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Biomedical subjects

T West

Publications and source records attributed to T West.

18 recordsLinked to original sources

Are initial demyelinating event recovery and time to second event under differential control?

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) begins with an initial demyelinating event (IDE) that can be monosymptomatic, polysymptomatic, or polyregional. Failure to recover from the IDE is a known predictor of later development of disability. Factors that predict IDE recovery (outside optic neuritis) and time to second event are relatively unknown. The authors speculate that IDE recovery and time to second event are under separate biologic or genetic control, and as such, their clinical predictors are different. METHODS: Data on all UCSF MS clinic patients are entered prospectively into an ACCESS database. The authors identified all patients seen at the UCSF clinic within 1 year of their IDE. Expanded Disability Status Scale scores, functional system scores, and visual acuity were used to define IDE severity and recovery. RESULTS: The cohort included 186 patients (127 women, 59 men) with an average onset age of 34 +/- 10 years with 150 whites (non-Hispanic), 15 African Americans, 11 Hispanics, eight Asians, and two unknown/unreported. Worse onset severity predicted worse IDE recovery (23.1% of the patients with severe onset vs 32.9% with moderate severity vs 56.4% with mild onset recovered completely, p < 0.001). Polyregional onset predicted poor recovery compared to monoregional onset (46.2% vs 14.4%, p < 0.001). Nonwhite patients were 2.48 times more likely than whites to experience a second episode within 1 year from onset (95% CI: 1.45 to 4.23, p < 0.001). Similarly, age younger than 30 years predicted higher risk of a second exacerbation (hazard ratio 1.92, 95% CI: 1.17 to 3.15, p = 0.010). CONCLUSION: Initial demyelinating event recovery and time to second event may have distinct predictors. These findings suggest that recovery and time to second event might be under separate biologic control.

Adult↗

TN/TN glottic carcinoma: a comparison of two fractionation schedules.

The aim of this paper is the retrospective comparison of accelerated/hypofractionated radiotherapy regimen (AHFX) with standard fractionation regimen (SFX) for patients with early glottic carcinoma. One hundred and forty-five patients with T(1)-T(2) glottic cancer between 1986 and 1998 were eligible. Before 1992, patients received 60-66 Gy in 30-33 fractions over 6-6.5 weeks (SFX) with (60)Co and 6-MV beams. After 1992, patients received 52.5-55 Gy in 20 fractions over 4 weeks (AHFX) using 6-MV beams. The end-points were overall survival, laryngectomy-free survival (LFS), loco-regional control and toxicity. One hundred and two were stage T(1)N(0); 43 were stage T(2)N(0). Median follow up was 4.9 years. The 5-year overall survival was 78%. Five-year loco-regional control in T(1)N(0) patients was higher in AHFX than in SFX group (95 vs 75%, P = 0.002). Loco-regional control in T(2)N(0) patients was similar for AHFX and SFX (81 vs 80%, P = 0.813). Overall LFS was 88%. T(1)N(0) AHFX patients had 5-year LFS of 95% compared with 75% for SFX (P = 0.003). For T(2)N(0) AHFX patients, overall LFS was 92% compared with 80% for the SFX group (P = 0.291). No grade 4 or 5 late toxicity occurred. One AHFX patient developed grade 3 toxicity; two of 51 SFX patients developed grade 2 toxicity versus five of 94 AHFX patients. AHFX using 6-MV beams for treatment of early glottic cancer resulted in equivalent LFS and toxicity when compared with SFX.

Carcinoma↗

Short-burst oxygen therapy for COPD patients: a 6-month randomised, controlled study.

