Viatical settlement may be a helpful option for many people with HIV.
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Biomedical subjects
Publications and source records attributed to J Chambers.
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The management of asymptomatic severe aortic stenosis remains controversial. Despite a good outcome in terms of mortality, the left ventricle may not recover fully after aortic valve replacement and patients may have impaired exercise ability. Routine assessment of the left ventricle is dominated by transverse systolic function to the relative neglect of long-axis and diastolic function. Long-axis dysfunction develops earlier than transverse dysfunction and may correlate with exercise ability. Reported symptoms can be unreliable and exercise testing reveals significant limitation in many apparently asymptomatic patients. Exercise testing and echocardiographic markers of early LV systolic dysfunction may help to refine the timing of surgery in patients with apparently asymptomatic severe aortic stenosis.
BACKGROUND AND AIMS OF THE STUDY: This study aimed to investigate the early postoperative Doppler-derived hemodynamic results from the first patients receiving the On-XR prosthetic heart valve, a new bileaflet, pyrolytic carbon valve. METHODS: Data were derived from 111 patients included in a 10-center international trial between September 1996 and December 1997. RESULTS: The effective orifice area (EOA) for the valve, when implanted in the aortic position, ranged from 1.5 to 2.7 cm2 in 19 mm to 25 mm valves. The corresponding mean pressure gradients ranged from 11.8 to 7.6 mmHg. Mitral EOA was 2.3 cm2 for all sizes, these values being combined because the housing was identical for all mitral valves used in this study. The mitral mean gradient was 4.7 mmHg. CONCLUSIONS: Early results of the study show the good hemodynamic performance of the On-X valve when implanted in the aortic or mitral positions.
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BACKGROUND: Patients with univentricular hearts have decreased exercise tolerance and may demonstrate exertional dyspnoea. It is not known if chronic hypoxaemia exacerbates exercise intolerance and contributes to symptomatic limitation. The extent to which surgical correction of a right-to-left shunt by a Fontan-type procedure can increase exercise tolerance by reducing arterial deoxygenation is not well documented. The cardiopulmonary exercise responses and the symptomatic status in two groups of univentricular patients, those who are cyanotic and those who are acyanotic with Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricular patients with rest or stress-induced cyanosis (age 30.5 +/- 2.3 [SE] years; 5 men) who had palliative or no surgery and eight patients (age 29.4 +/- 1.5 years; 4 men) with Fontan-type circulation. Peak oxygen consumption was comparable in both groups of univentricular patients (21.7 +/- 2.5 vs 21.0 +/- 1.9 ml.kg-1.min-1, P = 0.85) but was less than an age-matched group of 10 healthy subjects (34.7 +/- 1.9 ml.kg-1.min-1, P < 0.001 for both). Arterial oxygen saturation was 90.6% at rest in the cyanotic patients compared with 95.1% in the Fontan patients (P < 0.001) and at peak exercise, 66.2% compared with 90.5% (P < 0.001). Using a modified Borg scale (0-10), the symptoms of dyspnoea and fatigue were also assessed during exercise in the patient groups. The Borg scores for dyspnoea in the cyanotic and the corrected univentricular patients were, respectively, as follows: Stage 1: 0.5 vs 1.7; P= 0.04; Stage 2: 1.8 vs 2.3, P = 0.5; Stage 3: 3.0 vs 3.5, P = 0.7; Peak Exercise: 4.9 vs 4.8, P = 0.9. In addition, the Borg scores for fatigue were: Stage 1: 0.4 vs 1.6, P = 0.08; Stage 2: 2.0 vs 2.2, P = 0.9; Stage 3: 3.0 vs 4.3, P = 0.5; Peak Exercise: 4.9 vs 5.4, P = 0.5. The major limiting symptom at peak exercise was dyspnoea in four cyanotic patients compared with one in the Fontan group (Chi-square 0.982, P > 0.10). The arterial oxygen desaturation at peak exercise in the cyanotic patients limited by dyspnoea was not different from those limited by fatigue (67.5 +/- 10.1% vs 66.7 +/- 13.7%, P = 0.92). Exercise tolerance was also not related to the arterial oxygen saturation at peak exercise (r = 0.47, P = 0.17) in these patients. CONCLUSIONS: Despite correction with Fontan-type surgery, the exercise tolerance and symptoms of these univentricular patients remained similar to those who were cyanosed. Cyanotic patients have adjusted to chronic hypoxaemia and it does not appear to determine the exercise tolerance or the genesis of dyspnoea in these patients. Further randomized prospective studies are required to investigate the long-term benefits of Fontan-type procedures in these patients on exercise tolerance, symptoms and prognosis.
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The potential role of radiation in the prevention of coronary artery restenosis after angioplasty has generated much recent interest. Animal research and pilot clinical efforts have focused primarily on intraluminal methods of radiation delivery. This article reviews the experience to date with external beam radiation in restenosis prevention and suggests issues that should be considered from the standpoint of both external beam and intravascular radiotherapy. External beam radiation can certainly play an effective role in clinical studies of coronary artery restenosis, and a multicenter randomized trial of external beam radiation after coronary angioplasty has been initiated.
