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Biomedical subjects

J Spencer

Publications and source records attributed to J Spencer.

At least 73 records · Page 4Linked to original sources
PubMed1999

Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin.

Recurrent hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29). Outcomes were compared in three patient groups: group 1, precore mutant HBV infection not receiving lamivudine (n = 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n = 10); and group 3, HBV precore mutant patients undergoing liver transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9). In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 11 months. Six of these 10 patients developed mutations in the HBV polymerase gene associated with lamivudine resistance. There were two liver failure-related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.

Adult↗
PubMed1999

Characterization of enteroaggregative Escherichia coli isolated from outbreaks of diarrhoeal disease in England.

Twenty-two strains of enteroaggregative Escherichia coli (EAggEC), isolated from four outbreaks of diarrhoeal disease in England, were examined for a range of phenotypic attributes including the ability to produce fimbriae, haemolysins and siderophores, and cell-surface properties such as surface charge and hydrophobicity. Strains of EAggEC isolated from two of these outbreaks belonged to a diverse range of serotypes and were heterogeneous in phenotype. Strains of EAggEC isolated from the other two outbreaks belonged predominantly to serotypes 086:H34 and 098:H-, respectively. Only two strains expressed fimbriae and two strains produced an 18 kDa membrane associated protein (MAP), suggesting that EAggEC express a range of adhesion mechanisms to produce the cell arrangement recognized as the 'stacked brick' formation. The possible explanation for the diversity of EAggEC serotypes is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1999

Characteristics of IgVH genes used by human intestinal plasma cells from childhood.

Plasma cells secreting immunoglobulin M (IgM) and IgA in human intestinal mucosa are the largest antibody-producing population in the human body. Despite this there have been relatively few studies of the characteristics and maturation of the genes which encode the mucosal immunoglobulins. We have previously demonstrated that intestinal plasma cells use highly mutated IgVH genes, likely to reflect germinal centre origin. Here we show that IgVH genes used by intestinal lamina propria plasma cells secreting IgM and IgA are highly mutated from childhood, with no change in the frequency of mutation through to adulthood, though IgVH genes used by IgM are significantly less mutated than those used by IgA. There was no difference between the IgA subclasses in either the frequency or distribution of mutations. The frequency of mutation in IgVH4-34 genes used by IgG was also studied in the adult biopsies, and was found to be of the same order as that observed in IgA and was significantly higher than that observed in IgM. We have identified IgM and IgA sequences which share identical CDR3 and distribution of mutations. Isotype switching may therefore occur after extensive mutation of IgM sequences, and IgM- and IgA-secreting plasma cells with the same specificity may occur within the same microenvironment. IgM should therefore be considered to be a component of secondary immune responses in the gut.

Adolescent↗
PubMed1999

Patients as teachers: a qualitative study of patients' views on their role in a community-based undergraduate project.

OBJECTIVES: Patients have been used in clinical medical education for many years with, traditionally, a relatively passive role. Following the General Medical Council recommendations for curricular change and the development of more community-based teaching, 'ordinary patients' in the community are increasingly being partnered with undergraduate students for particular projects. Very little research has been undertaken on patients' perceptions of this role. DESIGN: Semi-structured interviews were carried out with 20 people to explore the views of patients taking part in a community-based undergraduate medical student project (the 'patient study') at Newcastle Medical School about their role as teachers of medical students, what they felt they had gained from participating, any problems or concerns and suggestions for change or improvement. SETTING: Newcastle Medical School, UK. SUBJECTS: Second-year medical students. RESULTS: Two major themes emerged. First, patients saw themselves in active roles as teachers: as experts in their medical condition; as exemplars of their condition; and as facilitators of the development of students' professional skills and attitudes. Secondly, patients felt they had benefited from participation, through talking about their problems; learning more about themselves; the satisfaction of helping; and from receiving gifts. In addition, a number of other issues were identified including interpersonal dynamics, gender and ethnic differences, inadequate briefing of participants and whether such community-based patient involvement might, in some situations, be felt to be exploitative. CONCLUSIONS: The study has shown that patients see themselves clearly as having specific contributions to make to medical students' education and training. This has implications for the further development of community-based teaching.

Adult↗
PubMed1999

Learning to value ethnic diversity--what, why and how?

