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Biomedical subjects

R Salter

Publications and source records attributed to R Salter.

At least 19 recordsLinked to original sources
PubMed2004

Ethics of refusing parental requests to withhold or withdraw treatment from their premature baby.

In the United Kingdom women have access to termination of pregnancy for maternal reasons until 24 weeks' completed gestation, but it is accepted practice for children born at or beyond 25 weeks' gestation to be treated according to the child's perceived best interests even if this is not in accordance with parental wishes. The authors present a case drawn from clinical practice which highlights the discomfort that parents may feel about such an abrupt change in their rights over their child, and argue that parents should have greater autonomy over treatment decisions regarding their prematurely born children.

Adult↗
PubMed2000

Presentation with influenza-like illness in general practice: implications for use of neuraminidase inhibitors.

General practitioners in the Midlands Research Practice Consortium (MidReC), combined list size 140,000, completed questionnaires about 918 patients in whom they had made working diagnoses of influenza-like illness during an outbreak of influenza A H3N2 from 1 December 1999 to 4 February 2000. Adults, more females than males consulted most, reflecting the age and sex distribution reported to the Royal College of General Practitioners Weekly Returns Service. Illness at presentation was considered severe in 4%, moderately severe in 49%, mild in 45%, and asymptomatic (for example, attended for certificates) in 1% of patients. In seven tenths of patients, the practitioner estimated that the likelihood of influenza was 70% or more and in just over half, 80% or more. Half of patients aged over 75 years were seen at home, but only 7% of those under 55 years. Less than a quarter of patients consulted within two days of having become ill, with the highest consultation frequency on the third and fourth days. Preschool children presented earliest: 75% were seen within two days, compared with only 17% of adults over 75 years. Four fifths of patients were seen on the same day as they contacted the practice, and 12% on the following day. Given the brief time window for effective antiviral treatment, only a small proportion of patients are likely to be prescribed these drugs unless consulting behaviour, especially in elderly people, changes considerably.

Adolescent↗
PubMed1998

How to pass the MRCP (UK) examination--ask a successful candidate!

Recently successful MRCP (UK) candidates were asked to rate the value of clinical experience, reading, practice with past or simulated examination papers and commercially organised courses as preparation for parts 1 and 2 of the examination. With respect to part 1, practice with past and simulated papers was unanimously felt to be of crucial importance with examination-focused reading helpful. Clinical experience was deemed irrelevant and commercially organised courses a matter of individual choice. For part 2, clinical experience was felt to be of fundamental importance but needed to be practised in an 'examination atmosphere'. Both general reading and practice with past and simulated papers were judged helpful and commercially organised courses were perceived to be of more value than for part 1. Trainees should be advised to seek advice on examination preparation from both 'authoritative sources' and their recently successful colleagues.

Attitude of Health Personnel↗
PubMed1996

Tumor escape from immune recognition: loss of HLA-A2 melanoma cell surface expression is associated with a complex rearrangement of the short arm of chromosome 6.

Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes. Human melanoma cells may escape immune recognition by a variety of means, including global or allelic down-regulation of MHC class I molecules. Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin. We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis. The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum. IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3. Karyotypic analysis and fluorescence in situ hybridization with chromosome 6 and MHC class I-specific probes showed complex rearrangement of one chromosome 6 involving the MHC class I locus on 6p and translocation of 6q to the long arm of chromosome 19. To evaluate the capability of melanoma Mz18 to present tumor-specific peptides to HLA-A2-restricted, melanoma-specific CTLs, we restored HLA-A2 surface expression by retroviral-mediated transfer of functional HLA-A2 cDNA. Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function. Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition. These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The sensitivity of chronic lymphocytic leukaemia lymphocytes to irradiation in vitro.

The inhibition of [3H]-thymidine incorporation into the DNA of mitogen-stimulated chronic lymphocytic leukaemia lymphocytes by chlorambucil or gamma-irradiation in vitro was measured in a series of patients, some of whom were untreated, some treated and some who were showing resistance to first-line or second-line treatment. There was evidence of resistance to irradiation developing in parallel with that to chlorambucil. The resistance to chlorambucil in chronic lymphocytic leukaemia (CLL) is not necessarily due to altered drug transport or metabolism but to a more fundamental process affecting DNA damage.

