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Biomedical subjects

R McFarland

Publications and source records attributed to R McFarland.

12 recordsLinked to original sources
PubMed2007

Mitochondrial disease--its impact, etiology, and pathology.

Mitochondria are ubiquitous organelles that are intimately involved in many cellular processes, but whose principal task is to provide the energy necessary for normal cell functioning and maintenance. Disruption of this energy supply can have devastating consequences for the cell, organ, and individual. Over the last two decades, mutations in both mitochondrial DNA (mtDNA) and nuclear DNA have been identified as causative in a number of well-characterized clinical syndromes, although for mtDNA mutations in particular, this relationship between genotype and phenotype is often not straightforward. Despite this, a number of epidemiological studies have been undertaken to assess the prevalence of mtDNA mutations and these have highlighted the impact that mtDNA disease has on both the community and individual families. Although there has been considerable improvement in the diagnosis of mitochondrial disorders, disappointingly this has not been matched by developments toward effective treatment. Nevertheless, our understanding of mitochondrial biology is gathering pace and progress in this area will be crucial to devising future treatment strategies. In addition to mitochondrial disease, evidence for a central role of mitochondria in other processes, such as aging and neurodegeneration, is slowly accumulating, although their role in cancer remains controversial. In this chapter, we discuss these issues and offer our own views based on our cumulative experience of investigating and managing these diseases over the last 20 years.

Aging↗
PubMed2006

A scale to monitor progression and treatment of mitochondrial disease in children.

Mitochondrial diseases affect all age groups, but those with childhood onset often seem to experience the greatest burden of disability. In some paediatric patients this can be explained by a cumulative disability acquired over many years. In others, additional factors, including the nature and severity of the molecular defect, must be considered. To date, no large-scale studies have attempted to document the natural history of paediatric mitochondrial disease. This is in part at least, because no assessment tool has been available to plot the temporal course of a disease with such a diverse clinical spectrum. This paper describes how a practical and semi-quantitative rating scale has been devised for children with mitochondrial disease, the Newcastle paediatric mitochondrial disease scale (NPMDS). The scale is multi-dimensional and reproducible, offering a tool through which mitochondrial disease progression can be objectively monitored. We anticipate that use of this tool will facilitate both longitudinal natural history studies and the assessment of future therapeutic interventions.

Adolescent↗
PubMed2006

Mitochondrial disease in adults: a scale to monitor progression and treatment.

The natural history of mitochondrial diseases is poorly understood, limiting our ability to offer prognostic advice to patients or to evaluate therapy. One major obstacle to improving our understanding is the lack of a clinical rating scale to monitor the extensive clinical spectrum of mitochondrial disease. In this article, the authors describe the development and validation of a practical and semiquantitative rating scale, the Newcastle Mitochondrial Disease Adult Scale.

Disease Progression↗
PubMed1995

Assessment of antiretroviral therapy by plasma viral load testing: standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays compared.

To assess the utility of quantitative competitive-polymerase chain reaction (QC-PCR) measurements of plasma human immunodeficiency virus type 1 (HIV-1) RNA and other viral load markers for assessment of antiretroviral therapy, we used archived cryopreserved specimens from a randomized controlled clinical trial of 135 patients (CD4+ T cell count < or = 500/mm3), comparing zidovudine (500 mg/day) versus the nonnucleoside reverse transcriptase inhibitor L-697, 661 (50, 300, or 1,000 mg daily). We evaluated treatment-associated changes in plasma viral load by standard and immune complex-dissociated (ICD) HIV-1 p24 antigen assays, and, in a representative subset of patients (n = 46), by QC-PCR determination of virion-associated HIV-1 RNA. At baseline, HIV-1 RNA was quantifiable by QC-PCR in all patients tested (100%), whereas standard and ICD HIV-1 p24 antigen tests were positive (> or = 30 pg/ml) in 42% and 56%, respectively. All viral load parameters showed significant decreases from baseline within 1 week of initiation of zidovudine, as measured by standard p24 antigen assay, ICD p24 assay, and QC-PCR. At 1 week, patients treated with either 300 or 1,000 mg/day of L-697,661 showed significant decreases from baseline in plasma standard and ICD p24 antigen and QC-PCR-determined HIV-1 RNA levels. Whereas viral load decreases seen with zidovudine were sustained for the duration of treatment, plasma viral markers often returned to pretreatment levels despite ongoing L-697,661 treatment, with evidence of the emergence of drug-resistant virus. Whereas standard p24, ICD p24, and viral RNA levels changed similarly in response to treatment, the superior sensitivity and available dynamic range of plasma viral RNA assays like QC-PCR analysis provide an advantage for clinical monitoring of plasma viral load, allowing tracking of treatment-related changes even in patients with earlier stage disease and lower levels of viral load.

Antiviral Agents↗
PubMed1995

Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy.

OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

Adolescent↗
PubMedDate not supplied

The surgery of aortic valve disease in neonates, infants and children.

The pre-operative findings and surgical results of forty-three patients under thirteen years of age undergoing isolated aortic valve surgery are reported. Twenty-six underwent open aortic valvotomy for isolated aortic valve stenosis. Of the nine who died, five were neonates. These deaths are attributed to an underdeveloped myxoid valve and aortic valve ring. Eleven children underwent excision of the subvalvar diaphragm but four developed asymptomatic left ventricular strain on ECG and required re-operation. There was one death. One child underwent successful surgery for supravalvar stenosis. Five children underwent surgery for isolated aortic regurgitation. Two underwent repair, but one required aortic valve replacement for uncontrolled regurgitation. Three had aortic valve replacement as a primary procedure. The management of left ventricular outflow tract obstruction and the choice of replacement valve is discussed.

Aortic Stenosis, Subvalvular↗