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J Spencer

Publications and source records attributed to J Spencer.

At least 145 records · Page 8Linked to original sources
PubMed1996

Ischemic heart disease in patients with end-stage renal disease.

Prevention and treatment of cardiovascular disease and, in particular, ischemic heart disease (IHD) in an increasingly elderly and diabetic population of patients with end-stage renal disease (ESRD) pose a challenge to all members of the renal failure treatment program. The patient described herein presents such a challenge, illustrating risk factors for IHD, the dilemma of performing surgery given his age and comorbid conditions, and the impact of IHD on his quality of life and capacity to function independently. The coordinated efforts of the nephrologist, cardiologist, cardiac surgeon, rehabilitation specialist, nutritionist, primary nurse, and social worker all contributed to a successful intervention.

Aged↗
PubMed1996

The distribution of dividing T cells throughout the intestinal wall in inflammatory bowel disease (IBD).

T cell hypersensitivity has been implicated in the tissue damage in Crohn's disease (CD). All studies to date have examined mucosal T cells, although much of the tissue damage occurs in the submucosa and muscle layers. The aim of this work was to study T cell proliferation throughout the intestinal wall in children with IBD. Surgical resection material from 19 children with CD (10 ileal, 10 colonic), seven with ulcerative colitis (UC), and 12 normal controls was studied. The distribution of dividing T cells was investigated by double-immunohistochemistry using Ki67 to identify proliferating cells, and CD3 to identify T cells. In ileal and colonic lamina propria virtually no Ki67+, CD3+ cells were seen in control, UC or CD tissue. In contrast, there were significantly more Ki67+, CD3+ cells within the lymphoid follicles of ileal and colonic CD than in the follicles in UC and controls. Increased numbers of Ki67+, CD3+ cells were present in the submucosa, muscle layers (M) and serosa in Crohn's ileitis and colitis compared with the lamina propria (LP), although only in the muscle of the colon was the difference statistically significant (LP, 0.4% (0-1%); M, 1.6% (0-5.2%); P = 0.03). Pooling data from ileal and colonic CD, however, did show significantly increased Ki67+, CD3+ cells in both serosa and muscle layers compared with the LP. Dividing T cells have been identified in the deeper layers of the gut wall in CD. These may contribute to the fibrosis and muscle hyperplasia characteristic of the condition.

Adolescent↗
PubMed1996

General practitioners' views about the need for a stress support service.

OBJECTIVES: We wished to determine general practitioners' (GPs') views regarding the need for a stress support service. METHOD: A postal questionnaire survey of GPs' views (n = 274) about the need for a stress support service, and what form such a service might take, was undertaken on Tyneside. RESULTS: A response rate of 79.5% was achieved with one reminder. A majority (78.8%) were in favour of a stress support service for GPs, the most popular options for the service being independently accessed counsellors and stress management groups. Over 90% of respondents thought that support should be available to any doctor, and 65% that is should be available to all primary health care team members. The five most commonly mentioned causes of stress were: time and workload problems; on call; expectations and demands of patients; administration and paperwork; and complaints and fear of litigation. CONCLUSIONS: The survey demonstrated widespread concern amongst GPs on Tyneside about stress levels and considerable interest in the idea of stress support. However, a variety of approaches would be required to meet the range of perceived needs, and any such services should be made accessible to all practitioners regardless of whether they are actually suffering from stress, as well as to other members of the primary health care team.

Adult↗
PubMed1996

Voluntary universal antenatal HIV testing.

