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Biomedical subjects

M Sheppard

Publications and source records attributed to M Sheppard.

At least 55 records · Page 3Linked to original sources

Audit of pleural biopsies: an argument for a pleural biopsy service.

We audited 203 consecutive pleural biopsies performed by medical and geriatric firms over a 3-yr period in our hospital (1987-9). For firms without a special respiratory interest only two to three biopsies per yr were performed, compared with 23 per yr for a respiratory team. Twenty percent of biopsies failed to obtain pleural tissue, 50% revealed normal or non-diagnostic pleural changes and 30% provided a diagnosis. For the respiratory team that performed a third (68) of the biopsies the failure rate for obtaining pleura was 9% compared with 27% for other teams. In view of this disparity a pleural biopsy service was offered by the respiratory team during routine bronchoscopy lists. A repeat audit (1990-2) following the introduction of this service revealed that 60% (84) of 141 biopsies were performed by the respiratory team with their failure rate for obtaining pleura being lower at 6% as compared to 16% for the general physicians. Thirty-one percent of biopsies provided a definitive diagnosis, being higher for those performed by the respiratory team (37%) as opposed to 23% for general physicians.

Biopsy, Needle↗

Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis.

OBJECTIVE: The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN: Case-control studies of patients on long-term T4 therapy who have or have not previously received radioiodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS: Twenty-seven premenopausal and 60 postmenopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group 1), 39 post-menopausal females with a past history of radioiodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS: BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS: No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences in BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3.9%, P < 0.05) and lumbar spine (5.6-8.5%, P < 0.01) BMD results were found in post-menopausal females in group 1 and reductions in femoral trochanter (3.9%, P < 0.01), Ward's triangle (5.6%, P < 0.05) and lumbar spine (8.5%, P < 0.01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS: Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.

Absorptiometry, Photon↗

Lung metastasectomy in patients with soft tissue sarcoma.

Metastases develop in 50-60% of patients with high grade soft tissue sarcomas despite primary treatment. Between 1970 and 1990, 189 patients with soft tissue sarcoma referred to the Royal Marsden Hospital Sarcoma Unit developed lung metastases as the sole first site of disseminated disease. 44 of these 189 cases have been treated by pulmonary metastasectomy. In an attempt to determine which patients benefit from this surgery the medical records, radiology and pathology of these cases have been reviewed. Both the overall 5 year survival (70% vs 19%) and the subsequent survival from the time lung metastases developed (52% vs 7.5%) of those selected for thoracotomy were better than in the 145 patients not undergoing surgery. On multivariate analysis, survival and control of lung disease following resection were not related to the number of metastases resected, completeness of excision, use of adjuvant chemotherapy or presence of bilateral disease. The most important factor was the use of lung resection itself as treatment, for which the risk of death was 0.2 compared with those not having metastasectomy. Age less than 40 years and primary tumour in a lower limb site were also factors associated with a reduced risk of death. Pulmonary metastasectomy should be considered in selected patients with soft tissue sarcoma after primary local cure. However, without collection of prospective data on all patients developing lung metastases or a randomized trial the true role of lung metatasectomy will never be clarified.

Adult↗

Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis.

The vasoconstrictor and mitogenic peptide endothelin-1 (ET-1) is believed to play a part in fibrosis and collagen production. We examined expression of ET-1 in lung tissue from 52 patients with interstitial lung fibrosis, of whom 45 had cryptogenic fibrosing alveolitis (CFA), 10 had CFA and concomitant pulmonary hypertension, and 7 had non-specific focal fibrosis. 17 normal unused donor lungs were studied as controls. Immunohistochemistry and in-situ hybridisation were done with polyclonal antisera to ET-1 and its precursor big ET-1, and complementary RNA probes for preproET-1. Normal lung tissue and that from patients with focal fibrosis expressed very little ET-1. By contrast, there was striking expression of ET-1 in lung tissue from patients with CFA. Immunostains for ET-1 and big ET-1 and expression of ET-1 mRNA were most prominent in airway epithelium and type II pneumocytes, particularly those lining areas of young granulation tissue. ET-1-like immunoreactivity and mRNA were also present in pulmonary vascular endothelial cells, particularly in specimens from patients with pulmonary hypertension. In all patients, there was a significant correlation between ET-1-like immunoreactivity and histological parameters of disease activity (r = 0.78, 95% CI 0.65-0.87, p < 0.001). These findings suggest a possible role for cell-specific expression of ET-1 in the pathogenesis of CFA and associated pulmonary hypertension.