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The region encompassing the Ma, Mb1, Mb2, and Lmp2 genes of the mouse class II major histocompatibility complex (MHC) was sequenced. Since this region contains clusters of genes required for efficient class I and class II antigen presentation, it was interesting to search for putative additional genes in the 21 kilobase gap between the Mb1 and Lmp2 genes. Computer predictions of coding regions and CpG islands, exon trapping experiments, and cross-species comparison with the corresponding human sequence indicate that no additional functional gene is present in that stretch. However, computer analysis revealed the possible existence of an alternative 3' exon for Mb1. Except for the fact that the mouse MHC contains two Mb genes, the genomic organization of the H2-M loci was found to be almost identical to the organization of the human HLA-DM genes. The promoter regions of the Ma and Mb genes also resemble classical class II promoters, containing typical S, X, and Y boxes. Like the human genes, the three H2-M genes displayed very limited polymorphism when we compared the cDNA sequences from six haplotypes. Finally, comparison of DMB with Mb1 and Mb2, both at the genomic level and in their coding regions, suggests that the Mb gene was recently duplicated, probably only in certain rodents.
Nineteen patients with angina were recruited in this study for comparison of two 1-day protocols (stress-4h rest and rest-4-h stress) and a 2-day protocol of technetium-99m tetrofosmin single-photon emission tomography (SPET). All of them underwent coronary angiography before or after the study. Exercise stress-rest study and rest-stress study were performed on two consecutive days. Delayed imaging was performed before the rest injection on the 2nd day. The stress study on the 1st day and rest study on the 2nd day were considered as a 2-day protocol. The 1-day stress-rest protocol had a sensitivity of 100% (18/18) and an accuracy of 100% (19/19) in diagnosing ischaemic heart disease. The 1-day rest-stress protocol had a sensitivity of 94.4% (17/18) and an accuracy of 94.7% (18/19). These differences were not statistically significant (P=0.5 for sensitivity and accuracy). There was also no statistically significant difference between the two protocols in the diagnosis of ischaemic heart disease in individual artery territories. For the left descending artery, sensitivity was 88.2% (15/17) vs 76.5% (13/17) (P=0.48) for the stress-rest and rest-stress studies respectively. For the left circumflex artery, sensitivity was 90% (9/10) vs 80% (8/10) (P=1) and specificity was 66.7% (6/9) vs 77.8% (7/9) (P=1) respectively. For the right coronary artery, the sensitivity was 100% (16/16) vs 94% (15/16) (P=1) respectively, while the specificity was 33.3% (1/3) in both studies. Three hundred and forty-two myocardial segments were analysed. The stress-rest and 2-day protocols showed no statistically significant difference in the overall identification of segments with reversible ischaemia (48/141 segments vs 48/141 segments) or in respect of individual artery territories. There was also no significant difference in the identification of reversible ischaemic segments between the rest-stress and 2-day protocols (48/141 segments vs 34/135 segments, P=0.14). Abdominal activity was seen in 36 studies and interpretation was affected in five of them. Five patients with 24-h delayed images were evaluated and 24 segments with washout were identified. It is concluded that 99mTc-tetrofosmin is a valuable new tracer in the investigation of ischaemic heart disease. The 1-day stress-rest protocol is as good as the 1-day rest-stress protocol in diagnosing coronary heart disease. The 1-day protocols and the 2-day protocol display no difference in identifying segments with reversible ischaemia.
Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.
PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still associated with a high mortality rate. A review of our experience over a 9-year period was undertaken to identify factors present on admission associated with 30-day operative mortality. METHODS: A retrospective analysis of 154 patients with ruptured abdominal aortic aneurysm submitted for operation in a university teaching hospital between January 1985 and December 1993 was undertaken. RESULTS: The hospital mortality rate was 39%. Logistic regression identified a set of five independent preoperative factors associated with mortality: age (> 76 years), creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9 g%), and electrocardiographic ischemia. In the 52 patients with a single risk factor present, the mortality rate was 37%, with two factors (32 patients) it was 72%, with three or more factors (8 patients), it was 100%, and no patient had all five risk factors. A 16% mortality rate was found in the 62 patients with no risk factors. CONCLUSION: These risk factors can be easily determined on admission and may be used to help improve patient selection for surgical intervention. The current operative mortality rate for ruptured abdominal aortic aneurysm remains high, and in some cases health care resources are used in a nonproductive fashion. Restricted patient selection and allocation of scarce resources will bring advantages to both the patient and the community.
