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Biomedical subjects

S J Smith

Publications and source records attributed to S J Smith.

At least 163 records · Page 9Linked to original sources
PubMed1995

Late mortality in elderly patients surviving acute peptic ulcer bleeding.

Acute peptic ulcer bleeding is associated with a substantial short term mortality but it is generally assumed that in the modern era of effective medical treatment the longer term prognosis is good. This study evaluated 487 patients aged over 60 years who were discharged from Nottingham University and City Hospitals after admission for acute peptic ulcer bleeding during 1986-91 and 480 age and sex matched community controls. Follow up information was obtained from hospital and general practitioner records and from the National Health Service central register. Mortality was compared with control mortality and with rates expected for England and Wales. During a mean follow up of 34 months 142 (29%) of 487 patients died compared with 58 (12%) of 480 community controls and with 81.5 deaths expected (observed/expected (O/E) = 1.74, 95% confidence limits (CL) 1.5 to 2.1). Six years after admission the actuarial survival estimate was only 50% for ulcer patients compared with 76% for community controls and 69% expected. The increased mortality was similar in men and women and was greatest in the 60-74 year age group. Much of the excess mortality was accounted for by deaths from cancer (O/E 34/19.7 = 1.73; CL 1.2 to 2.4), from respiratory disease (O/E 28/10.9 = 2.57; CL 1.7 to 3.7), and in men from vascular disease (O/E 31/22.4 = 1.38; CL 0.9 to 2.0). Eight deaths resulted from recurrent ulcer complications and four deaths from gastric cancers undetected at the index admission. In conclusion, patients discharged after peptic ulcer bleeding had a substantially reduced life expectancy. The increased mortality was predominantly due to a variety of smoking related diseases rather than recurrent peptic ulcer complications. Deaths from recurrent peptic ulcer complications were infrequent and were less than reported in earlier years possibly reflecting prolonged and widespread used of H2 receptor antagonists.

Acute Disease↗
PubMed1995

Morbidity and treatment in elderly patients surviving hospital admission with bleeding peptic ulcer.

Bleeding peptic ulcer in the elderly is associated with use of non-steroidal, anti-inflammatory drugs (NSAIDs) and aspirin, presenting a therapeutic dilemma for the treatment of survivors. To determine the longterm morbidity of patients surviving bleeding peptic ulcer and their treatment, with particular reference to NSAID use, this study followed up 487 patients aged over 60 years, who survived an episode of bleeding peptic ulcer in Nottingham during 1986 to 1991. Information was gathered by evaluation of general practitioner and hospital records, scrutiny of death certificates, and postal questionnaire to surviving patients. Of 487 patients surviving a bleeding peptic ulcer, 345 were alive at the follow up, a mean 34.2 months after discharge. Of these 201 (58%) had taken NSAIDs before their ulcer bleed (104 non-aspirin NSAIDs, 77 aspirin, 20 both). Compared with non-users, the patients using NSAIDs at the time of presentation were significantly more likely subsequently to consult their general practitioner with locomotor symptoms (56% v 35%, p < 0.001) and receive further NSAIDs (34% v 13%, p < 0.001), but significantly less likely to consult their general practitioner for dyspepsia (31% v 54%, p < 0.001). Antiulcer drug use was widespread in both groups, with an overall point prevalence of 44%. Seventy five patients received NSAIDs during the follow up period (69% with coprescription of antiulcer drugs, usually H2 antagonists). Recurrent peptic ulcer, ulcer complications, and ulcer related deaths were uncommon. Antiulcer drug use was lower in those with ulcer recurrence compared with the point prevalence in those without (17% v 44%, p < 0.05). Patient questionnaire responses confirmed a high level of locomotor symptoms especially in patients previously admitted with NSAID associated ulcer bleeding. In conclusion, in patients surviving peptic ulcer bleeding, recurrent ulcer complications and death seem to be lower than reported by studies that preceded the advent of antiulcer drugs. It is suggested that this low incidence may be a consequence of their use. Granted the low level of recurrent ulceration and the high level of locomotor symptoms in patients studied, current treatment may unduly emphasise the importance of stopping NSAIDs in this group of patients.

