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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 145 records · Page 8Linked to original sources
PubMed1994

Methods of establishing criteria for purchasing coronary angiography in the investigation of chest pain.

BACKGROUND: Purchasers may now define how many clinical procedures they wish to buy. In the investigation of chest pain, coronary angiography provides a definitive diagnosis. In clinical practice, the use of coronary angiography varies, so purchasers may choose the sort of service they wish to buy. We reviewed the extent of variation in the investigation of patients in the Trent Region and present a system for establishing criteria for the purchase of coronary angiography. METHODS: Three studies are presented, based on patients referred to the three referral centres in the Trent Region. First, the appropriateness for investigation, defined as benefit outweighing risk, is determined by expert panel; second, an audit of patients referred for coronary angiography is presented; and third, the likelihood or probability of significant coronary disease is assessed by application of a logistic regression model. RESULTS: According to the panel criteria, 27 per cent of patients in one centre were judged inappropriate for coronary angiography, 28 per cent in the second centre and 10 per cent in the third. When referred for angiography, extent of anti-anginal medication, symptom severity, use of exercise testing, and result of and planned management after angiography varied widely among centres. The likelihood of significant coronary artery disease could be predicted in 86 per cent of patients. CONCLUSIONS: Variation in clinical practice does not make the purchasers' task easy. Based upon these studies and clinical trials of coronary artery bypass surgery and coronary angioplasty, we present potential performance indicators which may form the basis of contracts or be used as audit measures.

Coronary Angiography↗
PubMed1994

Prostatitis: a review of diagnosis and management.

Prostatitis, the most common urologic disease in men, afflicts between 25% and 50% of all adult men. It is a complex and not well understood condition, partially because of its often obscure pathogenesis. There are four prostatitis diagnostic and treatment categories: 1) acute bacterial prostatitis; 2) chronic bacterial prostatitis; 3) nonbacterial prostatitis; and 4) prostatodynia. This article reviews prostatic anatomy and pathogenesis, as well as diagnostic and treatment categories. This information can assist the primary care practitioner in the identification and management of this common and often puzzling condition.

Acute Disease↗
PubMed1994

Preservation and storage of pancreatic islets.

UW solution is currently the best available for short-term cold storage of pancreatic islets for up to 3-5 days, culture for up to 10-14 days, and cryopreservation for longer periods. More research needs to be done to find a better solution, specifically for cold storage of islets. It seems that such a solution is likely to be a derivative of the UW solution.

Cryopreservation↗
PubMed1994

Kinetics of somatic mutation in lymph node germinal centres.

Somatic mutation activity in immunoglobulin V kappa genes during the response to the hapten 2-phenyl-5-oxazolone was measured in lymph node B-cell populations at various timepoints after footpad immunization. When the V kappa Ox1 genes rearranged to the J kappa 5 segment were amplified from genomic DNA using the polymerase chain reaction and sequenced, somatic mutations could be detected as early as day 4 after immunization. Somatic mutations were also detected after sequencing RNA from oxazolone-specific hybridomas derived from lymph node cells at day 4 after immunization. These early mutations were found mostly in cells with a germinal centre phenotype. No indication of selection at the population level by apoptosis was detected until day 7 after immunization. These results suggest somatic mutations can be induced very early during the immune response in lymph node cells, prior to the peak of clonal expansion and selection with regard to antigen binding.

Animals↗
PubMed1994

Structure and heterogeneity of the a sequences of human herpesvirus 6 strain variants U1102 and Z29 and identification of human telomeric repeat sequences at the genomic termini.

The unit-length genome of human herpesvirus 6 (HHV-6) consists of a single unique component (U) bounded by direct repeats DRL and DRR and forms head-to-tail concatemers during productive infection. cis-elements which mediate cleavage and packaging of progeny virions (a sequences) are found at the termini of all herpesvirus genomes. In HHV-6, DRL and DRR are identical and a sequences may therefore also occur at the U-DR junctions to give the arrangement aDRLa-U-aDRRa. We have sequenced the genomic termini, the U-DRR junction, and the DRR.DRL junction of HHV-6 strain variants U1102 and Z29. A (GGGTTA)n motif identical to the human telomeric repeat sequence (TRS) was found adjacent to, but did not form, the termini of both strain variants. The DRL terminus and U-DRR junction contained sequences closely related to that of the well-conserved herpesvirus packaging signal Cn-Gn-Nn-Gn (pac-1), followed by tandem arrays of TRSs separated by single copies of a hexanucleotide repeat. HHV-6 strain U1102 contained repeat sequences not found in HHV-6 Z29. In contrast, the DRR terminus of both variants contained a simple tandem array of TRSs and a close homolog of a herpesvirus pac-2 signal (GCn-Tn-GCn). The DRR.DRL junction was formed by simple head-to-tail linkage of the termini, yielding an intact cleavage signal, pac-2.x.pac-1, where x is the putative cleavage site. The left end of DR was the site of intrastrain size heterogeneity which mapped to the putative a sequences. These findings suggest that TRSs form part of the a sequence of HHV-6 and that the arrangement of a sequences in the genome can be represented as aDRLa-U-a-DRRa.

