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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 145 records · Page 8Linked to original sources

Anxiety disorders in cancer patients: their nature, associations, and relation to quality of life.

PURPOSE: We aimed to estimate the prevalence and types of anxiety disorders diagnosed according to standardized criteria in cancer patients, to compare screening tools in detecting them, and to examine their demographic, oncologic, and psychosocial associations. METHODS: In this cross-sectional observational study of 178 subjects with lymphoma, renal cell carcinoma, malignant melanoma, or plasma cell dyscrasia, we related responses to questionnaires (administered by computer touch-screen) measuring psychological symptoms, quality of life (QOL), and social support to standardized psychiatric interviews and cancer management. RESULTS: Forty-eight percent of subjects reported sufficient anxiety for anxiety disorder to be considered. At subsequent diagnostic interview, 18% fulfilled International Classification of Disorders, 10th Revision criteria for anxiety disorder, including 6% of patients who reported low levels of anxiety by questionnaire. When subjects reported anxiety by questionnaire, if disruptive somatic anxiety was present, this increased the probability of diagnosable anxiety disorder from.31 to.7. The most accurate screening questionnaires were the trait scale of the State-Trait Anxiety Inventory and the Hospital Anxiety and Depression scale. Female sex and negative aspects of social support were associated with anxiety disorder in multivariate analyses. Anxiety disorder was independently associated with a deficit in QOL, particularly insomnia. CONCLUSION: Anxiety symptoms are common in cancer patients. Screening by questionnaire seems to assess anxiety symptoms adequately but discriminates abnormal anxiety inadequately. To improve this, we may need to use criteria such as disruption from anxiety, as illustrated by the impact of anxiety disorders on QOL. There seem to be few oncologic variables that could target screening for anxiety disorders.

Adult↗

Improved measurement of Vub with inclusive semileptonic B decays.

We report a new measurement of the Cabibbo-Kobayashi-Maskawa parameter Vub made with a sample of 9.7 x 10(6) BB- events collected with the CLEO II detector. Using heavy quark theory, we combine the observed yield of leptons from semileptonic B decay in the end-point momentum interval 2.2-2.6 GeV/c with recent CLEO II data on B-->X(s)gamma to find Vub = (4.08+/-0.34+/-0.44+/-0.16+/-0.24)x10(-3), where the first two uncertainties are experimental and the last two are from theory.

Journal Article↗

Search for CP violation in tau--> K(pi)nu(tau) decays.

We search and find no evidence for CP violation in tau decays into the K(pi)nu(tau) final state. We provide limits on the imaginary part of the coupling constant Lambda describing a relative contribution of the CP violating processes with respect to the standard model to be -0.172<Im(Lambda)<0.067 at 90% C.L.

Journal Article↗

Observation of exclusive B --> D(*)K(*-) decays.

We report the first observation of the exclusive decays B-->D((*))K(*-), using 9.66 x 10(6) BB pairs collected at the Upsilon(4S) with the CLEO detector. We measure the following branching fractions: B(B--->D(0)K(*-)) = (6.1+/-1.6+/-1.7)x10(-4), B(B(0)-->D(+)K(*-)) = (3.7+/-1.5+/-1.0)x10(-4), B(B(0)-->D(*+)K(*-)) = (3.8+/-1.3+/-0.8)x10(-4), and B(B--->D(*0)K(*-)) = (7.7+/-2.2+/-2.6)x10(-4). The B-->D(*)K(*-) branching ratios are the averages of those corresponding to the 00 and 11 helicity states. The errors shown are statistical and systematic, respectively.

Journal Article↗

Development of a novel nasal nicotine formulation comprising an optimal pulsatile and sustained plasma nicotine profile for smoking cessation.

A novel nasal formulation, in the form of a nicotine-Amberlite resin complex powder has been developed that provided an optimal combined pulsatile and sustained plasma nicotine profile for smoking cessation. The adsorption isotherms of nicotine hydrogen tartrate salt on two types of Amberlite resins (IRP69 and IR120) were evaluated and the subsequent in vitro release properties of nicotine from the nicotine-Amberlite complex powders were tested using a Franz diffusion cell. Amberlite IRP69 and Amberlite IR120 are similar cationic exchange materials with the same ion-exchange capacity but due to a smaller particle size range (10-150 microm) Amberlite IRP69 had a better flow property and a better adsorptive capacity than Amberlite IR120. The material is used as an excipient in marketed pharmaceutical formulations. The highly water soluble salt, nicotine hydrogen tartrate, displayed good adsorption onto both types of Amberlite resin. The maximum adsorption of nicotine onto Amberlite IRP69 was 1.071 mg drug per mg resin. The cumulative release of drug from nicotine hydrogen tartrate-Amberlite complex powders showed that the higher the drug loading, the faster was the rate of release of the drug. Based on these results, various nicotine hydrogen tartrate-Amberlite IRP69 powder formulations containing different ratios of free to bound drug (50% to 100% bound) and a control solution were prepared and evaluated in a sheep model by nasal administration. The nicotine plasma profiles demonstrated that an initial rapid peak plasma level of nicotine followed by a sustained elevated level could be achieved by adjusting the ratio of free to bound nicotine in the Amberlite powder formulation. The curves obtained from some of the formulations were comparable to those predicted from a computer-generated pharmacokinetic model.

