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Biomedical subjects

L Gillam

Publications and source records attributed to L Gillam.

At least 19 recordsLinked to original sources
PubMed2006

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children.

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

Alleles↗
PubMed2006

Enhancing the ethical conduct of genetic research: investigating views of parents on including their healthy children in a study on mild hearing loss.

Clinical genetic research is often regarded as more ethically problematic than other forms of research, and in some countries is subject to specific regulation, requiring researchers to follow specialised guidelines. In this paper, an approach to enhancing the ethical conduct of genetic research is proposed, which is believed to be more effective than simply attempting to follow general guidelines. The potential concerns, likely areas of misunderstanding and negative reactions of the participant group are systematically investigated before starting a study on genetics. This would constitute, in effect, an ethical pilot study, similar to a feasibility pilot study to test equipment, procedures and logistics. The findings of the ethical pilot study would be used to help in designing ethically important aspects of research protocol, such as recruitment procedures, written and other information for potential participants, informed consent processes and reporting of results including ambiguous or uncertain results.

Child↗
PubMed2001

Confidentiality.

Issues of confidentiality are complicated by the relationships we have to patients and others who have valid interests in the confidential information. There are no straightforward answers to problems which involve complex relationships and sensitive information. The best we can do is to think thoroughly and carefully about the issues in each case, and use our knowledge of the people involved to reach a decision. Doctors faced with difficult decisions of this kind should be assured that everyone finds them difficult. Sharing the burden with experienced colleagues can be helpful.

Adolescent↗
PubMed1999

Prenatal diagnosis and discrimination against the disabled.

Two versions of the argument that prenatal diagnosis discriminates against the disabled are distinguished and analysed. Both are shown to be inadequate, but some valid concerns about the social effects of prenatal diagnosis are highlighted.

Abortion, Induced↗
PubMed1998

Use of an intravenous contrast agent (Optison) to enhance echocardiography: efficacy and cost implications. Optison Multicenter Study Group.

OBJECTIVE: To compare the overall diagnostic costs associated with non-contrast and contrast echocardiography. STUDY DESIGN: Phase III clinical trial. PATIENTS AND METHODS: In a secondary analysis of data from a phase III clinical trial of the intravenous contrast agent Optison, we compared the costs associated with obtaining a diagnosis in 203 patients who underwent non-contrast and contrast echocardiography. Costs for the initial test and any follow-up tests were derived from adjusted Medicare charges and a transition-1 microcost accounting system. RESULTS: Diagnostic yield from echocardiograms was 87% with the use of Optison (3 mL) and 49% when no contrast agent was used (P < 0.001). Because technically inadequate echocardiograms were more common in the non-contrast group, follow-up testing was recommended for 42% of patients in this group compared with 12% of those who had undergone a contrast-enhanced echocardiogram (P < 0.001). Although use of Optison increased the initial diagnostic cost by $125, overall costs were 17% lower when Optison was used (P < 0.0001). Use of Optison also resulted in a 17% to 70% decrease in confirmatory transesophageal echocardiography, catheterization, and nuclear studies. Optison improved diagnostic accuracy by 2.7-fold in patients with an initial non-diagnostic echocardiogram, resulting in a substantial cost savings of $269 per patient.

Cardiomyopathies↗
PubMed1998

The 'more-abortions' objection to fetal tissue transplantation.

One common objection to fetal tissue transplantation (FTT) is that, if it were to become a standard form of treatment, it would encourage or entrench the practice of abortion. This claim is at least factually plausible, although it cannot be definitively established. However, even if true, it does not constitute a compelling ethical argument against FTT. The harm allegedly brought about by FTT, when assessed by widely accepted non-consequentialist criteria, has limited moral significance. Even if FTT would cause more abortions to be performed, and abortion is taken to be a serious moral wrong, this is not sufficient in itself to make FTT wrong.

Aborted Fetus↗
PubMed1998

Toxic methemoglobinemia: a rare but serious complication of transesophageal echocardiography.

