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Biomedical subjects

M John

Publications and source records attributed to M John.

At least 37 records · Page 2Linked to original sources
PubMed2003

Endothelial function in HIV-infected patients receiving protease inhibitor therapy: does immune competence affect cardiovascular risk?

BACKGROUND: The use of HIV protease inhibitors (PIs) as a component of combination antiretroviral therapy in HIV-infected patients has been associated with dyslipidaemia, but its significance as a risk factor for cardiovascular disease is unclear. Endothelial dysfunction is an early phase of atherogenesis that may be assessed non-invasively with ultrasonography in vivo. AIM: To evaluate vascular function and investigate potential determinants of endothelial dysfunction of the peripheral circulation in PI-treated, HIV-infected men with dyslipidaemia. DESIGN: Observational, case-control study. METHODS: We studied 24 HIV-infected, PI-treated men with dyslipidaemia and 24 normolipidaemic, healthy male controls matched for age and body mass index. Brachial artery endothelial function was studied using high-resolution ultrasound and computerized edge-detection software. This non-invasive technique measured post-ischaemic flow-mediated dilatation (FMD), and the endothelium-independent vasodilatory response to glyceryl trinitrate (GTN). RESULTS: Within the HIV patient group, FMD was significantly associated with percentage of 'naïve' CD4 + 45RA + T cells (p = 0.03), while plasma lipid/lipoprotein and insulin levels, body mass, and smoking status did not correlate with endothelial function. FMD was not significantly different between the study group and the controls. CONCLUSIONS: The atherogenic potential of PI-associated dyslipidaemia may be attenuated in HIV-infected patients with decreased immune competence, reflecting a possible contribution of cell-mediated immune responses to the pathogenesis of atherosclerosis.

Adult↗
PubMed2002

Aetiology of suppurative corneal ulcers in Ghana and south India, and epidemiology of fungal keratitis.

BACKGROUND: A multicentre study was carried out in Ghana and southern India to determine the aetiology of suppurative keratitis in two regions located at similar tropical latitudes. Studies of fungal keratitis from the literature were reviewed. METHODS: Patients presenting at rural and urban eye units with suspected microbial keratitis were recruited to the study. Corneal ulceration was defined as loss of corneal epithelium with clinical evidence of infection with or without hypopyon. Microscopy and culture were performed on all corneal specimens obtained. RESULTS: 1090 patients were recruited with suspected microbial keratitis between June 1999 and May 2001. Overall the principal causative micro-organisms in both regions were filamentous fungi (42%): Fusarium species and Aspergillus species were the commonest fungal isolates. Pseudomonas species were most frequently isolated from cases of bacterial keratitis in Ghana but in India the commonest bacterial isolates were streptococci. CONCLUSION: Infections of the cornea due to filamentous fungi are a frequent cause of corneal damage in developing countries in the tropics and are difficult to treat. Microscopy is an essential tool in the diagnosis of these infections. A knowledge of the "local" aetiology within a region is of value in the management of suppurative keratitis in the event that microscopy cannot be performed.

Aspergillosis↗
PubMed2001

Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir.

BACKGROUND AND OBJECTIVES: To determine the factors contributing to changes in bone mineral density (BMD) over time in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Analyses of lumbar spine BMD in 183 male Caucasian participants in the Western Australian HIV Cohort study, comprising a longitudinal analysis of data from 54 patients on stable HAART regimens, and a cross-sectional analysis comparing data from 131 protease inhibitor (PI)-treated patients and 52 PI-naive (including 28 antiretroviral treatment-naive) patients. RESULTS: Average lumbar spine BMD remained stable or increased over the time frame considered. Although there was no evidence of a change of average BMD over time in patients receiving nelfinavir (P = 0.92), there was evidence of increasing bone density in the indinavir group (average increase, 0.31 z-score per year; P < 0.001). Lower initial z-scores in the longitudinal analysis were significantly associated with lower pre-HAART BMI (P = 0.003), consistent with results of the cross-sectional analysis in which lowest BMI prior to initial dual X-ray absorptiometry scan was associated with decreased BMD (P = 0.02, overall group). Although PI therapy was also associated with decreased BMD in a univariate analysis of the cross-sectional data (P = 0.04), this effect was abrogated in a multiple linear regression analysis (P = 0.11) with lowest BMI remaining significant (P = 0.04). CONCLUSIONS: We found no evidence, overall, of accelerated bone loss in patients treated with nelfinavir- or indinavir-containing HAART regimens, and propose that indinavir therapy may be associated with an increase in bone mineral density over time. Pre-HAART BMI was an independent and powerful determinant of an individual's initial z-score in the longitudinal analysis, and adjustment for this effect in a cross-sectional analysis abrogated the association between PI therapy and decreased lumbar spine z-score.

