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Biomedical subjects

C King

Publications and source records attributed to C King.

At least 19 recordsLinked to original sources
PubMed2007

Standardizing lung function laboratories for multicenter trials.

Multi-center studies provide advantages in clinical research but differences between centers can introduce bias. Three specialist pediatric respiratory laboratories standardized their methodology and examined differences between centers. The specific aims were to (i) assess the variability of measurements on adults within and between centers and (ii) to exchange and cross-analyze data from children to assess the extent of agreement between centers. Each laboratory used identical equipment and software. Inter-laboratory visits were used to (i) standardize protocols for data collection and analysis and (ii) make spirometric and plethysmographic measurements on participating staff at each location. Staff also had repeat measurements in their home laboratories. Measurements from children in each laboratory were exchanged on disk, cross-analyzed, and data compared by ANOVA. There were no significant within-subject, between-center differences in FVC, FEV1, FEF50, FRCpleth, or VC. There was a slight trend for TLC and RV (P=0.07) to be higher at one center. The 95% limits of agreement within and between centers were similar for all parameters. There were no differences between centers in cross-analyzed data from 10 children. By standardizing hardware, software, and protocol, potential inter-laboratory differences can be minimized. We recommend that this approach be adopted prior to multi-center studies.

Adult↗
PubMed2006

A multicentre, randomised trial examining the effect of test procedures measuring emergence from post-traumatic amnesia.

BACKGROUND: Post-traumatic amnesia (PTA) tests that record different PTA durations in the same patient, thereby raising measurement accuracy issues, have been reported previously. A major problem lies in determining the end point of PTA. AIMS: To delineate areas of discrepancy in PTA tests and to provide independent verification for a criterion signalling emergence from PTA. METHODS: In a randomised design, two related PTA procedures were compared, one purportedly more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT) and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements was made on three occasions: at the early stage of PTA (time 1), towards the end of PTA when the maximum score (12/12) was first obtained (time 2) and at the traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time 3). RESULTS: No significant difference was recorded in PTA duration between the MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By using Kaplan-Meier survival analyses, the WPTAS was found to show a more protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time lag of > or = 1 week in the resolution of disorientation as compared with amnesia was observed in 59% cases. Significant improvements occurred on all independent measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements between time 2 and time 3. CONCLUSIONS: Although no significant differences in the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of both orientation and memory items in PTA tests is highlighted by the frequency of disorientation-amnesia dissociations. The patterns of results on the independent measures suggest that patients who are in PTA for > 4 weeks have probably emerged from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can replace the traditional criterion.

Adolescent↗
PubMed2006

Influence of segmenting fluids on efficiency, crossing point and fluorescence level in real time quantitative PCR.

The two-phase segmented flow approach to the processing and quantitative analysis of biological samples in microdevices offers significant advantages over the single-phase continuous flow methodology. Despite this, little is known about the compatibility of samples and reactants with segmenting fluids, although a number of investigators have reported reduced yield and inhibition of enzymatic reactions depending on the segmenting fluid employed. The current study addresses the compatibility of various segmenting fluids with real time quantitative PCR to understand the physicochemical requirements of this important reaction in biotechnology. The results demonstrate that creating a static segmenting fluid/PCR mix interface has a negligible impact on the reaction efficiency, crossing threshold and end fluorescence levels using a variety of segmenting fluids. The implication is then that the previously reported inhibitory effects are the result of the dynamic motion between the segmenting fluid and the sample in continuously flowing systems. The results presented here are a first step towards understanding the limitations of the segmented flow methodology, which are necessary to bring this approach into mainstream use.

Complex Mixtures↗
PubMed2006

Partnered care in the Bahamas: A model of advanced healthcare delivery for developing countries.

