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Biomedical subjects

D Robinson

Publications and source records attributed to D Robinson.

At least 37 records · Page 2Linked to original sources

Antidiuresis: a new concept in managing female daytime urinary incontinence.

OBJECTIVE: To investigate the efficacy of desmopressin nasal spray on daytime urinary incontinence in women. PATIENTS AND METHODS: A multicentre, multinational, randomized, double-blind, placebo-controlled, cross-over exploratory study of women (aged 18-80 years) complaining of severe daytime urinary incontinence was conducted in three centres (King's College Hospital; Boras County Hospital and Skejby Hospital). Seventy-five patients were screened of whom 64 were randomized. In all, 60 women received study medication (safety population) and 57 completed the study. The intention-to-treat population comprised 59 patients and there were 41 in the per protocol analysis. The primary efficacy endpoint was the number of periods with no leakage for 4 h after dosing. Women were instructed to take the drug at a time of their choosing, but >/= 4 h before bedtime. Secondary efficacy variables included the time to first void or incontinence episode, volume leaked per incontinence episode, total volume voided and number of periods with no leakage. All measurements were made over 7 days on desmopressin and 3 days on placebo. RESULTS: There was a higher mean (sd) incidence of periods with no leakage in the first 4 h on desmopressin, at 62 (35)%, than on placebo, at 48 (40)%, and during the first 8 h, at 55 (37)% vs 40 (41)%. There was also a higher frequency of dry days on desmopressin than on placebo; 36% of patients had no leakage on virtually all treatment days (6 or 7) for 4 h after dosing. At 4-8 h the incidence of periods with no leakage on desmopressin was 68 (35)% vs 63 (41)% on placebo, and thereafter the incidence was similar. The time from dosing to first incontinence episode was longer on desmopressin, at 6.3 (2.5) h, vs 5.2 (3.3) h, whilst the volume leaked per incontinence episode was lower on desmopressin than placebo. The total volume voided was consistently lower on desmopressin, at 1180 (58) mL vs 1375 (57) mL, over the 24-h period after administration. There were no serious or severe adverse events reported. Seven women (11%) withdrew from the study, of whom five did not attend for the final visit and two (3%) because of mild adverse events. CONCLUSIONS: The results of this exploratory study suggest that desmopressin is an effective and safe treatment in women with daytime urinary incontinence, and allows them to choose when they need treatment, thus improving motivation, which may aid compliance with therapy.

Administration, Intranasal↗

Parameters associated with persistent airflow obstruction in chronic severe asthma.

The significance of severe airflow obstruction in severe asthma is unclear. The current study determined whether severe airflow obstruction is related to inflammatory or structural changes in the airways. Patients with severe asthma from a tertiary referral clinic were divided into two groups according to their postbronchodilator forced expiratory volume in one second (FEV1): severe persistent airflow limitation (FEV1 <50% predicted; group S; n=37) and no obstruction (FEV1 >80% pred; group N; n=29). Smoking history, atopic status, lung function tests, exhaled NO, blood eosinophil count, quality of life scores using St George's Respiratory Questionnaire and high resolution computed tomography (HRCT) of the lungs were assessed. Patients from group S were older and had longer disease duration. There was no difference in smoking history, atopic status, hospital admissions, quality of life scores and amount of treatment with inhaled or oral corticosteroids. Exhaled NO and peripheral blood eosinophils were higher in group S (21.0 +/- 2.4 versus 12.8 +/- 2.3 ppb; 0.41 +/- 0.06 versus 0.15 +/- 0.03 x 10(9) cells x L(-1) respectively). HRCT scores for bronchial wall thickening and dilatation were higher in group S with no differences in air trapping. Peripheral blood eosinophilia and bronchial wall thickening on HRCT scan were the only parameters significantly and independently associated with persistent airflow obstruction. Patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more high resolution computed tomography airway abnormalities suggestive of airway remodelling, despite being on similar treatments and experiencing equivalent impairment in quality of life.

Administration, Inhalation↗

Caffeine ingestion does not impede the resynthesis of proglycogen and macroglycogen after prolonged exercise and carbohydrate supplementation in humans.

