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Biomedical subjects

R Adamson

Publications and source records attributed to R Adamson.

At least 19 recordsLinked to original sources
PubMed2003

Assessment of secondary haemorrhage rates following adult tonsillectomy--a telephone survey and literature review.

Many previous studies have considered patient re-admission rates alone as the true rate of secondary haemorrhage following adult tonsillectomy. We aimed to determine the true rate of secondary haemorrhage following tonsillectomy in adults by performing a telephone interview with 60 consecutive patients. Whilst 40% (n = 24) of our patients reported a significant episode of bleeding (blood actively flowing from their mouth for more than 1 min) following discharge, only 8% (n = 5) were re-admitted and only 3% (n = 2) required return to theatre. Review of the current literature suggests that return-to-theatre rates are more consistent than hospital re-admission rates in large studies. We would suggest that although secondary haemorrhage can occasionally be very serious, the majority is minor, and it would therefore be more useful when comparing different techniques for tonsillectomy to consider numbers of patients returning to theatre rather than re-admission rates.

Adolescent↗
PubMed2002

Prime-boost: the way forward for recombinant vaccines against apicomplexan parasites. A Theileria perspective.

A good CD8+ response is required for immunity to many intracellular pathogens. Traditional antigen delivery using isolated sub-units or killed pathogens and adjuvant stimulates strong antibody responses but weak T-cell reactivity. Attenuated vaccines are usually more effective. The prime-boost delivery system based on immunisation with a naked DNA antigen-gene construct followed by boosting with an attenuated vaccinia virus expressing the same antigen is proving to be a powerful way to stimulate antigen-specific CD8 responses. Success using single epitopes is possible in malaria and we believe this approach holds much promise for other apicomplexan parasites such as Theileria spp.

Animals↗
PubMed2001

Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors.

BACKGROUND: Calcineurin inhibitors (CNI) and azole antifungal agents have been reported to interact in a disparate manner. The azole dose and route and the level of involvement of the liver and intestines have been implicated, although data are limited. A significant interaction may result in CNI toxicity, and withdrawal of the azole may result in subtherapeutic CNI concentrations. Fluconazole, available in both intravenous and oral formulations, is commonly used in transplant recipients and is ideal for determining the presence of a disparate effect on CNI concentrations. We retrospectively investigated the interaction of CNIs with fluconazole, evaluating CNI blood troughs corrected for daily CNI dose, the factors influencing the interaction, and the effect on clinical outcomes in renal and simultaneous pancreas kidney transplant recipients. METHODS: Twenty-eight patients received a CNI and fluconazole during the calendar year 1999, but only 19 patients had documented CNI blood troughs and outpatient follow-up. There were 25 episodes of use in the 19 included patients. CNI blood troughs were evaluated for changes induced by fluconazole, given by both routes, and clinical outcomes were tracked. RESULTS: Data demonstrated both intravenous and oral fluconazole alter CNI blood concentrations. Two metabolic patterns were observed, and we termed these convergent and divergent. Divergent metabolizers did not have significant interaction (n=5), and convergent metabolizers did have a significant interaction (n=15). One patient had a divergent episode after a previous convergent episode. The main contributors to the lack of interaction appeared to be female sex and African American ethnicity. Additionally, tacrolimus levels were significantly more affected than cyclosporine, during and after fluconazole administration. No patient experienced nephrotoxicity or cellular rejection related to antifungal therapy. CONCLUSIONS: Oral and intravenous fluconazole appear to increase oral CNI trough concentrations to a similar extent even after adjusting for daily calcineurin dose. These interactions appear to be chiefly influenced by sex and ethnicity. Further prospective study is necessary to clarify this issue.

Adult↗
PubMed2001

Transient transfection of Theileria annulata.

