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Biomedical subjects

Peter Fisher

Publications and source records attributed to Peter Fisher.

31 records · Page 2Linked to original sources
PubMed2004

Essential role for ADAM19 in cardiovascular morphogenesis.

Congenital heart disease is the most common form of human birth defects, yet much remains to be learned about its underlying causes. Here we report that mice lacking functional ADAM19 (mnemonic for a disintegrin and metalloprotease 19) exhibit severe defects in cardiac morphogenesis, including a ventricular septal defect (VSD), abnormal formation of the aortic and pulmonic valves, leading to valvular stenosis, and abnormalities of the cardiac vasculature. During mouse development, ADAM19 is highly expressed in the conotruncus and the endocardial cushion, structures that give rise to the affected heart valves and the membranous ventricular septum. ADAM19 is also highly expressed in osteoblast-like cells in the bone, yet it does not appear to be essential for bone growth and skeletal development. Most adam19(-/-) animals die perinatally, likely as a result of their cardiac defects. These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects.

ADAM Proteins↗
PubMed2003

Assessment of myocardial recovery in a patient with acute myocarditis supported with a left ventricular assist device: a case report.

Acute myocarditis may present with profound hemodynamic compromise; however, spontaneous resolution of the inflammatory process may occur in up to half of such patients. In patients with fulminant myocarditis, mechanical circulatory support may serve as a bridge to myocardial recovery. In this report we describe a 35-year-old man with acute myocarditis who required left ventricular assist device support as a bridge to recovery, and suggest a method for determining the suitability and timing of device explantation. A combination of echocardiography, right heart catheterization, exercise testing and serial endomyocardial biopsies was used to determine the resolution of myocarditis, recovery of myocardial function and timing for device explantation. Successful device explantation was performed after 37 days of device support. Further study is required to assess the role of ventricular assist devices in combination with immunosuppressive therapy in the management of fulminant myocarditis.

Acute Disease↗
PubMed2002

Observability of earth-skimming ultrahigh energy neutrinos.

Neutrinos with energies above 10(8) GeV are expected from cosmic ray interactions with the microwave background and are predicted in many speculative models. Such energetic neutrinos are difficult to detect, as they are shadowed by Earth, but rarely interact in the atmosphere. Here we propose a novel detection strategy: Earth-skimming neutrinos convert to charged leptons that escape Earth, and these leptons are detected in ground level fluorescence detectors. With the existing HiRes detector, neutrinos from some proposed sources are marginally detectable, and improvements of 2 orders of magnitude are possible at the proposed Telescope Array.

Journal Article↗
PubMed2002

Overgrowth of a mouse model of the Simpson-Golabi-Behmel syndrome is independent of IGF signaling.

The type 1 Simpson-Golabi-Behmel overgrowth syndrome (SGBS1) is caused by loss-of-function mutations of the X-linked GPC3 gene encoding glypican-3, a cell-surface heparan sulfate proteoglycan that apparently plays a negative role in growth control by an unknown mechanism. Mice carrying a Gpc3 gene knockout exhibited several phenotypic features that resemble clinical hallmarks of SGBS1, including somatic overgrowth, renal dysplasia, accessory spleens, polydactyly, and placentomegaly. In Gpc3/DeltaH19 double mutants (lacking GPC3 and also carrying a deletion around the H19 gene region that causes bialellic expression of the closely linked Igf2 gene by imprint relaxation), the Gpc3-null phenotype was exacerbated, while additional SGBS1 features (omphalocele and skeletal defects) were manifested. However, results from a detailed comparative analysis of growth patterns in double mutants lacking GPC3 and also IGF2, IGF1, or the type 1 IGF receptor (IGF1R) provided conclusive genetic evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by sequestering or downregulating an IGF ligand. Nevertheless, our data are compatible with a model positing that there is downstream convergence of the independent signaling pathways in which either IGFs or (indirectly) GPC3 participate.

Abnormalities, Multiple↗
PubMedDate not supplied

Volatile markers of breast cancer in the breath.

Breast cancer is accompanied by increased oxidative stress and induction of polymorphic cytochrome P-450 mixed oxidase enzymes (CYP). Both processes affect the abundance of volatile organic compounds (VOCs) in the breath because oxidative stress causes lipid peroxidation of polyunsaturated fatty acids in membranes, producing alkanes and methylalkanes which are catabolized by CYP. We performed a pilot study of breath VOCs, a potential new marker of disease in women with breast cancer. This was a combined case-control and cross-sectional study of women with abnormal mammograms scheduled for a breast biopsy. Breath samples were analyzed by gas chromatography and mass spectroscopy in order to determine the breath methylated alkane contour (BMAC), a three-dimensional display of the alveolar gradients (abundance in breath minus abundance in room air) of C4-C20 alkanes and monomethylated alkanes. BMACs in women with and without breast cancer were compared using forward stepwise discriminant analysis. Two hundred one breath samples were obtained from women with abnormal mammograms and biopsies read by two pathologists. There were 51 cases of breast cancer in 198 concordant biopsies. The breath test distinguished between women with breast cancer and healthy volunteers with a sensitivity of 94.1% (48/51) and a specificity of 73.8% (31/42) (cross-validated sensitivity 88.2% (45/51), specificity 73.8% (31/42)). Compared to women with abnormal mammograms and no cancer on biopsy, the breath test identified breast cancer with a sensitivity of 62.7% (32/51) and a specificity of 84.0% (42/50) (cross-validated sensitivity of 60.8% (31/51), specificity of 82.0% (41/50)). The negative predictive value (NPV) of a screening breath test for breast cancer was superior to a screening mammogram (99.93% versus 99.89%); the positive predictive value (PPV) of a screening mammogram was superior to a screening breath test (4.63% versus 1.29%). A breath test for markers of oxidative stress accurately identified women with breast cancer, with an NPV superior to a screening mammogram. This breath test could potentially be employed as a primary screen for breast cancer. Confirmatory studies in larger groups are required.

Aged↗
PubMedDate not supplied

Complementary medicine: evidence base, competence to practice and regulation.

This paper describes the current status and evidence base for acupuncture, homeopathy, herbal and manipulative medicine, as well as the regulatory framework within which these therapies are provided. It also explores the present role of the Royal College of Physicians' Subcommittee on Complementary and Alternative Medicine (CAM) in relation to these developments. A number of CAM professions have encouraged the Royal College of Physicians Subcommittee to act as a reference point for their discussions with the conventional medical profession and the subcomittee believes that they are able to fulfil this function.

Clinical Competence↗