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Biomedical subjects

P Morgan

Publications and source records attributed to P Morgan.

At least 37 records · Page 2Linked to original sources

Clinical management of psoriasis: principles and practice.

A chronic condition that compromises many patients' quality of life, psoriasis is treatable with a range of agents, either alone or in combination. Clinical management strategies using these therapies can be organized as a stepped-care approach. For mild disease, corticosteroids and other topical therapies (step 1) are often appropriate. When lesions are more pronounced or extensive, phototherapy (step 2) is often the treatment of choice, and topical treatments or the step 3 agent acitretin can be added to enhance or accelerate therapeutic responses. Step 3 agents, which also include cyclosporine and methotrexate, may be contemplated when psoriasis is moderate or severe. Acitretin may cause acute adverse effects, including mucocutaneous effects, which can be avoided by reducing dosage. Methotrexate treatment can lead to bone marrow suppression and hepatotoxicity, and cyclosporine can cause nephrotoxicity. The clinical uses of these agents are illustrated in part through case presentations drawn from the authors' practices, and the supportive role of the National Psoriasis Foundation is reviewed.

Adult↗

A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative thais.AFRIMS-RIHES Vaccine Evaluation Group. Armed Forces Research Institute of Medical Sciences and the Research Institute for Health Sciences.

Fifty-two human immunodeficiency virus type 1, seronegative Thai adults from the community were enrolled in a double-blind, placebo controlled, phase I/II trial of HIV SF2 gp120/MF59 vaccine to determine the safety and immunogenicity of this recombinant, B clade, HIV envelope protein vaccine. Twenty-six subjects were enrolled at each of two sites in Thailand, Bangkok and Chiang Mai. Twelve subjects received placebo and 40 subjects received vaccine (50 microg). Subjects were immunized according to one of two schedules, 0, 1 and 4 or 0, 1 and 6 months. The frequency of adverse reactions was not different between placebo and vaccine subjects, nor between immunization schedules. Of vaccinees, all developed high-titer binding antibody to the immunogen (rgp120), 39 developed neutralizing antibody (NA) responses against homologous virus (HIV-1(SF2)), and 22 developed NA against heterologous virus (HIV-1(MN)). No subject demonstrated intercurrent HIV infection, however screening EIA reactivity occurred in 27% of recipients. Thus, this candidate HIV vaccine was found to be safe and immunogenic in Thai adults, laying the foundation for development of a subtype E construct in this population.

AIDS Vaccines↗

Characteristics of human IgA and IgM genes used by plasma cells in the salivary gland resemble those used in duodenum but not those used in the spleen.

Immunologically, the parotid salivary gland is an effector site that secretes large quantities of polyspecific Abs into the saliva, mainly of the IgA isotype. It is considered to be part of the common mucosal immune system but the inductive site for the Ab-producing cells of the salivary gland has not yet been clearly identified. The origin and diversity of cells of B lineage can be investigated by analyzing their Ig heavy chain genes (IgH). We have obtained sequences of IgM and IgA VH4-34 genes from plasma cells in human salivary gland, duodenal lamina propria, and splenic red pulp. Related sequences were found in different areas sampled within each tissue studied, indicating that the plasma cells carrying these genes are widespread with limited diversity. Examples of related IgH genes that are isotype switched were also seen in the salivary gland. The genes from plasma cells of the salivary gland were highly mutated, as were duodenal plasma cell sequences. The level of mutation was significantly higher than that seen in splenic plasma cell sequences. Analysis of CDR3 regions showed that the sequences from salivary gland had significantly smaller CDR3 regions than sequences from spleen, due to differences in number and type of DH regions used. Sequences from duodenum also had smaller CDR3 regions. Therefore, plasma cells from human duodenum and salivary gland showed characteristics that differed from those of human splenic plasma cells.

Base Sequence↗

A role for tyrosine phosphorylation in the regulation and sensitization of adenylate cyclase by melatonin.

Mimicking short photoperiod melatonin signals (16 h exposure) on primary cell cultures of melatonin target cells of the ovine pars tuberalis (PT) results in an enhanced cAMP response to forskolin stimulation relative to untreated cells, a phenomenon termed sensitization. The sensitized response of PT cells may be an important aspect of the interpretation of the melatonin signal to initiate appropriate seasonal physiological responses. The aim of this study is to add to our understanding of the molecular mechanisms involved in the sensitization of PT cells by melatonin. We demonstrate that sensitization of PT cells by melatonin is mediated via a G(i)-coupled melatonin receptor. The sensitized cAMP response is not only obtained with the pharmacological tool forskolin, but also with cholera toxin, an activator of G(salpha). Changes in the level of G(salpha) or G(ialpha) G-protein subunits are ruled out as part of the sensitization mechanism. However, changes in tyrosine phosphorylation may be involved as tyrosine kinase inhibitors sensitize ovine PT cells and tyrosine phosphatase inhibitors significantly blunt adenylate cyclase activity, including the sensitized response to melatonin. The adenylate cyclase isoforms mediating the sensitized response may be broad as 7 of the 9 isoforms of adenylate cyclase are expressed in the PT.