Short-burst oxygen therapy (SBOT) remains widely advocated for patients with chronic obstructive pulmonary disease (COPD), despite a lack of supporting evidence. The aim of this randomised, double-blind, placebo-controlled, parallel group study was to determine whether SBOT improves health-related quality of life (HRQL) or reduces acute healthcare utilisation in patients discharged following an acute exacerbation of COPD. Consecutive patients were screened; 78 of 331 were eligible for randomisation to cylinder oxygen, cylinder air or usual care following discharge. Patients were elderly with high acute healthcare utilisation, forced expiratory volume in one second of <1 L and had dyspnoea limiting daily activity but were not hypoxaemic at rest. Over the 6-month study period, there were no significant differences between patient groups in HRQL (Chronic Respiratory Questionnaire (CRQ), 36-item Short-Form Health Survey, Hospital Anxiety and Depression Scale) except for CRQ emotion domain. There were no significant differences in acute healthcare utilisation. Time to readmission was greatest in the usual care group. Cylinder use was high initially, but rapidly fell to very low levels within weeks in both cylinder oxygen and air groups. In conclusion, the availability of short-burst oxygen therapy for chronic obstructive pulmonary disease patients discharged from hospital following an acute exacerbation did not improve health-related quality of life or reduce acute healthcare utilisation. These results provide no support for the widespread use of short-burst oxygen therapy.

Acute Disease↗

Percutaneous closure of patent foramen ovale.

AIM: To review the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) in symptomatic patients without the use of general anaesthesia or echocardiographic guidance. METHOD: All patients accepted for percutaneous PFO closure by our service from August 2002 to August 2004 were included. Patient demographics and clinical information were obtained from clinical records and by telephone interview. Follow-up outcomes recorded were recurrence of systemic thromboembolism, residual shunt, and change in pattern of migraines. RESULTS: Forty consecutive adult patients, of whom 19 (48%) had an atrial septal aneurysm (ASA), underwent PFO closure using the Amplatzer occluder device with fluoroscopic guidance alone. Their mean age was 45 +/- 10 years (range 23-63 years) and 24 (60%) were male. The indications for closure were ischaemic stroke (n = 26), transient ischaemic attack (TIA) (n = 8), both stroke and TIA (n = 2), refractory hypoxia (n = 2), platypnoea-orthodeoxia (n = 1) and severe migraine with seizures (n = 1). Twenty patients suffered a single neurological event and 16 suffered >1 event, including six with only radiographic evidence of >1 event. Mean procedure time was 17.7 +/- 9.6 min and fluoroscopy time was 6.7 +/- 7.3 min. Implanted device sizes were 18 mm (n = 1), 25 mm (n = 37) and 35 mm (n = 2). In 33 patients, the procedure was performed as a day-case. No complications were encountered. No further neurological events occurred in 39 patients at a mean follow-up time of 11 +/- 7 months (3-25 months) nor was a significant shunt detected in the 34 who underwent follow-up echocardiography. CONCLUSIONS: Percutaneous closure of PFO with or without ASA, under local anaesthesia and without echocardiographic guidance, is a safe and effective procedure which can be performed as a day-case. This has now become our standard clinical practice.

Adult↗

Acute toxicity of intravenously administered microfabricated silicon dioxide drug delivery particles in mice: preliminary findings.

BACKGROUND AND OBJECTIVE: Microfabricated particles with nanosized features may serve an important role in the next generation of drug delivery vehicles. Microfabrication (micro-electromechanical systems) technologies offer the promise of both structural elements (e.g., pores, reservoirs) and electromechanical features (e.g., timers, valves, actuators) built into a single particle. In order to serve as carriers to deliver drugs to systemic sites of action, such as tumors, the particles must be safe to administer intravenously. An acute safety study was performed in a mouse model, using intravenous injection of solid silicon dioxide particles created to simulate the size and shape of potential targeted drug delivery vehicles. DESIGN: Two-micron thick, square and circular, parallelepiped-shaped particles were produced with varying sizes of 2 microm, 5 microm and 10 microm using microfabrication techniques and injected into groups of mice (six mice per group) over a range of doses. End-points included acute lethality, clinical signs of toxicity and weight loss. Sections of major organs were sampled for histological examination. RESULTS: At dose levels of 1 x 10(8) particles per mouse, circular particles of 2 microm and 5 microm showed no signs of acute toxicity. Similar results were obtained with the 2 microm and 5 microm square silicon dioxide particles; however, 14-day necropsy indicates fewer 5 microm circular particles in the lung than 5 microm square particles, indicating that the shape of the particles may impact on safety. Acute lethality was observed for 10 microm particles; none of the mice injected with the 10 microm particles survived except at very low dose levels of 6 x 10(5) particles per mouse. CONCLUSIONS: Solid silicon particles greater than 5 microm in their largest dimension are cleared in the lungs and are not safe for intravenous delivery. Particles of 2-5 microm in size do not lodge predominantly in the lung and do not cause acute toxicity, but accumulate in organs such as the liver and spleen. Possible chronic toxicities associated with organ uptake of such non-biodegradable particles have yet to be addressed.

