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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 37 records · Page 2Linked to original sources

Breathlessness in hospitalised adult patients.

Dyspnoea is defined as a sensation of difficult breathing. It is common in hospitalised patients and is often a harbinger of serious and potentially fatal pathology. The pathophysiology of dyspnoea involves complex interactions between peripheral and central receptors and cognition. Given the myriad causes of dyspnoea, a systematic approach to diagnosis is important. A good history and systemic examination are necessary as it is important to quickly identify the cause and treat it promptly. Investigations are numerous but chest radiography and electrocardiography are among the commonest and most useful. It is important to understand the mechanisms underlying dyspnoea to treat breathless patients successfully.

Acute Disease↗

Changing the diagnostic criteria for myocardial infarction in patients with a suspected heart attack affects the measurement of 30 day mortality but not long term survival.

OBJECTIVES: To explore the effects of alternative methods of defining myocardial infarction on the numbers and survival patterns of patients identified as having sustained a confirmed myocardial infarct. DESIGN: An inclusive historical cohort of patients admitted with a suspected heart attack. Patients were recoded from raw clinical data (collected at the index admission) to the epidemiological definitions of myocardial infarction used by the Nottingham heart attack register (NHAR), the World Health Organization (MONICA), and the UK heart attack study. SETTING: Single health district. PATIENTS: The NHAR identified all patients admitted in 1992 with suspected myocardial infarction. OUTCOME MEASURES: Survival at 30 days and four year postdischarge. RESULTS: 2739 patients were identified, of whom 90% survived to discharge. Recoding increased the numbers of patients defined as having confirmed myocardial infarction from 26% under the original NHAR classification to 69%, depending on the classification system used. In confirmed myocardial infarction, subsequent 30 day survival from admission varied from 77-86% depending on the classification system; four year survival after discharge was not affected. The distribution of important prognostic variables differed significantly between groups of patients with confirmed myocardial infarction defined by different systems. Patients with suspected but unconfirmed myocardial infarction under all classification systems had a worse postdischarge mortality. CONCLUSIONS: The classification system used had a substantial effect on the numbers of patients identified as having had a myocardial infarct, and on the 30 day survival. There were significant numbers of patients with more atypical presentations, not labelled as myocardial infarction, who did badly following discharge. More research is needed on these patients.

Age Factors↗

Separation of Listeria from cheese and enrichment media using antibody-coated microbeads and centrifugation.

An immunoseparation system for the separation of Listeria from enriched cheese samples was developed. The system utilizes polystyrene microbeads (3.8 microm in diameter) coated with covalently bound anti-Listeria genus-specific antibody. The beads were incubated with cheese enriched in half-Fraser broth and the bead-bacterial complex was separated by centrifugation at 110 g then spread on selective agar plates. Although cross-reactivity with certain Gram-positive bacteria (Staphylococcus saprophyticus and Arthrobacter sp.) was determined, this had no negative effect on capture effectiveness of the beads to Listeria spp. The minimum density of Listeria cells positively detected by immunoseparation with subsequent plating was 10(0) cfu/ml. The application of the separation method facilitates a reduction in the time of Listeria detection in cheese by 2 days without affecting the sensitivity.

Animals↗

Signals that initiate somatic hypermutation of B cells in vitro.

Somatic hypermutation is initiated as B lymphocytes proliferate in germinal centers. The signals that switch on the mutation process are unknown. We have derived an in vitro system to define signals that will initiate mutation in normal, naive splenic B cells. We find that three signals are required to allow detection of somatic mutation in vitro; these are anti-Ig, anti-CD40, and anti-CD38. If any one of these is omitted, mutation remains off. We show that CD40 is obligatory in vivo, as CD40 knockout mice exhibit no Ag-driven mutation. In contrast, CD38 is not, as CD38 knockout mice mutate normally. We believe that, in vitro, CD38, in combination with other stimuli, drives extensive cell division, allowing the detection of mutated sequences. However, in germinal centers in vivo, proliferative activity is instigated by a different molecule. This is the first demonstration of the initiation of hypermutation in vitro with normal splenic B cells using defined stimuli.

