Immunology research in the UK: a scientific audit.
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Biomedical subjects
Publications and source records attributed to J Anderson.
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An algorithm for the early detection of acute myocardial infarction (MI) using body surface electrocardiographic potential mapping has been developed. The mapping system consists of a 64-hydrogel electrode harness applied rapidly to the anterior chest, from which electrocardiographic signals are stored on a memory card and processed by computer. At each of the 64 points, QRS and ST-T isointegrals and 10 other features of the QRST segment are measured. Using these measurements, new variables are derived that express the shape of the three-dimensional geometric surface of the map. The isointegrals, features, and shape variables are used in a variety of techniques to discriminate between MI and control subjects. Maps were recorded from 69 patients at initial presentation of chest pain suggestive of acute MI and from 80 healthy control subjects. Using a multiple logistic regression technique, 14 variables were identified that correctly classified 79 of the 80 control subjects (specificity, 98.8%) and 65 of the 69 MI patients (sensitivity, 94.2%). The algorithm based on these 14 variables was applied prospectively to maps recorded on a further 48 control subjects and 59 patients with acute MI. Of the MI patients, 31 had inferior, 13 inferoposterior, 10 anterior, 2 posterior, 1 lateral, 1 inferior with right bundle branch block, and 1 anterior non Q wave MI. The algorithm correctly classified all 48 control subjects (specificity, 100%) and 57 of the 59 MI patients (sensitivity, 96.6%). Marked differences in the three-dimensional geometric map surfaces between the control subjects and MI patients were demonstrated. Variables derived from these surfaces form the basis of an algorithm with a high sensitivity and specificity for the automated detection of acute MI. The design of adaptive algorithms and their application to patients with chest pain and atypical electrocardiographic changes, particularly ST depression, may lead to the earlier detection of MI and greater numbers of patients receiving thrombolytic therapy.
Weaning patients from mechanical ventilation and extubating them following cardiothoracic surgery has traditionally been the responsibility of medical staff. Within critical care settings some nurses, with the appropriate experience, actively take part in this process under the direction of an anaesthetist. In the Adult Intensive Care Unit (AICU) of Royal Brompton Hospital, a policy was developed to enable nurses to wean and extubate postoperative patients without the need for consultation with anaesthetic staff. It was envisaged that following the implementation of the policy other areas for nursing development and research would be highlighted. Issues relating to accountability, quality and practice are discussed.
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A two year follow-up of two matched groups of subjects with chronic severe mental illness was performed in order to evaluate a new psychiatric case management system. One group (n = 59) received care through psychiatric case management, using an assertive community treatment model that directly involved general practitioners. The other group, matched for age, sex, diagnostic group and number of hospital admissions, received standard outpatient care. Comparing the two years before and after case management, the experimental group showed a dramatic fall in inpatient admission days while the control group admission days remained the same (median difference in admission days across matched subject pairs = 64.5, 95% C.I. from 134.5 to 16). The experimental group remained out of hospital longer before first readmission (Kaplan-Meier survival analysis, P = 0.002). This type of case management programme can shorten or prevent admissions to psychiatric hospitals of patients with chronic mental illness, and increase their time before readmission.
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The ability of rinderpest virus (RPV) to replicate in vitro in adherent peripheral blood monocytes and monocyte-derived macrophages under non-stimulation conditions was investigated. When flow cytometry analysis on bovine peripheral blood mononuclear cells (PBMC) was performed, monocytic cells were seen to be targets for infection by the cell culture-attenuated RBOK vaccine strain of RPV. Viral glycoprotein (H) and nucleoprotein (N) expression in adherent blood monocytes and monocyte-derived macrophages was compared with the infection in Vero cells, in which a productive infection typical of morbilliviruses is obtained. In both cell types, the infection was m.o.i.-dependent, but the rate of viral protein accumulation was slower in monocytes/macrophages. Double-labelling experiments with monoclonal antibodies against RPV and the myeloid marker CD14 confirmed that the infected blood adherent cells were monocytes and macrophages. Productive infection of monocytes was confirmed by progeny virus titration. Permissiveness to infection was not dependent on macrophage differentiation: in vitro maturation of monocytes to macrophages before infection, did not increase the susceptibility of these cells to RPV infection. With the virulent Saudi RPV isolate, similar results were obtained, although the Saudi virus apparently had a higher rate of replication compared to the attenuated virus. These observations demonstrate clearly that bovine blood monocytes and monocyte-derived macrophages serve as hosts for a relatively slow but productive infection by rinderpest virus.