INTRODUCTION: Learning to value ethnic diversity is the appreciation of how variations in culture and background may affect health care. It involves acknowledging and responding to an individual's culture in its broadest sense. This requires learning the skills to negotiate effective communication, a heightened awareness of one's own attitudes, and sensitivity, to issues of stereotyping, prejudice and racism. This paper aims to contribute to debate about some of the key issues that learning to value ethnic diversity creates. CONTEXT: Although some medical training is beginning to prepare doctors to work in an ethnically diverse society, there is a long way to go. Promoting 'valuing ethnic diversity' in curricula raises challenges and the need to manage change, but there are increasing opportunities within the changing context of medical education. Appropriate training can inform attitudes and yield refinement of learners' core skills that are generic and transferable to most health encounters. CURRICULUM DEVELOPMENT: Care must be taken to avoid a narrow focus upon cultural differences alone. Learning should also promote examination of learners' own attitudes and their appreciation of structural influences upon health and health care, such as racism and socio-economic disadvantage. Appropriate training and support for teachers are required and learning must be explicitly linked to assessment and professional accreditation. CONCLUSION: Greater debate about theoretical approaches, and much further experience of developing, implementing and evaluating effective training in this area are needed. Medical educators may need to overcome discomfort in developing such approaches and learn from experience.

Culture↗
PubMed1999

The effects of topical vitamin E on the cosmetic appearance of scars.

BACKGROUND: Vitamin E is a generic term for a group of tocol and tocotrienol derivatives. Since the discovery that vitamin E is the major lipid soluble antioxidant in skin, this substance has been tried for the treatment of almost every type of skin lesion imaginable. Anecdotal reports claim that vitamin E speeds wound healing and improves the cosmetic outcome of burns and other wounds. Many lay people use vitamin E on a regular basis to improve the outcome of scars and several physicians recommend topical vitamin E after skin surgery or resurfacing. OBJECTIVE: We attempted to determine whether topically applied vitamin E has any effect on the cosmetic appearance of scars as suggested by multiple anectodal reports. METHODS: Fifteen patients who had undergone skin cancer removal surgery were enrolled in the study. All wounds were primarily closed in 2 layers. After the surgery, the patients were given two ointments each labeled A or B. A was Aquaphor, a regular emollient, and the B was Aquaphor mixed with vitamin E. The scars were randomly divided into parts A and B. Patients were asked to put the A ointment on part A and the B ointment on part B twice daily for 4 weeks. The study was double blinded. The physicians and the patients independently evaluated the scars for cosmetic appearance on Weeks 1, 4, and 12. The criteria was simply to recognize which side of the scar looked better if there was any difference. The patients' and the physicians' opinions were recorded. A third blinded investigator was shown photographs of the outcomes and their opinion was also noted. RESULTS: The results of this study show that topically applied vitamin E does not help in improving the cosmetic appearance of scars and leads to a high incidence of contact dermatitis. CONCLUSIONS: This study shows that there is no benefit to the cosmetic outcome of scars by applying vitamin E after skin surgery and that the application of topical vitamin E may actually be detrimental to the cosmetic appearance of a scar. In 90% of the cases in this study, topical vitamin E either had no effect on, or actually worsened, the cosmetic appearance of scars. Of the patients studied, 33% developed a contact dermatitis to the vitamin E. Therefore we conclude that use of topical vitamin E on surgical wounds should be discouraged.

Administration, Topical↗
PubMed1999

Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study.

BACKGROUND: Melasma is very difficult to treat and often refractory to treatment with topical creams and pigmented-lesion lasers. OBJECTIVE: Pulsed CO2 laser alone is compared with the combination of pulsed CO2 laser followed by Q-switched alexandrite laser in the treatment of dermal-type melasma. This combination is proposed to be effective by first destroying the abnormal melanocytes with the pulsed CO2 laser and then selectively eliminating the dermal melanin with the alexandrite laser. METHODS: Four patients were randomly chosen for each treatment arm. There were multiple follow-up visits for examination by an objective blinded investigator. RESULTS: All patients in the combination laser group showed complete resolution, and two patients in the CO2 laser only group had peripheral hyperpigmentation in the long-term follow-up evaluation. CONCLUSION: These laser therapies are safe, as there was no scarring and no infection. The combination laser therapy was highly effective in removing the hyperpigmentation and all patients in this group showed complete resolution without any peripheral hyperpigmentation.

Beryllium↗
PubMed1999

Relation of surgical volume to outcome in eight common operations: results from the VA National Surgical Quality Improvement Program.

