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Biomedical subjects

J Gill

Publications and source records attributed to J Gill.

At least 55 records · Page 3Linked to original sources
PubMed1999

Highly active anti-retroviral therapy (HAART) prolongs time to treatment failure in Kaposi's sarcoma.

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on Kaposi's sarcoma. DESIGN: Retrospective study of patients who had received systemic or local treatment for AIDS-related Kaposi's sarcoma who subsequently commenced HAART. METHODS: Case note review to determine time to treatment failure for Kaposi's sarcoma before and after starting HAART. Time to treatment failure was calculated from the end of last therapy to the start of the next new treatment for Kaposi's sarcoma. RESULTS: The cohort contained 78 patients. Only 38% had good risk Kaposi's sarcoma (stage T0I0) at presentation. The median time to treatment failure before starting HAART was 0.5 years. Initial HAART therapy was three or more drugs including a protease inhibitor for 38 (49%), three or more drugs without a protease inhibitor for 27 (35%) and a two-drug protease combination for 13 (16%). The median follow-up after starting HAART was 12 months (range, 0.5-52 months) and anti-Kaposi's sarcoma treatment has been required for 24 (31%) patients. The median time to treatment failure for Kaposi's sarcoma from the start of HAART is 1.7 years. This is statistically longer than the time to treatment failure for the same cohort of patients before they started HAART (log rank chi2 = 16.5, P < 0.0001). The serum HIV RNA viral load (VL) at the time of Kaposi's sarcoma progression revealed virological failure of HAART (defined as VL > 5000 copies/ml) in 14 of 24 (58%) and good control (VL < 200 copies/ml) in five of 24 (21%). CONCLUSION: HAART is associated with prolonged time to treatment failure in Kaposi's sarcoma. Progression of Kaposi's sarcoma while on HAART is not necessarily associated with virological failure as determined by rising viral RNA titre.

Adult↗
PubMed1999

The type II and X cellulose-binding domains of Pseudomonas xylanase A potentiate catalytic activity against complex substrates by a common mechanism.

Xylanase A (Pf Xyn10A), in common with several other Pseudomonas fluorescens subsp. cellulosa polysaccharidases, consists of a Type II cellulose-binding domain (CBD), a catalytic domain (Pf Xyn10A(CD)) and an internal domain that exhibits homology to Type X CBDs. The Type X CBD of Pf Xyn10A, expressed as a discrete entity (CBD(X)) or fused to the catalytic domain (Pf Xyn10A'), bound to amorphous and bacterial microcrystalline cellulose with a K(a) of 2.5 x 10(5) M(-1). CBD(X) exhibited no affinity for soluble forms of cellulose or cello-oligosaccharides, suggesting that the domain interacts with multiple cellulose chains in the insoluble forms of the polysaccharide. Pf Xyn10A' was 2-3 times more active against cellulose-hemicellulose complexes than Pf Xyn10A(CD); however, Pf Xyn10A' and Pf Xyn10A(CD) exhibited the same activity against soluble substrates. CBD(X) did not disrupt the structure of plant-cell-wall material or bacterial microcrystalline cellulose, and did not potentiate Pf Xyn10A(CD) when not covalently linked to the enzyme. There was no substantial difference in the affinity of full-length Pf Xyn10A and the enzyme's Type II CBD for cellulose. The activity of Pf Xyn10A against cellulose-hemicellulose complexes was similar to that of Pf Xyn10A', and a derivative of Pf Xyn10A in which the Type II CBD is linked to the Pf Xyn10A(CD) via a serine-rich linker sequence [Bolam, Cireula, McQueen-Mason, Simpson, Williamson, Rixon, Boraston, Hazlewood and Gilbert (1998) Biochem J. 331, 775-781]. These data indicate that CBD(X) is functional in Pf Xyn10A and that no synergy, either in ligand binding or in the potentiation of catalysis, is evident between the Type II and X CBDs of the xylanase.

Base Sequence↗
PubMed1999

The extended transbasal approach: a quantitative anatomical and histological study.

