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Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 253 records · Page 14Linked to original sources
PubMed1995

Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis.

One hundred and eight patients with cystic fibrosis were investigated over one year to determine whether an association existed between rhinovirus or other respiratory virus infection and clinical status. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), Shwachman score, Chrispin-Norman chest radiograph score, and percentage weight for height were recorded at the beginning and end of the study; days of intravenous antibiotics were noted. Nasopharyngeal aspirates were taken for viral studies during respiratory exacerbations. Serum was collected at enrollment and 2-6 weeks after each respiratory exacerbation. One hundred and fifty seven exacerbations occurred in 76 patients. Respiratory virus infection was detected in 44 exacerbations and rhinovirus was present in 16% (25/157) of exacerbations. Patients with one or more respiratory virus infections were compared with those who had none. When all respiratory virus infections were considered, patients had a significantly greater deterioration in Shwachman score and received significantly more days of intravenous antibiotics. When rhinovirus was considered separately, patients received significantly more days of intravenous antibiotics, but showed no deterioration in clinical status. However, patients infected with another respiratory virus had a significant decline in FEV1, with trends towards significance for decline in FVC and Shwachman score.

Adolescent↗
PubMed1995

Urgent full blood count in children over 3 months of age with bacterial meningitis.

Children with bacterial meningitis often have a full blood count (FBC) measured urgently on admission. We investigated whether urgent FBC gave results that aided immediate management or predicted outcome in children with meningitis. FBCs were measured on admission during 190 episodes of bacterial meningitis in children admitted between 1984 and 1991. Significant anaemia was found in seven children, but immediate transfusion was only necessary in the three subjects who were in the Paediatric Intensive Care Unit (PICU). A white blood count of less than 5 x 10(9) L-1 was significantly associated with death (P < 0.02), but a Glasgow Coma Score of less than 8 predicted death more accurately (positive predictive value of 40%). FBC yielded immediately useful information only in the 15% of children who were admitted to PICU. Conscious level was a better predictor of outcome than FBC. We recommend that urgent FBC should be performed in children with meningitis admitted to a PICU; in other children with meningitis FBC can be analysed during normal laboratory hours.

Age Factors↗
PubMed1995

Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment.

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p < 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.

Adult↗
PubMed1995

Faecal mucinase activity assessed in inflammatory bowel disease using 14C threonine labelled mucin substrate.

Previous studies have shown the presence in faeces of sulphatases, sialidases, glycosidases, and proteases relevant to mucus degradation, but the relative role of these enzymes in the degradation of colonic mucus has been unclear. A total mucinase assay using 14C threonine biologically labelled human colonic mucin as substrate was therefore developed in this study. Faecal mucinase activity of a pooled normal faecal filtrate was capable of removing 80% of the 14C threonine label from mucin within eight hours incubation, but 20% remained intact despite prolonged incubation. The pH profile of mucinase activity is broad (pH 4.5-9.5) suggesting contribution from multiple enzymes. Mucinase activity was reduced by preincubation with 100 micrograms/ml chymostatin (82.8%), 0.5 mg/ml EDTA (91.6%), and 4 g/l bismuth subsalicylate (72.0%). All 55 faecal samples studied contained detectable mucinase activity, measured as dpm release/micrograms protein/hour, which was greater in samples from patients with ulcerative colitis (n = 17, median 52.7, interquartile range 32.9-66.9), than controls (n = 26, 34.4, 26.8-40.4, p < 0.02) or patients with Crohn's disease (n = 12, 35.5, 17.5-55.7, p < 0.05). There was, however, no significant difference in faecal mucinase activity between inactive and active ulcerative colitis. These results suggest that faecal mucinase activity is one factor contributing to the thin mucus layer in ulcerative colitis and represents a potential target for drug treatment.

Colitis, Ulcerative↗
PubMed1995

Bacterial meningitis in the first three months of life.

