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Biomedical subjects

J S Ellis

Publications and source records attributed to J S Ellis.

At least 37 records · Page 2Linked to original sources

Molecular analysis of an outbreak of influenza in the United Kingdom.

The first outbreak of influenza virus in Europe in 1995/1996 occurred in a school in the south of England. RT-PCR-restriction analysis was performed on the HA1 portion of influenza haemagglutinin gene amplified directly from clinical samples. These were taken at the onset of the outbreak and indicated co-circulation of two distinct genetic variants of influenza virus which were antigenically identical. Investigations of this nature demonstrate the genetic diversity of circulating variants of influenza and have the potential to provide information on molecular evolution of strains within closed populations.

Adolescent↗

Chronic anemia due to parvovirus B19 infection in a bone marrow transplant patient after platelet transfusion.

BACKGROUND: Many reports document the transmission of human parvovirus B19 (B19) infection by clotting factor concentrates manufactured from large plasma pools. Transmission via other blood components originating from a single donor or a small number of donors, however, seems to occur only rarely. The study reported here identifies a B19 infection that was transmitted via a platelet donation. CASE REPORT: A multiply transfused allogeneic bone marrow transplant patient developed chronic anemia due to persistent B19 infection. The anemia responded to therapy with intravenous immunoglobulin. It was postulated that a transfusion was the source of the B19 infection. Archived sera from 90 implicated blood donors were tested for B19 IgM and DNA by the use of dot-blot hybridization and a nested polymerase chain reaction with primers from the B19 nonstructural gene. B19 DNA from patient and donor sera were sequenced. One of the 90 blood donors (Donor A) was B19 IgM positive and had a high level of B19 DNA. The patient was viremic 3 days after transfusion of platelets from this donor, and the sequence of B19 DNA from the patient exactly matched that of B19 DNA from the donor. A second blood donor (Donor B) had a low level of B19 DNA but was IgM negative. The patient showed no evidence of B19 infection after the transfusion of red cells from Donor B, and the sequence of this donor's B19 DNA was different from that in the patient. CONCLUSION: Blood Donor A with asymptomatic acute B19 infection was the source of B19 infection in the bone marrow transplant patient. Donor B with a low level of B19 DNA was not the source of infection.

Adult↗

Multiplex reverse transcription-PCR for surveillance of influenza A and B viruses in England and Wales in 1995 and 1996.

Multiple-target (multiplex) reverse transcription-PCR (RT-PCR) for detection, typing, and subtyping of the hemagglutinin gene of influenza type A (H3N2 and H1N1) and type B viruses was developed and applied prospectively to virological surveillance of influenza in England in the 1995-1996 winter season. During this season both influenza A H3N2 and H1N1 viruses were circulating, although at different times. Six hundred nineteen combined nose and throat swabs taken by general practitioners in sentinel practices from individuals presenting with "influenzalike illness" were analyzed by culture, multiplex RT-PCR, and immunofluorescence. Of the 619 samples, 246 (39.7%) were positive by multiplex RT-PCR compared with 200 (32.3%) which yielded influenza viruses on culture. There was 100% correlation between multiplex RT-PCR typing and subtyping and the influenza types and subtypes obtained from culture. There was also excellent correlation between the temporal detection of influenza A H3N2 and H1N1 viruses by multiplex RT-PCR and by culture. During the peak weeks of influenza virus activity, a total of 259 specimens were received, of which 101 (38.9%) yielded influenza viruses on culture while 149 (57.5%) were positive in multiplex RT-PCR, providing an increase in detection of influenza viruses of approximately 20%. The increased detection of influenza virus occurred in all the age groups sampled. Samples which were positive by multiplex RT-PCR but negative by culture were not detected significantly earlier or later in the winter of 1995-1996 but were detected during the peak weeks of clinical influenza virus activity. Multiplex RT-PCR was successfully used in surveillance of influenza to provide accurate, sensitive diagnosis directly on clinical specimens sent through the post.

Adolescent↗

Analysis of influenza A H3N2 strains isolated in England during 1995-1996 using polymerase chain reaction restriction.