Administration, Intranasal↗

Effects of caffeine on human behavior.

The literature suggests that the following effects on behavior of adult humans may occur when individuals consume moderate amounts of caffeine. (1) Caffeine increases alertness and reduces fatigue. This may be especially important in low arousal situations (e.g. working at night). (2) Caffeine improves performance on vigilance tasks and simple tasks that require sustained response. Again, these effects are often clearest when alertness is reduced, although there is evidence that benefits may still occur when the person is unimpaired. (3) Effects on more complex tasks are difficult to assess and probably involve interactions between the caffeine and other variables which increase alertness (e.g. personality and time of day). (4) In contrast to the effects of caffeine consumption, withdrawal of caffeine has few effects on performance. There is often an increase in negative mood following withdrawal of caffeine, but such effects may largely reflect the expectancies of the volunteers and the failure to conduct "blind" studies. (5) Regular caffeine usage appears to be beneficial, with higher users having better mental functioning. (6) Most people are very good at controlling their caffeine consumption to maximise the above positive effects. For example, the pattern of consumption over the day shows that caffeine is often consumed to increase alertness. Indeed, many people do not consume much caffeine later in the day since it is important not to be alert when one goes to sleep. In contrast to effects found from normal caffeine intake, there are reports that have demonstrated negative effects when very large amounts are given or sensitive groups (e.g. patients with anxiety disorders) were studied. In this context caffeine has been shown to increase anxiety and impair sleep. There is also some evidence that fine motor control may be impaired as a function of the increase in anxiety. Overall, the global picture that emerges depends on whether one focuses on effects that are likely to be present when caffeine is consumed in moderation by the majority of the population or on the effects found in extreme conditions. The evidence clearly shows that levels of caffeine consumed by most people have largely positive effects on behavior. Excessive consumption can lead to problems, especially in sensitive individuals.

Affect↗

Syndrome of myelofibrosis and osteosclerosis: a series of case reports and review of the literature.

Myelofibrosis (MF) is a chronic disorder characterized by bone marrow evidence of myeloid metaplasia associated with reactive fibrosis, angiogenesis, and osteosclerosis. We report serum biochemistry, noninvasive markers of bone turnover, tetracycline-labeled bone histomorphometry, and bone densitometry (DXA) data of four men presenting with newly diagnosed biopsy-proven MF and osteosclerosis. The mechanisms and putative growth factors responsible for this syndrome are examined.

Aged↗

Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles.

PURPOSE: To investigate whether the widely accepted advantages as sociated with the use of chitosan as a nasal drug delivery system might be further improved by application of chitosan formulated a nanoparticles. METHODS: Insulin-chitosan nanoparticles were prepared by the ionotropic gelation of chitosan glutamate and tripolyphosphate pentasodium and by simple complexation of insulin and chitosan. The nasal absorption of insulin after administration in chitosan nanoparticle formulations and in chitosan solution and powder formulations wa evaluated in anaesthetised rats and/or in conscious sheep. RESULTS: Insulin-chitosan nanoparticle formulations produced a pharmacological response in the two animal models, although in both cases the response in terms of lowering the blood glucose levels was less (to 52.9 or 59.7% of basal level in the rat, 72.6% in the sheep than that of the nasal insulin chitosan solution formulation (40.1% in the rat, 53.0% in the sheep). The insulin-chitosan solution formulation was found to be significantly more effective than the complex and nanoparticle formulations. The hypoglycaemic response of the rat to the administration of post-loaded insulin-chitosan nanopar ticles and insulin-loaded chitosan nanoparticles was comparable. As shown in the sheep model, the most effective chitosan formulation for nasal insulin absorption was a chitosan powder delivery system with a bioavailability of 17.0% as compared to 1.3% and 3.6% for the chitosan nanoparticles and chitosan solution formulations, respectively. CONCLUSION: It was shown conclusively that chitosan nanoparticles did not improve the absorption enhancing effect of chitosan in solution or powder form and that chitosan powder was the most effective for mulation for nasal delivery of insulin in the sheep model.