A retrospective study of infants with bacterial meningitis admitted to our hospital during 1949-52, highlighted the lack of 'classical' signs of meningitis in these infants. We carried out a similar review of 44 infants aged less than three months, admitted during 1982-91. We also determined the causative organisms and their antibiotic sensitivities. Symptoms and signs were similar in the two series. Forty infants in the later series were either febrile, irritable or had seizures on the day of admission. Overall mortality fell from 30% to 11%. Between 1982 and 1991 Group B Streptocococcus and Neisseria meningitidis were the commonest causes of meningitis. All organisms, except one, were sensitive to ampicillin and/or cefotaxime. Bacterial meningitis should be suspected in young infants who are febrile, irritable or having seizures. Initial treatment with ampicillin and cefotaxime is appropriate.

Ampicillin↗
PubMed1995

Bacterial meningitis after MMR immunisation.

Two children developed bacterial meningitis within five days of measles-mumps-rubella (MMR) immunisation. Diagnosis was delayed because symptoms were attributed to the vaccine, although both had a raised C-reactive protein. Fever or rash within five days of MMR vaccination are unlikely to be due to the vaccine and a raised C-reactive protein suggests bacterial infection.

Diagnosis, Differential↗
PubMed1995

Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation of meningitis.

We examined the measurement and the diagnostic value of cerebrospinal fluid interleukin-6 (CSF IL-6) in meningitis. The cytokine was measured by bioassay (B9 hybridoma cell line) and by immunoassay (in-house radioimmunoassay). We compared the diagnostic value of CSF IL-6 determination with that of other biochemical markers of meningitis. Although there was significant correlation between bioactive and immunoactive IL-6 (r = 0.724, P < 0.001), results were frequently different with biological/immunological ratios ranging from 0.2 to 24.3 (mean 4.6). Gel permeation chromatography suggested that the discrepancy in biological and immunological activities was not due to molecular heterogeneity, but may be explained by the presence of a synergistic factor. Interleukin-6 concentration was markedly elevated in CSF from most patients with bacterial meningitis compared to patients with viral meningitis and those without evidence of infection. However, low IL-6 levels by radioimmunoassay did not exclude bacterial meningitis (sensitivity 86%). CSF total protein and CSF glucose were significantly different between all three groups, but there was no significant difference in lactate concentration between virally infected and normal CSF, both of which had lower lactate concentrations than those in bacterial infection. CSF IL-6 measurement had greater sensitivity, specificity and predictive value than these other biochemical markers, and hence a rapid assay for IL-6 in CSF may contribute to the early diagnosis of bacterial infection.

Biomarkers↗
PubMed1995

Subcellular biochemical changes during the development of the small intestine of pony foals.

To examine the postnatal development of equine small intestine, biopsy specimens of jejunal mucosa from 8 ponies, between 6 and 28 weeks old, were subjected to analytical subcellular fractionation and assay of organelle marker enzymes. Fractionation revealed a reduction in the particulate brush border component of beta-galactosidase (lactase) activity between 6 and 28 weeks, and a corresponding increase in soluble activity, although the reduction in mean specific activity was not significant. There also was a decrease in the proportion of brush border to soluble aminopeptidase N activity, a relative loss of brush border gamma-glutamyltransferase activity, and a considerable decrease in the specific activity of alkaline phosphatase throughout the gradient fractions. In contrast, there were marked increases in activities of alpha-glucosidase (maltase) and sucrase in the older ponies, accompanied by considerable changes in the intracellular distribution of particulate alpha-glucosidase activity, which was predominantly associated with endoplasmic reticulum at 6 weeks, whereas the large increase in activity observed by 28 weeks was clearly associated with the brush border. The modal density of brush borders also increased with age, suggestive of an increase in the glycoprotein-to-lipid ratio of the microvillar membrane. In contrast to these brush border changes, there was relatively little alteration in the activities or density distributions of marker enzymes for endoplasmic reticulum, basolateral membranes, mitochondria, or lysosomes. These findings indicate that maturation of equine intestinal epithelium during the first few months of life results in major changes in the properties and enzyme composition of enterocyte brush borders.

Aging↗
PubMed1994

Reduced transfer of tetanus antibodies with placental malaria.

Placental malaria may limit antibody transfer to the fetus. We compared concentrations of tetanus antibody in paired maternal-cord sera from 224 women living in a malarious area of Papua New Guinea. With heavy placental infection (> 35 parasites per 200 white cells) the average cold tetanus antibody corresponding to a maternal level of 1 IU/mL was 0.18 (95% CI 0.12-0.26); corresponding figures after light (< 35 parasites per 200 white cells) or no infection were 0.23 (0.14-0.34) and 0.82 (0.57-1.21), respectively. About 10% of babies born to mothers with a placenta heavily infected with Plasmodium falciparum may fail to acquire protective levels of tetanus antibody despite adequate maternal antibody.

