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Biomedical subjects

J Edwards

Publications and source records attributed to J Edwards.

At least 127 records · Page 7Linked to original sources

Direct and indirect estimates of HIV-1 incidence in a high-prevalence population.

While the worldwide AIDS epidemic continues to expand, directly measured incidence data are difficult to obtain. Methods to reliably estimate human immunodeficiency virus type 1 (HIV-1) incidence from more easily available data are particularly relevant in those parts of the world where prevalence is rising in heterosexually exposed populations. The authors set out to estimate HIV-1 incidence in a population of heterosexual sexually transmitted disease clinic attendees in Trinidad who had a known high prevalence of HIV-1 subtype B. Over the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of early markers of HIV-1 infection (p24 antigen screening), and a cohort study of seronegative genital ulcer disease cases were compared. Measuring incidence density in the genital ulcer disease cases directly gave the highest estimate, 6.9% per annum. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0% per annum, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists gave estimates of 3.5% and 4.5% per annum, respectively. These results were found to be internally consistent. Indirect estimates of incidence based on prevalence data can give accurate surrogates of true incidence. Within limitations, even crude measures of incidence are robust enough for health planning and evaluation purposes. For planning vaccine efficacy trials, consistent conservative estimates may be used to evaluate populations before targeting them for cohort studies.

Blotting, Western↗

Interassay calibration as a major contribution to the comparability of results in clinical enzymology.

OBJECTIVE: Factors contributing to the applicability of interassay calibration of methods measuring enzyme catalytic activities are described. Also discussed are the properties essential for such a material. Similarity of specificity for the methods to be calibrated as well as commutability between the material(s) intended to be used as calibrator are the main criteria to be satisfied. RESULT: Several examples demonstrated that interassay calibration is feasible but a multi-enzyme calibrator with a wide commutability for the most popular methods remains to be developed. This is the project of the IFCC Working Group on Calibrators in Clinical Enzymology (WG-CCE). Several experimental data are also presented that indicate that the temperature at which the reaction is carried out is not a limiting factor in the implementation of interassay calibration in clinical enzymology.

Calibration↗

Validation of an enzyme calibrator--an IFCC guideline. International Federation of Clinical Chemistry.

OBJECTIVES: The objective of this guideline is to improve standardization in clinical enzymology in order to improve intermethod comparability of patients' results. DESIGN AND METHODS: The reference system, combination of the reference method and the reference material, is used to produce a reference value for a given catalytic activity. Sets of methods are formed of methods exhibiting the same analytical specificity. Materials intended to be used as enzyme calibrators are experimentally checked for their commutability. RESULTS: The transfer of accuracy from the reference value to patients' results is dependent on methods (analytical specificity) and on materials (experimentally assessed commutability). The feasibility of this approach was demonstrated with materials of high level for several enzymes and for each of them for several routine methods. CONCLUSION: Expected advantages of this approach in clinical enzymology are presented.

Calibration↗

Effect of PACAP-27 on 14C-aminopyrine accumulation in isolated rabbit parietal cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in gastric mucosa, but its direct effect on parietal cells is unknown. We examined this using 14C-aminopyrine uptake in elutriated rabbit cells. PACAP-27 had no effect on basal cells but significantly increased the response to histamine (10(-4) M) at 10(-9) M and to carbachol (10(-4) M) in the presence of ranitidine (10(-4) M) at 10(-7) M and 10(-8) M. PACAP (6-38), an antagonist of PACAP, inhibited the effect of PACAP-27 on carbachol-stimulated cells. Vasoactive intestinal peptide had no significant effect. In conclusion, PACAP-27 has a direct additive effect on stimulated rabbit parietal cells in vitro.

Aminopyrine↗

Screening patients in general practice with COPD for long-term domiciliary oxygen requirement using pulse oximetry.

Epidemiological data suggest long-term oxygen therapy (LTOT) delivered by oxygen concentrators in patients with severe hypoxic chronic obstructive pulmonary disease (COPD) is under-prescribed by General Practitioners (GPs) in England and Wales. One reason for this may be the unavailability to GPs of a measure of arterial oxygenation needed to fulfil the defined prescription criteria. Provision of a non-invasive measure of oxygenation may improve detection of hypoxic subjects and increase appropriate prescribing. This study aimed to evaluate pulse oximetry in a general practice setting and to screen for severe undetected hypoxaemia fulfilling the LTOT prescription criteria in patients with COPD. All COPD patients attending surgery in two practices were screened with oximeters for hypoxaemia. Those with an oxygen saturation of < or = 92% were referred to hospital for formal arterial blood gas analysis and an oxygen concentrator assessment. GPs were asked to evaluate their experience in the ease of use and application of oximetry. The number of patients receiving oxygen by concentrator before the study was compared with the national rate and the number after the study with the estimated need suggested by epidemiological studies. Over a 12-month period a total of 114 patients were screened in the two practices with a combined list size of 15,742. Thirteen patients had saturations of < or = 92%. Two refused and 11 underwent formal arterial gas analysis. Three had PaO2 < 7.3 kPa and new prescriptions for oxygen concentrators were made in these previously unsuspected severely hypoxaemic subjects as a result. One other hypoxaemic subject was referred and found to have another treatable medical condition. The initial prevalence of concentrator prescription (0.013% CI 0.003, 0.047) was similar to the national rate (0.024%) and the prevalence observed after screening (0.031%, CI 0.013, 0.073) fell within the lower suggested prescription need of previous epidemiological data (0.02-0.10%). All practitioners found the oximeters simple to use and helpful in assisting with assessment of the severity of their patient's condition. Oximetry provides a readily usable non-invasive method of screening and when applied to all COPD patients seen in general practice can reveal those fulfilling the criteria for long term oxygen who would otherwise not be identified as needing this treatment.