Biomarkers↗

The identification of genes for the major core proteins of fowl adenovirus serotype 10.

The sequence analysis of 1218 base pairs containing the probable fowl adenovirus (FAV) equivalents to the major core genes of human adenovirus (HAV) located on the late transcription unit number 2 (L2) has been completed. Two open reading frames (ORF) 3 prime to the gene for the penton base have been identified (41.3 to 43.4 map units). The putative poly A recognition sequence signalling the end of the L2 transcription unit has also been located. The two ORFs identified encode polypeptides that are highly basic in nature, especially rich in arginine. Both ORF appear to encode the FAV equivalents to the HAV major core polypeptides. The genomic map locations of these two ORFs have been determined and compared to the map locations of HAV-2 pV, pVII, and mu genes. A possible third core protein gene of FAV-10 that reads in the reverse direction was also tentatively identified.

Amino Acid Sequence↗

Use of lambda gt11 and monoclonal antibodies to map the gene for the 60,000 dalton glycoprotein of infectious laryngotracheitis virus.

To localize the gene encoding the 60 kD glycoprotein (gp60) of infectious laryngotracheitis virus (ILTV), a library of the ILTV genome was constructed in the lambda gt11 expression vector. Twelve recombinant bacteriophages expressing gp60 epitopes as fusion products with beta-galactosidase were detected by immunoscreening with monoclonal antibodies specific for gp60. The ILTV DNA sequence contained in one of these recombinants lambda 24-4 was used as a hybridization probe for mapping the insert sequence on the viral genome. The gene for the gp60 was located at map unit 0.72-0.77 in the unique long region (UL) of the ILTV genome. The DNA sequence of the 1.2 kb insert of lambda 24-4 containing the gp60 epitope was determined. The majority of deduced gp60 amino acid sequence has no homology with any of the known alphaherpesvirus glycoproteins.

Amino Acid Sequence↗

Identification of an infectious laryngotracheitis virus gene encoding an immunogenic protein with a predicted M(r) of 32 kilodaltons.

The nucleotide sequence of an infectious laryngotracheitis virus (ILTV) gene which maps immediately upstream from the glycoprotein 60 (gp60) gene was determined. The gene, designated p32, encodes a predicted polypeptide of 298 amino acids with an estimated M(r) of 32,000 daltons. The predicted protein sequence has four potential N-glycosylation sites and a signal sequence at the N-terminal region. Amino acid residues in the NH2-terminal region of the p32 protein exhibit similarity to glycoprotein X (gX) of pseudorabies virus (PRV) and its homolog in equine herpesvirus type 1 (EHV-1). Within the conserved (N-terminus) region, one putative N-linked glycosylation site and four cysteine residues are aligned in these proteins. These common structural features of the gX-like proteins were also found in glycoprotein G (gG) of human herpes simplex virus type 2 (HSV-2) and equine herpesvirus type 4 (EHV-4). High level bacterial production of the p32 protein was achieved by cloning the p32 open reading frame into a pGEX-2T expression vector. Western blot analysis of the fusion protein produced in E. coli using immune chicken sera confirms that p32 protein is of viral origin and is an immunogen in birds with infectious laryngotracheitis (ILT). An antiserum from chicken immunized with the fusion protein detected a substantial amount of p32 protein in the medium of ILTV-infected cells in Western blotting. Moreover tunicamycin treatment of cells infected with the virus indicated that p32 was glycosylated. This allows us to conclude that p32 is a glycoprotein and like gX of PRV accumulates in the medium of infected cells.

Amino Acid Sequence↗

Replication cycle and associated biosynthetic reactions for a non-oncogenic avian adenovirus.

The replication cycle of the non-oncogenic fowl adenovirus serotype 10 (FAV-10) has been examined. The onset of viral DNA synthesis was shown to commence at about 10 h postinfection (hpi) defining the early period of viral replication as prior to this time and the late phase as that time following the initiation of DNA replication. Virus titre rapidly increased between 18 and 24 hpi with maximum virus yield between 28 and 30 hpi. The late phase transcription profiles of the FAV-10 genome from 10 hpi to 24 hpi were determined. Late translation of virus protein began about 14 hpi increasing rapidly between 18 and 30 hpi.