Base Sequence↗
PubMed1994

Implication of prescriptions for nitrates: 7 year follow up of patients treated for angina in general practice.

OBJECTIVE: To determine the demand placed on local cardiological services by patients prescribed nitrates for ischaemic heart disease. DESIGN: A follow up study of a cohort of patients identified in 1985. SETTING: Nottingham Health District. PATIENTS: Four hundred and ninety nine patients prescribed nitrates in 1985 for presumed ischaemic heart disease. MAIN OUTCOME MEASURES: Referral to medical outpatients, admittance to hospital with chest pain, cardiological investigations, and mortality. RESULTS: Over the seven year period 26% of patients were admitted urgently with chest pain and 15% were referred to the medical outpatient department--a referral rate of 6% a year. 4% of patients had an exercise test and 6% a coronary angiogram. The death rate was 6% a year and a higher proportion died of cardiovascular causes than would be expected in the general population. CONCLUSIONS: Prescription of nitrate is useful in the determination of the prevalence of ischaemic heart disease. Most patients with angina are still treated within the community, and the rate of specialist investigation remains low.

Adult↗
PubMed1994

Variations in the use of coronary angiography in three cities in the Trent Region.

OBJECTIVE: To establish the characteristics of patients referred for coronary angiography and the outcome of investigation. DESIGN: Prospective study. SETTING: Three regional referral centres at Sheffield, Leicester, and Nottingham. PATIENTS: All patients referred for investigation from 1 July 1988 to 30 June 1989. INTERVENTIONS: Coronary angiography for suspected ischaemic heart disease. MAIN OUTCOME MEASURES: Site and extent of coronary artery disease at coronary angiography and subsequent intervention. RESULTS: There was a range of clinical activity with a trend towards symptomatic control in Nottingham where patients tended to have more severe angina of long duration and extensive drug treatment. Important coronary lesions were often found and most patients needed coronary artery bypass surgery or angioplasty. In Leicester and Sheffield, where angiography was used prognostically, patients tended to have mild angina of shorter duration and less extensive medical treatment; significant coronary disease was often found but fewer patients were recommended for further intervention. CONCLUSIONS: Referral for coronary angiography seems to reflect philosophical differences among the referring physicians. Referring patients late in the disease process ensures that most have a subsequent intervention but the benefits of revascularisation may be denied to those with mild symptoms but extensive coronary disease.

Adult↗
PubMed1994

Evidence of inadequate investigation and treatment of patients with heart failure.

OBJECTIVE: To determine the referral rates to hospital and level of investigation of patients with heart failure, and to assess whether they are receiving optimum management. DESIGN: A retrospective survey. SETTING: Nottingham Health District. PATIENTS: 505 patients receiving loop diuretic treatment prescribed by their general practitioner. MAIN OUTCOME MEASURES: Referral to hospital as an inpatient or outpatient for assessment of assumed cardiac failure; investigations--electrocardiography, chest radiography, and echocardiography; treatment with angiotensin converting enzyme inhibitors. RESULTS: Only 56% of patients prescribed loop diuretics fulfilled the diagnostic criteria for heart failure. Of these, 74% had been referred to hospital, of whom 80% had had an electrocardiograph, 75% a chest radiograph, but only 31% an echocardiogram. Only 17% of patients with heart failure were being treated with angiotensin converting enzyme inhibitors in conjunction with loop diuretics. CONCLUSIONS: Patients with heart failure in the Nottingham Health District are not being adequately investigated or receiving the optimum treatment.

Aged↗
PubMed1993

Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

Animals↗
PubMed1993

Single-cell analysis of Hodgkin and Reed-Sternberg cells: molecular heterogeneity of gene expression and p53 mutations.

