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Biomedical subjects

S C Hughes

Publications and source records attributed to S C Hughes.

At least 19 recordsLinked to original sources
PubMed2004

Mood and cognitive performance effects of "energy" drink constituents: caffeine, glucose and carbonation.

Three studies using healthy volunteers (n = 271) investigated the effects of caffeine, carbohydrates and carbonation in functional "energy" drinks (EDs) with the aim of determining their benefit in every-day life. The results showed caffeine to be the main ED constituent responsible for the effects found, with possible minor, relatively weak effects of carbohydrates. EDs were found to improve and/or maintain mood and performance during fatiguing and cognitively demanding tasks relative to placebo. In terms of absolute values, EDs maintained levels of arousal compared to a deterioration in arousal where placebo was consumed. These effects were found in caffeine-deprived participants, and so may be largely due to "withdrawal reversal". There were only minor differences in the effects of water vs. "sensory-matched" placebo, supporting previous findings indicating that the type of placebo does not alter the conclusions drawn about the effects of the full ED. Finally, carbonation had various effects on mood, some of which were present immediately following consumption, others were consistent with slower absorption of caffeine (and possibly carbohydrates) from carbonated drinks.

Adolescent↗
PubMed2001

Establishment and maintenance of parasegmental compartments.

Embryos of higher metazoans are divided into repeating units early in development. In Drosophila, the earliest segmental units to form are the parasegments. Parasegments are initially defined by alternating stripes of expression of the fushi-tarazu and even-skipped genes. How fushi-tarazu and even-skipped define the parasegment boundaries, and how parasegments are lost when fushi-tarazu or even-skipped fail to function correctly, have never been fully or properly explained. Here we show that parasegment widths are defined early by the relative levels of fushi-tarazu and even-skipped at stripe junctions. Changing these levels results in alternating wide and narrow parasegments. When shifted by 30% or more, the enlarged parasegments remain enlarged and the reduced parasegments are lost. Loss of the reduced parasegments occurs in three steps; delamination of cells from the epithelial layer, apoptosis of the delaminated cells and finally apoptosis of inappropriate cells remaining at the surface. The establishment and maintenance of vertebrate metameres may be governed by similar processes and properties.

Animals↗
PubMed2000

The dissolution of urinary catheter encrustation.

OBJECTIVES: To identify the optimum volume of acidic bladder washout solution to dissolve catheter encrustations and to compare the effectiveness of different bladder washout delivery devices. MATERIALS AND METHODS: Urinary catheter encrustation was generated in vitro using a model of the catheterized bladder adapted from previous work. An acidic bladder washout solution (Suby G) was applied via the catheter in the model and retained for 15 min. The amount of encrusting material dissolved was measured by colorimetric analysis of the magnesium and calcium content of the solution returned after the washout procedure. The relative effectiveness of different volumes of washout solution and different washout delivery devices (Optiflow, Bard Ltd, Crawley; UroTainer, B/Braun Medical Ltd, Aylesbury; and a bladder syringe) in dissolving catheter encrustations was compared to the 'standardized' conditions commonly used in practice. RESULTS: There was no statistically significant difference between washouts with 100 mL and washouts with 50 mL for any of the delivery devices tested. Gentle agitation with 50 mL Suby G did not significantly improve the dissolution of encrustation but the total amount of material dissolved when two washouts with 50 mL Suby G were used sequentially was significantly better than a single washout with either 100 mL or 50 mL. CONCLUSIONS: Under controlled laboratory conditions, smaller volumes of acidic bladder washout solution (50 mL) are as effective as the 100 mL commonly used in practice, but two sequential washouts with 50 mL are more effective than a single washout. The newly designed Optiflow delivery device is at least as effective as the other devices tested. This study provides new evidence which may contribute to decision-making by practitioners in relation to catheter care.

Calcium↗
PubMed2000

The development of a long, dual-platform triaxial walkway for the measurement of forces and temporal-spatial data in the clinical assessment of gait.