Since its introduction in 1972 the transbasal approach to the anterior fossa and sphenoethmoidal region has undergone a number of modifications. The extended transbasal approach with preservation of olfaction not only improves exposure of the anterior fossa, but also provides access to the clivus as far inferiorly as the foramen magnum. An anatomical study has been undertaken to photographically demonstrate and quantify the varying degrees of exposure that this technique provides. The pituitary stalk was used as an intracranial target. The amount of exposure was compared using a standard subfrontal approach, a transbasal approach and an extended transbasal with preservation of olfaction. In addition, a histological study was carried out to investigate the level to which identifiable olfactory nerves extended into the nasal mucosa. The anatomical study demonstrates the area of the "external window of exposure" can be doubled using a transbasal approach and more than quadrupled using the extended transbasal approach, when gaining access to the pituitary stalk. In addition, the study highlights the exposure of other anatomical areas, such as the medial orbit, the cavernous sinus, the clivus and the vertebrobasilar complex. The histological study establishes that the olfactory nerves extend only 10 mms below the cribriform plate.

Brain↗
PubMed1999

The extended transbasal approach: clinical applications and complications.

OBJECTIVES: To describe in detail key technical aspects of the extended transbasal approach which involves en-bloc mobilisation of the supraorbital rim, the orbital roof and the nasoethmoidal complex. In some patients osteotomies were performed around the cribriform plate with a view to maintaining olfaction. To review 18 patients with deep seated lesions located in the central skull base region (including 6 recurrences) to highlight patient selection, presentation, surgical morbidity and outcome. METHODS: Prospective data recording and clinical chart review. RESULTS: Outcome was assessed at a minimum of 1 year after operation using the Glasgow Outcome Score. Thirteen patients had made a good recovery, 1 was moderately disabled, 2 were severely disabled (both had been severely disabled before operation), and 2 died. By contrast, quality of life assessment indicated that only 7 of the surviving 14 adults had returned to normal levels of activity and perceived health; although 6 of the other 7 patients had resumed their former occupations, their follow up assessments showed a reduced quality of life. Of the 13 patients who had an olfaction preservation procedure, 6 showed appreciation of smell on formal testing. CONCLUSIONS: In patients with progressive and extensive deep seated lesions this technique provides wide exposure in a shallow surgical field. Complication rates although acceptable were significantly higher in patients with intradural lesions. In some selected patients it was possible to preserve olfaction. Specific surgical outcome assessments pointed to satisfactory results, but failed to reflect the degree of patient disability. There is a need for outcome measures that take into account the patient's expectations and which address his quality of life in order to validate the benefits of these procedures.

Adolescent↗
PubMed1999

Pharmacology of anthelmintic resistance.

Anthelmintic resistance has grown from a curiosity to an important economic problem in several animal industries and is now set to threaten the control of human parasites. The pharmacology of anthelmintics and anthelmintic resistance has been studied most extensively in the nematode parasites of sheep. Here, Nick Sangster and Jenny Gill discuss this veterinary experience, summarizing the progress made in understanding anthelmintic resistance and highlighting the tools available for research.

Animals↗
PubMed1999

Functionally distinct T-cell epitopes within the hepatitis C virus non-structural 3 protein.

Clearance of Hepatitis C Virus (HCV) infection is an uncommon phenomenon. To understand the mechanism of viral persistence despite active cellular and humoral responses, we examined the in vitro cytokine response of PBMC from an HCV sero-positive, asymptomatic individual to recombinant intact antigen and sixty-nine overlapping peptides of the HCV non-structural (NS) 3 protein. Whereas, intact antigen induced strong proliferation and significant levels of gammaIFN and IL-10, little or no IL-2 was produced. Only 7% of peptides induced IL-2, which also coincided with their ability to stimulate proliferation. In contrast, 38% of the peptides induced gammaIFN while 35% induced IL-10. All IL-2 stimulating peptides also induced significant levels of gammaIFN and among these, a peptide corresponding to residues 358-375 was the strongest. In addition, 16% of the peptides induced both gammaIFN and IL-10. Exogenous recombinant IL-10 inhibited proliferation and IL-2 induction in response to peptide 358-375. Furthermore, neutralization of IL-10 with an anti-IL-10 antibody resulted in enhanced IL-2 production in response to recombinant NS3 protein. We suggest that IL-10 inducing epitopes within HCV NS3 may thus down-regulate IL-2 dependent T-cell responses.

Cell Division↗
PubMed1999

In vitro human Th-cell responses to a recombinant hepatitis C virus antigen: failure in IL-2 production despite proliferation.