OBJECTIVES: To assess the uptake of universal voluntary named HIV testing of hospital booked antenatal women and to identify behavioural and demographic factors associated with testing. To identify the number of previously undiagnosed women detected by the new policy and to compare prevalence among those testing with that measured by unlinked anonymous monitoring. DESIGN: Self-completion questionnaire and data abstraction from structured booking forms and virology laboratory records. SETTING: Central London teaching hospital antenatal clinic. PARTICIPANTS: One thousand three hundred and seventy-four women booking with a hospital based midwife during the 49 weeks from 27 July 1993 to 1 July 1994. RESULTS: Before the introduction of the new testing policy fewer than 10 women per year had an HIV test, and during the study this rose to 41% (548/1340). In univariate analysis, caucasian and Mediterranean ethnic origin, fewer previous live births, and more than one lifetime sexual partner were associated with higher uptake of HIV testing. In a multivariate model only the number of previous live births and ethnic origin remained significantly associated with testing. Six women out of 828 (1%) who completed the question about nonprescribed drug use stated that they had injected drugs, and four of these women accepted a test. Two women, both with recognised major risk factors for HIV infection, were diagnosed HIV antibody positive (a prevalence in the tested women of 0.36%). A further three women were already known to be HIV antibody positive. During the 12 months from July 1993 seven women (0.24%) were found to be positive by unlinked anonymous testing. CONCLUSIONS: The introduction of a universal approach to antenatal HIV testing appears feasible: it increased the uptake of the test and detected previously unrecognised infections. Many women chose not to be tested, however, and cases remained undiagnosed. Further studies are required to examine different models of offering HIV testing, reasons for declining the test, and the cost-benefit of antenatal HIV screening.

Adolescent↗
PubMed1996

Squamous cell carcinoma arising in osteomyelitis and chronic wounds. Treatment with Mohs micrographic surgery vs amputation.

BACKGROUND: Squamous cell carcinoma (SCC) is a rare, but well-documented complication of osteomyelitis and chronic wounds. Treatment of choice for these tumors commonly occurring on the legs has been amputation. Two recent articles have suggested the utility of Mohs micrographic surgery (MMS) as a limb saving procedure. OBJECTIVE: To discuss the process of decision analysis in patients with SCC arising in osteomyelitis and chronic wounds. METHODS: Four patients with SCC (three developing in association with chronic osteomyelitis, one after a burn wound) are presented. RESULTS: Two patients underwent MMS as a limb-saving procedure, while the other two underwent amputation. Only two of our patients were able to have MMS since we were confronted with factors that precluded the use of this technique. These factors included the presence of metastatic disease and the potential for the loss of a functional limb after surgery. CONCLUSIONS: Our series confirms the utility of MMS as a potentially limb-saving procedure in patients with SCC arising in either chronic wounds or in association with osteomyelitis. Despite this, patients with distant spread of their disease or extensive local disease leading to the potential loss of functional stability of the leg postoperatively may not be candidates for MMS and may require amputation.

Aged↗
PubMed1996

Sequence analysis of immunoglobulin variable region genes that encode autoantibodies expressed by lymphomas of mucosa associated lymphoid tissue.

Aim-To determine whether the immunoglobulin genes used by three gastric mucosa associated lymphoid tissue type lymphomas with known autoreactivity are mutated from germline as mutation from germline is an indicator of exposure to a mutational mechanism which characteristically acts on B cells as they undergo a follicle centre response.Methods-Cell lines established from two cases of MALT type lymphoma secrete autoantibodies recognising follicular dendritic cells (one case) and basement membrane (one case). The immunoglobulin heavy chain variable region genes (IgV(H)) and light chain variable region genes (IgV(L)) used by these cell lines, and the IgV(H) genes from a third case recognising human IgG were sequenced.Results-All three cases studied had mutated IgV(H) genes, while the IgV(L) genes were unmutated.Conclusion-The presence of mutations in IgV(H) genes is consistent with the origin of gastric MALT type lymphomas from B cells which have traversed the lymphoid follicle.

Journal Article↗
PubMed1996

The role of blood flow in chronic duodenal ulcer.