We have developed a method to transiently transfect infective, uninucleate, Theileria annulata sporozoites. Transfection vectors have been constructed using a number of T. annulata 5' gene flanking sequences linked to the enhanced green fluorescence protein (eGFP) reporter gene. Sporozoites were transfected with these constructs using the lipid transfection agent SuperFect, then allowed to infect purified bovine mononuclear cells (PBMs). Green fluorescence was observed in developing trophozoites, 36-40 h post infection, using constructs containing the upstream regions of the T. annulata Hsp70, T. annulata merozite surface antigen 1 (TamS1) and T. annulata macroschizont-specific AT hook-containing protein2 (TashAT2) genes. A construct with the 5' TamS1 upstream sequence in reverse orientation gave no detectable fluorescence indicating fluorescence was derived by expression from the T. annulata promoter. A cytomegalovirus (CMV) promoter construct showed no activity in this stage of the parasite. However, when this construct was introduced directly into schizont-infected cells by electroporation, fluorescence was observed in the bovine cells but not the schizont. We describe the significance of these results in relation to novel control strategies and the fundamental biology of Theileria parasites.

5' Untranslated Regions↗
PubMed2000

Loss of matrix metalloproteinase 9 activity in Theileria annulata-attenuated cells is at the transcriptional level and is associated with differentially expressed AP-1 species.

The schizont stage of the protozoan parasite Theileria annulata reversibly transforms bovine monocytes into an immortalised and metastatic state. We have been studying T. annulata induction of host matrix metalloproteinases (MMP) which are involved in parasite dissemination and pathogenesis. We have observed that prolonged in vitro culture of T. annulata-infected cell lines results in their attenuation and this process is associated with alterations in both host and parasite gene expression. In particular, a loss in bovine MMP expression in later passage cultures suggests that these parasite-induced MMPs are virulence factors. As a means to further our understanding of the attenuation process we examine in detail the parasite-induced differential expression of one particular bovine proteinase, MMP9, in non-attenuated (p58) and attenuated (p158) passage levels of the Ode vaccine line. We show here that MMP9 expression is regulated at the transcriptional level and we suggest that a particular parasite-induced AP-1 recognition transcription factor present in the Ode non-attenuated line may have a role to play in the expression of this host gene.

Animals↗
PubMed2000

Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. UK Receptor Group, UK NEQAS, The Scottish Breast Cancer Pathology Group, and The Receptor and Biomarker Study Group of the EORTC.

The biochemical assay for the oestrogen receptor has shown the clinical value of knowing the concentration of the receptor within tissue. The immunohistochemical assay is rapidly taking over from the biochemical assay. Therefore, it is vital to have an equivalent scoring system that will have the same predictive value. This paper reports both a practical protocol and a scoring system that should achieve this aim. This approach should be applicable to many more biomarkers detected by immunohistochemistry.

Biomarkers, Tumor↗
PubMed1999

Comparison of functional capacity in patients with end-stage heart failure following implantation of a left ventricular assist device versus heart transplantation: results of the experience with left ventricular assist device with exercise trial.

BACKGROUND: Use of a permanent left ventricular assist device (LVAD) has been proposed as an alternate treatment of patients with end-stage heart failure. The purpose of this study was to compare the functional capacity of patients following implantation of a LVAD vs heart transplant (HTx). METHODS: Eighteen patients from 6 centers who received an intracorporeal LVAD as a bridge to HTx underwent treadmill testing 1 to 3 months post-LVAD and again post-HTx. Baseline and peak measurements, including oxygen consumption, blood pressures, and respiratory rate were made during each treadmill test. RESULTS: Peak oxygen consumption was 14.5+/-3.9 ml/kg/minute post-LVAD and 17.5+/-5.0 ml/kg/minute post-HTx (p < .005). The percentage of the predicted peak oxygen consumption based on gender, weight, and age was 39.5%+/-5.5% post-LVAD and 47.7%+/-10.9% post-HTx (p < .005). Exercise duration was lower post-LVAD than post-HTx (10.3+/-4.2 minute vs 12.5+/-5.4 minute, p < .05). After LVAD implantation, peak total oxygen consumption correlated with peak LVAD rate and output. Eight patients reached an LVAD rate of 120 beats per minute (bpm) before the conclusion of exercise, the maximum rate for the outpatient electric device. The peak respiratory exchange ratio post-LVAD was 1.15+/-0.22 and post-HTx was 1.15+/-0.18, consistent with a good effort in both groups. CONCLUSIONS: Patients demonstrated a lower functional capacity post-LVAD than post-HTx. For some patients functional capacity post-LVAD may be improved by a higher maximum LVAD rate and output.