ADP-ribosyl Cyclase↗

Geographical distribution of cardiac arrest in Nottinghamshire.

BACKGROUND: to analyse the incidence of out-of-hospital cardiac arrest in Nottinghamshire; to ascertain its geographical distribution; and to determine whether the geography of coronary heart disease mortality and out-of-hospital cardiac arrest are the same. METHODS AND RESULTS: population based, retrospective study in the County of Nottinghamshire with a total population of 993,914 in an area of 2183 km2 divided into 191 electoral areas. In the 4 years from 1 January, 1991 to 31 December, 1994, 1634 patients sustained a cardiac arrest attributed to a cardiac cause (International Classification of Diseases codes 390-414 and 420-429) and were attended by the Nottinghamshire Ambulance Service. The overall crude mean incidence rate of community cardiac arrest per electoral area was 40.2 per 100,000 population (range 0-121.2). Thirteen electoral areas, relatively deprived according to the Townsend score, had a significantly greater than expected incidence rate of cardiac arrest (median of 75.6/100,000 per electoral area; interquartile range (IQR) 65.3, 83.8). Twelve relatively affluent electoral areas had a significantly lower than expected incidence rate (median of 18.5/100,000 per area (IQR 13.0, 28.7). After adjusting for deprivation index, there were no differences in coronary heart disease (CHD) mortality and community cardiac arrest in urban and rural electoral areas. Apart from response times by ambulance crews, the events that follow the cardiac arrest such as bystander resuscitation, ventricular fibrillation found as the presenting rhythm and survival were similar in all electoral areas. CONCLUSIONS: increasing level of deprivation is associated with areas of increased incidence of out-of-hospital cardiac arrest in Nottinghamshire, and the effect is apparently different from that on CHD mortality. There is scope for reducing incidence rates of community cardiac arrest and to introduce strategies to improve survival in areas identified as having high rates of community cardiac arrest.

Age Distribution↗

Pathological features of witnessed out-of-hospital cardiac arrest presenting with ventricular fibrillation.

OBJECTIVES: To determine which characteristic pathological features are predictive of the presenting rhythm and survival in victims of community cardiac arrest. DESIGN: Case-controlled retrospective autopsy study. SETTING: County of Nottinghamshire with a total population of 993 914 and an area of 2183 square kilometers. SUBJECTS: Between January 1, 1991 and December 31, 1994, 1535 witnessed cardiac arrests attended by the Nottinghamshire Ambulance Service, of which 1083 had an autopsy performed. RESULTS: Ischaemic heart disease accounted for 72.3% of cases with a further 3.6% of deaths from other cardiac causes and the remainder from non-cardiac causes. Old healed myocardial infarction was present in 39.4%, and visible fresh occlusive thrombus was found in 23.8% of cases overall. Logistic regression analysis of deaths from cardiac causes revealed that younger age (odds ratio of 0.98 (95% CI 0.97-0.99)), two vessel coronary artery disease (odds ratio of 1.65 (95% CI 1.08-2.52)) and heart weight greater than 500 grams (odds ratio of 1.56 (95% CI 1.12-2.17)) were found to be independent predictors of developing ventricular fibrillation compared to other rhythms of arrest. Being male, visible occlusive thrombus and having survived a previous myocardial infarction were found not to be independent variables. There were no outstanding pathological features in the 31 patients who survived to hospital admission and subsequently died, compared with non-survivors who were considered to have died from a cardiac cause. CONCLUSIONS: Among those who had a witnessed out-of-hospital cardiac arrest from a cardiac cause, increasing heart weight (the most likely cause of which is left ventricular hypertrophy), younger age and two vessel coronary artery disease appear to be much more important pathological features in the development of ventricular fibrillation than a previous myocardial infarction and fresh visible occlusive thrombus.

Aged↗

Coronary heart disease inequalities: deaths and the socio-economic environment in Nottingham, England.