OBJECTIVE: To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity. SUMMARY BACKGROUND DATA: In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial. METHODS: The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA). RESULTS: Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found. CONCLUSIONS: In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

Adolescent↗
PubMed1999

Insulin receptor antibodies and insulin resistance.

The presence of insulin receptor antibodies is a rare cause of insulin resistance. Patients usually have a combination of hyperglycemia, insulin resistance, acanthosis nigricans, and autoimmune features. We report a patient with systemic lupus erythematosus and severe insulin resistance due to insulin receptor antibodies. The most striking aspect of the clinical presentation is the resistance to insulin therapy, with our patient unresponsive to doses of up to 154,075 units in a day. While on a low-dose glucocorticoid therapy, the patient had clinical improvement, and glucose levels subsequently became normal even without insulin and glucocorticoid.

Acanthosis Nigricans↗
PubMed1999

Seroprevalence of markers for hepatitis B, C and G in male and female prisoners--NSW, 1996.

OBJECTIVES: 1. Establish the prevalence of markers for hepatitis B (HBV), C (HCV) and G (HGV) in a sample of male and female inmates. 2. Examine exposure to multiple viruses. 3. Compare risk factors for HGV infection with known risk factors for HBV and HCV. DESIGN: Cross-sectional random sample stratified by sex, age and Aboriginality. Inmates were screened for three hepatitis markers. Participants were 789 inmates (657 male, 132 female) in 27 correctional centres in New South Wales, 1996. RESULTS: Overall detection of each of the three screening markers was 35% for HBV, 39% for HCV and 10% for HGV. Exposure rates were higher in female prisoners than males. Increased rates of anti-HBc were observed in Aboriginal inmates compared with non-Aboriginals (54% cf. 27%); anti-HCV and HGV-RNA were comparable between the two groups (36% cf. 41% and 9% cf. 10%). Markers were significantly higher in female injecting drug users (IDU), particularly HCV (90% cf. 66%). Thirty-five per cent of inmates were unaware of their HCV status. For HBV, 72% did not self-report past or present exposure despite serological evidence to the contrary. The multivariate analysis identified Aboriginality, long-term injecting and injecting while in prison as risk factors for HBV. HCV risk factors were female sex, non-Aboriginality, institutionalisation and IDU-associated behaviours. For HGV, female sex and previous imprisonment were significant risk factors but IDU was not. CONCLUSIONS: Blood-borne hepatitis viruses are common in prison inmates, particularly females (HBV, HCV and HGV), Aboriginals (HBV) and IDU (HBV and HCV). Infection can be related to a number of risk factors, which appear similar for HBV and HCV, but distinct from HGV.

Adolescent↗
PubMed1999

Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn's disease.

BACKGROUND: Ulcerative colitis is an inflammatory disease of the colonic and rectal mucosa. Autoantibodies have been observed in ulcerative colitis which may have a role in the pathogenesis of the disease. Evidence also suggests that there is an hereditary predisposition towards the disease, although no individual genes have been identified. AIMS: This is a pilot study of immunoglobulin heavy chain genes (IgH) in ulcerative colitis to determine whether they have any particular genetic characteristics which may lead to a better understanding of the disease aetiology. SUBJECTS: Colonic or rectal tissue was obtained from five children with ulcerative colitis. Tissue was also obtained from five children with Crohn's disease and five children who did not have inflammatory bowel disease as controls. METHODS: B cells and IgD+ B cells were identified by immunohistochemistry on frozen sections. Areas of lamina propria containing plasma cells, and areas of IgD+ B cells were microdissected. The immunoglobulin genes were PCR amplified, cloned, and sequenced. Sequences were analysed for content of somatic mutations and composition of heavy chain. RESULTS: An increase in the use of JH6 and DXP'1, and a decrease in the use of JH4, gene segments in immunoglobulin genes from lamina propria plasma cells, and from virgin IgD+ B cells, was found in patients with ulcerative colitis. These biases were not present in the control groups. CONCLUSIONS: There is a fundamental difference in the immunoglobulin genes from patients with ulcerative colitis. Whether this is caused by a difference in content of immunoglobulin gene segments in the germline or a difference in the recombination mechanism is not known.

Adolescent↗
PubMed1999

Expression of lymphocyte-endothelial receptor-ligand pairs, alpha4beta7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease.

