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Biomedical subjects

N Cooke

Publications and source records attributed to N Cooke.

At least 19 recordsLinked to original sources

The pathway study: results of a pilot feasibility study in patients suspected of having lung carcinoma investigated in a conventional chest clinic setting compared to a centralised two-stop pathway.

UNLABELLED: The best chance of cure in non-small cell lung cancer (NSCLC) is surgical resection, but UK rates of 8% compare poorly to 25% in the USA and Europe. Delays in diagnosis in the current UK system may be one reason for such discrepancy. To address this problem we set up a rapid diagnostic system and compared it to the conventional method of investigations in a pilot randomised trial. METHODS: Eighty-eight patients were prospectively enrolled from three District General Hospitals and randomised to either investigation locally or to the rapid system at The Royal Marsden Hospital. The pilot end-points were feasibility and audit of radical treatment rates to enable estimates for patient numbers for the full study. RESULTS: Forty-five and 43 patients were in the central and conventional arms, respectively (65% male, median age 69 years). There was a 4-week improvement in time to first treatment in those in the central arm (P=0.0025) with 13/30 (43%) and 9/27 (33%) patients having radical treatment in the central and conventional arms, respectively. Patients in the conventional arm felt the diagnostic process was too slow (P=0.02) while those in the central arm seemed to have a better care experience (P=0.01). There were significantly less visits to the general practitioner (GP) in the central arm (P=0.02). CONCLUSIONS: This pilot study demonstrates that the full study is feasible but would require the commitment and involvement of a large number of patients and physicians. The results show several advantages to investigations and diagnosis in the central arm, particularly in time to treatment initiation, patient satisfaction and rate of radical treatments. The improved rate of radical treatment could lead to an improved survival rate.

Aged↗

The multifunctional properties and characteristics of vitamin D-binding protein.

In recent years, our understanding of the many physiological, biochemical, and molecular functions and attributes of vitamin D-binding protein (DBP) has seen exciting and significant advances. Since its identification in 1959, many important functions of this abundant serum protein have been discovered. These range from the transport of vitamin D metabolites to possible roles in the immune system and host defense. With these discoveries, many questions regarding the biology of DBP have been raised and many remain to be answered. Our current understanding of the classic and less-recognized activities of DBP is discussed here.

Amino Acid Sequence↗

Incidence and prevalence of dementia in a multiethnic cohort of municipal retirees.

BACKGROUND: Multiethnic population-based studies of dementia are lacking in the literature; therefore, we conducted a study to determine the incidence and prevalence of dementia among, black, white, and Hispanic municipal retirees age 50 and older. METHODS: In 1991, city of Houston municipal workers who retired between 1980 and 1984 received in-home screening for cognitive impairment using the Mini-Mental State Examination and were referred for comprehensive neurologic evaluation if indicated. Families of deceased retirees were interviewed, medical records were reviewed, and death certificates were obtained to determine case status of the retiree. Study participation was 90%. RESULTS: Crude prevalence of dementia, among retirees age 60 and older, was 2.65 per 100 population. Age-adjusted to the 1970 US population, age 60 to 80, the prevalence was 1.85 per 100 population. Age-adjusted prevalence of dementia was similar among Hispanic and black men, 4.75 and 4.80 respectively, and lowest among white men, 2.42 per 100 population. Forty-three percent of the prevalent cases (30% of the incidence cases) were not previously diagnosed. The cumulative incidence of dementia calculated to age 80 was 39% for Hispanic men, 28% for black men, and 14% for white men. Fifty-five percent of the incidence cases were diagnosed as having ischemic vascular dementia (IVD), 20% as having probable or possible Alzheimer's dementia (AD), and 25% as having unspecified dementia. CONCLUSIONS: Risk of dementia by age 80 was more pronounced for Hispanic and black men compared with white men. IVD was the predominant cause of dementia among both black and white men. Grouping Hispanics with whites may mask differences when studying dementia.

Aged↗

Neuropsychological asymmetry in Alzheimer's disease: verbal versus visuoconstructional deficits across stages of dementia.

The incidence of clinically apparent asymmetric profiles of neuropsychological deficits in Alzheimer's disease (AD) patients similar to those reported in the PET literature is currently unclear. This study investigated lateral neuropsychological asymmetry using principal component factor analysis in a sample of 153 patients diagnosed with probable AD. Using factor scores, patients were classified into groups exhibiting asymmetric or symmetric profiles of neuropsychological deficits. In the analysis of lateral asymmetry, 27.5% of patients were classified as asymmetric (10% verbally and 17% visuospatially). Consistent with reports of continued asymmetry beyond the mild dementia stage, asymmetry was exhibited in the mild, moderate, and severely demented groups. These findings of neuropsychological asymmetry across stages of dementia are consistent with the picture of significant neuropsychological heterogeneity in AD that has been emerging in the decade.