Administration, Intranasal↗

Role of the histidine residue at position 105 in the human alpha 5 containing GABA(A) receptor on the affinity and efficacy of benzodiazepine site ligands.

1. A histidine residue in the N-terminal extracellular region of alpha 1,2,3,5 subunits of the human GABA(A) receptor, which is replaced by an arginine in alpha 4 and alpha 6 subunits, is a major determinant for high affinity binding of classical benzodiazepine (BZ)-site ligands. The effect of mutating this histidine at position 105 in the alpha 5 subunit to an arginine (alpha 5H105R) on BZ-site pharmacology has been investigated using radioligand binding on HEK293 and L(tk-) cells and two electrode voltage clamp recording on Xenopus oocytes in which GABA(A) receptors of subtypes alpha 5, alpha 5H105R, alpha 4 and alpha 6 were co-expressed with beta 3 gamma 2s. 2. The classical BZs, diazepam and flunitrazepam (full agonists on the alpha 5 receptor) showed negligible affinity and therefore negligible efficacy on alpha 5H105R receptors. The beta-carbolines DMCM and beta CCE (inverse agonists on the alpha 5 receptor) retained some affinity but did not exhibit inverse agonist efficacy at alpha 5H105R receptors. Therefore, the alpha 5H105R mutation confers an alpha 4/alpha 6-like pharmacology to the classical BZs and beta-carbolines. 3. Ro15-4513, flumazenil, bretazenil and FG8094, which share a common imidazobenzodiazepine core structure, retained high affinity and were higher efficacy agonists on alpha 5H105R receptors than would be predicted from an alpha 4/alpha 6 pharmacological profile. This effect was antagonized by DMCM, which competes for the BZ-site and therefore is likely to be mediated via the BZ-site. 4. These data indicate that the conserved histidine residue in the alpha subunit is not only a key determinant in the affinity of BZ-site ligands on alpha 5 containing GABA(A) receptors, but also influences ligand efficacy.

Anticonvulsants↗

Effect of venous ulcer exudates on angiogenesis in vitro.

BACKGROUND: Angiogenesis, the formation of new from existing capillaries, is an important mechanism in venous ulcer healing. The aim of this study was to determine whether venous leg ulcer wound exudates stimulate or inhibit angiogenesis. METHODS: Fluid exudate was obtained from 16 venous ulcers over a 4-h interval. Five of the ulcers had not healed after more than 1 year of compression bandaging, and five were rapidly healing ulcers. As a control, acute wound fluids were collected from subcutaneous drains in seven patients. Vascular endothelial growth factor (VEGF) at 2 ng/ml acted as a positive control. Tubules stained with an antiendothelial antibody were quantified using an image analysis system. The extent of angiogenesis was expressed as the ratio of the mean tubule length in the test wells over that in blank control wells. RESULTS: Venous ulcer exudates significantly inhibited angiogenesis (mean (95 per cent confidence interval) 0.72 (0.48 to 0.96)) compared with acute wound fluids (2.48 (0.86 to 4.10)) (P < 0.002) and VEGF (1.47 (1.32 to 1.61)) (P = 0.01). Exudates from the five non-healing venous ulcers inhibited angiogenesis (0.31 (0.15 to 0.46)) significantly more than exudates from the five rapidly healing venous ulcers (0.93 (0.21 to 1.65)) (P = 0.03). CONCLUSION: Fluid exudate from venous ulcers, in particular those that healed slowly, inhibited experimental angiogenesis in this study.

Adult↗

A comparison of therapeutic commitment, role support, role competency and empathy in three cohorts of nursing students.

This study investigated the perceptions of students regarding their therapeutic commitment, role competency, role support and empathy towards working with people who have mental health problems. These qualities play a key part in the development of therapeutic relationships, an important goal for working with individuals in most nursing situations. The sample comprised of three cohorts of nursing students undertaking the Diploma in Higher Education (Nursing) in Scotland. There were no significant differences in perceptions of empathy and therapeutic commitment among three cohorts of students, but third year students felt they received less role support than other cohorts. The findings also revealed that preregistration nursing students have perceptions of their role competency and empathic skills which are considerably greater than has been previously reported by registered nurses. The implications of these findings for nurse education are discussed.

Clinical Competence↗

Contaminated dental instruments.