Over a 15-month period, maternal serum screening (alpha fetoprotein, oestriol, chorionic gonadotrophin) and ultrasound were evaluated in the detection of all chromosomal abnormalities. Of the 981 screened, there were 8 chromosomally abnormal pregnancies. Six of these were considered to be at increased risk on serum screening, all of which were detected. Of the remaining 2, one was detected by ultrasound and the other resulted in a liveborn baby with trisomy 21. The positive and negative predictive values for serum screening for all chromosomal abnormalities was 7.8% and 99.9% respectively. The sensitivity and specificity was 87.5% and 91.5% respectively. Serum screening is useful in the detection of many chromosomal abnormalities, not just Down syndrome. The combination of maternal serum screening and ultrasound has a high negative predictive value and is valuable in providing reassurance of no underlying chromosomal abnormality. With a positive predictive value of 7.8% a chromosomal abnormality will be found once in every 13 amniocenteses performed.
UNLABELLED: Serial DFT Measures in Man. INTRODUCTION: The defibrillation threshold (DFT) may change throughout the first year following implantation of a cardioverter defibrillator, but it remains uncertain if changes are a consequence of changes in clinical condition or are related to fundamental alterations at the electrode-tissue interface. The purpose of this study was to evaluate the extent and time course of DFT changes over the first year following implantable cardioverter defibrillator (ICD) surgery when extraneous clinical and device variables potentially affecting the DFT were excluded. METHODS AND RESULTS: We prospectively enrolled 61 patients undergoing epicardial or nonthoracotomy/transvenous ICD therapy into a series of follow-up studies where the DFT was measured at implant and at 1, 6, 12, and 52 weeks following implantation in a uniform manner. Stored energy DFT was measured and recorded for all patients. Patient exclusion criteria were: (1) inability to complete all five measures of the DFT; (2) institution of Class I or Class III antiarrhythmic drugs at any time during the study; (3) lead system changes (relocation or new leads) or programming changes in pulse width or current pathway; or (4) development of a significant change in their clinical status, such as decompensated congestive heart failure or acute ischemia. Only 20 of the 61 patients satisfied the criteria required to complete the study. Two of the excluded patients developed high DFTs, which required reprogramming of the current pathway. Eight patients had an epicardial lead system, and 12 had a nonthoracotomy lead system.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To examine the use of a novel esophageal electrode system for countershock of atrial and ventricular tachyarrhythmias, with particular regard to the measurement of transesophageal and transthoracic impedances and their association with anthropometric variables. METHODS: Transesophageal cardioversion was attempted during 131 episodes of arrhythmia in 105 patients (including 109 episodes of atrial fibrillation). The esophageal system also used in 29 patients undergoing electrophysiologic studies for investigation of ventricular tachyarrhythmias. Transesophageal and transthoracic impedances were estimated during passage of a high-frequency, low-amplitude current between the respective electrodes. Impedance estimates were associated with anthropometric measurements using linear regression (least-squares method). RESULTS: In the group of patients undergoing attempted transesophageal cardioversion, the mean estimated transesophageal impedance of 52.6 +/- 11.7 omega was significantly lower than the mean estimated transthoracic impedance of 63.1 +/- 16.4 omega (n = 104, p < 0.01). For all the patients, transesophageal impedance was associated with weight, body mass index, and chest circumference (all r > or = 0.65, p < 0.01). Transthoracic impedance was associated with the same factors (all r > or = 0.55, p < 0.01). CONCLUSION: This esophageal electrode system results in lower impedance values for countershock between the esophagus and the cutaneous cardiac apex in comparison with standard transthoracic cutaneous electrode placement. Both techniques are dependent on anthropometric factors.