Body Mass Index↗
PubMed2001

Gene expression analysis of an H(2)O(2)-resistant lens epithelial cell line.

Gene expression patterns were examined in lens epithelial cells conditioned to grow in 125 microM hydrogen peroxide in order to define the protective mechanisms that may be involved in survival during oxidative stress. RNA was extracted from normal and hydrogen peroxide-resistant alphaTN4 mouse lens epithelial cells. Gene expression was evaluated using Differential Display (DD) and RT-PCR. Upregulation of mRNAs for antioxidant and cellular defense enzymes was observed. The highest elevation detected was a 14-fold increase in catalase in the hydrogen peroxide-resistant cells. Glutathione peroxidase, ferritin, and alphaB-crystallin were upregulated 2-fold, and reticulocalbin was upregulated 6-fold in the resistant cells. alphaA-crystallin was downregulated 5-fold, while aldose reductase and mitochondrial gene products were unchanged. Thus, in the alphaTN4 mouse lens cell line, long-term exposure to high levels of hydrogen peroxide elicited an upregulation of transcripts for enzymes involved in hydrogen peroxide degradation, metal binding, and chaperone function. Since mitochondrial gene transcription is sensitive to hydrogen peroxide, the presence of normal levels of mitochondrial transcripts, in this study, demonstrates the effectiveness of the antioxidant defense systems.

Animals↗
PubMed2001

Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy.

OBJECTIVE: To determine the prevalence, course and risk factors for hyperlactatemia in HIV-infected patients. DESIGN: A prospective, longitudinal study of venous lactate concentrations over an 18-month period in 349 participants of the Western Australian HIV Cohort Study. RESULTS: In 516 patient-years of observation, two patients experienced severe fulminant lactic acidosis (lactate > 5 mmol/l) and hepatic steatosis attributable to nucleoside analogue reverse transcriptase inhibitors (NRTI). A further five patients with lesser elevations of lactate (2.8-4.1 mmol/l) but with symptoms of nausea or abdominal discomfort and evidence of hepatic steatosis had NRTI therapy revised, with relief of symptoms and a fall in lactate levels. Most remaining patients on highly active antiretroviral therapy (HAART) had mild, chronic, asymptomatic hyperlactatemia, with mean lactate level between 1.5 mmol/l and 3.5 mmol/l most commonly. Longitudinal data was analysed in a non-linear mixed effects growth model which indicated that average lactate levels rose after the start of HAART but tended to stabilise at low-grade elevation, with an average 0.23 mmol/l greater long term level in stavudine users compared with zidovudine users (p < 0.01). A multiple linear regression model showed that the association between stavudine and higher lactate level was not confounded by longer duration of total NRTI exposure. Risk of hyperlactatemia was not significantly associated with use of other NRTIs, protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors or multiple immunological and virological factors in multivariate analyses. CONCLUSIONS: Chronic, compensated, asymptomatic hyperlactatemia is common in patients taking HAART. Decompensated, life-threatening lactic acidosis/hepatic steatosis is rare. Treatment with stavudine appears to be the predominant risk factor for development of chronic hyperlactatemia.

Acidosis, Lactic↗
PubMed2001

Late arterial responses (6 and 12 months) after (32)P beta-emitting stent placement: sustained intimal suppression with incomplete healing.