Antineoplastic Agents, Alkylating↗
PubMed1995

The US residency programme--lessons for pre-registration house officer education in the UK?

The 1994 NACT Wyeth-Ayerst Travelling Fellowship provided the opportunity to compare the education and welfare of pre-registration house officers in the UK with their nearest counterpart in the US residency system. Investment in all aspects of learning was impressive, as was the retention of the central role of the patient in education. Adequate clinical exposure must take into account both the changing pattern of care delivery and the need to limit junior doctors' hours of work. Service containment is difficult to achieve. The self-educating potential of junior medical staff should be maximised and a post analogous to 'Chief Resident' in the US could be considered. Explicit educational aims and objectives must be stated so that meaningful assessment can be carried out and feedback provided. Adequate support systems are essential and an earlier start to the working day is encouraged.

Adult↗
PubMed1993

Position 71 in the alpha helix of the DR beta domain is predicted to influence peptide binding and plays a central role in allorecognition.

Despite all the structural and functional data that have been accumulated regarding major histocompatibility complex (MHC) class II molecules during recent years, the relative contribution of putative T cell receptor (TcR)-contacting residues and peptide-binding MHC polymorphisms to MHC-restricted and allospecific T cell responses remains a point of contention. Some authors emphasize the importance of direct interaction between the allospecific TcR and polymorphic MHC residues whereas other emphasize the role of naturally processed MHC-bound peptides. We have previously described a new HLA-DRB1 allele: DR BON (DRB1*0103). This gene differs from DRB1*0101 by six base pairs clustered in the third variable region of the second exon leading to three amino acid changes at positions 67, 70 and 71 of the beta chain of the HLA-DR molecule. To define the respective role of these residues in allorecognition, we have performed site-directed mutagenesis on the DRB1*0103 allele to create six mutants which are intermediary between the DR BON and the DR1 alleles. These mutant cDNA were expressed in mouse fibroblasts and the transfectants with the highest expression of class II molecules were used as stimulators for a panel of ten anti-DR BON and five anti-DR1 alloreactive T cell clones. We demonstrate that the residue at the peptide-binding position 71 is of paramount importance in the alloresponse of these clones. In addition some clones were sensitive to amino acid substitution at the TcR-contacting position 70, while substitution at position 67 affects very few clones. The dominance of residue 71 was also observed with an influenza hemagglutinin-specific HLA-DR BON-restricted T cell line.

Amino Acid Sequence↗
PubMed1993

Cryopreservation of periosteum for transplantation.

The concept of biological joint resurfacing has been widely studied, with encouraging results to date in both animal and human experiments. Most investigators have studied autograft tissue, however, in the clinical setting, situations might arise where autografting would not be suitable. We were therefore interested in developing a method of storing allograft periosteal tissue for biological joint resurfacing. A total of 192 periosteal grafts were harvested from 48 New Zealand White rabbits using sharp dissection (to include the cambium layer of progenitor cells). The free grafts were placed in a culture medium containing the cryopreservative dimethyl sulfoxide, then cooled at a controlled rate in a programmable freezer at rates of -0.5, -1.0, -2.0, or -10.0 degrees C/min. Viability of the grafts was assessed upon thawing after frozen storage for 8 days or 4 months using autoradiography and radioactive isotope uptake into newly synthesized proteins. Fresh, noncryopreserved and killed grafts were used as controls. A rate of cooling of -1.0 degrees C/min yielded viability results that were not significantly different from those of fresh controls. Furthermore, there was no change in viability as measured by radioactive isotope uptake over 4 months of storage. These results indicate that cryopreservation is a simple and efficient means of storing periosteal tissue for up to 4 months.

Animals↗
PubMed1978

Urinary stress incontinence and common sense.

Retropubic bladder neck suspension has been used to treat 352 women presenting with the primary complaint of urinary stress incontinence. The author's concept of the proper assessment and management of such patients, in whom previous surgical treatment has failed, is stated. A plea is made for the abandonment of traumatic surgical methods and the confusing multiplicity of names that accompanies them.

Female↗