Aged↗

High-resolution capillary gel electrophoresis of reducing oligosaccharides labeled with 1-aminopyrene-3,6,8-trisulfonate.

High-resolution capillary gel electrophoresis was used for the separation of oligosaccharides labeled with a novel fluorophore 1-aminopyrene-3,6,8-trisulfonate (APTS) at the reducing termini by reductive amination. The APTS-saccharide adducts were detected by laser-induced fluorescence with excitation by the 488-nm Ar-ion laser and a 520-nm emission filter. The stoichiometry of labeling is such that only one molecule of fluorophore is attached to each molecule of oligosaccharide. Derivatization parameters, such as labeling reagent concentration, labeling temperature, and time as well as the influence of reaction solvent are thoroughly discussed. Desialylation of several sialylated oligosaccharides with different structures and linkages due to the effects of labeling temperature and time are also addressed. Employing the optimized conditions suggested in this paper, fluorophore labeling efficiency greater than 97% was achieved with no significant loss of sialic acid residues. The fluorescently labeled oligosaccharides are then separated and quantified by capillary gel electrophoresis. Practical examples of low-level derivatization and high-resolution capillary gel electrophoresis separation of N-linked glycans of ribonuclease-B and fetuin are also shown.

Acetylglucosamine↗

Prevalence and correlates of neuropsychological deficits in amyotrophic lateral sclerosis.

OBJECTIVE: To determine the prevalence and correlates of neuropsychological impairment in a large cohort (n = 146) of patients with typical, sporadic (non-familial) amyotrophic lateral sclerosis. METHODS: A battery of neuropsychological tests was administered to patients with amyotrophic lateral sclerosis who were attending a monthly outpatient clinic or who were in hospital undergoing diagnostic tests. RESULTS: Comparing individual patient's scores with relevant normative data, 35.6% of the patients displayed evidence of clinically significant impairment, performing at or below the 5th percentile on at least two of the eight neuropsychological measures. Deficits were most common in the areas of problem solving, attention/mental control, continuous visual recognition memory, word generation, and verbal free recall. Impairment was most prevalent in patients with dysarthria (48.5%), but 27.4% of non-dysarthric patients were also impaired. Impaired patients had more severe or widespread symptoms of amyotrophic lateral sclerosis than non-impaired patients, and had fewer years of education. CONCLUSION: Neither the conventional wisdom that cognition is intact in nearly all patients with amyotrophic lateral sclerosis, nor more recent suggestions that cognition is often at least mildly impaired seems to be correct. A minority of patients with amyotrophic lateral sclerosis displayed evidence of significant impairment. Dysarthria, low education, and greater severity of motor symptoms were risk factors for impairment.

Amyotrophic Lateral Sclerosis↗

Rapid chiral separation methods development by cyclodextrin-mediated capillary electrophoresis for acidic and basic compounds.

Chiral separation methods development using conventional techniques such as GC or HPLC requires a lot of experience, effort, and expense, due to the wide diversity of the optically active solutes and their possible chiral selectors. Capillary electrophoresis has received increased attention as an alternative technique for chiral separation due to its inherent high efficiencies and ease of methods development. However, due to the wide variety of chiral selectors available in CE, the benefits of this technique might be diminished without an appropriate methods development scheme. In this paper detailed examples are shown for fast, efficient, and predictable chiral capillary electrophoresis separation methods development based on a new and systematic theory. Optimized separations and their parameters are presented for several enantiomeric acids and bases. All the three possible cases, such as the use of low and high pH, as well as pH = pK buffer systems are thoroughly discussed.

Acids↗

Capillary electrophoresis separation of oligosaccharides: I. Effect of operational variables.

The influence of operating variables on the separation of labeled oligosaccharide molecules in capillary electrophoresis with polymer networks is presented. In this study, an equation was derived that relates the effects of electrophoresis variables such as field strength, temperature, molecular weight and gel concentration to the migration velocity. As a model system, 8-aminonaphthalene-1,3,6-trisulfonate ANTS-labeled wheat starch digest was examined to show the validity of the equation. As an illustration of the high resolving power achievable with capillary electrophoresis, oligosaccharide molecules up to the degree of polymerization of 25 were separated with the very high efficiency of N > 10(6) and efficiency generation rate of 3500 plates/m/s for maltose. Separation based on the size of the oligosaccharides was not obtained with either entangled or unentangled polymer solutions.