BACKGROUND: Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of beta-emitting radioactive stents in normal rabbit iliac arteries. METHODS AND RESULTS: Three-millimeter beta-emitting (32)P stents (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-microCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi stents also showed delayed healing of the intimal surface, characterized by persistent fibrin thrombus with nonconfluent areas of matrix, incomplete endothelialization, and increased intimal cellular proliferation. Stent edge stenosis was present at 12 months in the 24- and 48-microCi stent groups, characterized by both intimal thickening and negative arterial remodeling. CONCLUSIONS: Inhibition of intimal growth is maintained 6 and 12 months after (32)P beta-emitting stent placement. However, delayed arterial healing, incomplete endothelialization, and edge effects are present.

Animals↗
PubMed2001

Endotracheal balloon dilatation and stent implantation in benign stenoses.

BACKGROUND: Tracheal reconstruction is the treatment of choice in nontumorous tracheal stenoses, but recurrences and concomitant medical conditions limit this approach. We investigated the outcome after balloon dilatation and silicone stent implantation. METHODS: Forty-two patients with inoperable tracheal stenoses underwent balloon dilatation and afterward silicone stent implantation. Patients were divided into two groups, in group A 24 patients received tracheal stents as a temporary treatment. In group B, definitive stenting was done in 18 patients with severe concomitant medical conditions that did not allow for stent removal. RESULTS: Immediate results were satisfactory in all patients. In group A, stents could be removed in 12 patients after a mean interval of 20 months. Restenting was not required during the following 18.9 months. Twelve patients are still waiting for stent removal after a mean follow-up of 20 months. In group B, mean follow-up is now 48.4 months. Complications included retained secretions, dislocation, and granuloma formation. CONCLUSIONS: Stenting after balloon dilatation is safe and effective in benign tracheal stenoses. After temporary use, stents can be removed when local and general conditions permit. In all other patients, stenting proved beneficial for 5 years as more definitive treatment.

Adult↗
PubMed2001

Quantification of the effect of inhaled budesonide on airway inflammation in intermittent asthma by bronchitis index.

The bronchitis index (BI) is a scoring system for the visual quantification of airway inflammation by flexible bronchoscopy. A prospective study was carried out to determine whether patients with intermittent asthma present a considerable visible airway inflammation. Ten steroid-naive patients with intermittent asthma taking only inhaled beta2-agonists were enrolled and received budesonide (800 microg/day) over a period of 4 weeks. The airway inflammation was assessed by flexible electronic videobronchoscopy before and after the steroid treatment phase and quantified using the BI. Despite normal pulmonary function, all patients with intermittent asthma showed a marked visible airway inflammation that was reversed by a 4-week treatment with the inhaled steroid budesonide. The present study demonstrates that the BI may be useful as a clinical research tool for the assessment and quantification of airway inflammation in asthma. Furthermore, our results support the widely recognized theory that airway inflammation is present even in patients with mild asthma, and emphasize the necessity of an early therapy with inhaled steroids.

Administration, Inhalation↗
PubMed2001

Antiretroviral therapy and the lipodystrophy syndrome.

'Lipodystrophy syndrome' in the setting of HIV infection has come to encompass a collection of morphological and metabolic abnormalities linked with the use of antiretroviral therapy and other risk factors. We review the clinical literature on this subject as it has evolved historically, taking pertinent methodological issues into account.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Decreasing clinical response of quinolones in the treatment of enteric fever.

Multidrug resistant Salmonella infections in India have been encountered since 1990, for which Quinolones were introduced at that time. However, with indiscriminate use of Quinolones, the sensitivity of these drugs when used alone, to treat S. typhi and S. paratyphi are decreasing. From 1997 to 1999, we have noted a gradual decrease in clinical efficacy of Quinolone monotherapy in enteric fever (9.3% in 1997, 20% in 1998 and 34.88% in 1999). Hence we recommend the use of multidrug therapy for Quinolone resistant and complicated enteric fever. Addition of Ceftriaxone and/or Aminoglycoside is recommended.

4-Quinolones↗
PubMed2001

Antiretoviral therapy and the lipodystrophy syndrome, part 2: concepts in aetiopathogenesis.