Antibodies, Bacterial↗
PubMed1994

Absence of paramyxovirus RNA in cultures of pagetic bone cells and in pagetic bone.

It has been proposed that Paget's disease of bone is caused by the infection of bone cells with one or several paramyxoviruses. In this study we used the polymerase chain reaction (PCR), which allows the detection of very low levels of a target nucleic acid sequence, to study cultures of pagetic bone cells and samples of pagetic bone. Oligonucleotide primers were designed to flank a sequence of the nucleocapsid genome of measles virus and canine distemper virus (CDV). Within this fragment there were contrasting restriction endonuclease sites specific to measles or CDV that allowed identification of the original template. We were unable to detect paramyxovirus RNA in four strains of human bone cells outgrown from pagetic bone and one strain derived from an uninvolved site of a patient with Paget's disease. Furthermore, paramyxovirus sequences were not detected in cDNA prepared from six samples of pagetic bone biopsies. The work presented here further questions the role of measles and CDV in the abnormal remodeling observed in Paget's disease.

Aged↗
PubMed1994

Genomic characterization of rotavirus strains obtained from hospitalized children with diarrhoea in Bangladesh.

Faecal samples were obtained from 111 children hospitalized with acute watery gastroenteritis in a children's hospital in Bangladesh from January to December, 1989. Rotavirus was detected as the aetiologic agent in 35 (32%) of these patients. The electrophoretic pattern of ds-RNA extracted from the rotaviruses showed 11 different migration patterns (six short and five long), as well as some short and long mixed profiles. All four major G serotypes were identified by amplification of a segment of the gene for VP7 using the polymerase chain reaction. A specific serotype could be assigned in 32 (91%) cases. Serotypes G1-G4 accounted for 11%, 37%, 11%, and 23% of isolates respectively. Three (9%) mixed serotypes were identified by this method and were found to be mixtures of serotypes G1 and G4, G2 and G4, and G3 and G4.

Adolescent↗
PubMed1994

Mortality from group C meningococcal disease: a case for a conjugate vaccine?

This 17-year retrospective review of children with meningococcal disease (MCD) has determined the mortality due to serogroup C, in order to assess the potential impact of a group C conjugate vaccine. Four hundred and forty-nine cases of MCD were admitted to our hospitals during 1977-1993; 78 due to group C, 11 of whom died. There was a significant increase in the proportion of cases due to group C from 1986 onwards (10% vs 21%), and an increase in the total number of cases of MCD (151 vs 298). The currently available group C polysaccharide vaccine has low efficacy below 2 years of age and could not have prevented 54 cases of group C disease. A conjugate group C vaccine administered between 2 and 4 months of age could have prevented 68 cases, including all fatal cases. The recent increase in MCD is partly due to an increase in group C disease. A meningococcal group C conjugate vaccine could prevent most cases of infection due to group C, and decrease the mortality from MCD by up to 30%.

Age Factors↗
PubMed1994

Effect of 3'azido-2',3'-deoxythymidine (AZT) on experimental feline immunodeficiency virus infection in domestic cats.

The compound 3'azido-2',3'-deoxythymidine (AZT) inhibits the replication of feline immunodeficiency virus (FIV) in cell culture, and treatment with the compound has been reported to induce some clinical improvement in some cases of feline FIV infection. In order to determine the effect of prophylactic treatment with AZT on experimental FIV infection, cats were treated with the compound at 0.2, 1.0, 5, 25 or 50 mg kg-1 day-1 for 29 days. One day after the treatment was started, they were inoculated with 150 cat infectious doses of FIV. All the cats became viraemic, seroconverted and developed lymphadenopathy, although the onset of each was delayed in the cats given higher doses of AZT. Anaemia developed in the cats given high doses of AZT. Virus re-isolated from the cats given 50 mg kg-1 day-1 was as susceptible to AZT in cell culture as the inoculated virus. Thus AZT is much less effective in cats than might have been expected from the results of in vitro studies.

Animals↗