Adenylate Cyclase Toxin↗

Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL) for assessment of cerebral hemodynamics in acute stroke by magnetic resonance.

RATIONALE AND OBJECTIVES: To compare cerebral perfusion data obtained by using a low-dose, T1-weighted MRI technique with radionuclide (single positron emission computed tomography [SPECT]) brain imaging and to assess the reproducibility of parametric MRI data (cerebral blood flow [CBF], cerebral blood volume [CBV], and time to peak [TTP]) by applying a previously described nuclear medicine technique to derive quantitative perfusion data. METHODS: Single-slice brain and neck images were rapidly acquired during the passage of a small (1/10th of normal dose) bolus of contrast. Parametric images were constructed from the MR data by extracting the bolus transit curve for the brain and the peak arterial input curve from the carotid vessels in the neck. These were compared with SPECT perfusion imaging. Twenty-four patients with acute stroke were studied with both techniques; 13 underwent repeated scanning to assess data reproducibility. RESULTS: Relative CBF data were comparable to SPECT data (r = 0.584, P = 0.01). Results were reproducible for relative CBF, CBV, and TTP. The arterial input function was significantly different on the second injection with an average difference of 73.5, suggesting that the signal-concentration relationship had lost linearity with increased contrast load. Absolute quantitative MRI data produced values in the expected range (CBF = 42.6 mL x 100 g(-1) x min(-1)). CONCLUSIONS: This technique allows estimation of CBF in the setting of acute stroke with quantitative values in the expected range. Repeated measurements in the same patients showed that this technique provides a reproducible measure of relative CBF, CBV, and TTP.

Brain↗

DTH responsiveness of HIV-infected Thai adults.

A study was carried out in Thailand to determine the frequency of reactivity to delayed-type hypersensitivity (DTH) skin tests used for the staging of HIV patients in the United States. A four-antigen panel which included tetanus toxoid (1:10), Candida (1:10), mumps and Trichophyton antigens was assessed in 221 adult subjects from across the full immunological spectrum of HIV disease. Complete anergy was found in 38 per cent of 73 subjects with CD4 counts of 0-200 cells/ml and in 6 per cent of 78 subjects with 201-400 cells/ml. Partial anergy (response to 1 of 4 antigens) was found in 26 per cent of the 0-200 cell/ml group and decreased progressively with increasing CD4 cell count. Results suggested that a 3-member recall antigen panel would provide nearly all the clinically useful information gained by the more standard 4-member panel. In conclusion, DTH skin testing was confirmed to provide a method of assessing the integrity of cellular immune function of HIV-infected Thai adults which correlated with disease progression.

Adult↗

Narrow-band UVB: a practical approach.

Narrow-band UVB therapy offers a new and exciting treatment option and area of study in phototherapy. The narrow-band skin type protocol offers a safe and effective treatment plan for those who do not routinely use, or wish to use, minimal erythema dosing to establish starting doses for narrow-band UVB therapy.

Dose-Response Relationship, Radiation↗

Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.

Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1alpha variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1alpha residues Asp26 and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1beta and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1alpha has enabled comparison of these residues in hMIP-1beta and RANTES. Aggregated and disaggregated forms of hMIP-1alpha, hMIP-1beta, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1alpha, hMIP-1beta, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.

Amino Acid Sequence↗

Accuracy and reproducibility of one-day disposable contact lenses.

One-day disposable contact lenses are experiencing rapid market growth in certain markets, such as the United Kingdom. Because of the huge numbers of lenses required to satisfy this modality of wear, both practitioners and patients need to be reassured about the quality of these products. Analysis of the accuracy and reproducibility of each of three currently available 1-day disposable lenses was conducted with respect to the following lens parameters: total diameter, back optic zone radius, center thickness, water content, and back vertex power. Fourteen of the 15 parameters measured (three lenses x five parameters per lens) were found to fall within ISO-defined tolerances. Reproducibility was similar for the three lens types and was considered clinically acceptable. Practitioners and patients can be confident that the current generation of 1-day disposable lenses can be relied on to give consistent ocular and visual performance.

Journal Article↗

Waiting lists. On a knife edge.

Achieving the government's waiting list targets relies heavily on the willingness of theatre staff to do overtime. A survey of acute trusts in England found that more than three-quarters were having difficulty recruiting staff. A third were using local pay incentives, including double time for waiting list initiative work and bonus schemes. Theatre management needs a more strategic approach.

Absenteeism↗

Randomised controlled trial comparing hospital at home care with inpatient hospital care. I: three month follow up of health outcomes.