We have used a single-cell based polymerase chain reaction (PCR) amplification technique to examine the gene expression pattern in single Hodgkin's and Reed-Sternberg (H&RS) cells from seven patients with Hodgkin's disease. Single cells were isolated from lymph nodes obtained at diagnosis (5 of 7 patients) or in first or second relapse (2 of 7 patients). Gene expression was examined by hybridization to a panel of 22 cDNA probes. Forty-nine H&RS cells (and 23 CD3+ or CD20+ lymphocytes as controls) from four patients with nodular sclerosing Hodgkin's disease (HD) and one patient each with lymphocyte predominant and mixed-cellularity HD were successfully analyzed by PCR. This analysis provides evidence that single H&RS cells can coexpress genes characteristic of several hematopoietic lineages (monocytes and lymphocytes). Genes characteristic of activated lymphoid cells are expressed in most H&RS cells. Heterogeneity of expression for certain genes between different cases was found and may eventually define molecular subgroups of HD. These findings indicate that H&RS cells of HD resemble activated hematopoietic cells. Phenotypically similar cells from different cases exhibit characteristic molecular differences. In one patient, 5 of 7 single RS cells showed identical p53 cDNA mutations at codon 246 on specific reverse transcriptase [RT]-PCR and sequencing of exons 5 through 8. The novel experimental approach may provide a valuable tool for understanding the molecular events in newly diagnosed Hodgkin's disease and progression of the disease.

Adolescent↗
PubMed1993

Impact of hospital thrombolysis policy on out-of-hospital response to suspected myocardial infarction.

The treatment of acute myocardial infarction changed when several trials reported that thrombolytic agents given within a few hours of infarction improved outcome. We present data from the Nottingham Heart Attack Register comparing 1982-84, when thrombolysis was not available, and 1989-90, when it was hospital policy to give thrombolysis to all patients who arrived within 6 hours of the onset of symptoms, in the absence of a specific contraindication. The number of patients referred with symptoms suggestive of acute myocardial infarction increased by 75% from 1982 to 1990; a diagnosis of "possible infarction" was made in about half of all patients in 1982-84 and 23% in 1989-90. Our current thrombolytic policy has had little impact on patient and general practitioner (GP) behaviour. The GP was contacted by most patients. The median time between the onset of a patient's symptoms and admission to hospital when the GP was involved was 229 min in 1982-84 and 210 min in 1989-90; when he was not involved in arranging the admission median times to admission were 89 min and 75 min, respectively. By 6 hours from symptom onset, 60% of patients had been admitted; by 12 hours, about 70% were in hospital and by 24 hours, 80%. Of 7855 patients admitted with suspected acute myocardial infarction in 1989-90, 4465 were admitted within 6 hours of symptom onset. Of these, 736 (16%) patients received a thrombolytic drug. 389 (9%) patients had a specific, documented contraindication to thrombolysis. Although we estimate that the policy has saved about 8 lives per year, it is not surprising that there has been no improvement in overall case fatality after myocardial infarction.

Emergency Medical Services↗
PubMed1993

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny.

During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8+ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.

Animals↗
PubMed1993

The appropriateness of the use of cardiovascular procedures. British versus U.S. perspectives.

To determine whether patients are less likely to receive an inappropriate procedure in countries that devote fewer resources to health care than does the United States, we studied how appropriately coronary angiography and coronary artery bypass surgery were performed in the Trent region of the United Kingdom. The medical records of 320 patients who underwent coronary angiography and 319 who underwent coronary artery bypass surgery in 1987 and 1988 were randomly selected for review. Despite the United Kingdom's more limited use of coronary angiography and coronary artery bypass surgery, a substantial proportion were still performed for less than appropriate reasons, by both U.S. and U.K. criteria. Merely reducing the rate of use of these procedures will not be sufficient to eliminate such inappropriate use.

Aged↗
PubMed1993

Sensitivity and specificity of the initial working diagnosis in acute myocardial infarction: implications for thrombolysis.

Diagnosing acute myocardial infarction promptly allows all eligible patients to be considered for thrombolysis. Objective evidence from the first electrocardiograph may be inadequate and often the doctor must base his immediate management on limited information; an incorrect initial working diagnosis might deny some patients the benefits of thrombolysis or expose others to inappropriate, expensive and potentially harmful treatment. We were interested to find out how accurate our junior doctors were in their assessment of patients admitted with a suspected MI. All patients entered onto the Nottingham Heart Attack Register admitted with suspected acute MI from 1982 to 1986 and 1989 were identified. The initial working diagnosis on admission was obtained from the patient case record. A final diagnosis was assigned according to strictly defined criteria using 'cardiac' enzyme and electrocardiographic results. Sensitivity and specificity of the initial working diagnosis was calculated. Using the initial working diagnosis as a 'screening' test, we found that, while our doctors successfully identified patients with myocardial ischaemia, they were less good at recognizing acute MI--an admission diagnosis of 'MI' carried a sensitivity of 55% and specificity of 88%. This may explain the low utilization of thrombolysis in the Nottingham hospitals. In the first full year since thrombolysis became available, we estimated that we might have exposed 65 patients to the risks of thrombolysis inappropriately and we might have missed treating 244 patients.

Diagnosis, Differential↗
PubMed1993

Analysis of somatic mutation activity in multiple V kappa genes involved in the response to 2-phenyl-5-oxazolone.

We have studied somatic mutation activity early in a response to 2-phenyl-5-oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later.

Animals↗