There is current concern in the UK over the possible transmission of prions via contaminated surgical instruments. Some dental instruments (endodontic files) raise particular concerns by virtue of their intimate contact with terminal branches of the trigeminal nerve. A visual assessment using a dissecting light microscope and scanning electron microscopy of endodontic files after clinical use and subsequent decontamination was performed. The instruments examined were collected from general dental practices and from a dental hospital. Seventy-six per cent (22/29) of the files retrieved from general dental practices remained visibly contaminated, compared with 14% (5/37) from the dental hospital. Current methods for decontaminating endodontic instruments used in dentistry may be of an insufficient standard to completely remove biological material. Improved cleaning methods and the feasibility of single use endodontic instruments require further investigation.

Creutzfeldt-Jakob Syndrome↗

Current practice of hysterectomy and oophorectomy in the United Kingdom and Republic of Ireland.

The purpose of this study was to estimate current surgical practice of hysterectomy and prophylactic oophorectomy of UK and Irish consultant gynaecologists. Individual and regional variation in surgical practice and factors influencing surgical practice were assessed. A postal questionnaire was sent to all 1536 consultants in obstetrics and gynaecology currently practising in the United Kingdom and Ireland, with a 52.7% response rate. Approximately 60% of hysterectomies were abdominal, 37% vaginal and 4% laparoscopic-assisted, with junior consultants performing a greater proportion of hysterectomies vaginally. There was a wide variation in method of hysterectomy, both individually and regionally. Only 21% of consultants would routinely consider performing prophylactic oophorectomy and of these the majority would perform this procedure in women aged between 46 and 50 years old. This large variation in surgical practice indicates a need to form a consensus on optimal surgical techniques and to ensure adequate surgical training for all gynaecologists.

Female↗

Scrapie epidemic in a fully PrP-genotyped sheep flock.

In scrapie-affected sheep flocks, host PrP genotype plays a vital role in determining which sheep will succumb to scrapie and the incubation period. Consequently, within-flock scrapie dynamics is best understood within the context of the genotype profile of the flock. Here we describe a 17 month epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep. At the start of the study, 70% of the sheep were of three genotypes only: ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated VRQ allele and only a single sheep (0.4%) was of the most susceptible VRQ/VRQ genotype. For susceptible genotypes there was a marked deficit (P<0.025) of older animals (> or =3 years), implying that some cases of scrapie had occurred previously. In the ensuing 17 months, 18 sheep of known genotype were confirmed positive for the disease: seven VRQ/ARQ, six VRQ/ARH, two VRQ/ARR, three ARQ/ARQ. Median ages at death were 2.7, 2.8, 4.2 and 3.8 years respectively. Mortality rates were 55, 86, 13 and 3% respectively. Survival analysis revealed a highly significant effect of genotype on survivorship, but no difference between VRQ/ARQ and VRQ/ARH, or between VRQ/ARR and ARQ/ARQ. There was no difference in the survivorship of middle- and older-age cohorts of susceptible sheep. Scrapie risk group (as defined by PrP genotype) was not associated with submission as a scrapie suspect but later found to be negative, or with dying of unknown causes on the farm.

Age Factors↗

Intra-muscular ketorolac administered as a supplemental analgesic for removal of impacted third molar teeth: a prospective study.

BACKGROUND: Post-operative pain follows dentalveolar oral surgery. Ketorolac is a potent non-steroidal analgesic with moderate anti-inflammatory effects. The purpose of this study was to test whether a single supplementary dose of ketorolac reduced post-operative pain experienced by patients having third molar teeth removed. METHODS: A prospective double-blind trial utilizing 30mg of ketorolac and a standard anaesthetic and surgical technique was performed on 65 female patients having impacted third molar teeth removed. Assessment was made by means of a patient questionnaire and visual analogue pain scales and subjected to statistical analysis. RESULTS: There was a statistically significant difference confirming improved pain relief for patients receiving ketorolac 30mg at the early postoperative stage (two hours) but at later time intervals (four and six hours) there was no significant difference. Seventy two per cent of patients found ketorolac to be a satisfactory analgesic for postoperative pain. There were minimal side effects. CONCLUSION: A single supplemental dose of ketorolac 30mg provides improved pain relief in the immediate post-operative phase following the removal of third molar teeth. Oral ketorolac can be recommended as a oral analgesic for post-operative pain, with minimal side effects.

Adolescent↗

Type 2 diabetes in obese white children.

We report four white adolescents aged 13 to 15 years (three females, one male) from the south and west region of England who presented with type 2 diabetes mellitus associated with significant obesity (body mass index more than +3SDS) in the past two years. Although these are the first reported obese, white cases from the UK to present with diabetes, we believe this clinical scenario will become more prevalent given the epidemic of childhood obesity in this country.

Adolescent↗