Cyanosis occurring during a transesophageal echocardiogram (TEE) is usually related to the respiratory depressant effect of the administered sedative. However, acute toxic methemoglobinemia related to topical benzocaine is a rare and not well recognized but potentially life threatening cause of cyanosis during or after TEE. A case of this condition is presented and the literature on its frequency, diagnosis and management is briefly reviewed.

Adult↗
PubMed1997

Nitroglycerin enhances the ability of dobutamine stress echocardiography to detect hibernating myocardium.

BACKGROUND: A biphasic response of wall thickening with initial improvement and subsequent deterioration during dobutamine stress echocardiography (DSE) has been increasingly used for detection of hibernating myocardium. However, the improvement of wall thickening at low-dose DSE may be limited in hibernating myocardium by severe hypoperfusion. Nitroglycerin (NTG) improves myocardial perfusion, reduces oxygen demand, and may enhance low-dose dobutamine to improve wall thickening. METHODS AND RESULTS: A pig model of myocardial hibernation of 24 hours to 7 days was created through severe left anterior descending coronary artery stenosis with coronary flow reductions of approximately 40%, producing severe regional left ventricular dysfunction but no infarction in seven pigs. Myocardial infarction was produced in five pigs with occlusion of the artery. DSE was performed with incremental doses with and without an NTG infusion of 50 to 100 microg/min. In the hibernating group, NTG alone improved wall thickening in the hibernating region modestly from 11.4+/-7.2% at baseline to 19.1+/-7.0%. The improvement was associated with increased regional coronary flow from 0.46+/-0.12 to 0.55+/-0.13 mL x beat(-1) x 100 g myocardium(-1) (P<.05). There was an additive effect of NTG to low-dose (2.5 to 5 microg x kg(-1) x min(-1)) dobutamine on wall thickening in the hibernating region. The improvement of wall thickening of hibernating myocardium with NTG and dobutamine, from 23.7+/-11.1% to 31.1+/-8.9% (P<.001), was associated with an increase in regional coronary flow (P<.01). NTG did not prevent high doses of dobutamine from inducing deterioration of wall thickening in hibernating myocardium. In the infarcted group, no improvement in wall thickening was observed in infarcted regions during NTG infusion, dobutamine infusion, or the combination. CONCLUSIONS: NTG enhances the improvement of wall thickening at low-dose dobutamine and does not prevent high-dose dobutamine from inducing ischemia in hibernating myocardium. Thus, NTG augments the biphasic response of wall thickening and improves the accuracy of DSE for detecting viable myocardium.

Animals↗
PubMed1997

Lupus-related mitral valve disease: embolic coronary occlusion as a unique cause of myocardial infarction.

Early diagnosis and greatly improved treatment have markedly altered the clinical evolution of systemic lupus erythematosus; the pattern of cardiac involvement in lupus has also changed. To illustrate this, a young woman who died from severe mitral valve disease, including a coronary embolus from verrucous endocarditis, is presented. Mitral valve involvement in lupus is no longer limited to the small benign lesions described by Libman and Sacks.

Adolescent↗
PubMed1996

Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography.

OBJECTIVES: This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine. BACKGROUND: Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial. METHODS: In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose. RESULTS: Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05). CONCLUSIONS: A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.

Adrenergic beta-Antagonists↗
PubMed1995

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Animals↗
PubMed1990

Aortic regurgitation shortens Doppler pressure half-time in mitral stenosis: clinical evidence, in vitro simulation and theoretic analysis.