Electric Conductivity↗

Effect of operational variables on the separation of proteins by capillary sodium dodecyl sulfate-gel electrophoresis.

Capillary sodium dodecyl sulfate (SDS)-gel electrophoresis, for fast and high-resolution separations of protein molecules based on their molecular masses was investigated, employing a polymeric sieving network of polyethylene oxide (PEO). A standard mixture of five proteins ranging from 14.2-66.0 kDa in molecular mass was used to evaluate the sieving matrix. A general migration velocity equation was derived for capillary SDS-gel electrophoresis of proteins and supported by the experimental data. This equation gives a better understanding of SDS-protein separations via capillary gel electrophoresis. Results are presented regarding the effects of different operational variables such as gel concentration, electric field strength, molecular mass, and temperature on the electrophoretic migration properties of the different size protein molecules.

Electromagnetic Fields↗

Social and family factors in adolescent psychiatry.

A retrospective analysis of referrals to a regional adolescent psychiatric service over two years was conducted, focusing on selected social and family variables, to identify areas of potential unmet need and the relationship between these factors and clinical variables. Social and family disadvantage was well represented in our patients, but few were over the age of 17 and fewer from ethnic minority backgrounds. Associations between social, family factors, diagnostic and treatment variables are presented and their implications discussed.

Adolescent↗

Prediction of migration behavior of oligonucleotides in capillary gel electrophoresis.

The influence of the primary structure (base composition) on the electrophoretic migration properties of single-stranded oligodeoxyribonucleotides in capillary polyacrylamide gel electrophoresis was investigated using homo- and heterooligomers under denaturing and non-denaturing conditions. Homooligodeoxyribonucleotides of equal chain lengths but of different base composition showed significant differences in mobility. In addition, the migration properties of heterooligomers were found to be highly dependent on their base composition. A simple equation is presented for predicting relative migration times using denaturing and non-denaturing polyacrylamide capillary gel electrophoresis. Orange-G was used as an internal standard and as the basis of the relative migration time calculations. Examples are presented using homo- and heterooligomers in the 10-20-mer range to show the correlation of the primary structure and their predicted and observed migration rates.

Base Sequence↗

Establishing the limits of the Mini-Mental State. Examination of 'subtests'.

It has been suggested that the Mini-Mental State examination can be used to examine a patient's cognitive profile. We therefore examined the validity of Mini-Mental State subtests and individual items. The memory item, attention-concentration items, and constructional item had satisfactory sensitivity-specificity and correlated significantly with scores on neuropsychological tests. In contrast, four of the five Mini-Mental State language items had very low sensitivity, and three of five failed to correlate with neuropsychological test scores. These findings establish limits with regard to the ability of the Mini-Mental State to generate a cognitive profile. Our data also provide information regarding validity, difficulty level, and optimal cutoff scores for widely used mental status tasks.

Adult↗

Capillary gel affinity electrophoresis of DNA fragments.

The incorporation of an affinity ligand within a polyacrylamide gel provides a general means of manipulating the selectivity of capillary gel electrophoresis separations. As an example of this approach, high resolution of DNA restriction fragments by capillary gel affinity electrophoresis has been achieved by adding a soluble intercalating agent, ethidium bromide, to the gel-buffer system. A migration model has been developed that can be used for selectivity optimization. Various parameters, such as ligand concentration and applied electric field, have been examined in terms of their influence on retention and selectivity of different-size DNA molecules. From this study, high-resolution separations have been developed with efficiencies as high as 10(7) theoretical plates per meter.

Chromatography, Affinity↗

The metabolism of ceramic and non-ceramic forms of uranium dioxide after deposition in the rat lung.

Ceramic and non-ceramic forms of uranium dioxide, produced industrially, were administered to rats either by inhalation or as an aqueous suspension which was injected directly into the pulmonary region of the lungs. The results showed that: 1 both materials should be assigned to inhalation class Y as defined by the International Commission on Radiological Protection; 2 whilst the translocation of uranium to the blood for the non-ceramic UO2 was about twice that obtained for the ceramic form, the two dioxides were unlikely to be differentiated on the basis of their lung retention kinetics; 3 the distribution of uranium amongst body tissues and the relationship between systemic content and cumulative urinary excretion indicated that it was transported in the hexavalent form; 4 in addition to air sampling procedures, lung radioactivity counting measurements could be used to advantage for assessing occupational exposures; 5 the exposure limits should be based on radiation dose rather than chemical toxicity.

Administration, Inhalation↗

Metabolism of uranium in the rat after inhalation of two industrial forms of ore concentrate: the implications for occupational exposure.

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O8 bearing material should be governed by radiation dose.

Aerosols↗