Force-plate measurement of the ground reaction force (GRF) has, for many years, been considered a vital component of the comprehensive assessment of human gait in the clinical context. For example, the data can be used in the adjustment of prostheses and orthoses and in identifying the mechanisms underlying a gait dysfunction. However, commercial force plates are usually only capable of measuring GRF data from one step in a single traverse. That can lead to problems of 'targeting' and, with less able subjects, fatigue before the necessary data have been collected. Previous work at the University of Surrey resulted in a prototype dual-platform force walkway capable of measuring the vertical component of the GRF and estimating the position of application of that force for multiple foot contacts in a single traverse. In addition, temporal-spatial information, e.g. speed and step length, could also be determined. This paper describes the development of a longer walkway that can measure the three orthogonal components of the GRF and provide and a more accurate estimate of the position of application of that force. Software to allow the rapid reduction of gait data to useful clinical information has also been developed.

Calibration↗
PubMed2000

Finite element analysis of bone stress and strain around a distal osseointegrated implant for prosthetic limb attachment.

Direct skeletal attachment techniques have recently been identified as an alternative method for percutaneous attachment of prosthetic limbs. Osseointegrated implants for prosthetic attachments are subjected to a complex load condition. This finite element study investigates the effect of varying geometries of the implant on the stress and strain distribution in the area of the bone/implant interface. Simplified three-dimensional axisymmetric models of the femur and seven implants with different core diameters, external diameters, implant lengths and thread pitches were derived. The resulting stress and strain distributions were compared. The significance of each implant geometry was identified for improving implant design in the light of benefit to the bone/implant osseointegration and the bone remodelling of the femur.

Artificial Limbs↗
PubMed1998

Intravenous remifentanil: placental transfer, maternal and neonatal effects.

BACKGROUND: Remifentanil has not been studied in obstetric patients. This study evaluates the placental transfer of remifentanil and the neonatal effects when administered as an intravenous infusion. METHODS: Nineteen parturients underwent nonemergent cesarean section with epidural anesthesia and received 0.1 microg kg(-1) x min(-1) remifentanil intravenously, which was continued until skin closure. Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood samples were obtained at delivery for analysis of drug concentrations of remifentanil, its metabolite, and blood gases. Maternal vital signs were monitored continuously, and pain and sedation levels were assessed intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients and newborns were observed for at least 24 h after surgery for side effects. RESULTS: The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88+/-0.78 and 0.29+/-0.07, respectively. Mean clearance was 93 ml x min(-1) kg(-1). The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56+/-0.29 and 1.23+/-0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was 2.92+/-3.65. There were no adverse effects on the neonates, but there was a sedative effect and respiratory depressant effect on the mothers. CONCLUSIONS: Remifentanil crosses the placenta but appears to be rapidly metabolized, redistributed, or both. Maternal sedation and respiratory changes occur, but without adverse neonatal or maternal effects.

Adolescent↗
PubMed1997

Growth hormone therapy in patients with cirrhosis: a pilot study of efficacy and safety.

BACKGROUND & AIMS: The protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3. The aim of this study was to conduct a randomized, double-blind, placebo-controlled pilot study of GH therapy in 20 cirrhotic patients to assess the reversibility of GH resistance and subsequent impact on protein economy and safety. METHODS: Patients were treated with GH (0.25 IU/kg body wt) or placebo for 7 days. Serum levels of GH, IGF-I, IGFBP-3, and insulin were measured by radioimmunoassay and 24-hour urinary nitrogen by the Kjeldahl technique. RESULTS: IGF-I levels increased only in the GH-treated group (mean, 69.2 +/- SE 7.0 to 170.6 +/- 48.8 ng/mL; P < 0.05) together with IGFBP-3 (1.65 +/- 0.3 to 2.94 +/- 0.6 mg/L; P < 0.005). Cumulative nitrogen balance similarly improved only in the GH group (2.87-24.16 g; P < 0.05). No significant side effects of GH were observed. CONCLUSIONS: GH therapy can overcome the GH resistance of cirrhosis. The resulting improvement in nitrogen economy and possible influences on clinical outcomes will need to be confirmed in controlled studies of longer duration.

Aged↗
PubMed1997

The insulin-like growth factors (IGFs) in follicular fluid are predominantly bound in the ternary complex.