Aged↗
PubMed1995

Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults.

Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset. Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.

Adolescent↗
PubMed1995

Nerve conduction studies, skeletal muscle EMG, and sphincter EMG in multiple system atrophy.

Although autonomic failure, parkinsonism, and cerebellar and pyramidal signs are well documented in multiple system atrophy, much less is known about the frequency and severity of involvement of the peripheral nervous system. The frequency and nature of peripheral nerve involvement has therefore been determined in 74 patients with multiple system atrophy using nerve conduction studies and skeletal muscle EMG. These findings were compared with those on sphincter EMG. Ninety per cent of the patients had an abnormal sphincter EMG, indicating denervation and reinnervation consistent with anterior horn cell loss in Onuf's nucleus, but only 40% had either abnormal nerve conduction studies (mixed sensorimotor axonal neuropathy in 17.5%) or abnormal skeletal muscle EMG (suggesting partial denervation in 22.5%). These data indicate a remarkable selective vulnerability of the anterior horn cells of Onuf's nucleus innervating external sphincter muscles relative to those supplying skeletal muscle in patients with multiple system atrophy. If this selective pattern of involvement can be explained it may be a clue to pathogenetic mechanisms in multiple system atrophy.

Adult↗
PubMed1995

Circulating human IgG autoanti-IgE antibodies in asthma patients block the binding of IgE to its high affinity receptor.

Aims-To investigate the ability of circulating human IgG autoanti-IgE antibodies from asthma patients to block the binding of IgE to the alpha chain of the high affinity receptor (FcepsilonRI).Methods-This involved the use of a well validated flow cytometric method to detect inhibition of FITC labelled IgE binding to a fibroblast cell line (CHK1E1) transfected with the alpha chain of FcepsilonRI.Results-IgG autoanti-IgE-containing sera blocked the binding of IgE-FITC to the CHK1E1 cells. No such inhibition was demonstrable with rheumatoid sera containing autoanti-IgG (that is, rheumatoid factor) but lacking autoanti-IgE. Percentage inhibition (up to 50%) of IgE binding to the CHK1E1 cells was directly related to the titre of IgG1, but not IgG4, autoanti-IgE in the sera tested (correlation coefficient 0.66, probability 0.003).Conclusions-The capacity of anti-IgE to block the binding of IgE to FcepsilonRI has important clinical implications, particularly in terms of downregulation of allergic reactions.

Journal Article↗
PubMed1995

Circulating IgG autoanti-IgE antibodies in atopic patients block the binding of IgE to its low affinity receptor (CD23).

Aims-To investigate the ability of circulating IgG autoanti-IgE antibodies from atopic rhinitis patients to block the binding of IgE to its low affinity receptor (FcepsilonRII), also termed CD23.Methods-This involved the use of a well validated flow cytometric method to detect inhibition of FITC labelled IgE binding to human B cells expressing CD23 (RPMI 8866 cell line).Results-Taking inhibition values greater than 20% as being significant, 15 out of 20 IgG anti-IgE containing sera inhibited the binding of IgE-FITC to the RPMI 8866 cells. The inhibitory effect was recoverable in the IgG fraction of serum, but was not related to the titre of either IgG1 anti-IgE or IgG4 anti-IgE, thus suggesting that it might be related to epitope specificity. No such inhibition was demonstrable with rheumatoid sera containing autoanti-IgG (that is, rheumatoid factor), but lacking autoanti-IgE.Conclusions-The capacity of anti-IgE to block the binding of IgE to CD23 has important implications, particularly in terms of upregulation of IgE synthesis and the consequent perpetuation of the inflammatory response.

Journal Article↗
PubMed1995

Evaluating lyophilized human serum preparations for suitability as proficiency testing materials for high-density lipoprotein cholesterol measurement.