Hepatitis C Virus (HCV) causes chronic infection in 80-90% of those exposed and persists despite evidence of immune recognition. To understand the immunological basis of this phenomenon, we have synthesized a non structural (NS) protein that is critical to HCV infection and replication, NS3, and used it to study in vitro helper T-cell responses from infected individuals. Strong proliferative responses were generated by peripheral T-cells isolated from a subset of chronically infected patients, but not by normal, non-infected controls. Interestingly, though gamma-interferon (gammaIfn) and IL-10 were both secreted in response to stimulation by NS3 antigen, IL-2 was not. In contrast, IL-2 was secreted in response to influenza virus vaccine antigen. Lack of IL-2 induction was confirmed by a failure to amplify IL-2 mRNA upon NS3 antigen stimulation, whereas IL-4, IL-15, and gammaIfn mRNA were seen as early as 24 h. The predominance of IL-4 and IL-10 and the lack of IL-2 suggests that in vitro responses to at least some HCV antigens are biased towards a Th2 phenotype, which may be conducive to viral persistence.

Hepatitis C↗
PubMed1999

Alterations in atrial electrophysiology associated with chronic atrial fibrillation in man.

BACKGROUND: The purpose of this study was to determine the changes in atrial electrophysiology associated with chronic persistent atrial fibrillation in man. METHODS AND RESULTS: Atrial monophasic action potential duration at 90% repolarization and the effective refractory period were measured in 13 patients with chronic persistent atrial fibrillation after low-energy endocardial cardioversion, and compared to eight controls without a history of atrial fibrillation. Measurements were made at the right atrial appendage and midlateral right atrial wall at basic, 600 ms and 400 ms drive cycle lengths. In control patients, the effective refractory periods were significantly longer at the atrial appendage than the lateral wall at 600 ms (right atrial appendage 265 ms, midlateral right atrial wall 228 ms, P<0.05), and 400 ms cycle lengths (right atrial appendage 270 ms, midlateral right atrial wall 218 ms, P<0.05), but this was not evident in patients with atrial fibrillation. The monophasic action potentials and effective refractory periods at both atrial sites were shorter in the atrial fibrillation patients compared to controls; however, only the effective refractory periods at atrial appendage at 600 ms (atrial fibrillation 210 ms, controls 265 ms, P<0.001), and 400 ms cycle lengths (atrial fibrillation 200 ms, controls 270 ms, P>0.001) reached statistical significance. Effective refractory period dispersion was significantly greater in controls than in patients with atrial fibrillation (cycle length 600 ms: controls 36, atrial fibrillation 13, P=0.01; cycle length 400 ms: controls 54, atrial fibrillation 18, P<0.01). CONCLUSIONS: In patients without a history of atrial fibrillation, the refractory period at the right atrial appendage is significantly longer than at the midlateral right atrial wall. This 'normal' pattern of atrial refractory dispersion is lost in patients with chronic persistent atrial fibrillation, with marked shortening of the effective refractory period at the right atrial appendage. This may explain the high risk of recurrence of atrial fibrillation following successful electrical cardioversion.

Action Potentials↗
PubMed1999

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Administration, Inhalation↗
PubMed1999

Identification of human herpesvirus 8-specific cytotoxic T-cell responses.

Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma-associated herpesvirus) is implicated in the etiopathogenesis of Kaposi's sarcoma (KS) and certain lymphoproliferations. The introduction of more effective therapies to treat human immunodeficiency virus infection has led to a decline in the incidence of KS and also in the resolution of KS in those already affected. This suggests that cellular immune responses including cytotoxic T lymphocytes (CTLs) could play a vital role in the control of HHV-8 infection and in KS pathogenesis. Here we elucidate HLA class I-restricted, HHV-8-specific cellular immune responses that could be important in the control of HHV-8 infection and subsequent tumor development. We show the presence of CTLs against HHV-8 latent (K12), lytic (K8.1), and highly variable (K1) proteins in infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1999

Cost-effectiveness analysis of a home-based social work intervention for children and adolescents who have deliberately poisoned themselves. Results of a randomised controlled trial.

BACKGROUND: Little evidence exists regarding the effectiveness or cost-effectiveness of alternative treatment services in the field of child and adolescent psychiatry. AIMS: To assess the cost-effectiveness of a home-based social work intervention for young people who have deliberately poisoned themselves. METHOD: Children aged < or = 16 years, referred to child mental health teams with a diagnosis of deliberate self-poisoning were randomly allocated to either routine care (n = 77) or routine care plus the social work intervention (n = 85). Clinical and resource-use data were assessed over six months from the date of trial entry. RESULTS: No significant differences were found between the two groups in terms of the main outcome measures or costs. In a sub-group of children without major depression, suicidal ideation was significantly lower in the intervention group at the six-month follow-up (P = 0.01), with no significant differences in cost. CONCLUSIONS: A family-based social work intervention for children and adolescents who have deliberately poisoned themselves is as cost-effective as routine care alone.

