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Biomedical subjects

G Wheeler

Publications and source records attributed to G Wheeler.

At least 19 recordsLinked to original sources
PubMed2006

Management of paediatric thyroid carcinoma: recent experience with recombinant human thyroid stimulating hormone in preparation for radioiodine therapy.

BACKGROUND: Thyroid carcinoma in children is rare and raises unique management issues. Although metastatic disease is more common in this age group, prognosis remains good with appropriate treatment. The aim of the study was to report recent experience in the management of differentiated thyroid carcinoma in children, especially in the use of radioiodine after recombinant human thyroid stimulating hormone (rhTSH) stimulation. METHODS: Eight patients, aged 5-17 years (five were boys) presented following total thyroidectomy for thyroid carcinoma between May 2003 and June 2005. Seven had papillary carcinoma and one had follicular carcinoma. Five had known lymph node metastases and one had pulmonary metastases at presentation. Four patients had previously received therapeutic irradiation for malignancy. All eight underwent diagnostic iodine scans, seven with rhTSH stimulation. Seven went on to receive radioiodine treatment as hospital inpatients, comanaged by the paediatric and nuclear medicine units. The dosage of 131I ranged from 1.5 to 3.7 x 10(9) Bq. All except one were prepared by rhTSH stimulation. RESULTS: Seven of eight patients had significant uptake in the neck on diagnostic scan and two had pulmonary abnormalities. Six of seven evaluable patients achieved complete thyroid ablation. Both patients with pulmonary abnormalities had scan resolution, although one of them only after a second radioiodine treatment. All patients had thyroxine replacement in doses to suppress TSH and all remain alive and well at time of carrying out this study. CONCLUSION: Optimal management of paediatric thyroid carcinoma necessitates a multidisciplinary approach. Radioiodine therapy under rhTSH is an effective and safe adjuvant treatment in this special subgroup.

Adolescent↗
PubMed2001

Repifermin. Human Genome Sciences/GlaxoSmithKline.

Human Genome Sciences (HGS) and GlaxoSmithKline (formerly SmithKline Beecham) are developing topical and injectable formulations of repifermin, keratinocyte growth factor-2 (KGF-2), also known as fibroblast growth factor-10 (FGF-10) for the potential treatment of wound care, oral and intestinal mucositis, and inflammatory bowel diseases [385959,396786]. A phase IIb trial of the topical formulation in chronic venous ulcers is ongoing, as well as phase II trials for the systemic, injectable formulation in ulcerative colitis and in the prevention of mucositis after chemotherapy with bone marrow transplantation [352908,368013, 385959,404294]. In May 2001, UBS Warburg predicted that HGS would receive approval of repifermin for the treatment of venous ulcers by yearend 2004, mucositis in 2005, and ulcerative colitis in the second half of 2004 [412015]. In October 2000, SmithKline Beecham exercised an option to codevelop repifermin for phase III trials and beyond [385959,399183]. In May 2001, UBS Warburg valued repifermin's worldwide market at 2 billion dollars for treating venous ulcers and predicted sales of 33 million dollars in 2004 and 118 million dollars in 2005 for this indication. In addition, the analysts regarded repifermin as having potential in the treatment of diabetic foot ulcers and pressure ulcers (a market valued at over 1.8 billion dollars) and estimated that the drug might earn another 103.5 million dollars for these indications in 2005. Furthermore, the analysts predicted sales of 6.8 million dollars for repifermin's mucositis indication and, for ulcerative colitis, sales of 27.3 million dollars in 2004 and 54.8 million dollars in 2005. Overall, the analysts estimated that repifermin represented a 3.5 billion dollars market opportunity for HGS/ GlaxoSmthKline and that commercialization of the drug might earn more than 61 million dollars by 2004 [412015].

Journal Article↗
PubMed1999

A national facility for small area disease mapping and rapid initial assessment of apparent disease clusters around a point source: the UK Small Area Health Statistics Unit.