OBJECTIVE: To evaluate the suitability of various commercial preparations for use by the College of American Pathologists as survey materials in assessing high-density lipoprotein cholesterol measurement performance. DESIGN: Lyophilized human serum preparations from six vendors (vendors A through F) were evaluated to determine which material(s) best mimicked the commutability of fresh human serum. Two freshly collected unfrozen pools prepared from donor specimens were analyzed concurrently with the vendor materials to identify sources of variation and possible matrix bias. Each material was evaluated using 5 common precipitation reagents (phosphotungstate-magnesium, phosphotungstic acid, dextran sulfate [50K and 500K], and heparin-manganese). To evaluate how each reagent separates lipoproteins in each material, the lipoprotein separation patterns were profiled using high-pressure liquid chromatography and compared with separation patterns observed for the fresh human serum pools. MAIN OUTCOME MEASURES: Similarities in performance characteristics of vendor material(s) were compared with fresh human serum. RESULTS: Two of the six materials gave separation profiles for the lipoproteins similar to the typical patterns observed for human serum. Material from vendor B showed the best commutability across all of the precipitation reagents and had the best combination of low overall variability (10% for level 1 and 9.4% for level 2) and minimal concentration differences among reagents. CONCLUSIONS: Vendor B was selected by the College of American Pathologists to provide materials for use in assessing performance of lipid and lipoprotein testing in the 1994 Comprehensive Chemistry Surveys. This study demonstrates the great variability that different vendor preparations introduce into the measurement of high-density lipoprotein cholesterol. It also emphasizes the effort required to evaluate the suitability of processed materials for use in proficiency testing.

Analysis of Variance↗
PubMed1994

Neural signalling. Neuromodulatory astrocytes.

The discovery that waves of increased cytoplasmic free Ca2+ in astrocytes can trigger neuronal Ca2+ responses hints at previously unrecognized active neuromodulatory roles for glial cells.

Animals↗
PubMed1994

Nitric oxide synthase inhibitors 7- and 6-nitroindazole relax smooth muscle in vitro.

7-Nitroindazole induced concentration-dependent relaxation of precontracted rabbit aorta, dog middle cerebral artery, rat anococcygeus muscle and rat stomach fundus. Relaxations to 7-nitroindazole in rabbit aorta were unaffected by nitric oxide synthase blockade or endothelial removal. 6-Nitroindazole also caused concentration-dependent relaxation in dog middle cerebral artery and rabbit aorta, being equipotent with 7-nitroindazole in both tissues. These data suggest that indazole derivatives can induce an endothelium- and nitric oxide synthase-independent relaxation of smooth muscle in vitro.

Alprazolam↗
PubMed1994

Multiple ubiquitin conjugates are present in rat brain synaptic membranes and postsynaptic densities.

The pattern of ubiquitin-protein conjugates present in a range of adult rat forebrain subcellular fractions has been investigated by immunoblotting with a monoclonal antibody specific for ubiquitin and its conjugates. Each fraction contains a complex and characteristic pattern of ubiquitin conjugates. Many integral synaptic membrane proteins are ubiquitinated, including a subset of high M(r) (> 120 kD) concanavalin A-binding glycoproteins. Postsynaptic densities are also enriched in ubiquitin conjugates, the profile being distinct from that of synaptic membranes. These results suggest that many plasma membrane and synaptic proteins are ubiquitinated.

Animals↗
PubMed1994

Effect of human leucocyte antigen matching on the incidence of acute rejection in renal transplantation.