We undertook an ecological study to investigate differences in coronary heart disease mortality within Nottingham health authority, England, to establish whether coronary mortality varied according to socio-economic status, and how mortality rates changed over a decade. An index of socio-economic status was developed from Census variables. This was used to group enumeration districts into quintiles to examine mortality inequalities. Death rates fell from 1982 to 1992, but at differential rates between the socio-economic zones. The gap in death rates between the most disadvantaged and advantaged areas widened in most population groups.

Adult↗

An MRP system for surgical linen management at a large hospital.

Materials Requirements Planning (MRP) has been used extensively in manufacturing and other industries to improve on-time delivery and to reduce costs. In this paper, we illustrate how an MRP-type system was developed to monitor surgical linen at a large teaching hospital. We also describe a bar-code scanning 'tag and recapture' study to estimate total inventory. The hospital implemented several changes based upon our recommendations that resulted in time savings and a smoother flow of materials throughout the surgical linen supply chain.

Bedding and Linens↗

Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes.

Individual B lymphocytes normally express immunoglobulin (Ig) proteins derived from single Ig heavy chain (H) and light chain (L) alleles. Allelic exclusion ensures monoallelic expression of Ig genes by each B cell to maintain single receptor specificity. Here we provide evidence that at later stages of B cell development, additional mechanisms may contribute to prioritizing expression of single IgH and IgL alleles. Fluorescent in situ hybridization analysis of primary splenic B cells isolated from normal and genetically manipulated mice showed that endogenous IgH, kappa and lambda alleles localized to different subnuclear environments after activation and had differential expression patterns. However, this differential recruitment and expression of Ig alleles was not typically seen among transformed B cell lines. These data raise the possibility that epigenetic factors help maintain the monoallelic expression of Ig.

Alleles↗

Rewiring of CD40 is necessary for delivery of rescue signals to B cells in germinal centres and subsequent entry into the memory pool.

Memory B-cell development is impaired by in vivo blockade of the CD40-CD40 ligand (CD40L) interaction using human Fc immunoglobulin G1 (IgG1)-mouse CD40 fusion protein (CD40-Ig); however, germinal centre (GC) formation is not. We show here that the block in B-cell differentiation in these mice is at the stage of rescue from apoptosis and exit from the GC. Thus, GC from CD40-Ig-treated mice contain a three- to fourfold higher level of apoptotic cells than found in control mice injected with human IgG1 alone. This increase in apoptosis is not caused by a blockade of the CD40L-mediated rescue signal but is the result of an intrinsic defect of GC B cells in CD40-Ig-treated mice to receive rescue signals via CD40. While anti-CD40 stimulation maintained the viability in culture of GC B cells from control mice, it did not rescue GC B cells from CD40-Ig-treated mice. This data is consistent with the notion that a 'rewiring' of the CD40 molecule is induced by CD40 ligation early in the response and is necessary to allow B-cell rescue from apoptosis when they subsequently enter the GC.

Animals↗

Effect of prophylactic transfusion of stored RBCs on oxygen reserve in response to acute isovolemic hemorrhage in a rodent model.

BACKGROUND: The storage of RBCs results in a time-related decline in 2,3 DPG that may reduce the ability to unload oxygen (O(2)) to tissue. The objective of this study was to compare the effect that transfusion of stored 2,3 DPG-depleted rat blood (7 days in CPDA-1) had on the O(2) reserve in conscious rats, with that of the transfusion of fresh blood (<2-hour storage). STUDY DESIGN AND METHODS: Anemic rats (Hb, 80 g/L) received either fresh packed RBCs or stored RBCs to raise Hb levels to 140 g per L. They then underwent isovolemic hemorrhage mimicking surgical blood loss to the point of O(2) supply dependency (OSD). Critical O(2) delivery (DO(2)crit), Hb concentration, and O(2) extraction at OSD were measured in a metabolic chamber. RESULTS: After transfusion, RBC DPG decreased by 50 percent in the stored-blood group, and the p50 value decreased by 5 mmHg (32.1 +/- 2.5 mmHg vs. 37.5 +/- 3.0). DO(2)crit was similar in the two groups (fresh blood: 2.79 +/- 0.44 mL/min x g(-1); stored blood, 2.99 +/- 0.76 mL/min x g(-1)). The critical Hb concentration at DO(2)crit was higher in the stored-blood group (44 +/- 4 g/L) than in the fresh-blood group (38 +/- 5 g/L); the cardiac index and O(2) extraction ratio in the two groups were not different. Under conditions of severe normovolemic anemia in rats, depletion of DPG and a decrease in p50 had only minor effects on the O(2) reserve. At OSD, under these conditions, O(2) consumption is not limited by diffusion. CONCLUSION: The physiologic impact of DPG depletion in transfused stored blood on oxygen availability in normal rats appears to be small and may be clinically inconsequential.