OBJECTIVE: To assess the delivery of advanced specialized medical care using The Partnered Care Model as a means of providing affordable access to all, irrespective of ability to pay. DESIGN AND METHODS: A retrospective analysis of all persons presenting to a specialized, private, cardiac unit, The Bahamas Interventional Cardiology Center (BICC), over an 8.5-year period from March 1996 to September 2004 was conducted. The Bahamas Heart Center's Discounted Service System had been applied since inception to all patients in three groups including insured patients billed at 100% of the fee schedule of The Medical Association of the Bahamas for the procedures performed, private self-pay and government patients billed at 75% and 50% respectively. Their respective distribution and contributions to total revenue was analyzed. A series of financial models were constructed taking into consideration variables that could influence the percentages of revenues collected from each sector and the number of individuals served RESULTS: One thousand five-hundred and forty-two patients received services in BICC over the 8.5 year period (56% males and 44% females age range: 0.25 - 96 years, with mean age of 55.7 years). One thousand eight-hundred and eighty-eight patient-procedures were performed, with 51% insured generating 69% total revenue, 18% Private producing 16% Revenue, and 31% Government patients generating 15%. Financial models were created to predict revenue behaviour in various scenarios. CONCLUSION: Partnered Care is a viable alternative for Governments (Ministries of Health) of developing countries to provide costly specialized healthcare to their populations at minimal expense and capital outlay. Partnered Care reduces the otherwise overwhelming burden of healthcare cost to governments, particularly in developing countries, by sharing the burden of care between the private, user and government sectors.

Bahamas↗
PubMed2005

Segmenting fluid effect on PCR reactions in microfluidic platforms.

This paper evaluates the compatibility of segmenting fluids for two phase flow applications in biomedical microdevices. The evaluated fluids are chosen due to the variations in fluid properties and cost, while also reflecting their use in the recent literature. These segmenting fluids are examined to determine their compatibility with the Polymerase Chain Reaction (PCR), through controlled experiments. The results are the first to provide a quantitative measure of segmenting fluid compatibility with PCR.

Chemical Fractionation↗
PubMed2005

Inherited pericentric inversion (X)(p11.4q11.2) associated with delayed puberty and obesity in two brothers.

We report two brothers with hypogonadotropic hypogonadism (HH), obesity and short stature associated with a maternally inherited pericentric inversion (X)(p11.4q11.2). On the basis that either breakpoint might disrupt a gene whose function is critical to normal sexual development we mapped the chromosomal breakpoints using two-colour fluorescent in situ hybridisation (FISH). The position of both the Xp11.4 and Xq11.2 breakpoints was refined using a panel of ordered BAC clones. No known genes were shown to map to the breakpoint regions. While we cannot entirely exclude the possibility that association between the clinical and cytogenetic phenotypes in the family is coincidental, it is possible that the inversion is responsible for HH through alternative molecular mechanisms such as position effects.

Adolescent↗
PubMed2005

Tuberculosis infection among health care workers in Kampala, Uganda.

Nosocomial tuberculosis (TB) is a serious problem in sub-Saharan Africa due to the absence of protective measures for health care workers (HCWs). To determine the prevalence of TB infection among HCWs in Kampala, Uganda, a cross-sectional study was conducted between June and August 2001. A tuberculin skin test (TST) survey was conducted among 396 HCWs from three hospitals within Kampala, The prevalence of TST > or = 10 mm was 57%. Age and department of employment were associated with TST > or = 10 mm, while occupation and BCG status were not. Health care workers in Kampala, Uganda, have a high prevalence of latent TB infection.

Adult↗
PubMed2004

A re-examination of the potential impact of preventive therapy on the public health problem of tuberculosis in contemporary sub-Saharan Africa.

BACKGROUND: To estimate the effect size of tuberculosis preventive therapy (PT) on the public health problem of tuberculosis in contemporary sub-Saharan Africa. METHODS: A compartmental flow model that considers high levels of tuberculosis and human immunodeficiency virus (HIV) infection in contemporary sub-Saharan Africa was used to assess the impact of PT on the prevalence of tuberculosis and tuberculosis-associated mortality. RESULTS: Model implementation shows that giving PT to 25% of HIV-positive individuals with latent tuberculosis infection (LTBI) leads to a 3.9% reduction in the prevalence of tuberculosis in 10 years and a 5.1% reduction in 20 years. This intervention also prevents a cumulative total of 3.0% of tuberculosis-associated deaths in a decade and 5.5% in two decades. Doubling PT coverage to 50% approximately doubles the effect size, suggesting a linear relationship within the 20-year period. The effect size is slightly sensitive to changes in level of HIV transmission, level of tuberculosis transmission, and level of case detection and treatment cure rates in the population. CONCLUSIONS: Contrary to suggestions by previous authors that PT can significantly reduce the public health problem of tuberculosis in sub-Saharan Africa, this model-based analysis suggests that the impact of PT on tuberculosis in the population is likely to be small.