The presence of IGFs and their associated binding proteins (IGFBPs) in human follicular fluid is well documented. Furthermore, most of the constituents of the IGF system in follicular fluid have been found to vary, either in total amount or by proteolytic cleavage, depending on the health status of the follicle. In this study we have examined the acid-labile subunit (ALS) and found that levels in follicular fluid (mean 146 nmol/l) were almost 50% of those in the circulation. This amount of ALS was considerably greater than that found in other extracirculatory fluids (20.9 for synovial fluid and 31.4 nmol/l for skin blister fluid). As in the circulation, ALS levels were in molar excess and did not vary between atretic and dominant follicles. Although the source of ALS is probably from blood (conditioned medium from ovarian cell cultures had no measurable ALS) it would appear that this glycoprotein is not merely diffusing from the circulation as the capillary endothelium becomes more permeable in dominant follicles and this is not reflected in the level of ALS. Analysis of the distribution of IGF-I, IGF-II and IGFBP-3 in fluid from healthy and atretic follicles revealed that the majority of these growth factors (> 80% of total IGF-II) were in the 150KDa complex, indicating that the ALS present was functional, in that it formed the ternary complex with a molecule of IGFBP-3 and IGF. No free IGF-II was found in any of the follicular fluids analysed nor was there any increase in the amount of unsaturated IGFBP-3 in atretic follicles. In summary, we have shown that the majority of IGF measured in follicular fluid, whether from healthy or atretic follicles, is bound in the ternary complex.

Culture Techniques↗
PubMed1996

The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery.

OBJECTIVES: Patients undergoing abdominal surgery often suffer from morbidity associated with increased protein catabolism. Therapeutic recombinant human insulin-like growth factor (rhIGF)-I has been proposed as a means of reversing this process. As IGFBPs modulate the bioavailability of the IGFs, we have studied the changes in the circulating levels of these peptides during surgery. DESIGN: Patients undergoing elective intestinal surgery were recruited prospectively. Blood samples were taken before, during and after surgery. Standard anaesthetic techniques were used. METHODS: Twelve adults (aged 30-70 years; 9 female, 3 male) undergoing surgery were studied. Serum was taken before premedication (preop), end of surgery (end surg), 2 h, 6 h post surgery, on days 1-4, 7, 10 and 14, and on recovery at 6 weeks. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, insulin and C-peptide were measured by radioimmunoassay. IGFBP profiles were also assessed by Western ligand blot (WLB). Samples taken preop and at 2 days were separated by fast-phase liquid chromatography (FPLC) using a Superose 12 column under neutral conditions (pH 7.4), and the fractions were analysed subsequently by WLB and immunoblot using a specific IGFBP-3 antiserum. RESULTS: IGF-I fell rapidly during surgery from 170 +/- 21 (preop) to 133 +/- 14 micrograms/l (end surg) (P < 0.05). The magnitude of this fall could not be explained by haemodilution. IGF-I levels then fell further to a nadir of 103 +/- 10 micrograms/l at day 4 (P < 0.05). IGF-II fell from 580 +/- 46 (preop) to 397 +/- 38 micrograms/l (day 2). Both IGF-I and IGF-II recovered to preop levels at 6 weeks (205 +/- 14 micrograms/l and 623 +/- 30 micrograms/l respectively). IGFBP-3 levels fell similarly from 4.46 +/- 0.45 to 3.2 +/- 0.3 mg/l (end surg) and to a nadir of 2.66 +/- 0.19 mg/l at day 2. There was a close correlation between IGFBP-3 levels and the sum of IGF-I and IGF-II levels before surgery (r = 0.9, P < 0.01) and this was maintained throughout the post-operative period (mean correlation coefficient of 0.86 +/- 0.02, P < 0.05). On days 2 and 3 there was a small but significant increase in the ratio between serum IGF-I and IGFBP-3 levels compared with the preop ratio (P < 0.05 and < 0.005, respectively). WLB demonstrated almost complete absence of IGFBP-3 by day 2. This discrepancy between RIA and WLB analysis of IGFBP-3 suggested the presence of IGFBP-3 protease activity between days 1 and 4. This was confirmed by WLB and immunoblot analyses of samples taken 2 days after surgery. The decrease in IGFBP-3 on WLB was shown to be associated with an increase in the proteolytically cleaved fragments of IGFBP-3. These fragments following FPLC were detected in the high molecular weight fractions, suggesting that the fragments were still able to form the high molecular weight IGFBP-3/ALS complex which is thought to form only when IGF is bound by IGFBP-3. IGFBP-1 levels rose during surgery (mean duration of surgery was 125 minute) from 18 +/- 3 (preop) to 51 +/- 12 micrograms/l (end surg) (P < 0.05). This rise in IGFBP-1 paralleled increases in insulin from 7.3 +/- 1.0 to 20.8 +/- 7.5 mU/l and glucose from 4.6 +/- 0.3 to 8.7 +/- 1.2 mmol/l. IGFBP-1 levels then fell to basal values by 6 hours. IGFBP-2, in contrast, fell slightly during surgery from 636 +/- 14 to 599 +/- 96 mg/l and then returned to basal levels by 6 hours. CONCLUSION: After major surgery there are complex and diverse changes in the IGFs and IGFBPs. The effect of these changes on IGF bioavailability may significantly affect the therapeutic potential of IGF-I in this setting.

