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Biomedical subjects

J Chambers

Publications and source records attributed to J Chambers.

At least 91 records · Page 5Linked to original sources

Genomic organization of a mouse MHC class II region including the H2-M and Lmp2 loci.

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.

Animals↗

Technetium-99m tetrofosmin myocardial perfusion scan: comparison of 1-day and 2-day protocols.

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.

Adult↗

Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients.

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.

Adolescent↗

Ruptured abdominal aortic aneurysms: who should be offered surgery?

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.

Aged↗

Cloning differentially expressed mRNAs.

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.

Antiviral Agents↗

Mild traumatic brain injuries in low-risk trauma patients.

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.

Adolescent↗

Contribution of peripheral chemoreceptors to ventilation and the effects of their suppression on exercise tolerance in chronic heart failure.

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.

Chemoreceptor Cells↗

Echocardiography and the small aortic root.

Two-dimensional echocardiography gives an estimate of the diameter of the annulus or sinotubular junction accurate to one millimeter. The diameter of the aortic annulus is related to body surface area or height, while the sinotubular junction is related additionally to age with a small effect from blood pressure and gender. A small aortic root may be defined theoretically as an annulus or sinotubular junction smaller than 1.0 cm/m2. If the aorta and replacement valve are considered as a unit, the effective area should be no less than 1.2 cm2/m2. The first gives an over-exclusive, the second an over-inclusive definition of prosthesis-patient mismatch. However, attention to hemodynamic or anatomic parameters alone may be biologically simplistic. We should probably incorporate an assessment of exercise ability, morbidity, mortality, LVH and measures of dynamic left ventricular diastolic and systolic function in the definition of patient-prosthesis mismatch.

Aortic Valve↗

Life-threatening degeneration of the Accufix active-fixation atrial-pacing electrode.

More than 47,000 patients world wide have had the Accufix atrial-pacemaker lead implanted. The company has issued warnings because degeneration of the electrode has occurred, with two deaths. We detected a fractured electrode that was successfully removed with insertion of a new type of electrode. Action is required to prevent further possibly fatal complications occurring.

Adolescent↗

Ethical dilemmas in the lived experience of nursing practice.

Through a series of semistructured interviews with 12 nurses delivering direct patient care in acute, long-term and home care settings, information was sought regarding the ethical concerns of practicing nurses. Although these nurses frequently did not specifically identify the areas of expressed concern as ethical in nature, thematic analysis of the transcribed interviews uncovered four major ethical areas of concern common to these 12 nurses. These areas are: (1) Withholding of information and truth-telling; (2) Unequal access or inequalities in care; (3) Differences between business and professional values; (4) Breaking and reporting broken rules. Several reasons are offered to explain the failure of nurses accurately to identify specific practice dilemmas as ethical in nature and the sequelae of these failures. Possibilities involving ongoing education and mentored experiences in practice areas are reported.

Adult↗