Animals↗

Fractures after stroke: frequency, types, and associations.

BACKGROUND AND PURPOSE: Stroke patients may have an increased risk of fractures because of weak bones or an increased risk of falling. Our goal was to estimate the frequency of fracture after stroke and to identify those at greatest risk. METHODS: This study incorporated 2 complementary strategies: a prospective, single-center, cohort study and an analysis of Scottish routine hospital discharge data. RESULTS: Eighty-eight fractures (30% hip) occurred in 2696 hospital-referred stroke patients. The proportions sustaining any fracture or hip fracture within 2 years were 4% and 1.1%, respectively, 1.4 (95% CI, 0.92 to 2.07) times the rate of hip fracture in the general population (ie, observed number divided by expected number or standardized morbidity ratio). Female sex, older age, low abbreviated mental test score, and prestroke dependence were associated with an increased hip fracture rate. Routine data identified 129 935 acute stroke patients admitted to Scottish hospitals. During 363 447 patient-years, 4528 patients had hip fractures, 2.0% had fractures by 1 year, and 10.6% had fractures by 10 years. This is 1.7 times the rate of hip fracture in the general population and 2.3 times that in patients with myocardial infarction. Older patients predictably had the highest rate of poststroke hip fractures but a lower standardized morbidity ratio than younger patients. CONCLUSIONS: Fractures after stroke are probably frequent and serious enough to justify the development of preventive strategies, but the modest event rate would mean that randomized, controlled trials to test these strategies specifically in stroke patients would need to enroll thousands of patients.

Age Factors↗

Using an integrated measurement system as a common language: lessons from the U.S. Army medical department.

The Process of developing an integrated measurement system for the U.S. Army Medical Department (AMEDD) is examined in this study. A fundamental issue is whether the measures of performance accumulated by any information system are the correct ones and whether these measures appropriately reflect managers' decision making. Measurement is proposed as a solution to performance barriers. The four steps involved in building the AMEDD integrated measurement system (IMS) model are set out. Strategy is explored as the key input to the IMS model. An activity-based management (ABM) model that can support the required IMS cost-based measures is also described and the interrelationship between the two models is illustrated. The key test for application of the IMS model will be whether linking strategy and measurement results in information that improves decision making.

Benchmarking↗

Stent longitudinal flexibility: a comparison of 13 stent designs before and after balloon expansion.

Longitudinal flexibility is an important property of coronary stents, facilitating delivery and allowing the expanded stent to conform to vessel contour. Subjective descriptions of flexibility abound, but there are few independent quantitative data to aid stent selection. A three-point bend test was employed to measure stiffness, the reciprocal of flexibility, for 13 stent designs in the unexpanded (bare) state, then after expansion with a 3.5-mm balloon. For eight of the designs, stiffness of the proprietary stent/balloon delivery system was also measured. In the unexpanded state, there was a wide spread of stiffness, which ranged from 0.5+/-0.2 to 91.5+/-10.0 g force/mm, depending on design. Stiffness was least for the coil (Wiktor and Crossflex) and hybrid (AVE GFX and Bard XT) designs. The MultiLink was the most flexible and the Crown the stiffest of the slotted tube designs. All stents became stiffer upon expansion. For most manufacturer-mounted stents, the delivery balloon was the main determinant of stent/balloon delivery system stiffness. Manufacturer-mounted stent profile ranged from 1.15+/-0.11 mm for the Jostent to 1.53 +/- 0.05 mm for the MultiLink system. Independent quantitative assessment of characteristics such as flexibility and profile should aid rational comparison of stent designs.

Equipment Design↗

The analgesic tropane analogue (+/-)-SM 21 has a high affinity for sigma2 receptors.