Adolescent↗
PubMed1999

Hepatotoxicity possibly caused by amphotericin B.

OBJECTIVE: To report a case of possible amphotericin B-induced hepatotoxicity in a patient with pulmonary blastomycosis. SUMMARY: A 26-year-old white man with life-threatening pulmonary blastomycosis developed elevation of his liver enzymes after the addition of amphotericin B to his initial itraconazole therapy. The hepatotoxicity resolved rapidly with discontinuation of the amphotericin B, and the blastomycosis was successfully treated with itraconazole alone. DISCUSSION: This case illustrates an unusual occurrence of hepatotoxicity associated with a short course of amphotericin B. Liver biopsy was compatible with drug-induced changes and showed no evidence of blastomycosis. Discontinuation of amphotericin B with no other therapeutic changes resulted in a rapid resolution of hepatotoxicity. A possible adverse drug interaction with itraconazole and amphotericin B is postulated based on the mechanism of action of each drug. CONCLUSIONS: Amphotericin B therapy can be associated with many adverse effects, but reports of hepatotoxicity are rare. Closer monitoring of liver enzymes in patients receiving amphotericin B, especially in combination with potentially hepatotoxic agents, including azole antifungal drugs, would be prudent.

Adult↗
PubMed1998

Unguarded tricuspid orifice with pulmonary atresia: successful radiofrequency ablation of an accessory pathway in an infant.

A male infant with the rare lesion of unguarded tricuspid orifice in the setting of pulmonary valve atresia, intact ventricular septum, and a hypoplastic right ventricle is described. The patient presented with cyanosis at 1 day old; transcutaneous oxygen saturations were between 20% and 30% in room air, and 60% in 100% inspired oxygen. Pre-excitation was found incidentally on the ECG and the potential for rapid antegrade conduction of atrial tachyarrhythmias, after eventual extended palliation with the Fontan procedure, was demonstrated at electrophysiological study. By 11 months old the patient was becoming increasingly cyanosed and interim palliation with a bidirectional cavopulmonary shunt was proposed. Successful radiofrequency ablation of the accessory pathway was performed before bidirectional cavopulmonary shunt, which would have prevented access to the heart via the superior vena cava. Difficulty with femoral venous access because of previous occlusion of a femoral vein was overcome by the use of 2 F pacing electrodes and a 5 F ablation catheter.

Catheter Ablation↗
PubMed1998

Detection of thyroglobulin, thyroid peroxidase, and RET/PTC1 mRNA transcripts in the peripheral blood of patients with thyroid disease.

PURPOSE: Detection of mRNA transcripts for thyroglobulin (TG), thyroid peroxidase (TPO) and RET/PTC1 in the peripheral blood of patients with thyroid disease. PATIENTS AND METHODS: TG, TPO, and RET/PTC1 mRNA were analyzed in 52 peripheral-blood samples from 44 patients diagnosed with thyroid carcinoma (24 patients), adenoma (five patients), and nodular hyperplasia (15 patients) by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: TG and TPO were identified in 13 patients (54.2%) with thyroid carcinoma, which includes five of eight patients with no clinical evidence of disease at the time of blood collection. Four of 5 patients had cervical lymph node metastases and/or extrathyroid extension at the time of the initial surgery. RET/PTC1 mRNA was detected in the peripheral blood of only one patient with papillary thyroid carcinoma. This sample was also positive for TG and TPO. TG and TPO were detected in two patients (10%) with benign thyroid nodules. All positive samples from patients with benign thyroid lesions were collected before surgery, whereas all samples collected after surgery were negative. RET/PTC1 mRNA was not detected in any of the patients with benign thyroid nodules. RT-PCR positivity for TG and TPO mRNA was higher in patients with carcinoma than in patients with benign lesions (P = .002). CONCLUSION: TG, TPO, and RET/PTC1 mRNA are detectable in the peripheral blood of patients with thyroid disease, which correlates with a diagnosis of carcinoma.

Adolescent↗