Clinical research has indicated that the use of nucleoside reverse transcriptase inhibitor (NRTI) and HIV protease inhibitor (PI) therapy is associated with a risk of long-term toxicity syndromes, and that the aetiopathogenesis of these adverse effects is independent of the antiretroviral effects of these drugs. In relation to the lipodystrophy syndrome, it appears that the most powerful determinant of subcutaneous fat wasting is an interaction between these two drug classes. In this review, possible mechanisms underlying the contributions of both PI and NRTI drugs are reviewed, with an emphasis on their effects on adipose tissue. On this basis, an 'adipocentric', or minimal model of the syndrome is developed, in which divergent effects at the adipocyte of NRTIs (mitochondrial toxicity) and PIs (insulin resistance and impaired adipocyte maturation) interact to produce a phenotype that is consistent with clinical observations.

Adipocytes↗
PubMed2000

Assessment of immune function by lymphoproliferation underestimates lymphocyte functional capacity in HIV patients treated with highly active antiretroviral therapy.

The objective of this study was to evaluate T cell responses in HIV-infected patients after highly active antiretroviral therapy (HAART), using four assays of immune function, and to determine which best reflects the presence of CD4(+) T cells able to respond to CMV antigen. Peripheral blood mononuclear cells from 41 HIVinfected patients and 31 healthy HIV-seronegative controls were cultured with mitogen (PMA/Ca(2+) ionophore) or antigen (CMV). Production of interferon gamma (IFN-gamma) determined by ELISpot assay was compared with lymphoproliferation, IFN-gamma production assessed by ELISA, and CD69 expression and intracellular IFN-gamma assessed by flow cytometry. Cells from patients whose CD4(+) T cells counts increased 4-fold or to >200 cells/microl after HAART responded as well as control cells when assessed by IFN-gamma production and CD69 expression after mitogenic stimulation, but lymphoproliferation responses were depressed by about 52%. Patients who did not meet these criteria for immune reconstitution had lymphoproliferative responses up to 30-fold lower than control subjects, while intracellular IFN-gamma and CD69 expression and ELISpot counts were less than 3-fold lower. Responses to CMV antigen could not be detected by flow cytometry, but were readily detected by ELISpot in CMV-seropositive patients whose CD4(+) T cell counts had increased after HAART. This included patients with low responses assessed by lymphoproliferation. Moreover, ELISpot responses measured with fresh and frozen cells were comparable, while lymphoproliferation assays required fresh cells. In conclusion, the ELISpot assay is a sensitive and efficient technique for detecting CMV-specific IFN-gamma responses in samples that display poor responses when assessed by lymphoproliferation assays.

Adult↗
PubMed2000

The relation between ion pair structures and reactivities of lithium cuprates

From Li+ well-solvating solvents or complex ligands such as THF, [12]crown-4, amines etc., lithium cuprates R2CuLi(*LiX) crystallise in a solvent-separated ion pair (SSIP) structural type (e.g. 10). In contrast, solvents with little donor qualities for Li+ such as diethyl ether or dimethyl sulfide lead to solid-state structures of the contact ion pair (CIP) type (e.g. 11). 1H,6Li HOESY NMR investigations in solutions of R2CuLi(*LiX) (15, 16) are in agreement with these findings: in THF the SSIP 18 is strongly favoured in the equilibrium with the CIP 17, and in diethyl ether one observes essentially only the CIP 17. Salts LiX (X=CN, Cl, Br, I, SPh) have only a minor effect on the ion pair equilibrium. These structural investigations correspond perfectly with Bertz's logarithmic reactivity profiles (LRPs) of reactions of R2CuLi with enones in diethyl ether and THF: the faster reaction in diethyl ether is due to the predominance of the CIP 17 in this solvent, which is the reacting species; in THF only little CIP 17 is present in a fast equilibrium with the SSIP 18. A kinetic analysis of the LRPs quantifies these findings. Recent quantum-chemical studies are also in agreement with the CIP 17 being the reacting species. Thus a uniform picture of structure and reactivity of lithium cuprates emerges.

Journal Article↗