The analgesic properties of the tropane analogue (+/-)-SM 21 have been attributed to the antagonism of presynaptic m2 receptors resulting in a potentiation of acetylcholine release. However, drugs targeting a number of other neurotransmitter receptors have been shown to enhance acetylcholine release. In the current study, in vitro studies were conducted in order to determine the affinity of (+/-)-SM 21 for serotonin 5-HT3, 5-HT4, and sigma receptors. Our results indicate that (+/-)-SM 21, and its structural congeners, have a relatively high affinity for sigma2 receptors relative to their reported affinity for muscarinic receptors. The higher affinity for sigma2 versus sigma1 receptors indicates that (+/-)-SM 21 may be a suitable lead compound for developing sigma2-selective ligands.

Analgesics↗

Age, testing at preferred or nonpreferred times (testing optimality), and false memory.

Two experiments investigated whether age and testing at preferred (optimal) times of day or nonpreferred (nonoptimal) times affected the ability to select relevant from irrelevant but thematically related alternatives in a verbal false memory paradigm. A 3rd experiment pursued the same issues with a visual false memory paradigm. In all 3 experiments, younger adults (n = 195) correctly recalled studied items more often than older adults (n = 121), whereas the 2 age groups correctly recognized about the same numbers of previously studied items. In all 3 experiments, nonoptimally tested older adults had more difficulty excluding nonstudied but thematically related items than the other groups; thus, they showed the greatest evidence of false memory, although all groups did so to a significant extent. The results suggest that optimality and its circadian determinants need to be considered with some tasks for the elderly. Various models and mechanisms are discussed.

Adolescent↗

Quantitative modelling of the effects of selected intracellular metabolites on pH in fish white muscle

A model is presented that provides guidelines to the identification of key experimental variables influencing proton balance and intracellular pH in vertebrate white muscle. We have drawn on data from the literature on rainbow trout (Oncorhynchus mykiss) in an attempt to quantify the influence of metabolic, ionic and transport components of proton generation and proton consumption after exercise. Only minor changes in proton balance and in calculated intracellular pH were caused by considering changes in the concentration of bicarbonate or including the acid&shy;base characteristics of purine nucleotides. Intracellular pH, as estimated by the model, was more acidic at some time points in recovery compared with in vivo measurements, and this would appear to result mainly from inaccuracies in quantifying the phosphate component of proton buffering. Nevertheless, the model was able to simulate the typical pattern of muscle acidosis and recovery observed for trout, including the transient post-exercise acidification and the slow recovery rate. As with previous pHi models, comparison of model estimates with experimental observations is essential in this approach in order to identify whether all of the relevant metabolic processes have been considered for accurate quantification of proton balance within the white muscle compartment.

Journal Article↗

IMPLICATIONS OF HYPERGLYCEMIA FOR POST-EXERCISE RESYNTHESIS OF GLYCOGEN IN TROUT SKELETAL MUSCLE

Rates of whole-body glucose turnover and muscle-specific glucose utilization were determined in rainbow trout (Oncorhynchus mykiss) at rest and at intervals during recovery from burst swimming. Plasma glucose level was high in the experimental animals (range 6&shy;38 mmol l-1), but hyperglycemia was not related specifically to exercise. Estimated glucose turnover, 19.3&plusmn;2.6 (rest) and 15.8&plusmn;3.9 &micro;mol min-1 kg-1 (recovery), was also highly variable, but was linearly associated with plasma glucose concentration (turnover=0.97[glucose]+0.57, r=0.93) in both resting and recovering fish. While utilization of glucose in the whole animal was clearly responsive to plasma glucose availability, estimated total skeletal muscle disposal of glucose accounted for less than 15 % of glucose turnover, indicating that glucose was utilized largely by tissues other than locomotory muscle. Rates of glucose utilization in white muscle (range 0.5&shy;4 nmol min-1 g-1) provide direct evidence that glucose, regardless of plasma concentration, accounted for less than 10 % of glycogen repletion during exercise recovery. In red muscle, glucose uptake was influenced by plasma glucose level below 10&shy;12 mmol l-1 (utilization range 1&shy;15 nmol min-1 g-1), but was independent of glucose concentration above about 12 mmol l-1 (utilization plateaued at 15&shy;20 nmol min-1 g-1). Trout red muscle is similar to mammalian white muscle in the sense that glucose is estimated to account incompletely for glycogen restoration (25&shy;60 %), suggesting dependence on both glycogenesis and glyconeogenesis during recovery. It is concluded that hyperglycemia may be important to the pattern of substrate incorporation into red muscle glycogen and to the rate of repletion observed, but glucose availability has, as predicted from earlier indirect studies, little relevance to white muscle glycogen restoration. The regulatory mechanisms that govern apparently very high glucose turnover rates during extreme hyperglycemia, concomitant with low disposal rates in skeletal muscle, require further investigation.