The influence of human leucocyte antigen (HLA) matching on the incidence of acute rejection and graft survival was examined in 181 consecutive patients receiving cadaveric renal transplants. Allografts with better HLA-DR and HLA-B matching showed significantly lower rejection rates than less well matched grafts on both univariate (rejection rates 25, 62 and 82 per cent for zero, one and two DR mismatches; P < 0.001) and multivariate analysis. Rejection episodes occurred earlier in mismatched grafts (P < 0.001). Superior matching was associated with improved graft function at 1 year after transplantation (mean serum creatinine level 137, 180 and 225 mumol l-1 for zero, one and two DR mismatches; P < 0.05). No association was, however, demonstrated between the degree of matching and overall graft survival. Good HLA matching reduces the number of acute rejection episodes, producing significant savings in drug costs and hospital stay. Long-term graft function is improved and minimizing early graft damage helps to avoid later development of chronic rejection.

Acute Disease↗
PubMed1994

Spontaneous Ca2+ transients in developing hippocampal pyramidal cells.

To determine the spatiotemporal pattern of hippocampal pyramidal cell activity during development, we examined cytosolic Ca2+ dynamics in tissue slices derived from early postnatal rats. After a brief (12-60 h) culture period, slices were stained with a calcium-sensitive dye, Fluo-3. Fluorescence imaging of the Fluo-3-stained slices with a scanning laser confocal microscope afforded simultaneous observation of many cells at high spatial resolution. Time-lapse imaging revealed spontaneous Ca2+ transients in the somata dendrites of many pyramidal cells in areas CA1 and CA3. For the most part, Ca2+ activity in neighboring pyramidal cells appeared to be uncorrelated, although we occasionally observed synchronous Ca2+ transients in adjacent cells. The transients were blocked by both tetrodotoxin (1 microM) and a mixture of the glutamate receptor antagonists, APV (50 microM) + CNQX (10 microM). Thus, spontaneous Ca2+ transients appear to be a consequence of activity-dependent release of glutamate acting postsynaptically through ionotropic glutamate receptors. Although gamma-aminobutyric acid (GABA) is thought to be an excitatory neurotransmitter during hippocampal development (Cherubini et al., 1991, Trends Neurosci. 14 (12):515-519), the spontaneous Ca2+ transients were not blocked by the GABAA receptor antagonist picrotoxin (100 microM). Furthermore, application of GABA (50 microM) abolished the spontaneous Ca2+ events, possibly via GABAB receptor-mediated inhibition of postsynaptic cells. The present results join other recent observations suggesting that isolated neural tissues support spontaneous activity, although the patterns and mechanisms of the activity reported here appear to differ from those of previous studies. Differences in the patterns of spontaneous activity during development may contribute to variations in the functional organization of different regions of CNS tissue.

2-Amino-5-phosphonovalerate↗
PubMed1994

Localization and topology of VirB proteins of Agrobacterium tumefaciens.

Agrobacterium tumefaciens causes tumors on plants by transferring part of its Ti (tumor inducing) plasmid, the T-DNA or transferred DNA, to plant cells. The virB operon, the largest operon of the virulence (Vir) region located on the Ti plasmid, is necessary for tumor induction on all plant species. Previously, the complete nucleotide sequences of the virB operons of several Ti plasmids of A. tumefaciens were determined. The 11 predicted proteins mostly have signal sequences and/or hydrophobic domains. Hence, these proteins are thought to be located in or transported over the agrobacterial inner membrane. The VirB proteins are suggested to form a pore structure in the membrane through which the T-DNA-protein complex is transported. To obtain direct evidence for transport of these proteins over the inner membrane, we made fusions between genes of the virB operon and the gene for the enzyme alkaline phosphatase. Here we show the localization of several VirB proteins in the bacterial membrane and predict the topology of the membrane-localized VirB proteins. The finding of a fusion between the VirB7 protein and the enzyme alkaline phosphatase provides the first evidence for the expression of the small virB7 gene. The VirB2 protein shows similarity with the TraA propilin of the Escherichia coli F plasmid. Here we show that the predicted topology of the VirB2 protein in the inner membrane is identical to that of the TraA protein. Therefore, we hypothesize that the VirB2 protein is part of an agrobacterial pilus-like structure.

Agrobacterium tumefaciens↗