Africa South of the Sahara↗
PubMed2004

Increased osmolality of breast milk with therapeutic additives.

AIM: To evaluate the changes in the osmolality of expressed breast milk (EBM) after the addition of seven additives and four proprietary fortifiers commonly used during neonatal intensive care. METHODS: The osmolality of 5 ml EBM was measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose-effect curves were plotted, and the volume of milk that must be added to the above additives to maintain osmolality below 400 mOsm/kg was calculated. RESULTS: The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a significant increase in the osmolality of EBM with increasing doses of all additives except caffeine. The osmolality of EBM with many additives in clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase occurred with sodium ironedetate syrup, where the osmolality of EBM increased to 951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to a maximum of 395 mOsm/kg. CONCLUSION: Routine additives can significantly increase the osmolality of EBM to levels that exceed current guidelines for premature infant feeding. A simple guide for clinical use is presented, which indicates the amount of milk required as diluent if hyperosmolality is to be avoided.

Dose-Response Relationship, Drug↗
PubMed2001

The Master Settlement Agreement with the tobacco industry and cigarette advertising in magazines.

BACKGROUND: In 1998, the attorneys general of 46 states signed a Master Settlement Agreement with the four largest tobacco companies in the United States. The agreement prohibits tobacco advertising that targets people younger than 18 years of age. METHODS: We analyzed the trends in expenditures for advertising for 15 specific brands of cigarettes and the exposure of young people to cigarette advertising in 38 magazines between 1995 and 2000. We defined cigarette brands as "youth" brands if they were smoked by more than 5 percent of the smokers in the 8th, 10th, and 12th grades in 1998; all others were considered to be "adult" brands. We classified magazines as youth-oriented magazines if at least 15 percent of their readers or at least 2 million of their readers were 12 to 17 years old. "Reach," a standard measure of exposure to advertising, was defined as the number of young persons who read at least one issue of a magazine containing an advertisement for a particular brand of cigarette during a given year. RESULTS: In 2000 dollars, the overall advertising expenditures for the 15 brands of cigarettes in the 38 magazines were $238.2 million in 1995, $219.3 million in 1998, $291.1 million in 1999, and $216.9 million in 2000. Expenditures for youth brands in youth-oriented magazines were $56.4 million in 1995, $58.5 million in 1998, $67.4 million in 1999, and $59.6 million in 2000. Expenditures for adult brands in youth-oriented magazines were $72.2 million, $82.3 million, $108.6 million, and $67.6 million, respectively. In 2000, magazine advertisements for youth brands of cigarettes reached more than 80 percent of young people in the United States an average of 17 times each. CONCLUSIONS: The Master Settlement Agreement with the tobacco industry appears to have had little effect on cigarette advertising in magazines and on the exposure of young people to these advertisements.

Adolescent↗
PubMed2001

A comparison of memory for verbal and non-verbal material in schizophrenia.

Verbal memory impairment has been well explored in schizophrenia, but it is unclear whether findings relate to the type of material to be learned or the component process required by the memory task. Also, sparse data on non-verbal memory also open the question of how well schizophrenia patients encode this material. We tested whether episodic memory performance in schizophrenia varies as a function of stimulus material (verbal/non-verbal) and determined the integrity of various component memory processes. Memory tests that differ in stimulus material (words, California Verbal Learning Test, CVLT; designs, Biber Figure Learning Test-Extended, BFLT-E) yet produce similar memory component measures were used. Subjects were 28 neuroleptic-medicated inpatients with a diagnosis of chronic schizophrenia. Results showed that both verbal and non-verbal memory performance was impaired relative to age-matched controls. Learning and recall measures were most severely impaired, with memory storage problems and impairment in recognition memory evident. On the verbal task, the relative sparing of recognition memory suggested retrieval processes, in addition to encoding processes, were disrupted. On the non-verbal task, the deficits appeared more limited to encoding. Therefore, while the operational integrity of components such as encoding were compromised regardless of material, retrieval processes showed material-specific effects. To the degree verbal and non-verbal memory functions can be lateralized in the brain, these data support the possibility of deficits in both right and left hemisphere declarative memory systems in schizophrenia.