Journal Article↗

Efficacy of clindamycin hydrochloride in refractory periodontitis. 12-month results.

The purpose of this study was to evaluate the use of clindamycin hydrochloride as an adjunct to conventional periodontal therapy in the treatment of patients who had previously been unsuccessfully treated with scaling, periodontal surgery and the use of tetracycline. Thirteen patients with a history of "refractory" periodontitis were thoroughly scaled and monitored by repeated attachment level measurements for the presence of active destructive periodontitis. Disease activity was defined as a 3-mm loss in attachment from baseline measurements or the occurrence of a periodontal abscess. When active disease was detected, each patient was scaled again and placed on clindamycin hydrochloride 150 mg qid for 7 days. Following the adjunctive use of clindamycin in combination with scaling, the incidence of gingival sites demonstrating active disease in the group of 13 patients decreased from an annual rate of 10.7 to 0.5%. Each patient demonstrated a decreased incidence of active sites per unit of time. Clinical parameters such as probing depth, gingival redness, bleeding on probing and suppuration showed dramatic improvement at 12 months after clindamycin therapy. The percentage of pockets with probing depths greater than 6 mm, 4 to 6 mm and 1 to 3 mm changed from 11 to 2%, 38 to 24% and 51 to 74% respectively, following clindamycin therapy as compared to scaling alone. The percentage of sites bleeding on probing decreased from 33% after scaling alone to 8% following clindamycin and scaling. Gingival redness decreased from 36 to 1% of sites. Suppuration also decreased from 8% of buccal or lingual surfaces after scaling alone to 1% of surfaces following scaling and clindamycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Interferon and interferon inactivators in patients with acquired immune deficiency syndrome and Kaposi's sarcoma. A preliminary report.

The interferon system has been implicated in the diagnosis and potential treatment of acquired immune deficiency syndrome (AIDS). In our study of AIDS patients we have identified the presence of circulating serum interferon inactivator(s). These interferon inactivators were not detected in AIDS prodrome patients or in patients with classical Kaposi's sarcoma. The evidence suggests that interferon inactivators may play a role in the clinical manifestation of AIDS.

Acquired Immunodeficiency Syndrome↗

Measuring imaging ability in children.

INTRODUCTION: Guided imagery has been suggested as an intervention to help children cope with noxious symptoms associated with medical care. A measure of imaging ability, that is, the ability to generate vivid mental images and to experience those images as if they were real, could be helpful in identifying children most likely to succeed in relieving symptoms with guided imagery. The purpose of this study was to test psychometric properties of a new instrument, the Kids Imaging Ability Questionnaire (KIAQ). METHOD: Three expert clinicians and researchers were asked to review the KIAQ to assess content validity. A convenience sample of 58 children were invited to complete the questionnaire twice to obtain data for tests of reliability and criterion-related validity. RESULTS: Content validity, internal consistency (alpha =.75-.76), and test-retest reliability (r =.73) were acceptable. Criterion-related validity using the Singer Fantasy Proneness Interview as a standard was poor (rho =.31-.46). DISCUSSION: Some psychometric properties were acceptable; however, continued research will be necessary to test validity of the questionnaire and demonstrate a relationship between KIAQ score and success with imagery. With continued research, pediatric nurses may use the KIAQ in practice to identify children most likely to benefit from guided imagery.

Adolescent↗