Mitral valve areas determined by Doppler pressure half-time were compared with areas obtained by planimetry in two groups of patients with mitral stenosis: 24 patients without aortic regurgitation and 32 patients with more than grade 1 aortic regurgitation. The severity of aortic regurgitation was assessed by color flow mapping; 17 patients had grade 2, 10 had grade 3 and 5 had grade 4 aortic regurgitation. Regression equations for pressure half-time area versus planimetry mitral valve area were calculated separately for the aortic regurgitation (r = 0.88) and the nonaortic regurgitation group (r = 0.86); analysis of covariance revealed a significant (p less than 0.001) difference between the two groups leading to overestimation of planimetry area by the pressure half-time method in the aortic regurgitation group. The mitral valve areas in the group without regurgitation were best calculated with the expression 239/T1/2 (r = 0.77) as compared with a best fit of 195/T1/2 (r = 0.85) for the aortic regurgitation group. To elucidate the mechanisms affecting pressure half-time in aortic regurgitation, an in vitro model of mitral inflow in the presence of varying regurgitant volumes and different ventricular chamber compliances was used. Aortic regurgitation shortened directly measured pressure half-time proportional to the regurgitant fraction but an increase in left ventricular compliance could offset this effect. Finally, in a mathematic model of mitral inflow the competing effects of aortic regurgitation and chamber compliance could be confirmed. In conclusion, aortic regurgitation results clinically in a significant net shortening of pressure half-time leading to mitral valve area overestimation. However, the effect is moderate and individually unpredictable because of changes in chamber compliance.

Adult↗
PubMed1982

Congenital aneurysms of the left atrium: recognition by cross-sectional echocardiography.

The two-dimensional echocardiographic features of three patients with congenital aneurysms of the left atrium are described. The aneurysm arose from the left atrial appendage in two patients and from the posterior left atrial wall in one. The aneurysms were characterized by their origin from an otherwise normal left atrium, a well-defined neck, their position within the pericardial space, and distortion of the left ventricular free wall by the aneurysmal body. The differentiation of these structures from other abnormalities of the left atrium are also discussed. Two-dimensional echocardiography is a safe and reliable method for diagnosing congenital aneurysm of the left atrium, and such studies should be considered in any patient with an otherwise unexplained abnormality on the chest radiograph.

Adult↗
PubMedDate not supplied

Biplane transesophageal color Doppler echocardiography for assessment of mitral valve area with mitral inflow jet widths.

Biplane transesophageal color Doppler echocardiography can image the mitral valve orifice in two orthogonal views. If the maximal stenotic jet width through the mitral valve obtained with the vertical transducer represents the major axis, the stenotic jet width dissected by the horizontal transducer should be the minor axis of the mitral orifice. Thus the mitral valve area can be calculated assuming an oval shape of mitral orifice. Nineteen patients with mitral stenosis were investigated. Maximal mitral stenotic jet width (JW1) was searched on a vertical plane and the jet width from the orthogonal view (JW2) was obtained on a horizontal plane. Mitral valve areas from the color Doppler jet widths were calculated by pi.JW1/2.JW2/2 and compared with those derived from Gorlin's formula. Adequate quality of echocardiographic images could be obtained in all patients for transesophageal color Doppler jet width measurements or Doppler pressure half-time determinations and in 16 of 19 patients for transthoracic planimetery of the mitral orifice at the parasternal short axis. Mitral valve areas derived from biplane transesophageal color Doppler imaging (1.31 +/- 0.53 cm2) were not different from those calculated according to Gorlin's formula from the catheterization data (1.25 +/- 0.50 cm2), those determined by transthoracic echocardiographic planimetery (1.38 +/- 0.5 cm2), or those calculated from the Doppler pressure half-time method (1.32 +/- 0.41 cm2) (difference not significant by analysis of variance). There was a very strong correlation between transesophageal echocardiographic mitral valve areas and those derived from catheterization data (r = 0.94; standard error of the estimate = 0.13 cm2). A similar correlation was obtained for the planimetric echocardiographic method (r = 0.94; standard error of the estimate = 0.14 cm2). A slightly less strong correlation was found between mitral valve areas derived from the Doppler pressure half-time method and those derived from Gorlin's formula (r = 0.83; standard error of the estimate = 0.24 cm2). The pressure half-time method accurately predicted the mitral valve area in most (15/19) patients, but it significantly (> 0.4 cm2) overestimated mitral valve area in two patients with aortic regurgitation and underestimated (< 0.4 cm2) mitral valve area in two patients with left ventricular hypertrophy. Determination of mitral valve area by color Doppler biplane transesophageal echocardiography is an alternative for accurate estimation of mitral valve area and may be most useful in intraoperative monitoring during surgical or balloon mitral commissurotomy or in the case of inadequate imaging quality of transthoracic echocardiography.