BACKGROUND: Reports of disease clusters are often received by district health authorities and are, in some cases, associated with concerns about a pollution source. The Small Area Health Statistics Unit (SAHSU) has developed a Rapid Inquiry Facility, which will produce an estimated relative risk for any given condition for the population within defined areas around a point source, relative to the population in a local reference region. The system can also facilitate the production of annual reports and other health studies for Departments of Public Health Medicine through the creation of ward-level maps to illustrate disease variation across small areas. METHODS: The facility uses routinely collected morbidity, mortality and population data at a small area scale, together with the computing facilities and expertise necessary to run such analyses quickly and efficiently. Using this facility SAHSU can supply a report within three working days. To aid interpretation, smoothed small area maps that account for sampling variability in the observed data can also be produced. RESULTS: The paper reports on two case studies where the pilot system has been utilized by health authorities for both point source analyses and small area disease mapping. CONCLUSIONS: We believe that this facility would be of considerable use to districts. The local knowledge and expertise of the local public health specialist is essential in the interpretation and presentation of the facility's output. Feedback from public health specialists is helping SAHSU refine the output of the facility, so as to make the information presented as comprehensive and as useful as possible.

Data Interpretation, Statistical↗
PubMed1998

A study of metalloporphyrin-polynucleotide interactions by microcalorimetry and circular dichroism.

In this paper we examine the interactions of Calf Thymus DNA and the model polynucleotides poly(dA).poly(dT), poly(dAdT)2 and poly(dG.dC)2 with a group of metalloporphyrins derived from the freebase porphyrin tetrakis(4-N-methylpyridyl)porphine, H2(TMpy-P4), by means of ultraviolet absorption spectroscopy, circular dichroism spectroscopy and microcalorimetry. We have studied the interactions of the copper, cobalt, nickel and zinc derivatives of H2(TMpy-P4) in addition to the free base porphyrin itself. We have found strong evidence for an external self-stacking interaction of the Cu(TMpy-P4) and Zn(TMpy-P4) derivatives with poly(dA).poly(dT) and poly(dAdT)2 even at low concentrations of porphyrin, and all of the porphyrin derivatives studied appear to display such a self-stacking in interaction with poly(dA.dT)2 at sufficiently high ratios of porphyrin to polynucleotide.

Animals↗
PubMed1997

Expanding handgun bullets.

BACKGROUND: Many new types of expanding or fragmenting handgun ammunition have been developed. Knowledge of these unusual bullets may aid in the management of patients and their wounds. METHODS: Eleven different expanding or fragmenting .45 caliber bullets and a nondeforming, full metal jacketed bullet for comparison were fired multiple times from the same handgun into both a water reservoir and ordnance gelatin. Performance was observed and recorded. Muzzle velocities were measured using a chronograph. Bullets were disassembled and cross-sectioned to facilitate inspection. RESULTS: The distinguishing surface and internal features of each bullet are described. When fired into water and ordnance gelatin, the bullets reliably expanded to 1.49 to 1.89 times their prefired diameters. Rates of kinetic energy loss of bullets of equal mass fired into ordnance gelatin were plotted. Full metal jacketed bullets penetrated twice as deeply as deforming bullets. Jackets of some of the expanding bullets separated when fired into water. CONCLUSION: Expanding/fragmenting bullets produce larger, shallower wounds than do full metal jacketed bullets. Recognition of the wound and roentgenographic appearances of these unusual bullets will help the trauma surgeon to properly treat gunshot victims. Because of the occurrence of jacket separation in water, ordnance gelatin should be used for optimal evaluation of bullet performance.

Firearms↗
PubMed1996

Personal styles and ways of coping in individuals who use wheelchairs.

To obtain information about the psychological needs of wheelchair users, 45 subjects participating in a university-based drop-in physical activity centre and outpatient rehabilitation program completed the Personal Styles Inventory and the Ways of Coping Inventory. Three groups of subjects were formed, differentiated by etiology for their disability. Results suggested that subjects with brain injury possessed the most limited coping resources. Subjects with multiple sclerosis were highest of the three groups in the frequency of utilization of emotional coping, they also revealed a fundamentally introverted and stability-based personality style. Subjects with spinal cord injuries utilized a predominantly Problem-solving means of coping: and they revealed a basic personality style characterized as extroverted and stable. The findings suggest that disease process (perhaps through common preexisting psychological characteristics, the nature of the onset and progression of the disease process, and/or tissue damage) may modify the ability to adapt and cope with the need to use a wheelchair. The nature of psychological support to be offered should reflect not only the use of a wheelchair but also the underlying personality and its modification by the nature of the disease process.

Adaptation, Psychological↗
PubMed1995

Chromosome instability in ICF syndrome: formation of micronuclei from multibranched chromosomes 1 demonstrated by fluorescence in situ hybridization.