Abdomen↗
PubMed1996

Effects of oral and transdermal oestrogen replacement therapy on plasma levels of insulin-like growth factors and IGF binding proteins 1 and 3: a cross-over study.

OBJECTIVE: Conflicting results have been reported on the effects of oral and transdermal oestrogen replacement therapy on IGF-I, while little information exists regarding the effects on IGFBP -1 and -3. In this study we evaluated the effects of oral and transdermal oestrogens on these parameters in post-menopausal women in a randomized cross-over study. PATIENTS: A group of 14 post-menopausal women were randomized to receive progestin-opposed oestrogen replacement therapy administered orally (Trisekvens Novo: 17 beta-oestradiol 2 mg daily on days 1-22 and 1 mg daily on days 23-28, norethisterone 1 mg days 13-22) or transdermally (Estracomb CIBA: oestradiol 50 micrograms/24 h on days 1-28, norethisterone 250 micrograms/24 h on days 15-28) for 6 months after which they were crossed over to the alternative treatment option. Fasting blood samples were obtained before treatment, and after 3, 6, 9 and 12 months on treatment. MEASUREMENTS: IGF-I, IGF-II, IGFBP-1, IGFBP-3, oestradiol and norethisterone were analysed by radioimmuno-assays. In addition, IGFBPs were evaluated with Western ligand blots (WLB) in a subgroup of 12 patients. RESULTS: Plasma levels of oestradiol were not significantly different during oral and transdermal treatment. Norethisterone levels were below the detection limit in all situations in 8 patients, while 6 patients had detectable levels in one or several samples during treatment. Oral treatment caused a significant decrease (16%, P < 0.005) in IGF-I and a non-significant decrease in IGFBP-3. A similar effect was observed when samples containing detectable levels of norethisterone were excluded from the analysis. No significant effect on IGFBP-1 was observed when all samples were included in the analysis. However, when samples with detectable norethisterone were excluded IGFBP-1 increased by 46% (P < 0.01) during oral therapy. Contrary, transdermal treatment with oestrogens did not influence any of the parameters measured. None of the treatments had any effect on plasma IGF-II levels or IGFBP profile evaluated by WLB. CONCLUSIONS: Treatment with oral hormone replacement therapy significantly suppresses plasma IGF-1 levels and increases plasma IGFBP-1 while transdermal treatment had no influence. This may be due to the route of administration, as plasma oestradiol levels showed little difference between the groups. The effect of oral oestrogens on IGFBP-1 seems to be attenuated by progestins.

Administration, Cutaneous↗
PubMed1996

Critical illness is associated with low circulating concentrations of insulin-like growth factors-I and -II, alterations in insulin-like growth factor binding proteins, and induction of an insulin-like growth factor binding protein 3 protease.

