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Biomedical subjects

J A Barrett

Publications and source records attributed to J A Barrett.

At least 55 records · Page 3Linked to original sources

Nonamplifying alleles at microsatellite loci: a caution for parentage and population studies.

While genotyping wild red deer (Cervus elaphus) at microsatellite loci for paternity assignment, we found three loci (MAF65, BOVIRBP and CelJP23) with segregating nonamplifying alleles. Nonamplifying alleles were detected through mismatches between known mother-offspring pairs and by significant deviations from Hardy-Weinberg equilibria. In a wide range of molecular ecology application, and especially in parentage assignment, the possible existence of undetectable alleles must be taken into account; this may be particularly important for microsatellite data.

Alleles↗

Limiting cardiac evaluation in patients with suspected myocardial contusion.

A great deal of time and effort is spent attempting to diagnose myocardial contusion in patients with blunt thoracic trauma. Many diagnostic protocols have been proposed in the past. However, there is no test with sufficient specificity to predict which patients will develop complications that will require therapy. Recent studies have raised the question of limiting the cardiac evaluation in certain selected patients with blunt thoracic trauma. We prospectively studied the safety of limiting the cardiac evaluation in patients who were hemodynamically stable, had no history of cardiac disease, had a normal baseline ECG, did not require surgery or neurological observation for associated injuries, and were less than 55 years of age. These patients represent the majority of patients considered at risk for myocardial contusion when mechanism is the sole criterion. These patients were simply admitted for 24 hours of continuous cardiac monitoring. No patient developed any complications of myocardial contusion requiring therapy. We conclude that it is safe to limit the cardiac evaluation in this group of patients.

Adult↗

A case-control study of risk factors that predict femoral arterial injury in penetrating thigh trauma.

STUDY HYPOTHESIS: Femoral artery injuries can be predicted by the mechanism of injury, wound location and tract, and physical findings following penetrating thigh trauma. DESIGN: Retrospective case-control study. PARTICIPANTS: All 808 consecutive patients undergoing femoral arteriography for penetrating thigh trauma from September 1986 through December 1990 were eligible for inclusion in the study. All 50 patients in the eligible population with proven femoral artery injuries diagnosed by angiogram were the study subjects. Fifty patients with penetrating thigh trauma who had angiograms negative for injury and were systematically chosen from the eligible population served as controls. INTERVENTIONS: Data included mechanism of injury; location of wound entrance, tract, exit, and retained missile; physical findings (including ankle-brachial index); and the presence of femur fractures. Physical findings were divided into hard findings (pulse abnormality, expanding hematoma, or pulsatile bleeding) or soft findings (neurologic deficit, hypotension without another source, or bruit/thrill). RESULTS: Of the 808 eligible patients, 50 (6.2%) had a femoral arterial injury on angiography, 20 (40%) of which were clinically occult injuries. A medial thigh tract made an arterial injury 58 times more likely (odds ratio [OR], 57.5; P < .001) and was present in 100% of cases and 64% of controls. An anteromedial thigh tract made an arterial injury 12 times more likely (OR, 11.5; P < .001) and was present in 92% of cases and 50% of controls. A wound with hard physical findings was 118 times more likely to have an arterial injury (OR, 118; P < .00001) and was found in 54% of cases and none of the controls. The presence of any physical finding made an arterial injury 36 times more likely (OR, 36; P < .00001) and was found in 60% of cases and 4% of controls. The presence of a femur fracture or a gunshot mechanism was not predictive of injury. CONCLUSION: Only patients with medial thigh wounds need to undergo angiography for the detection of femoral artery injuries. This approach would have reduced the angiography rate by 36% in this series. Had angiography been performed only on patients with any physical findings, a 70% reduction in the rate of angiography would have been achieved, although five occult arterial injuries per year would have been missed. Angiography should not be performed solely because of a gunshot mechanism or the presence of a femur fracture.

Adult↗

Treatment and survival among elderly Americans with hip fractures: a population-based study.

OBJECTIVES: This study was undertaken to examine the patterns of treatment and survival among elderly Americans with hip fracture. METHODS: A 5% national sample of Medicare claims was used to identify patients who sustained hip fractures between 1986 and 1989. In comparing treatment patterns across regions, direct standardization was used to derive age- and race-adjusted percentages. Logistic regression and Cox regression were used to examine short- and long-term survival. RESULTS: In the United States, 64% of femoral neck fractures were treated with arthroplasty; 90% of pertrochanteric fractures were treated with internal fixation. Higher short- and long-term mortality was associated with being male, being older, residing in a nursing home prior to fracture, having a higher comorbidity score, and having a pertrochanteric fracture. Blacks and Whites had similar 90-day postfracture mortality, but Blacks had a higher mortality later on. For femoral neck fracture, internal fixation has a modestly lower short-term mortality associated with it than arthroplasty has. CONCLUSION: Variation in the treatment of hip fracture was modest, The increased delayed mortality after hip fracture among Blacks requires further study.

Age Factors↗

DNA fingerprinting: parentage studies in natural populations and the importance of linkage analysis.