We report on a new patient with immunodeficiency, centromeric heterochromatin instability, and facial anomalies (the ICF syndrome). Studies with traditional cytogenetic methods demonstrate that aberrations in this syndrome primarily involve the centromeric regions of chromosomes 1 and 16. We applied fluorescence in situ hybridization (FISH) using "painting" probes for chromosomes 1 and 16 to document the progression of centromeric instability from simple decondensation aberrations to the subsequent formation of complex multibranched chromosomes 1, and finally to the interphase aberrations of nuclear projections and micronuclei involving both chromosomes 1 and 16. The loss of the large multibranched chromosome 1 configurations from the cells as micronuclei suggests that the centromeric aberrations subsequently interfere with normal chromosome movement at anaphase in ICF syndrome. Circular areas of counterstained chromatin were observed by FISH in the micronuclei corresponding to the intertwined segments of centromeric heterochromatin seen involving multibranched chromosomes 1 in the patient's G-banded chromosome study. The current hypothesis of recessive inheritance for this disorder suggests that the chromosomal aberrations are not a causative event in this syndrome; however, the chromosome aberrations are clearly an important basic diagnostic criterion.

Abnormalities, Multiple↗
PubMed1995

In vitro detection of specific IgE antibodies to erythromycin.

BACKGROUND: In vitro tests for detecting drug-specific IgE would be useful in identifying patients at risk for immediate hypersensitivity reactions to therapeutic doses of a drug. OBJECTIVE: We attempted to verify that IgE-mediated reactions to erythromycin occur and to identify IgE antibodies specific for erythromycin in serum from a patient who had urticaria immediately after administration of the drug. METHODS: Skin prick testing was performed on the patient and five control subjects. Serum from the patient, pooled sera from nonatopic subjects allergic to common aeroallergens, and cord blood controls were analyzed for erythromycin-specific IgE by radioimmunoassay. Sepharose (Pharmacia, Uppsala, Sweden) was used as solid phase covalently linked to erythromycin. RESULTS: We were able to detect erythromycin-specific IgE antibodies in serum from the patient who had an allergic reaction to this antibiotic, but specific IgE could not be detected in control sera. CONCLUSION: Immunologic IgE-mediated reactions to erythromycin do occur, and in vitro diagnosis of such reactions can be made by using Sepharose as a solid phase covalently linked to this drug.

Adult↗
PubMed1994

Testosterone, cortisol and catecholamine responses to exercise stress and autonomic dysreflexia in elite quadriplegic athletes.

Episodes of short high intensity exercise are associated with an increase in circulating total testosterone (T) in men. Mechanisms may include hemoconcentration, decreased metabolic clearance and/or increased synthesis. Beta-blockade abolishes the T response suggesting a direct beta-adrenergic effect on the testes. Some spinal cord injured (SCI) athletes deliberately induce autonomic dysreflexia (boosting) to enhance performance. Associated with this practice are elevated catecholamine (CA) levels and exaggerated responses to serum catecholamine levels. Since basal T levels are reported to be normal in the SCI male, the T response to acute high intensity exercise might be expected to be exaggerated by boosting and associated elevated CA levels. The acute exercise T response has not been examined in SCI men to date. To determine whether the increased CA values associated with boosting enhanced the exercise-induced T elevation we measured circulating levels of T, cortisol (C), norepinephrine (NE) and epinephrine (E) before and after maximal exertion and a simulated 7.5 km race with and without boosting in eight elite quadriplegic athletes. Maximal incremental exercise and a simulated 7.5 km race resulted in a rise in T similar to able bodied men under normal exercise conditions. Under boosted conditions the rise in T was eliminated while NE levels were significantly elevated above unboosted levels. The data may suggest an inhibitory role for CA on T production or release under conditions of extreme stress. Other possible mechanisms include C induced suppression, impaired gonadotropin stimulation of the Leydig cell and CA mediated alterations in gonadal blood supply.

Aerobiosis↗
PubMed1993

Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain.

Three members of a family who died with renal amyloidosis were found to share a single nucleotide substitution in the fibrinogen alpha-chain gene. The predicted arginine to leucine mutation (Arg554Leu) was proven by amino acid sequence analysis of amyloid fibril protein isolated from postmortem kidney of an affected individual. Direct genomic DNA sequencing and restriction fragment length polymorphism analysis demonstrated that all three affected individuals had the guanine to thymine 4993 transversion. This is the first demonstration of hereditary amyloidosis associated with a variant fibrinogen alpha-chain. Variants of circulating fibrinogen may be the cause of a number of systemic amyloidoses with primarily renal involvement.