BACKGROUND: Changes in gastroduodenal blood flow have been implicated in the pathogenesis of duodenal ulcer. We have studied duodenal blood flow during the development of an acute to chronic duodenal ulcer by using the abscopal model, in which ulcers are generated as an indirect effect of lower mediastinal irradiation. METHODS: Female CFLP mice (n = 108) weighing 25-40 g were randomly allocated to one of three groups. Controls were not irradiated. Irradiated 'controls' received 18 Gy 250 kV X-rays to the upper mediastinum (which does not cause duodenal ulceration). The lower mediastinum group received the same dose of irradiation, which has been shown to induce typical chronic duodenal ulcers in 45% of animals so treated. Animals were studied by means of radiolabelled microspheres 3 or 7 days later (that is, during and at the end of the lag period for ulcer induction). RESULTS: Proximal duodenal blood flow specifically was reduced by 32% in the lower mediastinum group compared with irradiated controls at 7 days (4.3 versus 6.3 ml/g tissue/min; P = 0.025 by ANOVA with contrast); there was no significant difference in blood flow to the stomach and to the distal duodenum. The decrease in proximal duodenal blood flow in the lower mediastinum group did not differ in the five animals that developed ulcer compared with the seven that did not. CONCLUSION: Although there is an overall decrease in duodenal blood flow associated with chronic duodenal ulcer, reduced blood flow may not explain individual susceptibility to ulceration.

Acute Disease↗
PubMed1996

An histological and ultrastructural study of the 'dirty neck' appearance in atopic eczema.

The 'dirty neck' appearance is a characteristic disorder of pigmentation, which has previously been found to affect approximately 2% of adult atopics. This disorder results in a rippled pattern of hyperpigmentation similar to that seen in macular amyloidosis. Biopsy specimens from affected skin of three patients were examined by histological and electron microscopical techniques. In addition to eczematous changes, marked pigmentary incontinence was observed. Amyloid-like material was detected by electron microscopy but not by light microscopy in all three specimens. Some deposition of amyloid occurs in this condition but the pigmentary changes are attributable to melanin incontinence. In 1987, two separate groups, Manabe et al. and Colver et al., described a distinctive type of hyperpigmentation, found particularly on the neck in some patients with chronic atopic eczema. Manabe's group found that 1.7% of 700 patients with atopic eczema showed this clinical characteristic, and that only adolescents and adults were affected. This condition has been called the 'dirty neck' appearance or 'ripple pigmentation of the neck in atopic dermatitis'. The clinical features are a rippled pattern of hyperpigmentation seen particularly on the anterior and lateral aspects of the neck (Fig. 1). We have also observed the same appearance in the inguinal areas. A number of factors could contribute to the development of hyperpigmentation in chronic atopic eczema. It is possible that the 'dirty neck' appearance is a form of post-inflammatory pigmentation due to previous eczema, ultraviolet exposure or even the application of photosensitizing products, and that the rippled appearance is related to the cutaneous anatomy of the neck. The pathogenesis of the 'dirty neck' is obscure, but in common with previous authors, we have noted that the rippled appearance of the hyperpigmentation resembles that seen in macular amyloidosis. In order to determine whether deposition of amyloid contributes to the development of this type of pigmentation in atopic dermatitis, an histological and ultrastructural examination of skin biopsies from three patients with the condition was undertaken.

Adult↗
PubMed1996

Gastric lymphoma and Helicobacter pylori.

The clinical and experimental work suggests the following scheme for the pathogenesis of gastric lymphoma. The first step is accumulation of lymphoid tissue (MALT) in response to infection of the stomach by H. pylori. In rare instances, this lymphoid infiltrate contains cells with a growth advantage, possibly because of a genetic change (trisomy 3?). The result is a monoclonal lymphoproliferative lesion that is responsive to H. pylori-driven T-cell help. Further genetic changes [t(1;14)?] may lead to escape from T-cell dependency and, ultimately, high-grade transformation. Low-grade B-cell gastric lymphoma serves as the paradigm for the entire group of MALT lymphomas that occur in a wide variety of extranodal sites. It is likely that the growth of this group of lymphomas is governed by a series of different antigens, many of which, like H. pylori, might be microbiologic. The challenge is to identify these agents and apply this knowledge to the treatment of other MALT lymphomas. This work also emphasizes the importance of paying attention to the histologic structure and nature of the ancillary cells in low-grade B-cell lymphomas. These cells, particularly the T cells, are not accidental passengers or necessarily representative of a "host response" to the neoplastic B cells. In low-grade MALT lymphomas, they are vital for the survival of the tumor. Similar mechanisms may be operative in nodal low-grade B-cell lymphomas and could offer new approaches to therapy.