Adult↗
PubMedDate not supplied

Impact of delayed reperfusion of myocardial hibernation on myocardial ultrastructure and function and their recoveries after reperfusion in a pig model of myocardial hibernation.

UNLABELLED: This study examined the effect of delayed reperfusion of myocardial hibernation from 24 hours to 7 days on myocardial ultrastructural and functional changes and their recoveries after reperfusion. BACKGROUND: We have previously shown in pigs that after reperfusion the functional and structural alterations in short-term myocardial hibernation which was reperfused in 24 hours can recover in 7 days. The effect of delayed reperfusion of hibernating myocardium on the extent and severity of cellular and extracellular structural changes of hibernating myocardium, and their recoveries after reperfusion is not known. METHODS AND RESULTS: A severe LAD stenosis was created in 27 pigs, reducing resting flow by 30-40% immediately after placement of the stenosis and producing acute ischemia as evidenced by regional lactate production, a decrease in regional coronary venous pH, reduced regional wall thickening (from 38.5 +/- 5.1% to 10.4 +/- 8.0%) and a 33% reduction of regional oxygen consumption. The stenosis was maintained either for 24 hours in 9 pigs (group 1) with LAD flow of 0.65 +/- 0.13 ml/min/g (38% reduction), or for 7 days in 17 pigs (group 2) with LAD flow of 0.67 +/- 0.14 ml/min/g (36% reduction). There were no differences (p = NS) in the reduction of wall thickening, rate-pressure product, lactate production, or regional oxygen consumption between group 1 and group 2. Quantitative morphometric evaluation of the ultrastructure on electromicrographs revealed a greater decrease in sarcomere volume and a higher incidence of myocytes with reduced sarcomere volume in 7-day than in 24-hour hibernating regions (53 +/- 19% versus 33 +/- 14%, p < 0.05). Patchy myocardial necrosis with replacement fibrosis was common, but 6 of the 18 pigs had no myocardial necrosis or replacement fibrosis in the 7-day hibernating group, and 4 of 9 pigs had no patchy myocyte necrosis in the 24 hour hibernating group. In 6 pigs in group 1 in which the stenosis was then released and hibernating myocardium reperfused in 24 hours, regional wall thickening recovered to 30 +/- 6% (p = NS compared to baseline) after one week of reperfusion. In 12 pigs in group 2 in which the stenosis was released and hibernating myocardium reperfused in 7 days, regional wall thickening recovered slowly, from 10.1 +/- 7.2% to 18.1 +/- 8.3% at one week (n = 5) and to 28.0 +/- 3.6% at 3-4 weeks of reperfusion (n = 7, p < 0.05 compared to baseline). Similarly, the sarcomere volume or myofilament recovered significantly (p < 0.01) and was not different compared to the normal region (p = NS) in the 24-hour hibernating region of group 1, but the recovery was much slower and was incomplete at 4 weeks (p < 0.01) compared to baseline in the 7-day hibernating region of group 2. Recovery of regional wall thickening correlated with ultrstructural recovery (p < 0.01). By multivariate stepwise regression analysis, the degree of LAD flow reduction, the extent of fibrosis, and myofilament loss were independent predictors of the extent of functional recovery. CONCLUSIONS: In a porcine model of myocardial hibernation with myocardial hypoperfusion, systolic dysfunction, and metabolic adaptations, a longer period of myocardial hibernation with delayed reperfusion was associated with more severe abnormalities of myocytes. an increasing interstitial fibrosis, and more protracted myofibrillar and functional recoveries after reperfusion. The extent of functional recovery is related to the degree of coronary flow reduction, the severity of the ultrastructural changes, and the extent of interstitial fibrosis.

Animals↗