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Biomedical subjects

M Plunkett

Publications and source records attributed to M Plunkett.

11 recordsLinked to original sources
PubMed2006

Asian MODY: are we missing an important diagnosis?

AIMS: Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes where correct diagnosis alters treatment, prognosis and genetic counselling. The first UK survey of childhood MODY identified 20 White, but no Asian children with MODY. We hypothesized that MODY causes diabetes in UK Asians, but is underdiagnosed. METHODS: Children with dominant family histories of diabetes were recruited. Direct sequencing for mutations in the two most common MODY genes; HNF1A (TCF1) and GCK was performed in autoantibody-negative probands. We also compared MODY testing data for Asian and White cases from the Exeter MODY database, to 2001 UK census data. RESULTS: We recruited 30 families and identified three Asian families with MODY gene mutations (two HNF1A, one GCK) and three White UK families (two HNF1A, one GCK). Heterozygous MODY phenotypes were similar in Asians and Whites. Only eight (0.5%) of 1369 UK referrals for MODY testing were known to be Asian, but in 2001 Asians represented 4% of the English/Welsh population and have a higher prevalence of diabetes. CONCLUSIONS: We identified three cases of childhood MODY in UK Asians and demonstrated reduced rates of MODY testing in Asians, which has negative implications for treatment. It is unclear why this is. MODY should be considered in autoantibody-negative Asian diabetes patients lacking evidence of insulin resistance.

Adolescent↗
PubMed2000

The latent structure of substance use among American Indian adolescents: an example using categorical variables.

Researchers frequently have only categorical data to analyze and cannot, for theoretical or methodological reasons, assume that the observed variables are discrete representations of an underlying continuous variable. We present latent class analysis as an alternative method of measuring latent variables in these circumstances. Latent class analysis does not require the assumptions of factor analyses about the nature of manifest and latent variables, but does allow the use of more precise model selection than techniques such as cluster analysis. We modeled the lifetime substance use of American Indian youth. The latent class model of American Indian teenagers' substance use had four classes: Abstaining, Predominantly Alcohol, Predominantly Alcohol and Marijuana, and Plural Substance. We then demonstrated the usefulness of this latent variable by using it to differentiate levels of several variables in a manner consistent with Social Cognitive Theory.

Adolescent↗
PubMed2000

Physiologic periosteal changes in infancy.

Surface modulation is part of normal bone growth. However, the radiologic appearance of physiologically growing bone in infancy may resemble changes secondary to trauma. This case report reviews bone remodeling in the postnatal infant and describes its unique radiologic and pathologic characteristics, allowing normal to be differentiated from healing and repair.

Autopsy↗
PubMed1996

Analysis of prostate and seminal vesicle motion: implications for treatment planning.

PURPOSE: To quantify prostate and seminal vesicle positional changes (target motion) between treatment planning and delivery, and to identify the factors contributing to target motion. METHODS AND MATERIALS: Thirty patients with adenocarcinoma of the prostate were prospectively evaluated by analyzing two sequential planning computerized tomography (CT) scans (S1, obtained prior to treatment, and S2, obtained during the fourth week of treatment) for each patient. All anatomical volumes of interest (soft tissue and bony) were reconstructed from transverse CT images and projected onto anterior and lateral beam's-eye view projections. Positional changes between S1 and S2 were eliminated by applying a rigid body translation and rotation. Target motion was then measured by recording the positional change between S1 and S2 at the edges (right, left, superior, inferior). Potential correlation of target motion with bladder volume, rectal volume, and rectal diameter changes were evaluated by linear regression analysis. RESULTS: Neither the prostate nor seminal vesicles remained fixed with respect to bony anatomy between S1 and S2. The distribution of positional changes were generally small (< 0.5 cm), but maximum displacements of 1.5-2.2 cm did occur, particularly in the lateral view. In this study, bladder volume changes between the scans were small and did not correlate with target motion (P = 0.67). Both rectal volume and rectal diameter changes correlated with target motion for both the prostate (p = 0.004 and 0.005, respectively) and seminal vesicles (p < 0.001 and < 0.001, respectively). However, neither the initial rectal volume nor the initial rectal diameter could be used to predict subsequent target motion when evaluated either singly or as part of a multiple regression model. CONCLUSIONS: Target motion occurs during the course of treatment planning and delivery and should be considered when designing conformal radiation fields. Although the target position at the time of planning CT may differ substantially from the mean treatment position, target motion cannot be predicted by evaluating simply measured parameters from a single scan, or double scan sequence.

Adenocarcinoma↗
PubMed1995

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.

Adenocarcinoma↗
PubMed1995

Basic fibroblast growth factor and epidermal growth factor downmodulate the growth of hematopoietic cells in long-term stromal cultures.

The bone marrow microenvironment consists of stromal cells and extracellular matrix components which act in concert to regulate the growth and differentiation of hematopoietic stem cells. There is little understanding of the mechanisms which modulate the regulatory role of stromal cells. This study examined the hypothesis that mesenchymal growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) modulate stromal cell activities and thereby influence the course of hematopoiesis. Both bFGF and EGF were potent mitogens for marrow stroma. However, both factors proved to be inhibitory to hematopoiesis in primary long-term marrow cultures. Inhibition was also observed when hematopoietic cells and bFGF or EGF were added to subconfluent irradiated stromal layers, demonstrating that the decline of hematopoiesis was not due to overgrowth of the stromal layer. Loss of hematopoietic support in bFGF and EGF was dose-dependent. Removal of bFGF and EGF permitted stromal layers to regain their normal capacity to support hematopoiesis. In stroma-free long-term cultures, neither factor affected CFU-GM expansion. Basic FGF slightly enhanced granulocyte-macrophage colony forming unit (CFU-GM) cloning efficiency in short-term agarose culture. Basic FGF did not reduce the levels of interleukin-6 (IL-6), GM-CSF, or G-CSF released by steady state or IL-1-stimulated stroma. Similarly, the constitutive levels of steel factor (SF) mRNA and protein were not affected by bFGF. Basic FGF did not alter the level of TGF-beta 1 in stromal cultures. We conclude that bFGF and EGF can act as indirect negative modulators of hematopoietic growth in stromal cultures. The actual mediators of regulation, whether bound or soluble, remain to be identified.

Bone Marrow↗
PubMed1993

Immunomagnetic positive selection and colony culture of CD34+ cells from blood.

Immunomagnetic separation has been used to enrich CD34-positive cells in umbilical cord blood. Cell purities were increased from 0.59% preseparation to 92.7% postseparation (n = 16) with a mean yield of 75.7%. CFU were enriched 127 fold by immunomagnetic separation. Addition of combinations of recombinant growth factors resulted in cloning efficiencies of greater than 50%.

Antibodies, Monoclonal↗
PubMed1993

Colony-stimulating factors in the modulation of sepsis.

Colony-stimulating factors, a complex family of cytokines often referred to as hematopoietic growth factors, are a family of glycoprotein hormones that regulate production and differentiation of hematopoietic cells. The study of colony-stimulating factors was originally confined to stimulation and formation of clonal colonies in in vitro culture systems. The study of hematopoietic growth factors has since evolved into an expanding number of clinical applications in the treatment of patients with hematopoietic and immunologic diseases. Increased occurrence rates of infection have been demonstrated to be associated with both severity and duration of neutropenia. Sepsis has also been associated with phagocytic functional abnormalities. Both neutropenia and neutrophil dysfunction have been shown, in part, to be corrected by granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor. In clinical trials to date, neither of these growth factors has shown significant toxicity. This article discusses the possible use of these and other growth factors in the treatment of sepsis.

Animals↗