A polymerase chain reaction-restriction (PCR-restriction) endonuclease assay was developed to allow rapid analysis of influenza A H3N2 viruses circulating in England during 1995-1996. Restriction endonuclease digestion with two enzymes of amplicons derived from PCR of the HA1 portion of the influenza haemagglutinin (HA) gene was able to differentiate antigenically similar influenza strains into two groups. Group I variants were similar genetically to the 1995/96 vaccine strain, A/Johannesburg/33/94, whereas the HA sequences of Group II variants were similar genetically to the reference virus A/Thessaloniki/1/95. Of the 700 England A H3N2 strains isolated between February 1995 and the end of April 1996, 384 were analysed by this method. PCR-restriction analysis of sequential influenza isolates revealed a temporal alteration in prevalence of two variants. Groups I and II variants cocirculated with equal frequency during a period of sporadic influenza activity, but following the onset of epidemic influenza activity in 1995, only Group II variants were detected. PCR- restriction analysis was found to be a rapid method for studying genetic variation which could be applied to a large number of samples and provide information about the direction of genetic drift in the HA gene of influenza virus.

Animals↗

Automated gas chromatographic assay for amlodipine in plasma and gingival crevicular fluid.

This paper describes an automated capillary gas chromatographic method for the determination of amlodipine in plasma, and in sub-microlitre volumes of gingival crevicular fluid (GCF), in order to assess if amlodipine is present in GCF under conditions of gingival overgrowth, as has been shown for nifedipine, another dihydropyridine drug. Liquid-liquid extraction followed by derivatisation was employed to isolate amlodipine and render it suitable for gas chromatography. Amlodipine was analysed in plasma and GCF of four patients undergoing amlodipine therapy for cardiovascular disorders, three of whom had significant gingival overgrowth. Amlodipine was detected in the plasma of all patients and in massive concentrations in the GCF of those patients with overgrowth, 23- to 290-fold greater than in their plasma. Like nifedipine, amlodipine sequestration into GCF appears to be linked with gingival overgrowth.

Amlodipine↗

Determinants of gingival overgrowth severity in organ transplant patients. An examination of the rôle of HLA phenotype.

The role of HLA phenotype as a risk factor for drug-induced gingival overgrowth was investigated in a cohort of 172 transplant recipients. Clinically significant overgrowth warranting surgical correction was observed in 72 patients (42%). Using stepwise regression modelling, 6 clinical parameters were identified as significant risk factors for the severity of gingival overgrowth. These were; age, sex, creatinine plasma level, duration of therapy, papilla bleeding index and concomitant medication with a calcium channel blocking drug. 3 HLA alleles were also identified as risk factors when adjusted for other clinically significant risk factors (HLA -DR2, A24, B37). However, when the p-values for the HLA variables were corrected to compensate for the use of multiple significance testing, only HLA-B37 remained statistically significant at the 5% level. Organ transplant patients are at risk of developing gingival overgrowth, with approximately 25% medicated with cyclosporin alone requiring corrective gingival surgery. This figure more than doubles in patients concomitantly medicated with a calcium blocking drug. The data at present available would suggest that the severity of gingival overgrowth is also significantly associated with the HLA-B37 phenotype.

Adolescent↗

The pathogenesis of drug-induced gingival overgrowth.

Gingival overgrowth is a well-documented unwanted effect, associated with phenytoin, cyclosporin, and the calcium channel blockers. The pathogenesis of drug-induced gingival overgrowth is uncertain, and there appears to be no unifying hypothesis that links together the 3 commonly implicated drugs. In this review, we consider a multifactorial model which expands on the interaction between drug and/or metabolite, with the gingival fibroblasts. Factors which impact upon this model include age, genetic predisposition, pharmacokinetic variables, plaque-induced inflammatory and immunological changes and activation of growth factors. Of these, genetic factors which give rise to fibroblast heterogeneity, gingival inflammation, and pharmacokinetic variables appear to be significant in the expression of gingival overgrowth. A more thorough understanding of the pathogenesis of this unwanted effect will hopefully elucidate appropriate mechanisms for its control.

Adult↗

Genetic and antigenic variation in the haemagglutinin of recently circulating human influenza A (H3N2) viruses in the United Kingdom.