Aged↗
PubMed1996

General practice audit as a quality assurance activity. An evaluation of the Morbidity and Therapeutic Index.

Quality assurance is a topical issue in general practice. This study examined the Morbidity and Therapeutic Index (MTI), a self-audit activity, offered as a QA option by the RACGP. GP response to this activity was generally positive and it appears to be an adequate tool for performance review. The study highlights the problems of assessing the extent to which the MTI leads to change and improvement in quality of care.

Adult↗
PubMed1996

Sequence analysis of rearranged IgVH genes from microdissected human Peyer's patch marginal zone B cells.

The Peyer's patches of the terminal ileum are a source of IgA plasma cells in the intestinal lamina propria of experimental animals. They are also thought to harbour IgA memory cells. However, the microanatomical location of Peyer's patch memory cells, and whether they are also present in man is not known. Human Peyer's patches have a pronounced marginal zone (MGZ) of sIgD-negative B cells. In this study we analysed the sequence of polymerase chain reaction-amplified, rearranged IgVH genes from microdissected MGZ B cells, to determine whether this is a site of B-cell memory in Peyer's patches. We observed that the majority of Peyer's patch MGZ B cells contain heavily mutated IgVH genes and are therefore clearly memory B cells. Sequences of rearranged mutated genes in the MGZ have a pattern of replacement and silent mutations expected of selected products of the affinity maturation process. Related clones, with identical CDR3 but different patterns of mutation, are seen. This suggests that either these memory cells are formed as the germinal centre selection process proceeds, or a memory cell has re-entered the germinal centre for further rounds of mutation. Interestingly, in one patient, the MGZ in the Peyer's patches also contains a proportion of B cells with unmutated IgVH 4.21 genes.

Aged↗
PubMed1996

Immunohistochemical and ultrastructural analysis of an extracellular matrix bound antigen preferentially associated with mucosal postcapillary venules.

Human lymphoma derived monoclonal antibody (anti "mucosal vessel associated antigen' [MVAA]) binds to high endothelial venules (HEV) in gut-associated lymphoid tissue, but shows only weak reactivity with HEV in peripheral lymphoid tissues. We have used immunohistochemistry and immunoelectron microscopy to define the precise ultrastructural distribution of the molecule, and to determine whether there is any association between this molecule and cellular traffic. We have observed that MVAA is a component of basement membrane which is only expressed by a subset of blood vessels. Although it is restricted to vessels which support lymphocyte traffic within lymphoid tissue, we did not observe any association between the distribution of MVAA and extravasating lymphocytes. MVAA is expressed in the fetal intestine in association with a subset of larger vessels. It is therefore not necessarily induced as a consequence of antigenic challenge. It is likely that MVAA has a structural role related to its restricted microanatomical distribution; possibly the maintenance of integrity of vessel walls which are continuously disrupted by the extravasation of lymphocytes.

Adenoids↗
PubMed1996

Immunologic aspects of Helicobacter pylori infection and malignant transformation of B cells.

Infection of the human gastric mucosa with Helicobacter pylori induces the development of mucosa-associated lymphoid tissue (MALT), and H pylori-specific local humoral and T-cell responses. H pylori infection also results in the mucosal production of proinflammatory cytokines, which are important in stimulating neutrophil infiltration. Strains of H pylori expressing the cytotoxin associated protein A (CagA) induce gastric epithelial cells to secrete interleukin-8, the neutrophil chemotactic and activating peptide. Variation in the extent of mucosal injury may be a consequence of H pylori strain variability. Gastric B-cell lymphomas of MALT arise from a background of lymphoid follicles, which are acquired in response to H pylori infection. In many cases, eradication of H pylori from patients with low-grade gastric lymphoma results in lymphoma regression, including large tumor masses, implying a causal relationship between H pylori infection and lymphoma growth. Experiments studying the properties of tumor cell and tumor infiltrating T cells in vitro have suggested that rather than stimulating the tumor cells directly, H pylori stimulates tumor infiltrating T cells, which provide help for lymphoma growth. Unlike the active inflammatory response associated with infection with CagA positive strains, but consistent with the acquisition of lymphoid follicles in all infected individuals, the development of MALT lymphomas is independent of bacterial CagA status.