Differential gene expression occurs in the process of development, maintenance, injury, and death of unicellular as well as complex organisms. Differentially expressed genes are usually identified by comparing steady-state mRNA concentrations. Electronic subtraction (ES), subtractive hybridization (SH), and differential display (DD) are methods commonly used for this purpose. A rigorous examination has been lacking and therefore quantitative aspects of these methods remain speculative. We compare these methods by identifying a total of 58 unique differentially expressed mRNAs within the same experimental system (HeLa cells treated with interferon-gamma). ES yields digital, reusable data that quantitated steady-state mRNA concentrations but only identified abundant mRNAs (seven were identified), which represent a small fraction of the total number of differentially expressed mRNAs. SH and DD identified abundant and rare mRNAs (33 and 23 unique mRNAs respectively) with redundancy. The redundancy is mRNA abundance-dependent for SH and primer-dependent for DD. We conclude that DD is the method of choice because it identifies mRNAs independent of prevalence, uses small amounts of RNA, identifies increases and decreases of mRNA steady-state levels simultaneously, and has rapid output.
BACKGROUND: Moderate or severe traumatic brain injury (TBI) resulting from cranial trauma is usually easily recognizable. Mild TBI (MTBI), however, may escape detection at presentation because of delayed symptoms and the absence of radiographic abnormalities. Despite its subtle or delayed presentation, the spectrum of symptoms often experienced after MTBI, collectively referred to as "postconcussive syndrome," may cause serious psychosocial dysfunction. METHODS/RESULTS: To assess the sensitivity of emergency department screening for MTBI, a prospective follow-up study was conducted on a group of patients (N = 129) who had been evaluated at a regional trauma center after blunt trauma. None had symptoms or signs of TBI at presentation, nor any history of direct cranial trauma. All were discharged to home from the emergency department without a diagnosis of TBI. At 1 month after injury, 41 of 129 (32%) patients described an increase in symptoms consistent with MTBI. The most common symptoms were insomnia (62%), headaches (58%), irritability (56%) and fatigue (56%). At 2 months, most symptoms had decreased significantly, and none had increased in severity. Despite improvement in their symptoms over that time period, 11% of those with persistent symptoms remained unable to resume their premorbid daily activities. CONCLUSIONS: These data, obtained from a population of patients considered to be at extremely low risk for TBI, indicate that MTBI occurs more often among blunt trauma patients than is commonly appreciated, even in busy trauma centers. Because early recognition of MTBI may expedite referral of these patients for appropriate outpatient follow-up care, thereby avoiding potentially serious social and financial repercussions, emergency department personnel should have a high index of suspicion for MTBI in any patient sustaining blunt systemic trauma. Current measures that screen for MTBI appear to be inadequate; follow-up protocols may prove to be more sensitive screening tools.
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OBJECTIVES: To assess the contribution of peripheral chemoreceptors to ventilation and the effects of continuous inspired oxygen on exercise tolerance in chronic heart failure patients. The role of peripheral chemoreceptors in mediating hyperpnoea in chronic heart failure is unknown. Hyperoxia is known to suppress the peripheral chemoreceptor drive. The magnitude of decrease in ventilation with transient inhalations of oxygen thus provides a measure of the contribution of the peripheral chemoreceptors to ventilation. SETTING: Tertiary specialist hospital. SUBJECTS AND METHODS: Three breaths of 100% oxygen were given at rest and also during cycle ergometry at 25 W to 8 healthy controls (age 52.0 (4.7) (SEM) years) and 13 patients with chronic heart failure (age 60.5 (2.1) years (P = NS); radionuclide left ventricular ejection fraction 25.5 (4.3)%). The peripheral chemoreceptor sensitivity was also measured by assessing the ventilatory response to hypoxia using transient inhalations of pure nitrogen. Another group of 12 patients with chronic heart failure (age 65.5 (1.5) years; left ventricular ejection fraction 21.3 (3.0)%) underwent treadmill exercise testing on 2 occasions, breathing air or 100% oxygen in a randomised single-blind manner, to examine the effects of continuous inspired oxygen on exercise tolerance. RESULTS: The reduction in ventilation with transient hyperoxia was 18.1 (2.9)% v 17.9 (2.6)% (P = NS) at rest and 20.4 (2.8)% v 21.0 (1.6)% (P = NS) during cycle ergometry, for controls and patients respectively. The hypoxic chemosensitivity was higher in patients (0.232 (0.022) v 0.572 (0.082) 1/min/%SaO2; P = 0.002). Continuous inspired oxygen increased exercise time (517 (31) v 455 (27) seconds; P = 0.003), and a trend towards a reduction in the ventilatory response to exercise, characterised by the regression slope relating ventilation to carbon dioxide output, was evident (31.27 (2.60) v 34.19 (2.35); P = 0.08). CONCLUSIONS: Despite an increased peripheral chemoreceptor sensitivity, the proportionate contribution of peripheral chemoreceptors to ventilation remained similar in heart failure patients (about 20%). This suggests that the peripheral chemoreceptors are not the main mediator of increased ventilation and there are other non-peripheral chemoreceptor-mediated mechanisms involved. Hyperoxia reduced ventilation at rest and during cycle ergometry. The increase in exercise duration with continuous inspired oxygen that was associated with a reduction in exercise ventilatory response suggests that suppression of the peripheral chemoreceptors may improve exercise tolerance; the effects of possible reduced skeletal muscle anaerobiosis cannot be excluded, however.