Adult↗
PubMed1993

Electrical systems for improving locomotion after incomplete spinal cord injury: an assessment.

Simple systems for electrical stimulation (1-4 channels) with either surface, percutaneous, or implanted electrodes during locomotion were assessed in 10 subjects who had chronic, incomplete spinal cord injury (SCI). On average, the speed of locomotion was increased by 4 m/min independently of the subject's speed of locomotion without stimulation (0-50 m/min) while oxygen consumption was reduced somewhat. These simple systems can provide practical help, particularly for incomplete SCI subjects who can stand but are lacking or have very limited ability to walk. Further improvement in locomotion requires stabilization and reduction in the duration of the stance phase of locomotion.

Adult↗
PubMed1990

Physiologic and perceptual responses during treadmill running with ankle weights.

This study examined the effects of ankle weighting on physiologic and perceptual responses during treadmill running in seven healthy, female recreational runners with a mean maximal aerobic power of 48.4 +/- 4.0 ml/kg/min. Each subject completed four experimental one-mile runs at individually selected treadmill running speeds with 0, 1.6, 3.2 and 4.8 kg weights on their ankles. The subjects selected a speed at which they would run (train) if their objectives were to significantly improve cardiovascular function and induce weight loss. Metabolic and cardiovascular responses were continuously monitored, and ratings of perceived exertion were recorded near the end of the activity. During the unweighted run, the subjects selected a running speed of 6.87 +/- 0.63 mph which resulted in a net energy expenditure of 0.153 kcal/kg/min or 1.34 +/- 0.16 kcal/kg/mile. This corresponded to a training intensity of 76.3% +/- 5.1% of maximum oxygen consumption or 88.1% +/- 9.7% of maximum heart rate. Addition of weight to the ankles caused a significant decrease (p less than .05) in the running speed selected and, therefore, did not result in any significant changes (p greater than .05) in the rate of oxygen consumption, heart rate or ratings of perceived exertion when compared to the unweighted condition. These observations are in contrast to previous studies on ankle weighting which were conducted at fixed treadmill running speeds. However, the use of ankle weights did have a tendency to increase gross and net energy expenditure of running when values were expressed in kcal/mile because of slower self-selected running speeds under these conditions. This increase in energy expenditure could be of physiologic significance if running with ankle weights was performed on a regular basis at a fixed distance.

Adult↗
PubMed1989

Amyloidosis related to a lambda IV immunoglobulin light chain protein.

Amyloid subunit proteins related to the lambda IV subgroup of immunoglobulin light chains have not been previously reported. We have determined the amino acid sequence of an AL amyloid protein BAK and shown that it has the structure typical of lambda IV light chain proteins. This protein, which was isolated from the spleen of a patient with AL amyloidosis, has 111 residues in the variable domain and also includes the first tryptic peptide of the constant domain for a total of 130 residues. Comparison of the primary structure of this protein with the only other completely characterized lambda IV protein (SH) reveals that they are highly homologous with only one amino acid change in FR1, two changes in FR2, and one change in FR3. The CDR regions also show few changes, with only three in CDR1, one in CDR2, and five in CDR3. To test the hypothesis that the formation of AL amyloid is related to changes in the FR regions which could affect molecular aggregation, the structure of BAK was compared with the myeloma protein SH with respect to the presumed tertiary structure. Only limited amino acid substitution was found in the surface positions that might affect intradimer and interdimer aggregation. These included an isoleucine for leucine change at position 43 and phenylalanine for valine at 45, which may affect intradimer interaction and a change of histidine to asparagine at position 67.

Amino Acid Sequence↗
PubMed1979

Predictive value of the analogy between hormone-sensitive adenylate cyclase and light-sensitive photoreceptor cyclic GMP phosphodiesterase: a specific role for a light-sensitive GTPase as a component in the activation sequence.

We report experiments which involve a light sensitive GTPase in the light dependent activation of retinal rod 3'5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE). The data suggest that the light activated GTPase is intermediate between rhodopsin and PDE in the light-dependent activation sequence. We list the many striking similarities between hormone sensitive adenylate cyclase and light activated PDE in order to emphasize that the findings presented herein may have predictive value for ongoing studies of the hormone sensitive adenylate cyclase specifically regarding the role of the hormone activated GTPase in the activation sequence.

3',5'-Cyclic-GMP Phosphodiesterases↗