Aviadenovirus↗

Client satisfaction, extended intervention and interpersonal skills in community mental health.

Some reservations have been expressed about the use of the concept of client satisfaction in relation to clients' views of services received. There has also been little research on clients' perspectives of mental health work. This paper explores client satisfaction with extended intervention from practitioners based at a community mental health centre. Considerable differences are identified between satisfied and not satisfied clients in the service received and their perception. These relate clearly to the use of interpersonal skills such as those of communication, empathy, listening, openness and genuineness. Taken together with research on brief intervention, this paper both indicates that the concept of satisfaction does meaningfully represent the client's experience and provides considerable support for the fundamental importance of the acquisition and use of these skills in practice.

Communication↗

Restriction enzyme maps for equine adenovirus 1 genome.

Physical maps were constructed for the genome of equine adenovirus 1 (EAV1) using the restriction enzymes; DraI, EcoRV, NotI and SfiI. The total size of the EAV1 genome was 34.4 kb estimated by comparison with known DNA standards and the polarity of the fragment order, with respect to the left and right molecular ends, was determined by hybridization with known regions of the human adenovirus 2 (HAV2) genome.

Adenoviridae↗

Infectious laryngotracheitis virus growth, DNA replication, and protein synthesis.

The polypeptides associated with infection of primary chicken kidney (CK) cells with infectious laryngotracheitis virus (ILTV) were examined by metabolic labelling with [35S]methionine and SDS-PAGE. Polypeptide synthesis was followed over the first 24 h post-infection (p.i.) as this was shown to be the period of viable virus production. A total of 16 ILTV encoded or induced polypeptides were identified using metabolic labelling. The use of inhibitors of protein and DNA synthesis in conjunction with metabolic labelling and viral DNA replication studies enabled a cascade pattern of gene expression, similar to that of herpes simplex virus type 1 (HSV-1), to be established for ILTV. Representatives of alpha, beta, gamma 1 and gamma 2 classes of genes were identified. In contrast to infection with HSV types 1 and 2, which leads to a rapid inhibition of total host cell polypeptide synthesis, ILTV infection of CK cells did not result in a complete inhibition of cellular protein synthesis, with only a small number of host cell polypeptides absent from infected cells.

Animals↗

Characterization of the avian adenovirus penton base.

A portion of the fowl adenovirus 10 (FAV-10) penton base gene was located within a Sau3A genomic DNA fragment by the combination of a plasmid expression library and colony immunoassays with rabbit anti-FAV-10-sera. The coding portion of the sequence contained in the expression vector was mapped to a 11.6-kb Bg/II fragment and more precisely mapped to the right-hand end of the 11.6-kb fragment at map units 37.7 to 41.3. Nucleotide sequence analysis of the region revealed an open reading frame of 1575 bp with translation of the sequence producing a polypeptide of 525 amino acids in length. The polypeptide predicted from the open reading frame would have a molecular weight of 57.4 kDa. Analysis of the amino acid sequence revealed an overall homology of 41.8% with the human adenovirus 2 (HAV-2) penton base. However, a region near the center of the polypeptide (amino acids 219 to 311) showed a significantly greater level of homology to the HAV-2 penton base (71%). Time course experiments using mRNA confirmed that this gene is expressed at late times postinfection. Upon probing genomic DNA from other FAV serotypes the penton base coding region hybridized to all six different serotypes tested, indicating a relatively conserved DNA sequence among a variety of FAVs.

Amino Acid Sequence↗

The association of germ cell tumours of the testis with sarcoid-like processes.

Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases.

Adult↗

Gallid herpesvirus 1 (infectious laryngotracheitis virus): cloning and physical maps of the SA-2 strain.

Clones representing 90% of the genome of Gallid herpesvirus 1 (infectious laryngotracheitis virus; ILTV) were obtained and used in hybridization experiments to construct EcoRI, KpnI amd SmaI physical maps. The genome was 155 kilobase pairs (kbp) and comprised of a long unique sequence (120 kbp) and a short unique sequence (17 kbp) bounded by repeat sequences each of 9 kbp. An unrelated second pair of repeat sequences was located at 0.67 and 0.88 map untis. A terminal repeat of the unique long region (UL) was also detected, but no isomerization of UL was detected.

Animals↗