OBJECTIVES: To compare hospital at home care with inpatient hospital care in terms of patient outcomes. DESIGN: Randomised controlled trial with three month follow up. SETTING: District general hospital and catchment area of neighbouring community trust. SUBJECTS: Patients recovering from hip replacement (n=86), knee replacement (n=86), and hysterectomy (n=238); elderly medical patients (n=96); and patients with chronic obstructive airways disease (n=32). INTERVENTIONS: Hospital at home care or inpatient hospital care. MAIN OUTCOME MEASURES: Dartmouth COOP chart to measure patients' general health status; SF-36 to measure possible limitations in physical functioning of patients with hysterectomy; disease specific measures-chronic respiratory disease questionnaire, Barthel index for elderly medical patients, Oxford hip score, and Bristol knee score; hospital readmission and mortality data; carer strain index to measure burden on carers; patients' and carers' preferred form of care. RESULTS: At follow up, there were no major differences in outcome between hospital at home care and hospital care for any of the patient groups except that those recovering from hip replacement reported a significantly greater improvement in quality of life with hospital at home care (difference in change from baseline value 0.50, 95% confidence interval 0.13 to 0.88). Hospital at home did not seem suitable for patients recovering from a knee replacement, as 14 (30%) of patients allocated to hospital at home remained in hospital. Patients in all groups preferred hospital at home care except those with chronic obstructive airways disease. No differences were detected for carer burden. Carers of patients recovering from knee replacement preferred hospital at home care, while carers of patients recovering from a hysterectomy preferred hospital care. CONCLUSIONS: Few differences in outcome were detected. Thus, the cost of hospital at home compared with hospital care becomes a primary concern.

Adult↗

Randomised controlled trial comparing hospital at home care with inpatient hospital care. II: cost minimisation analysis.

OBJECTIVES: To examine the cost of providing hospital at home in place of some forms of inpatient hospital care. DESIGN: Cost minimisation study within a randomised controlled trial. SETTING: District general hospital and catchment area of neighbouring community trust. SUBJECTS: Patients recovering from hip replacement (n=86), knee replacement (n=86), and hysterectomy (n=238); elderly medical patients (n=96); and patients with chronic obstructive airways disease (n=32). INTERVENTIONS: Hospital at home or inpatient hospital care. MAIN OUTCOME MEASURES: Cost of hospital at home scheme to health service, to general practitioners, and to patients and their families compared with hospital care. RESULTS: No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement, or elderly medical patients. Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy (ratio of geometrical means 1.15, 95% confidence interval 1.04 to 1.29, P=0.009) and for those with chronic obstructive airways disease (Mann-Whitney U test, P=0.01). Hospital at home significantly increased general practitioners' costs for elderly medical patients (Mann-Whitney U test, P<0.01) and for those with chronic obstructive airways disease (P=0.02). Patient and carer expenditure made up a small proportion of total costs. CONCLUSION: Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial, and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease. There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease.

Adult↗

Thymic function in young/old chimeras: substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution.

Age-associated thymic involution results in a diminished capacity to regenerate T cell populations, although the magnitude of this effect is unknown. In this report, thymic function was studied in aged vs. young adult mice after lethal irradiation and administration of T cell-depleted bone marrow (BM) from young mice. Abnormalities observed in aged thymi (reduced thymocyte numbers, histologic abnormalities) were not reversed by administration of young BM via bone marrow transplantation (BMT), but aged thymi displayed a normal thymocyte subset distribution and appropriately deleted MIs-reactive T cells after BMT. Aged BMT recipients regenerated significantly reduced numbers of splenic T cells compared to young recipients and showed increased peripheral expansion of thymic emigrants since a higher proportion of BM-derived T cells expressed a memory phenotype in aged vs. young BMT recipients. Because peripheral expansion of thymic emigrants could substantially increase the number of thymic progeny present in the spleen, we sought to measure thymic T cell regenerative capacity after BMT in a setting devoid of peripheral expansion. To do this, TCR-transgenic (Tg+) T cell-depleted BM was administered to aged and young recipients lacking antigen specific for the Tg+ TCR. Aged recipients regenerated approximately 50 % of the TCR Tg+ cells regenerated in young BMT recipients, providing evidence that even very aged thymi retain the capacity to regenerate significant numbers of mature T cell progeny. Therefore, thymic function is reduced with aged but it is not lost, suggesting that therapeutic approaches to enhance thymic function may be successful even in very aged hosts.

Aging↗

Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination.

We describe a case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination. This was particularly evident for the C9neo antigen, which is a marker for the activated lytic complement complex and was exclusively deposited in the areas of active myelin destruction. In addition, macrophages in the lesions contained degradation products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo antigen. Destruction of myelin sheaths was associated with incomplete loss of oligodendrocytes in the active areas and reappearance of oligodendrocytes with remyelination in the inactive plaque center.

Biomarkers↗