Variation in the haemagglutinin (HA) gene of influenza A (H3N2) viruses isolated in the U.K. and abroad from 1992-1994, was determined by nucleotide sequencing of the HA1 domain of the HA gene. Viruses isolated in the U.K. early in the 1992-93 season were from the A/Beijing/353/89 lineage and were replaced later that season by viruses from the A/Beijing/32/92 lineage. Viruses from the new lineage continued to be isolated during the 1993-94 season, but were heterogeneous. Most of these isolates were more closely related to an A/Beijing/32/92 variant, A Hong Kong/23/92, but could be distinguished into three groups by serology (of which one group was circulating during the previous season) and four groups based on sequence variation in the HA gene. However, phylogenetic analysis of antigenically-distinct isolates showed that the HA gene is evolving along one lineage. Sequence analysis identified mainstream, subgroup and strain specific amino acid substitutions. There was a broad correlation between the observed amino acid changes and the antigenic sites of the HA. The results of this study highlight the value of regular molecular analysis of circulating viruses.

Antigenic Variation↗

Periodontal variables affecting nifedipine sequestration in gingival crevicular fluid.

We previously demonstrated the sequestration of nifedipine in gingival crevicular fluid (GCF), especially in patients exhibiting significant gingival overgrowth. The aim of the present study is to determine the role of site specific periodontal factors in this phenomenon. 10 adult patients exhibiting nifedipine induced gingival overgrowth were studied. In each patient GCF was harvested from two sites that demonstrated inflammation and increased probing depth as well as from two clinically healthy sites. The concentration of nifedipine was determined using gas chromatography. Drug concentrations were significantly increased in the presence of inflammation (p = 0.004) and plaque (p = 0.029) whilst increased probing depths and gingival overgrowth were not significantly related to drug sequestration. We can conclude that inflammatory changes in gingival tissues appear to be a significant determinant for the sequestration of nifedipine in the GCF.

Adult↗

Iatrogenic gingival overgrowth in cardiac transplantation.

It is well established that both cyclosporin and nifedipine are associated with gingival overgrowth. Although both drugs are widely used in the management of organ transplant patients, there is little information on the prevalence and severity of this unwanted effect in cardiac transplant patients. This study evaluated the gingival health of 94 dentate cardiac transplant patients, all of whom were medicated with cyclosporin as a component of their immunosuppressive therapy. Sixty-three (63) of the patients were also medicated with nifedipine. Significantly higher gingival overgrowth scores (P < 0.0001) and periodontal probing depths (P = 0.001) were observed in patients medicated with the combination of cyclosporin and nifedipine than those medicated with cyclosporin alone. Likewise, there was a significantly greater need to carry out gingival surgery on patients taking the combination (62%), than those medicated with cyclosporin alone (25.8%) (P = 0.001). Patient's age, sex, duration of therapy, gingival bleeding index, and nifedipine therapy were important determinants for both the expression of gingival overgrowth and the need for surgery. Significant sequestration of nifedipine in the gingival crevicular fluid (GCF) was observed. The concentration of nifedipine in GCF did not relate to either the gingival changes or plasma concentration of the drug. Cardiac transplant patients are at risk of developing gingival overgrowth and approximately 50% require surgical intervention. This risk increases significantly when patients are medicated concomitantly with nifedipine.

Adolescent↗

Amlodipine-induced gingival overgrowth.

Amlodipine is a calcium channel blocker used in the management of angina and hypertension. We report 3 cases of gingival overgrowth in adult dentate patients associated with chronic usage of this drug. Gingival changes occurred within 3 months of dosage and appeared to be compounded by the patient's existing periodontal condition. In all 3 patients, there was sequestration of amlodipine in their crevicular fluid. The significance of this finding in relation to the pathogenesis of this unwanted effect remains to be elucidated.

Adult↗

Oral and dental problems in the organ transplant patient.

The number of people receiving organ transplants has dramatically increased over the last decade. It is now likely that a dental surgeon will come across patients who have undergone transplantation. This paper considers the particular problems that these patients are likely to present their general dental practitioners.

Anti-Bacterial Agents↗

Determination of nifedipine in gingival crevicular fluid: a capillary gas chromatographic method for nifedipine in microlitre volumes of biological fluid.