It has been suggested that a full linkage analysis is a prerequisite for confident paternity testing, by using DNA fingerprinting, in natural populations. These fears are based on a confusion between linkage and linkage disequilibrium and a misplaced assumption that linkage between bands will necessarily reduce the effective number of paternal-specific bands. Several methods for detecting linkage without resorting to the analysis of large sibships are considered, for example, by analysing half-sibships, by band-association, and by altering the experimental conditions used. Even if linkage is present, the magnitude of its effects are unlikely to undermine the accuracy of the technique, given the average levels of variability being detected. We conclude that the effects of linkage are only likely to present a problem when sample sizes are very small or when closely related individuals are being tested together.

Animals↗

Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid.

Sensitisation to retinal S-antigen has been implicated in the pathogenesis of several clinical forms of posterior uveitis. S-antigen-like molecules have recently been demonstrated in the brain and choroid plexus of experimental animals. We used a panel of four monoclonal antibodies (MAbs), MAbF4-C1, MAbC10-C10, MAbA2-G5 and MAbA9-C6, which define specific epitopes in the amino, mid and carboxyl terminal portions of S-antigen in order to identify an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid (CSF). Three MAbs, MAbF4-C1, MAbC10-C10 and MAbA9-C6, localised an S-antigen-like molecule to the cytoplasm of the epithelial cells of the human choroid plexus. Polymerase chain reaction of cDNA from choroid plexus verified the presence of S-antigen homologues in the choroid plexus. The presence of an S-antigen-like molecule in the CSF was demonstrated by western blots in seven CSF samples from patients with a variety of neuropathological disorders. It is proposed that immunological cross-reactivity and biochemical similarity between retinal S-antigen and an S-antigen-like molecule in human choroid plexus and CSF could form a basis for neurological manifestations observed in certain clinical forms of uveitides.

Adult↗

The effect of retinal autoantigens and their peptides on the inhibition of experimental autoimmune uveitis.

Experimental autoimmune uveitis is an immune-mediated inflammation of the retina and uveal tract. Such inflammation can be induced in eyes of experimental animals by inoculating them with retinal autoantigens. This animal model of uveitis closely resembles idiopathic uveitis in humans and lends itself ideally for the study of mechanisms involved in the aetiopathogenesis of uveitis and for the evaluation of methods used to control or prevent immune-mediated intraocular inflammation. In this study we used the retinal proteins S-antigen, interphotoreceptor retinoid binding protein and some synthetic peptides of S-antigen to modulate the immune response of Lewis rats. Following immunomodulation these animals did not develop uveitis when challenged with the retinal proteins. The discovery of small, non-pathogenic peptides of retinal antigens that down-regulate the immune response has relevance in developing strategies for immune intervention in human uveitis.

Amino Acid Sequence↗

The law and medical fitness to drive--a study of doctors' knowledge.

We assessed doctors' knowledge on laws and recommendations regarding fitness to drive in certain medical conditions by a questionnaire survey. A total of 646 doctors consisting of 400 general practitioners and 246 hospital doctors of all grades were circulated with the questionnaire. The survey was anonymous so non-responders could not be re-circulated. The response rate was 26% general practitioners and 32% (hospital doctors). The results show the poor knowledge of doctors on several aspects of fitness to drive. It is necessary for all doctors to have a basic knowledge on the laws and recommendations on fitness to drive so that they can advise their patients correctly. Our survey clearly shows that doctors' knowledge is poor. Many drivers may therefore be placing themselves and others at risk. It is mandatory that this subject receives more attention in undergraduate and postgraduate education and that doctors should be regularly updated on new recommendations from the Driver and Vehicle Licensing Agency.

Automobile Driving↗

Epitopes and idiotypes in experimental autoimmune uveitis: a review.

Retinal S-antigen (SAg) and interphotoreceptor retinol-binding protein (IRBP) induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are good models for studying the mechanisms involved in autoimmune diseases. Many immunogenetically active epitopes have been identified in these proteins but immunodominance of one or more epitopes in vivo, has not yet been established. In this paper we present and discuss some experiments that led to the discovery of a dominant "tolerogenic" epitope in SAg. We also demonstrate the presence of cross reactive epitopes in the two potent retinal antigens, SAg and IRBP and finally introduce early data on a unique anti S2.4.c5 idiotypic (Id) monoclonal antibody (MAb) which appears to be a site non associated antibody that binds not only to s2.4.c5 but also to SAg.

Amino Acid Sequence↗

Induction of experimental autoimmune uveitis by the retinal photoreceptor cell protein, phosducin.

Experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are CD4+ T cell mediated inflammatory diseases of the retina and uveal tract of the eye and the pineal gland respectively. They can be induced in experimental animals by immunization with several well characterized retinal autoantigens. We induced a mild to moderate EAU and EAP in Lewis rats by immunization with phosducin, a 33K retinal phosphoprotein which is involved in the phototransduction of vision. In contrast to the severe EAU induced by other retinal antigens like S-antigen (SAg) or interstitial retinoid binding protein (IRBP), the clinical disease was late in onset, low grade in severity and predominantly affected the posterior segment of the eye. Our study demonstrates that another photoreceptor cell protein, phosducin, is capable of eliciting EAU and EAP.