Adult↗
PubMed1999

Mechanism(s) of attenuation of Theileria annulata vaccine cell lines.

Attenuated vaccines are an important means of controlling Theileria annulata infection of cattle. Production is by prolonged cultivation of macroschizont-infected cells. The mechanism of attenuation remains unclear. There are three general nonmutually exclusive possibilities: Selection of avirulent subpopulations, genome rearrangements and alterations in gene expression. Several groups, including ours, have provided evidence that the population structure usually tends to simplify during attenuation. Our data on the T. annulata (Ta) Ankara cell line show that attenuation is not necessarily accompanied by the population becoming clonal. We have been unable to detect large DNA rearrangements. Evidence for alterations in host and parasite gene expression during attenuation is available. With respect to the host we have shown that attenuation is accompanied by loss of expression of parasite induced matrix metalloproteinases (MMPs). However, in different lines different protease activities are involved. In the T. annulata Ode line we have shown that 8 activities (including MMP9) are downregulated and that this correlates with a loss of metastatic behaviour. This has previously been shown in vitro using reconstituted basement membrane (Matrigel) and is demonstrated in vivo using scid mice in this study. Thus part of the pathology, namely the ability to disseminate, mediated by host MMPs, is lost upon attenuation. Re-isolation experiments have shown that the reduction/loss of MMP is a stable transferable trait. A logical extension is that loss of MMP activity (and virulence in general) must be at the most fundamental level a genetic trait of the parasite. Evidence for loss of parasite gene expression is implied by the loss of the ability to differentiate into merozoites on attenuation. Specific evidence for loss of parasite gene expression has been obtained using differential RNA display. We view virulence as a multifactorial phenomenon involving interacting subpopulations of cells and attenuation is a threshold effect whereby the number of virulence factors is reduced below a critical level. On this basis there will be many different ways to achieve attenuation.

Animals↗
PubMed1998

Upregulation of Jun and Fos family members and permanent JNK activity lead to constitutive AP-1 activation in Theileria-transformed leukocytes.

Theileria parasitises bovine leukocytes and transforms them into proliferating, metastatic tumours, where the infection resembles a leukaemia-like disease. We have studied the signal transduction pathways leading to activation of the transcription factor AP-1 in different transformed leukocytes. Parasite infection leads to an up-regulation of all members of the Jun/Fos family of proteins and surprisingly, this occurs in the absence of any detectable ERK, or p38 MAP kinase activity. In the parasitised B-sarcoma TBL3, AP-1 induction occurs in the absence of any JNK activity. In contrast, in infected macrophage and B-cell lines, AP-1 transcriptional activity is strictly associated with the parasite-induced constitutive activation of JNK and subsequent c-Jun N-terminal phosphorylation. Thus, constant AP-1 transcriptional activity involves both an upregulation in the levels of Jun and Fos proteins and constitutive JNK activation.

Animals↗
PubMed1997

Effects of exercise during long-term support with a left ventricular assist device. Results of the experience with left ventricular assist device with exercise (EVADE) pilot trial.

BACKGROUND: Long-term implantation of a left ventricular assist device (LVAD) may be a future alternative treatment for end-stage heart failure. The objective of the present study was to determine the hemodynamic effects of supine bicycle exercise and functional capacity during upright treadmill exercise in 10 patients after LVAD implantation placed for refractory heart failure as a bridge to cardiac transplantation. METHODS AND RESULTS: With supine bicycle exercise, 46 +/- 25 days after device placement, heart and LVAD rates increased in parallel from 87 +/- 12 to 117 +/- 14 bpm and 82 +/- 18 to 107 +/- 21 bpm, respectively. Peak O2 consumption was 8.2 +/- 1.7 mL O2.kg-1.min-1. Fick Systemic blood flow rose from 5.0 +/- 1.2 to 7.8 +/- 2.5 L/min. Right atrial and pulmonary capillary wedge pressures increased from 6 +/- 4 and 5 +/- 3 mm Hg to 12 +/- 5 and 13 +/- 8 mm Hg, respectively. End-diastolic left ventricular dimension increased from 3.9 +/- 1.3 to 4.8 +/- 1.6 cm; however, right ventricular dimension decreased from 3.2 +/- 1.0 to 2.3 +/- 0.9 cm. With upright treadmill exercise, peak O2 consumption was 14.1 +/- 2.9 mL O2.kg-1.min-1. CONCLUSIONS: This study indicates that exercise during long-term LVAD support is safe and is not limited by right heart decompensation. It also justifies a larger study to examine how exercise after LVAD implantation compares with that after cardiac transplantation.