OBJECTIVES: To describe the sequential changes in the circulating concentrations of insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding proteins in critically ill patients. To determine whether critical illness is associated with induction of a specific protease directed against insulin-like growth factor binding protein 3 and to relate these changes to outcome. DESIGN: Prospective, descriptive study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Eighteen heterogeneous critically ill patients, requiring ventilatory support. INTERVENTIONS: Serial daily blood samples were collected until death or discharge from the ICU. In five patients, samples were also obtained on the ward before discharge from the hospital. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding proteins 1, 2, and 3 were measured by radioimmunoassay. After 5 days, insulin-like growth factor binding protein 3 concentrations were measured on alternate days. Alterations in binding of insulin-like growth factor-I to insulin-like growth factor binding protein 3 and the presence of protease activity directed against insulin-like growth factor binding protein 3 were investigated by Western ligand blotting. Circulating concentrations of insulin-like growth factor-I and insulin-like growth factor-II were low and remained low throughout the 7-day study period. Insulin-like growth factor binding protein 1 concentrations were initially increased to within the fasting range, but subsequently decreased. There was considerable variability in insulin-like growth factor binding protein 2 concentrations, but generally, concentrations were at the upper end of the normal range throughout. Insulin-like growth factor binding protein 3 concentrations were consistently low and Western ligand blotting at the nadir of the insulin-like growth factor-I concentration demonstrated the presence of a protease directed against insulin-like growth factor binding protein 3. The last recorded concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein 3 were higher in survivors than in nonsurvivors (p < .05). Two patients were also studied for a prolonged period. In one patient, a survivor, insulin-like growth factor-I and insulin-like growth factor binding protein 3 were low initially, but later increased in association with recovery and cessation of protease activity over a period of 33 days. In another patient, a nonsurvivor, insulin-like growth factor-I and insulin-like growth factor binding protein 3 remained low and protease activity persisted until the patient died 38 days after admission to the ICU. CONCLUSIONS: Critical illness is associated with low circulating concentrations of insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein 3 and these low values are associated with induction of protease activity specifically directed against insulin-like growth factor binding protein 3. In survivors, recovery is associated with increasing insulin-like growth factor-I and insulin-like growth factor binding protein 3 concentrations and cessation of protease activity. The therapeutic effects of exogenous growth factors are likely to be influenced by these changes.

Adolescent↗
PubMed1995

Inhibition of some aspects of acute inflammation of guinea-pig lung by intraperitoneal dexamethasone and mifepristone: demonstration of agonist activity of mifepristone in the guinea-pig.

We have determined the inhibitory activity of dexamethasone as an inhibitor of histamine-induced plasma protein extravasation (PPE) in guinea-pig lung and skin, and of lipopolysaccharide (LPS)-induced neutrophilia and platelet activating factor (PAF)-induced eosinophilia in guinea-pig lungs. Dexamethasone inhibited PAF-induced eosinophilia in guinea-pig lung (ED50 1.4 mg/kg i.p.). Higher doses of dexamethasone were required to inhibit LPS-induced neutrophilia (ED50 10.8 mg/kg i.p.). However, at doses up to 150 mg/kg i.p. dexamethasone did not inhibit histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, but did inhibit PPE in guinea-pig skin. These preparations have previously been shown to be equally sensitive to inhibition by the beta 2-adrenoceptor agonist salmeterol. Dexamethasone inhibited PAF-induced eosinophilia (5 mg/kg) or LPS-induced neutrophilia (50 mg/kg) when given 3 h or 1 h prior to challenge. Inhibitory activity was lost when dexamethasone was administered 23 h prior to LPS or 1 h after PAF. The glucocorticoid antagonist mifepristone (1-100 mg/kg i.p.) caused dose-related inhibition of PAF-induced eosinophilia but not of LPS-induced neutrophilia. The highest dose of mifepristone used (100 mg/kg) did not reverse the inhibitory actions of dexamethasone (50 mg/kg) on LPS-induced neutrophilia. We suggest that the different inhibitory activity of dexamethasone in the preparations studied indicates differences in the sensitivity of the target cells involved to inhibition by dexamethasone. We also suggest that inhibition of PAF-induced eosinophilia by mifepristone reflects the partial agonist activity of this agent, demonstrated by others in different experimental systems.

Acute Disease↗