Anemia↗

Prenatal diagnosis of esophageal atresia using sonography and magnetic resonance imaging.

BACKGROUND: The diagnosis of esophageal atresia may be suspected on prenatal ultrasound scan in fetuses with a small or absent stomach or unexplained polyhydramnios. However, these findings are thought to have a low positive predictive value and clinical decisions affecting timing or site of delivery may be made erroneously. The authors evaluated the accuracy of fetal sonography followed by magnetic resonance imaging (MRI) for the diagnosis of this lesion. METHODS: Fetuses considered to be at risk for esophageal atresia based on detailed obstetric sonography underwent fetal MRI using a single-shot rapid-acquisition technique, and the T(2)-weighted images were evaluated prospectively. Scans were considered to be positive if the proximal esophagus was dilated, and the distal esophagus was not seen and negative if the esophagus was visualized throughout its length. RESULTS: Ten fetuses underwent MRI scanning. All had a small or absent stomach bubble with unexplained polyhydramnios. Four scans were considered to be negative for esophageal atresia; all 4 were found to have a normal esophagus after delivery. Six scans were considered to be positive; 5 had esophageal atresia (2 with tracheoesophageal fistula and 3 without), and one had a neurologic syndrome with a normal esophagus. CONCLUSIONS: Magnetic resonance imaging appears to be accurate for establishing or ruling out a prenatal diagnosis of esophageal atresia, and should be considered in fetuses who are at high risk based on ultrasound findings.

Esophageal Atresia↗

A comparison of individual and family psychology of adolescents with chronic fatigue syndrome, rheumatoid arthritis, and mood disorders.

Chronic fatigue syndrome (CFS) is a controversial diagnosis with unknown cause. Adult studies indicate high rates of psychosocial dysfunction and psychiatric comorbidity. The authors compared three groups of pediatric patients selected by diagnosis-(1l) CFS (n = 15), (2) juvenile rheumatoid arthritis (n = 15), and (3) mood disorders (n = 15)-across many psychological measures. CFS subjects had dramatic elevation of the Somatic Complaints subscale (mean T score = 75), whereas the mood disorders group had higher externalizing scores (mean T score = 68) on the Child Behavior Checklist. The CFS subjects missed significantly more school compared with the two control groups. After the onset of CFS, 13 of 15 of the CFS patients required significant educational accommodation. Only 4 of the 15 CFS patients had an Axis I psychiatric diagnosis, as determined by the Computerized Diagnostic Interview for Children. Despite a low rate of psychiatric diagnosis in the CFS sample, these data attest to their psychosocial and school dysfunction.

Adolescent↗

Comparison of two skin care regimes for incontinence.

It is estimated that 30% of nursing home residents may be faecally incontinent, with those figures rising to 60% for patients in long-stay hospitals (Royal College of Physicians, 1995). Maintaining skin integrity for these patients can be complex. With little clinical information to support carers, choosing a skin care regime that maintains skin integrity for this high-risk group can be difficult. This study aims to compare two recognized skin care regimes, used in the cleansing of patients' skin following an episode of incontinence, and their impact on patients' skin integrity. A total of 93 patients were recruited to the trial from five care of the elderly or dependent service providers. The subjects were randomly allocated to either group A (soap and water; n = 49), or group B (Clinisan (Vernacare); n = 44). Initially, 33 patients in both groups started with healthy skin. However, the results of the final assessment identified only 17 subjects in group A remaining healthy, compared with 27 in group B.

Aged↗