Cell Transformation, Neoplastic↗
PubMed1995

An integrated kinetic analysis of intermediates and transition states in protein folding reactions.

Relaxation rates for folding and unfolding of two proteins have been measured over a range of denaturant concentrations to examine the reaction pathways leading to the late transition state. The proteins were chosen for their marked differences in both kinetic and structural properties. Results for the N-terminal domain of phosophoglycerate kinase (N-PGK), from Bacillus stearothermophilus, reveal the existence of a single intermediate (pathway = U-I-F), and obey the general relationship: kobs = k(U-I) + k(I-U)/[1 + 1/KU/I]. Hen egg white lysozyme folds through two intermediates (pathway = U-I-I.-F) and the relaxation kinetics for formation and decay of the fully folded state are described by: kobs = k(F-I.)+KI.-F)/[1+ 1/KI./I+ 1/(KI/U.KI./I)]. Rate constants apply to the first step in unfolding and the last step in folding, respectively, these being rate-limiting in the stated directions. Equilibrium constants describe the stability of transient intermediates, as indicated by the subscripts. Rate constants alter with denaturant according to the generalized equation k = kw.exp((mg-mt).D), where kw is the rate constant in water, mg and mt are parameters describing the relative solvent exposures of the ground and transition state conformations respectively, and D is the calculated denaturant activity. The same principle applies to equilibrium constants for rapid steps, i.e. for a process A = B; KA/B = KA/B(w).exp((mB-mA).D). The combined application of these relationships allows measurement of the relative free energy and degree of solvation or compactness of intermediates and transition states in folding pathways from a single set of kinetic data. In the case of lysozyme, the fast but measurable rates of interconversion of intermediate states (I and I.) have been examined by use of a sequential mixing technique, so providing additional information on a transition state which is not rate-limiting in the overall pathway. The analysis of rate profiles for folding and unfolding of these proteins yields parameters which are in precise agreement with those derived from equilibrium data.

Animals↗
PubMed1995

Molecular structure of the Menkes disease gene (ATP7A).

We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene.

Adenosine Triphosphatases↗
PubMed1995

Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells.

The splenic marginal zone (MGZ), which surrounds the mantle zone (MTZ) in human splenic white pulp, contains a phenotypically and morphologically distinct population of B cells. The origin of MGZ B cells is uncertain. Whereas some experiments in rodents have suggested that they are a distinct cell lineage responsible for the immune response to T-independent type 2 antigens, others have suggested that they are memory B cells derived from a germinal center (GC) response. The progeny of a GC reaction is expected to have rearranged immunoglobulin (Ig) genes that are mutated. The distribution of mutations would be expected to reflect the selection of Ig by its affinity for antigen. We have analyzed rearranged Ig heavy chain variable region (VH) 6 and VH 4.21 genes in MGZ and MTZ B cells microdissected from frozen sections of human spleen to determine whether these genes have the properties of an affinity-selected memory B cell population. MTZ B cells contained germline Ig VH genes, confirming previous reports and providing an internal control for mutational analysis. MGZ B cells contained Ig VH genes that were mutated, showing that these cells had been subjected to a mutational mechanism characteristically active in the GC. The rearranged VH 6 genes showed patterns of mutation indicative of an antigen selection process, whereas the distribution of mutations in VH 4.21 genes was not characteristic of gene selection by conventional T-dependent antigen. Our studies provide the first evidence that the human splenic MGZ is a reservoir of memory B cells.

Adult↗