Aged↗

Pharmacokinetics of two multiple-dosing regimens of D0870 in human immunodeficiency virus-positive patients: a phase I study.

D0870 is a triazole with a broad antifungal spectrum, and it has been shown to have both in vitro and in vivo activities against wild-type and fluconazole-resistant strains of Candida albicans. Twenty-two human immunodeficiency virus (HIV)-positive male subjects were enrolled in an open, nonrandomized trial investigating the pharmacokinetics of two different dosing regimens of D0870 and assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and their ability to tolerate multiple oral doses. Nine subjects received an initial loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A further nine subjects received an initial 200-mg loading dose followed by four daily maintenance doses of 25 mg. All subjects were fasting. A single loading dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (Cmax) of 107 +/- 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once-daily dosing regimen as seen by the similar values of the area under the concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a mean accumulation ratio close to unity (0.90). The terminal plasma half-life of D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A single loading dose of 200 mg of D0870 resulted in a Cmax of 431 +/- 186 ng/ml. Concentrations in plasma were again maintained by the 25-mg daily dosing regimen, with the mean accumulation ratio being close to unity (1.17). The terminal half-life of D0870 in plasma following dosing on day 5 of phase II of the study ranged from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the plasma of these HIV-positive subjects were similar to the values predicted from simulations based on data derived from normal, healthy subjects. D0870 was well tolerated. No serious adverse events were experienced during the course of the study, and all volunteers completed the trial. A total of 15 adverse events were reported, but none were considered to be related to the administration of D0870 and all had resolved by the end of the trial. No changes in the hematology, clinical chemistry, or urinalysis parameters were considered to be related to dosing with D0870. No clinically significant changes in the electrocardiogram parameters were noted during the trial. The data generated in this trial support further investigation of these regimens with HIV-positive subjects with fluconazole-susceptible or -resistant oropharyngeal candidosis.

Adolescent↗

Foot pump prophylaxis for deep venous thrombosis: the rate of effective usage in trauma patients.

Trauma patients are at risk for deep venous thrombosis (DVT) but often cannot receive systemic anticoagulation therapy. The major reason for failure of mechanical methods of DVT prophylaxis is ineffective usage. It has been postulated that foot pumps may have a better compliance rate than do other devices. One thousand observations were performed on trauma patients in both the intensive care unit (ICU) and on the surgical ward. Foot pumps were applied properly and functioning correctly 59% of the time. Patients in the ICU had significantly better compliance than did patients on the surgical ward. These rates are not better than published rates for other devices for DVT prophylaxis.

Adult↗

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. Cognitively-oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

Adult↗

Prolonged recovery in first-episode psychosis.

BACKGROUND: Early identification and specialised treatment of individuals with enduring positive symptoms may assist in alleviating symptoms and has the potential to change the course of illness. METHOD: Prevalence and descriptive data on enduring positive symptoms in two first-episode samples are outlined. Attempts to incorporate the focus of early intervention for persisting psychosis into routine clinical care of individuals with first-episode psychosis are described. RESULTS: Of the 227 individuals with first-episode psychosis who were assessed using the Brief Psychiatric Rating Scale at 3/6 months and 12 months following initial stabilisation (from a total sample of 347), 6.6% experienced enduring positive symptoms at all three time points. When the analysis was restricted to schizophrenia, schizophreniform and schizoaffective disorders (n = 158) the percentage increased to 8.9%. These patients had significantly longer mean duration of untreated psychosis prior to initiation of treatment and, at 12-month follow-up, significantly higher depression and poorer psychosocial functioning. CONCLUSIONS: The association of untreated psychosis with treatment resistance supports the argument for early intervention as soon as possible following the onset of psychotic symptoms.

Adolescent↗

Small bowel obstruction as a complication of laparoscopic extraperitoneal inguinal hernia repair.

Laparoscopic hernia repair is associated with its own set of complications, such as intra-abdominal organ and vascular injury, gas embolism, penumoperitoneum, small bowel obstruction secondary to trocar site fascial defects, intra-abdominal adhesion, and reaction to synthetic mesh. With the extraperitoneal approach, the abdominal cavity is not violated, thereby eliminating the risks for these complications. However, small bowel obstruction, albeit rarely, do occur with this approach because of inadvertent violation of the peritoneal cavity, or failure to close the peritoneal opening of the hernia sac, as shown in this case presentation.

Adult↗

Creation and maintenance of Helix, a Web based database of medical genetics laboratories, to serve the needs of the genetics community.

Helix (healthlinks.washington.edu/helix) is a web accessible database that serves as the main U.S. directory of laboratories offering genetic testing. The database was designed to address the previously unmet need for a centralized, continuously updated source of information about clinical and research genetic testing to keep pace with the rapid rate of gene discovery resulting from the Human Genome Project. The Helix project began in 1992 at the University of Washington and Children's Hospital and Regional Medical Center. It has evolved from a single user stand alone relational database to a fully Web enabled database queried and maintained via the web and linked to other web accessible genomic databases. As of February, 1998 it lists more than 500 diseases and 290 laboratories, with over 5,200 registered users making approximately 250 queries/day (90% via the Internet). We describe the iterative design, implementation, population and assessment of the database over a six year period.

Database Management Systems↗

Catering services. Measuring the wasteline.

The study found that overall almost half (46 per cent) of the food served in the hospitals surveyed was wasted. Waste was higher where meals were put onto plates in wards (57 per cent) than where meals were plated in the hospital kitchen (35 per cent). The researchers observed that meals often arrived late and were not well presented.

Age Factors↗

Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor.

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.

3T3 Cells↗