This paper describes a sensitive capillary gas chromatographic (GC) method for the determination of nifedipine in sub-microliter samples of gingival crevicular fluid (GCF) in order to assess if nifedipine is present in the GCF and if so, whether the local tissue concentrations of this drug are an important determinant in the development of gingival overgrowth. Liquid-liquid and solid-phase extraction were combined to give adequate sample clean-up and concentration for measurement by automated capillary GC with electron capture detection. Nifedipine and its principal metabolite, M-I, were analysed in both plasma and GCF in 9 adult male patients who had been taking nifedipine for over six months. M-I could not be measured in GCF. Plasma nifedipine and M-I levels were normal, but the nifedipine levels found in the GCF of 7 patients (including all those with overgrowth) were remarkably elevated, 15 to 316-fold greater. This massive concentration of nifedipine into the GCF is therefore linked with gingival overgrowth. This is the first time that a GC method has been developed which permits determination of GCF pharmacokinetics of a drug which causes gingival overgrowth, and further investigation will lead to a better understanding of the tissue mechanisms involved.

Adult↗

Disposition of nifedipine in plasma and gingival crevicular fluid in relation to drug-induced gingival overgrowth.

The present study investigates the relationship between the pharmacokinetic variables of nifedipine with the incidence and severity of gingival overgrowth in 9 adult male patients medicated with the drug for at least 6 months. Five of the patients had experienced significant gingival changes and were thus designated "responders". The remaining four patients exhibited no gingival overgrowth, and thus acted as a control. A baseline periodontal examination (plaque scores, bleeding index and gingival overgrowth assessment) was carried out on each patient, and confined to the upper and lower anterior teeth. Serial blood and gingival crevicular fluid samples were collected over an eight-hour investigation period. Samples were analyzed for nifedipine by gas chromatography. No significant difference (p > 0.05) was seen between responders and non-responders with regard to drug therapy, periodontal parameters or plasma pharmacokinetics of nifedipine. Nifedipine was detected in the gingival crevicular fluid of seven subjects (all responders, and two non-responders). The peak concentration of nifedipine in crevicular fluid was 15-90 fold greater than levels observed in plasma.

Adult↗

Drug-induced gingival overgrowth and its management.

Gingival overgrowth is associated with the chronic usage of phenytoin, cyclosporin and the dihydropyridines. The pathogenesis of this unwanted effect is uncertain but appears to be enhanced by plaque-induced gingival inflammation. Certain patients appear to be more susceptible to gingival overgrowth and this may be related to gingival fibroblast phenotypes. In most cases, treatment involves surgical excision, followed by a concentrated oral hygiene programme. Recurrence of gingival overgrowth is a persistent problem particularly in the 'responder' patients. If an alternative, suitable medication is available, it may be worth while considering such a change through consultation with the patient's physician. Since patients are retaining their teeth into old age, the prevalence of this unwanted effect is likely to increase.

Calcium Channel Blockers↗

Gingival sequestration of nifedipine in nifedipine-induced gingival overgrowth.

The mechanism of gingival overgrowth associated with long-term use of nifedipine and of other drugs that affect calcium homoeostasis, such as cyclosporin and phenytoin, is unknown. With an ultrasensitive assay, we measured the pharmacokinetics of nifedipine in plasma and gingival crevicular fluid (GCF) of nine patients receiving this drug for angina and hypertension. In seven patients, the maximum nifedipine concentration was in the range 15-316 (mean 84 [SD 105]) times greater in GCF than in plasma. The two patients with low (undetectable) GCF nifedipine did not have overgrowth. We propose that gingival tissues sequester nifedipine and that the very high nifedipine concentrations predispose the tissues to overgrowth.

Gingiva↗

Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E.

Proteolytic degradation (processing) of antigen by antigen-presenting cells is a major regulatory step in the activation of a T lymphocyte immune response. However, the enzymes responsible for antigen processing remain largely undefined. In this study we show that cathepsin E, and not the ubiquitous lysosomal cathepsin D, is the major aspartic proteinase in a murine antigen-presenting cell line, A20. This enzyme is localized to a non-lysosomal compartment of the endosomal system in these cells. Functional studies using a highly specific inhibitor of cathepsin E show that this enzyme is essential for the processing of ovalbumin by this cell line. Thus, cathepsin E, whose function was hitherto unknown, may play a major role in antigen processing.

Animals↗