Animals↗

Doctors' knowledge of socio-legal aspects of patient care.

Doctors' knowledge of socio-legal aspects of patient care is poor. To quantify this a questionnaire on certain socio-legal topics was sent to 400 general practitioners and 250 hospital doctors. The responses were compared to a group of social workers. Both hospital doctors and general practitioners did badly on all topics considered. Social workers' knowledge was significantly better overall, (P < 0.01). Our results confirm the lack of knowledge amongst a broad spectrum of doctors. We suggest that this may be related to a lack of emphasis on these aspects in both undergraduate and postgraduate education.

Aged↗

Preclinical pharmacology of celiprolol: a cardioselective beta-adrenergic antagonist and mild vasodilator.

Celiprolol is a new antihypertensive agent that represents a new generation of beta-blockers. It combines cardioselective beta-adrenergic antagonism (beta 1) with a mild vasodilation via vasoselective beta-adrenergic agonism (beta 2). Results of animal studies show that celiprolol has beta 1-antagonist potency similar to that of propranolol and atenolol, and cardioselectivity slightly greater than that of atenolol. Celiprolol does not produce bronchoconstriction but has mild propranolol-resistant bronchodilatory properties in cats. The compound also relaxes vascular smooth muscle in a propranolol-sensitive fashion, suggesting a mechanism of beta 2-agonism. The beta 2-agonism results in a selective downregulation in beta 2-receptor number and response in tissue culture, as well as in peripheral tissue from celiprolol-treated volunteers. The decreases in beta 2-receptors are blocked by concomitant treatment with propranolol. Celiprolol is devoid of cardiac depressant activity and in fact has mild cardiostimulatory actions. The cardiostimulation is not via beta 1-stimulation, since it is not abolished by beta-blocking doses of propranolol. In a model of severe myocardial ischemia, celiprolol attenuates the ischemia-induced myocardial acidosis and improves the regional segment function. These results are suggestive of myocardial protection. In summary, celiprolol distinguishes itself from other beta-blockers by virtue of its cardioselectivity, vasorelaxation via beta 2-agonism, and the lack of bronchoconstriction and cardiodepression. These properties observed in animal studies have also been documented in clinical trials.

Adrenergic beta-Antagonists↗

Hip fracture incidence and mortality in New England.

We used Medicare data to conduct a population-based study of osteoporotic hip fracture incidence and outcomes among New England residents. To reduce bias and improve data reliability, we combined data from multiple files; we found that 6% of cases would have been missed had we relied on hospital claims alone. Hip fracture incidence (per 1,000 person-years) increased for white females from 2.2 for ages 65-69 to 31.8 for ages 90-94 and for white males from 0.9 for ages 65-69 to 20.8 for ages 90-94. Incidence among blacks was lower in all age/sex groups. The female/male relative risk was greater among whites than among blacks. Case fatality following hip fracture was 12.5% at 90 days and 23.7% at 1 year and was higher among males, older patients, and those who had documented comorbidity or who were residents of nursing homes.

Age Factors↗

Triple-contrast CT scans in penetrating back and flank trauma.

Triple-contrast CT scanning (3-CT) is a diagnostic modality that has been introduced recently for the work-up of patients with penetrating injuries to the back or flank. Triple-contrast CT consists of giving oral, intravenous (IV), and rectal contrast medium. Our hypothesis was that this test is an accurate predictor of the absence of a retroperitoneal injury requiring surgical repair. We prospectively enrolled 88 clinically stable patients who sustained penetrating wounds to the back or flank. Seventy-eight received a diagnostic peritoneal lavage (DPL) before 3-CT. The scans were classified according to the risk of a retroperitoneal injury requiring repair. Patients who did not go to the operating room (OR) were observed for 48 hours. Of 88 patients entered, nine had high-risk scans, five of these patients underwent exploratory laparotomy, two of whom had significant injuries. Seventy-nine patients had non-high-risk scans. Seventy-seven were observed without complication, and two were explored for positive DPL, with no significant lesion found. The negative predictive value of a low- or moderate-risk 3-CT scan is 100% +/- 11%.

Back↗

Absorbable mesh splenorrhaphy for severe splenic injuries: functional studies in an animal model and an additional patient series.

Polyglycolic acid mesh has been introduced as a method of controlling hemorrhage in severely damaged spleens. This study examines the effect of splenic wrapping on the immune function of the spleen, and also on its ability to control splenic bleeding in trauma patients. Thirty purebred beagle dogs were divided into three groups and subjected to sham operation (Group 1), splenectomy (Group 2), and splenic wrap (Group 3). Immunologic studies showed no difference between the wrapped group (Group 3) and those with their spleens intact (Group 1) in the induction of specific antibody-producing lymphocytes in splenic tissue after the injection of attenuated Pneumococci. All splenic injuries treated at Cook County Hospital between January 1985 and May 1988 were retrospectively analyzed. Of 60 patients with splenic injuries, 14 underwent mesh splenorrhaphy without mortality or serious complications. This study demonstrates that the immune function of spleen is preserved following mesh splenorrhapy, and that this technique can be used in a clinical setting with safe and efficacious results.

Absorption↗