patients were female (87%), the average age at implantation was 19 +/- 13 years, the mean QTc was 0.55 +/- 0.08 second, and 57% were receiving antiadrenergic treatment for LQTS when the pacemaker was placed. Using birth as the time origin, the median cardiac event rate was significantly (p less than 0.001) reduced by pacing from 0.5 to 0 events per patient per year, with 21 patients experiencing no cardiac events during an average pacemaker follow-up of 49 months per patient. In 10 patients in whom the demand atrial pacing rate was faster than the intrinsic sinus rate, the average heart rate was increased 23 beats/min (from 58 to 81 beats/min) with pacing with reduction in the QT interval from 0.59 seconds to 0.46 seconds. CONCLUSIONS: The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals--factors that are known to be arrhythmogenic in this syndrome. Permanent cardiac pacing reduces the rate of recurrent syncopal events in high-risk LQTS patients, but it does not provide complete protection.

Adult↗