BACKGROUND: The interaction between leucocytes and vascular endothelial cells is essential for leucocyte migration into inflammatory sites. AIMS: To study the local expression of the pairs of complementary molecules, alpha4beta7/mucosal addressin cell adhesion molecule (MAdCAM-1) and OX40/OX40 ligand in the lamina propria of the colon and jejunum of patients with inflammatory bowel disease. METHODS: Ten patients with active ulcerative colitis (UC), nine with active Crohn's disease (CD), and seven irritable bowel syndrome (IBS) controls were submitted to endoscopic and peroral jejunal biopsies. Specimens were immunostained by indirect alkaline phosphatase using antibodies against CD3, intercellular adhesion molecule (ICAM) 1, alpha4beta7, MAdCAM-1, and OX40. An OX40-mouse-IgG fusion protein was used to detect OX40 ligand on frozen sections. Immunohistological analysis was carried out by optical microscopy using a computer assisted image analyser. RESULTS: Colonic lamina propria of patients with CD and UC showed increased density of CD3+, alpha4beta7+, and OX40+ cells compared with IBS controls. ICAM-1, MAdCAM-1, and OX40 ligand positive vessels were also increased compared with IBS controls. No significant difference was found in the density of any of these cells in the jejunal mucosa of patients compared with IBS controls. CONCLUSIONS: The expression of MAdCAM-1 and OX40 ligand on gut endothelial and OX40+ cells is increased in sites of mucosal inflammation in patients with inflammatory bowel disease. No evidence was found for increased lamina propria T cells or increased vascular adhesion molecule expression in the proximal intestine of patients with distal inflammatory bowel disease.

Adult↗
PubMed1999

Does teaching during a general practice consultation affect patient care?

BACKGROUND: General practice differs from hospital medicine in the personal nature of the doctor-patient relationship and in the need to address social and psychological issues as well as physical problems. Recent changes in undergraduate medical education have resulted in more teaching and learning taking place in general practitioner (GP) surgeries. AIM: To explore patients' experiences of attending a surgery with a medical student present. METHOD: A questionnaire was designed, based on semi-structured interviews. Questionnaires were posted to patients who had attended teaching surgeries in London and Newcastle-upon-Tyne. RESULTS: Four hundred and eighty questionnaires were sent; of these, 335 suitable for analysis were returned. The response rate in Newcastle was 79%, and in London 60%. Ninety-five per cent of responders agreed that patients have an important role in teaching medical students. Patients reported learning more and having more time to talk, however, up to 10% of responders left the consultation without saying what they wanted to say and 30% found it more difficult to talk about personal matters. CONCLUSION: The presence of a student has a complex effect on the general practice consultation. Future developments in medical education need to be evaluated in terms of how patient care is affected as well as meeting educational aims.

Family Practice↗
PubMed1998

Extrathymic T cell differentiation in the human intestine early in life.

It is clear from experimental studies in mice that T cell maturation can occur outside the thymus, especially in the intestine. There is little sound evidence so far that extrathymic T cell maturation occurs to any significant extent in human gut, and, postnatally, there is abundant evidence that the gut mucosa is an immune effector organ. Here, we describe a large population of T lymphocytes in human fetal intestinal mucosa that are proliferating (Ki67+) in the absence of foreign Ag (CD3+, Ki67+ lamina propria lymphocytes (LPL) 22 +/- 1.8% and CD3+, Ki67+ intraepithelial lymphocytes (IEL) 9.1 +/- 1.4%), that express the T cell activation markers CD103, HLA-DR, and L-selectin(low), and that express mRNA transcripts for pre-TCR-alpha. There is also a substantial proportion of CD7+ LPLs that do not express CD3 (CD3-7+, 14 +/- 7% of all LPLs) in the fetal gut that may be differentiating into CD3+ cells. Rearranged TCR-beta transcripts of fetal LPLs, IELs, and paired blood lymphocytes were cloned and sequenced, and virtually no overlap of clonality was observed between blood and intestine, suggesting that gut T cells may not be derived from the blood. In addition, 30 days after engraftment of SCID mice with fetal intestine, CD3-7+ cells, proliferating T cells, and pre-TCR-alpha transcripts were abundant, and there is a threefold increase in CD3+ IELs. These data show that in the human intestine before birth a population of precursor T cells exists that may be differentiating into mature T cells in situ.

Aging↗