The X chromosome-linked PLP/DM-20 gene is the CNS myelin gene most frequently associated with mutations, resulting in dysmyelination in several species including man (Pelizaeus-Merzbacher disease, X-linked Spastic Paraplegia). The pathology of most PLP gene mutations is characterized by hypomyelination, glial cell proliferation, increased numbers of microglia, and premature oligodendrocyte death. In most mutants, residual myelin structures have an abnormal ultrastructure and periodicity. Surprisingly, transgenic mice which carry extra copies of the wild type PLP gene show dysmyelination, demonstrating that the PLP gene is dosage sensitive. Pathological changes of transgenic mice vary from the phenotype of natural mutants. Specifically, many Golgi saccules of oligodendrocytes are vacuolated and the cytoplasm contains autophagic vacuoles hinting at a perturbation in protein trafficking. In fact, upon transgenic overexpression PLP becomes a prominent peripheral myelin protein, whereas in normal Schwann cells PLP is restricted from entering the myelin compartment. Surprisingly, transgenic animals which overexpress PLP/DM-20 at a low level appear normal during early development, but later spontaneously demyelinate. The mechanisms underlying this demyelination phenotype is unknown but an immune-mediated process has been suggested. All attempts to correct the phenotype of natural PLP mutants, such as jimpy mice, with a wild type transgene have had little effects, indicating a dominant-negative effect of the mutant gene product. On the other hand, mice with a targeted disruption of the PLP/DM-20 gene have surprisingly minor clinical signs. This suggests that the lethal phenotype associated with the majority of PLP gene mutations is a complex combination of loss and gain-of-function effects of a mutant myelin protein.
Use of nurse practitioners in major accident and emergency (A&E) departments is rapidly increasing: currently they are used in 30% of such departments and this is expected to rise to 63% by the end of 1995. Most are trained by a formal programme in the employing hospital but 12% claim to have no formal training. The nurse practitioner could prescribe a limited range of drugs in 82% of major departments with 'official' nurse practitioners, but radiograph requesting was permitted in only 57% of such departments: of those not able to request radiographs, 95% blamed radiographers for preventing this.
This study examined the acute role of glucagon in sustaining the increased hepatic gluconeogenesis observed in the conscious infected dog. After a basal sampling period, arterial glucagon levels were selectively decreased for 180 min by a peripheral infusion of somatostatin and basal intraportal infusion of insulin (GGN deficient; n = 6). In a separate protocol (GGN replaced; n = 5) glucagon was also infused intraportally to maintain the glucagon level at that seen during sepsis. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism and gluconeogenesis. In the GGN-deficient group the arterial plasma glucagon level fell from 416 +/- 49 to 88 +/- 21 pg/ml, whereas in the GGN-replaced group it remained elevated throughout (321 +/- 48 to 248 +/- 22 pg/ml). When glucagon was reduced, endogenous glucose production decreased by 1.6 +/- 0.3 mg.kg-1.min-1, and an exogenous glucose infusion was required to maintain euglycemia. Glucose metabolism remained unaltered when glucagon was replaced. When glucagon was deleted, net hepatic gluconeogenic precursor uptake was not altered. In contrast, the efficiency of gluconeogenesis was decreased by 33% compared with the GGN-replaced group. Liver biopsies taken at the end of the experiment indicated that a diversion of gluconeogenic carbon to glycogen accounted for 50% of the fall in gluconeogenic efficiency. In summary, the basal hyperglucagonemia seen during an infection helps sustain glucose production both through its effects on hepatic glycogen metabolism and on gluconeogenic efficiency.