Adult↗
PubMed1997

A role for matrix metalloproteinases in the pathology and attenuation of Theileria annulata infections.

Upon infection with Theileria annulata, bovine leukocytes are induced to express eight novel metalloproteinase activities. In this article, Rachel Adamson and Roger Hall suggest that these enzymes are virulence factors and their presence may explain some of the features of the pathology of the disease. Specifically, they discuss the possibility that the metastatic properties of infected cells, the 'cigarette burn' ulcers and the cachexia characteristic of tropical theileriosis are associated with metalloproteinase expression. Furthermore, they propose that loss of metalloproteinase activity during the generation of a vaccine line could explain the attenuated phenotype.

Journal Article↗
PubMed1996

Breast MRI: early experience with a 3-D fat-suppressed gradient echo sequence in the evaluation of breast lesions.

The early clinical experience with a 3-Dimensional Fourier Transform Gradient Echo sequence with fat suppression in the evaluation of breast masses is reported. Ten female patients with breast malignancies were pre-operatively evaluated with this sequence and the results compared with the pathological specimens. The scanning protocol included a non-contrast sequence followed by an immediate post-contrast sequence (completed 4.5 min after intravenous contrast injection) and a delayed sequence. Images were assessed for maximum lesion and parenchymal enhancement, lesion size and additional enhancing abnormalities. In six patients, malignant masses enhanced maximally on the immediate post-contrast sequence with parenchyma enhancing maximally on delayed images. In three cases, there was preferential enhancement of malignant lesions over normal parenchyma but to a similar degree on both post-contrast sequences. In one case, both the lesion and parenchyma enhanced maximally on the delayed sequence. Magnetic resonance assessed lesion size accurately and also detected satellite malignancies in one case. However, lesion grade, associated in situ carcinoma and lymphovascular invasion did not impact on lesion enhancement. In this small series, a contrast-enhanced, fat-suppressed 3-D Gradient Echo Sequence detected breast carcinoma with high sensitivity. The technique holds promise but further evaluation is required.

Breast↗
PubMed1995

Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour-suppressor genes. We have undertaken an extensive allelotype of 80 specimens of squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic microsatellite markers on 39 chromosome arms. Allelic imbalances were found most frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were found in more than 20% of SCCHN. These LOH data were analysed against a range of clinicopathological parameters which included previously untreated and previously treated tumours; correlations were found between LOH on 9q and nodes at pathology (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q (P = 0.01). In the group of previously untreated tumours, a correlation was found between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80). Correlations were found between FAL > median value and nodes at pathology (P = 0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph node metastasis often had LOH at multiple sites. FAL > median value was found to correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value correlated with poor survival in the previously untreated patients (P < 0.019). These results indicate that assessment of the accumulation of genetic damage, as provided by allelotype data, provides a useful molecular indicator of the tumour behaviour and clinical outcome.

Alleles↗
PubMed1994

Cutaneous leishmaniasis in Tachira State, Venezuela.

Cutaneous and mucocutaneous leishmaniases are widely spread in the mountainous Andean regions of South America. In Venezuela, these regions consist of the coffee-growing states of Trujillo, Merida and Tachira. Entomological and parasitological investigations in three geographically different climatic zones (Lomas Bajas, Delicias and La Grita) in Tachira state have shown a predominance of the sandfly species Lutzomyia spinicrassa (verrucarum group) and two Leishmania species, Leishmania mexicana and Leishmania braziliensis. Two transmission cycles appear to occur: a peridomestic cycle in Lomas Bajas and a sylvatic one in Delicias and La Grita.

Adolescent↗