The purpose of this study was to examine the effects of caffeine (Caf) ingestion on pro- (PG) and macroglycogen (MG) resynthesis in 10 healthy men. Subjects completed two trials, consisting of a glycogen-depleting exercise, while ingesting either Caf or placebo capsules. Throughout recovery, biopsies were taken at 0 (exhaustion), 30, 120, and 300 min, and 75 g of carbohydrate were ingested at 0, 60, 120, 180, and 240 min. Whereas Caf ingestion resulted in a higher blood glucose concentration and decreased glycogen synthase fractional velocity (P <or= 0.05), no effect was observed in either the amount or rate of PG and MG resynthesis. PG concentration increased significantly at each time point during recovery, whereas MG concentration remained unchanged until 120 min. The net rate of PG resynthesis was 115 mmol x kg dw(-1) x h(-1) during the first 30 min of recovery, and then it significantly decreased by 62% throughout the remaining 4.5 h of recovery. The net rate of MG resynthesis was 77% lower than the net rate of PG resynthesis during the first 30 min of recovery and remained constant throughout 5 h of recovery despite increasing levels of insulin. In conclusion, Caf ingestion does not impede the resynthesis of PG or MG after an extensive depletion of muscle glycogen and with the provision of exogenous dietary carbohydrate.

Adult↗

Effect of the UK government's 2-week target on waiting times in women with breast cancer in southeast England.

A government target of a maximum 2-week wait for women referred urgently with suspected breast cancer was introduced in April 1999. We have assessed changes in the distributions of waiting times and the proportions of cases meeting proposed targets before and after this date, using clinical audit data on 5750 women attending 19 hospitals in southeast England during the period July 1997-December 2000, who were subsequently found to have breast cancer. The proportion of cases being seen within 2 weeks of referral rose from 66.0 to 75.2%, and the median wait to first appointment fell from 13.6 to 12.3 days, following the introduction of the government target. The proportion of cases waiting 5 weeks or less between first hospital appointment and treatment fell from 83.8 to 80.3%, and median waits for treatment increased from 21.4 to 24.1 days. We also examined the effects on waiting times of various sociodemographic and care related factors. A total of 85.7% of screening cases vs 67.9% of symptomatic cases were seen within 2 weeks, and 95.0% of cases treated with tamoxifen received treatment within 5 weeks, as opposed to 77.6% of cases treated with surgery, 81.2% of chemotherapy cases and 52.8% of radiotherapy cases. While waiting times from GP referral to first hospital appointment have improved since the introduction of the government target, times from first appointment to treatment have increased, and consequently total waiting times have changed little.

Adult↗

Potential role of head lice, Pediculus humanus capitis, as vectors of Rickettsia prowazekii.

Since the pioneering work of Charles Nicolle in 1909 [see Gross (1996) Proc Natl Acad Sci USA 93:10539-10540] most medical officers and scientists have assumed that body lice are the sole vectors of Rickettsia prowazekii, the aetiological agent of louse-borne epidemic typhus (LBET). Here we review the evidence for the axiom that head lice are not involved in epidemics of LBET. Laboratory experiments demonstrate the ability of head lice to transmit R. prowazekii, but evidence for this in the field has not been reported. However, the assumption that head lice do not transmit R. prowazekii has meant that head lice have not been examined for R. prowazekii during epidemics of LBET. The strong association between obvious (high) infestations of body lice and LBET has contributed to this perception, but this association does not preclude head lice as vectors of R. prowazekii. Indeed, where the prevalence and intensity of body louse infections may be high (e.g. during epidemics of LBET), the prevalence and intensity of head louse infestations is generally high as well. This review of the epidemiology of head louse and body louse infestations, and of LBET, indicates that head lice are potential vectors of R. prowazekii in the field. Simple observations in the field would reveal whether or not head lice are natural vectors of this major human pathogen.

Animals↗

Multiple primary tumours following head and neck cancer in southern England during 1961-98.

BACKGROUND: Successful initial treatment of oral and oro-phayngeal cancer has led to the emergence of second primary tumours (SPTs). Population data are meagre. METHODS: Occurrence of multiple primary cancers following a malignancy in a head and neck site was computed using data from a population-based cancer registry covering a population of 14 million. RESULTS: Among 59,958 subjects reported to the registry, 5.5% males and 3.6% females developed a second primary cancer. At the sites studied, a total of 2771 second primary cancers were found, compared with an expected number of 2341. The standardised incidence ratio (SIR) for contracting a new primary cancer was 1.14 (95% CI=1.09-1.19) for men and 1.34 (95% CI=1.24-1.44) for women. There was a significantly increased risk for a second cancer in most of the upper aerodigestive tract sites that are generally regarded as tobacco associated, with an SIR for subsequent oral cancer of 5.56 in men and 15.31 in women. Subjects first detected with a pharyngeal cancer experienced the highest SIR for a subsequent tumour. Excluding tobacco-associated sites, the risk of a subsequent cancer was not significantly raised in either sex (SIR 0.87 (95% CI 0.81-0.93) for men; SIR 0.99 (95% CI 0.90-1.09) for women). CONCLUSIONS: The relative risk for multiple primary cancer was higher in younger subjects, those detected with a head and neck cancer during the 1990s as compared with earlier decades of the study, and among patients who received radiotherapy for their first tumour. By 20 years from the time of the first head and neck cancer, we estimate that approximately 30% of male patients and 20% of female patients will have developed an SPT.