Adult↗
PubMed2001

External beam radiotherapy for synchronous rectal and prostatic tumors.

Two patients were diagnosed with large rectal tumors and localized prostate cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0 ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close proximity allowed creation of a modified three-dimensional conformal radiotherapy plan to treat both tumors. The patients had no evidence of rectal tumor recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL at 1 and 2 years after therapy, respectively. We conclude that efficient, effective pelvic irradiation can be designed for synchronous rectal and prostate malignancies.

Adenocarcinoma↗
PubMed2001

Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses.

The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has remained unexplained. Here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. The molecular basis for this regulation is the alteration of the expression ratio of the costimulatory ligands B7.1/B7.2 on dendritic cells. Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualitative differences in T-cell responses, providing the basis for counter-regulation mediated by IL-4.

Animals↗
PubMed2001

Drosophila heterochromatin protein 1 (HP1)/origin recognition complex (ORC) protein is associated with HP1 and ORC and functions in heterochromatin-induced silencing.

Heterochromatin protein 1 (HP1) is a conserved component of the highly compact chromatin of higher eukaryotic centromeres and telomeres. Cytogenetic experiments in Drosophila have shown that HP1 localization into this chromatin is perturbed in mutants for the origin recognition complex (ORC) 2 subunit. ORC has a multisubunit DNA-binding activity that binds origins of DNA replication where it is required for origin firing. The DNA-binding activity of ORC is also used in the recruitment of the Sir1 protein to silence nucleation sites flanking silent copies of the mating-type genes in Saccharomyces cerevisiae. A fraction of HP1 in the maternally loaded cytoplasm of the early Drosophila embryo is associated with a multiprotein complex containing Drosophila melanogaster ORC subunits. This complex appears to be poised to function in heterochromatin assembly later in embryonic development. Here we report the identification of a novel component of this complex, the HP1/ORC-associated protein. This protein contains similarity to DNA sequence-specific HMG proteins and is shown to bind specific satellite sequences and the telomere-associated sequence in vitro. The protein is shown to have heterochromatic localization in both diploid interphase and mitotic chromosomes and polytene chromosomes. Moreover, the gene encoding HP1/ORC-associated protein was found to display reciprocal dose-dependent variegation modifier phenotypes, similar to those for mutants in HP1 and the ORC 2 subunit.

Amino Acid Sequence↗
PubMed2001

Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac.

In the current study, the identification of the rat and human UDP-glucuronosyltransferase (UGT) isoforms responsible for the glucuronidation of diclofenac was determined. Recombinant human UGT1A9 catalyzed the glucuronidation of diclofenac at a moderate rate of 166-pmol/min/mg protein, while UGT1A6 and 2B15 catalyzed the glucuronidation of diclofenac at low rates (<20-pmol/min/mg protein). Conversely, human UGT2B7 displayed a high rate of diclofenac glucuronide formation (>500 pmol/min/mg protein). Recombinant rat UGT2B1 catalyzed the glucuronidation of diclofenac at a rate of 250-pmol/min/mg protein. Rat UGT2B1 and human UGT2B7 displayed a similar, low apparent Km value of <15 microM for both UGT isoforms and high Vmax values 0.3 and 2.8 nmol/min/mg, respectively. Using diclofenac as a substrate, enzyme kinetics in rat and human liver microsomes showed that the enzyme(s) involved in diclofenac glucuronidation had a low apparent Km value of <20 microM and a high Vmax value of 0.9 and 4.3 nmol/min/mg protein, respectively. Morphine is a known substrate for rat UGT2B1 and human UGT2B7 and both total morphine glucuronidation (3-O- and 6-O-glucuronides) and diclofenac glucuronidation reactions showed a strong correlation with one another in human liver microsome samples. In addition, diclofenac inhibited the glucuronidation of morphine in human liver microsomes. These data suggested that rat UGT2B1 and human UGT2B7 were the major UGT isoforms involved in the glucuronidation of diclofenac.

Animals↗