Leukotrienes (LT) and platelet-activating factor (PAF) are synthesized by several lung cells, including alveolar macrophages (AM), and may contribute to the airway inflammation that characterizes asthma. Phospholipases A2 (PLA2) can release arachidonic acid and lysophosphatidylcholine (lysoPC), precursors for leukotriene and PAF synthesis, respectively, from membrane phospholipids. The present study sought to determine the extent to which this common initial step contributes to leukotriene and PAF synthesis in rat AM. AM were obtained by lung lavage, cultured, and exposed to one or more of the following: PAF, zileuton (5-lipoxygenase inhibitor), Ro 25-4331 (dual PLA2 inhibitor), and either A23187 (Cal) or zymosan. The following measurements were made: LTB4 synthesis, PAF synthesis, and PLA2 activity. CaI stimulation increased PAF synthesis 3-fold (P < 0.001), LTB4 synthesis 20-fold (P < 0.001), and PLA2 activity 52% (P < 0.001). Incubation with PAF (2.5 microM) for 10 min decreased basal LTB4 synthesis 33% (P < 0.001), but it had no effect on basal PAF synthesis or PLA2 activity. The same dose of PAF (2.5 microM) decreased CaI-stimulated PAF synthesis 40% (P < 0.02). After CaI stimulation of PAF-pretreated cells, a relationship was found between PAF-induced changes in PLA2 activity and LTB4 synthesis (r = 0.68; P < 0.001) but not between changes in PLA2 activity and PAF synthesis. Zileuton (1 microM) decreased basal and CaI-stimulated LTB4 synthesis 50% (P < 0.02), and 80% (P < 0.002) respectively, but it did not alter PAF synthesis.
Twenty-four clinicians (five psychiatrists, five registered nurses, and 14 counselors) participated in a psychophenomenological study of the decision-making process in assessing clients for involuntary psychiatric hospital admission. In interviews, the clinicians were asked to describe a situation in which the admission assessment was especially difficult. Analysis of the interviews identified nine essential structural elements of the decision-making process: systematic and individualized process, state-mandated criteria, investigation of alternatives, decision not made alone, intuitive reasoning, connection with the client, caution, and inability to control all contingencies.
This study examined the attitudes toward breastfeeding of medical professionals working with pregnant or new mothers. Most advocated breastfeeding to mothers who had not made an infant feeding decision; fewer talked about breastfeeding during the first trimester; and many recommended that mothers supplement a breastfed infant with prepared commercial baby milk. All agreed that a mother's return to work led to early discontinuance of breastfeeding and that the family is a major influence on a mother's decision to breastfeed. To increase the prevalence of breastfeeding, the study group recommended prenatal education, participation in support groups, and promotion of breastfeeding through the media.
OBJECTIVES: The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening. METHODS: Forty work-sites were randomly assigned to one of two educational interventions: a "usual" intervention of 5 minutes of counseling, or a "special" intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol. Costs were monitored, and cholesterol levels were retested 6 and 12 months later. RESULTS: The total per-person cost for screening and the educational intervention was about $50. Cholesterol levels differed little between the two intervention groups 6 months after screening, but after 12 months those in the special intervention worksites showed a 6.5% drop in cholesterol, whereas those at the usual intervention worksites showed a drop of only 3.0%. Hence a 3.5% cholesterol reduction was attributable to the special intervention. CONCLUSIONS: A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost. Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities.
1. Psychiatric nurses, psychiatrists, and counselors value their previous clinical experiences and appear empathetic with patients. 2. Clinical experience facilitates the development of expertise in clinical skills, more willingness to include clients in the decision-making process, and increase self-confidence when making less restrictive treatment recommendations. 3. Psychiatric nurses differ from psychiatrists and counselors in their perceptions of teamwork, responsibility, role expectation, and in connecting with clients.