Age Factors↗

Resolution of late-onset asthma following high-dose chemotherapy.

We describe a patient with moderately severe (British Thorax Society Step IV/V) asthma requiring regular inhaled and oral corticosteroids to control symptoms who experienced resolution of her asthma following high-dose chemotherapy and autologous stem cell transplantation for breast cancer. As far as the authors are aware this is the first reported case.

Antibiotics, Antineoplastic↗

Splitting of the body image as somesthetic aura symptom in migraine.

Splitting of the body image was illustrated as a somesthetic aura symptom in three of the 562 entries to the national Migraine Art competitions, confirming previous descriptions of this rare phenomenon in the migraine literature. In this type of self-experienced paroxysmal body schema disturbance, the own body is perceived as being split, usually in the mid-line, into two halves that may be displaced or separated from each other. Splitting of the body image most frequently applies to the migraine sufferer's head. The said phenomenon, the pathomechanisms of which are obscure, must not be confused with the visual illusion of illusory splitting.

Adolescent↗

The effect of storage temperatures on the in vitro properties of a polyanhydride implant containing gentamicin.

Septacin is a biodegradable sustained-release implant containing 20% (w/w) gentamicin sulfate. The matrix of the implant is a polyanhydride copolymer composed of erucic acid dimer (EAD) and sebacic acid (SA) in a one-to-one weight ratio. The effect of storage temperatures (-15 degrees C and 25 degrees C) on the stability of Septacin was evaluated with respect to gentamicin potency, copolymer molecular weight, and in vitro drug release. The drug in polymer matrix was stable for at least 12 months when stored at 25 degrees C, but the molecular weight of the copolymer declined rapidly at this temperature. At -15 degrees C, there was no change in the molecular weight of the copolymer. However, the placebo (copolymer without gentamicin) exhibited a significant drop in copolymer molecular weight at both temperatures. The drug release profiles showed no change for samples stored at -15 degrees C for the duration of this study, while the release of drug slowed down significantly for samples stored at 25 degrees C for longer than one month. A pronounced difference in the morphology of the -15 degrees C samples and the 25 degrees C samples was observed during the in vitro dissolution test; cracking of the -15 degrees C samples was evident, but the 25 degrees C samples remained intact.

Anhydrides↗

Phenotype/genotype associations for yield and salt tolerance in a barley mapping population segregating for two dwarfing genes.

Barley traits related to salt tolerance are mapped in a population segregating for a dwarfing gene associated with salt tolerance. Twelve quantitative trait loci (QTLs) were detected for seven seedling traits in doubled haploids from the spring barley cross Derkado x B83-12/21/5 when given saline treatment in hydroponics. The location of QTLs for seedling growth stage (leaf appearance rate), stem weight prior to elongation, and tiller number are reported for the first time. In addition, four QTLs were found for the mature plant traits grain nitrogen and plot yield. In total, seven QTLs are co-located with the dwarfing genes sdw1, on chromosome 3H, and ari-e.GP, on chromosome 5H, including seedling leaf response (SGa) to gibberellic acid (GA(3)). QTLs controlling the growth of leaves (GS2) on chromosomes 2H and 3H and emergence of tillers (TN2) and grain yield were independent of the dwarfing genes. Field trials were grown in eastern Scotland and England to estimate yield and grain composition. A genetic map was used to compare the positions of QTLs for seedling traits with the location of QTLs for the mature plant traits. The results are discussed in relation to the study of barley physiology and the location of genes for dwarf habit and responses to GA.

Adaptation, Physiological↗

Brain injury-related heterotopic bone formation: treatment strategy and results.

OBJECTIVES: Heterotopic bone formation (HO) is a phenomenon occurring in some neurologically injured patients that can adversely affect their rehabilitation. The current study aimed at evaluating functional results and recurrence rates after recurrence of such lesions. DESIGN: The results of 12 excisions of HO in 9 patients were assessed. A single-dose of 750 cGy delivered 24 hr postoperatively was used in seven of nine patients. RESULTS: One year postintervention, the arc of motion averaged 92.5 degrees in the hips, 66.6 in the knees, and 60 degrees in the elbow. Despite increased uptake on bone scans in all patients, recurrence did not occur in any patient. Ambulation levels improved in four of eight hips. Ease of personal hygiene was improved in all patients, although some patients still require assistance. CONCLUSIONS: Excision of symptomatic HO is recommended if limitation of joint motion seems to hinder the patient's rehabilitation. Some motor control is desirable to achieve significant improvement in the patient's quality of life. Increased uptake on bone scans is not a contraindication to surgical excision of HO, provided the neurologic status is stabilized.

Adult↗

Modulation transfer function of digitally reconstructed radiographs using helical computed tomography.

We have measured the modulation transfer function (MTF), at a distance from CT isocenter, in digitally reconstructed radiographs (DRR) using a bar pattern phantom for axial and helical data acquisitions. Spatial resolution in DRR increases for thinner slice thicknesses (43% at 1.6 lp/cm for 2 mm versus 16% for 5 mm). For the three slice thicknesses studied, the axial scanning mode provided better spatial resolution in DRR than helical scans performed at pitches > or = 1.5 (41% at 1.6 lp/cm for axial, 3 mm slice versus 18% for pitch = 2), but is similar to helical scans with pitch of 1. The reconstruction of overlapping slices from helical acquisitions of pitch = 1.5 results in spatial resolution of the DRR that is similar to that resulting from axial scans with contiguous reconstruction, but also results in the fine streaks known as "zebra" artifacts in the DRR.

Image Processing, Computer-Assisted↗

Dosimetric verification of inverse planned step and shoot multileaf collimator fields from a commercial treatment planning system.

An inverse treatment planning (ITP) module on a commercial treatment planning system (TPS) (Helax AB, Uppsala, Sweden) is being used for an in-house clinical trial for treatment of nasopharyngeal cancer with contralateral parotid sparing. Intensity modulated radiation therapy (IMRT) fields are delivered by step and shoot multileaf collimator (MLC) with a DMLC enabled Varian 2300 CD (Varian Associates, Palo Alto, CA). A series of testing procedures have been devised to quantify the modeling and delivery accuracy of routine clinical inverse planned IMRT using Helax TMS and the Varian step and shoot MLC delivery option. Testing was done on specific aspects of the TPS modeling germane to DMLC. Measured relative dose factors (head scatter plus phantom scatter) for small MLC fields, normalized to a 10x10 cm2 non-MLC field, were found to differ by 2-3% from the TPS values for the smallest of the fields tested. Relative distributions for small off axis fields were found to be in good agreement. A process for the routine clinical verification of IMRT fields has been implemented. Each IMRT field in an inverse plan is imported into a flat water tank plan and a "beam's eye view" (BEV) dose distribution is generated. This is compared to the corresponding measured BEV dose distribution. The IMRT verification process has also been performed using an anthropomorphic phantom. Large clinical fields (i.e., greater than 14.5 cm in the leaf direction) caused difficulties due to a vendor specific machine restriction, and several techniques for dealing with these were examined. These techniques were (i) the use of static stepping of closed junctions, (ii) the use of two separate IMRT fields for a given gantry angle, and (iii) restricting the overall maximum field size used. The overall process has allowed implementation of an in-house protocol for IMRT use on an initial clinical site. Results of the verification measurements for the first ten patients treated at this center reveal an average maximum dose per IMRT field delivered of 71.0 cGy, with a mean local deviation from the planned dose of -1.2 cGy, and a standard deviation of 2.4 cGy.

Algorithms↗

Genetically engineered analogs of ascomycin for nerve regeneration.

The polyketides FK506 (tacrolimus) and FK520 (ascomycin) are potent immunosuppressants that function by inhibiting calcineurin phosphatase through formation of an FKBP12-FK506/520-calcineurin ternary complex. They also have calcineurin-independent neuroregenerative properties in cell culture and animal models of nervous system disorders. Based on the crystal structure of the FKBP12-FK506-calcineurin complex, we deduced that the 13- and 15-methoxy groups of FK506 or FK520 are important for inhibition of calcineurin phosphatase but not for binding to FKBP12. By genetic modification of the FK520 gene cluster, we generated 13- and 15-desmethoxy analogs of FK520 that contain hydrogen, methyl, or ethyl instead of methoxy at one or both of these positions. These analogs bind FKBP12 tightly, have decreased calcineurin phosphatase inhibition and immunosuppressive properties, and enhance neurite outgrowth in cell cultures. A representative compound was also shown to accelerate nerve regeneration and functional recovery in the rat sciatic nerve crush model.

Acetyltransferases↗