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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 19 recordsLinked to original sources

Minimally invasive parathyroidectomy using the lateral focused mini-incision technique without intraoperative parathyroid hormone monitoring.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) involves scan-directed removal of a single adenoma through a 2.0-cm mini-incision without intraoperative monitoring. The aim of this study was to analyse the outcomes of MIP using such a simplified technique. METHODS: The study group comprised 500 consecutive patients undergoing MIP via a lateral mini-incision from August 2000 to September 2005. Levels of parathyroid hormone (PTH) were measured after operation solely to aid informed discharge. RESULTS: Some 97.4 per cent of patients were initially cured by MIP. Eight patients remained hypercalcaemic and a further five were normocalcaemic on the day after surgery but became hypercalcaemic again within 3 months of the procedure. Eleven of these patients were cured with subsequent re-exploration. Analysis of postoperative PTH data indicated that, at best, the use of intraoperative PTH measurement during surgery would have increased the cure rate by only a further 1 per cent. Three (0.6 per cent) of 500 patients had permanent recurrent laryngeal nerve palsy after MIP. CONCLUSION: MIP performed by the lateral focused mini-incision technique, without the use of intraoperative PTH monitoring, is a safe and effective procedure that results in outcomes equal to those of bilateral neck exploration.

Adenoma↗

Inaccuracy of high-performance liquid chromatography estimation of haemoglobin F in the presence of increased haemoglobin A1c.

Increasingly high-performance liquid chromatography is being used for identification and quantification of normal and variant haemoglobins. In many laboratories, the Beta Thal Short programme of the Bio-Rad Variant II instrument is used for this purpose. We noted that a factitious elevation of haemoglobin F was sometimes observed in diabetic patients and therefore carried out a systematic study of this phenomenon. We found discrepant results in 41% of samples from diabetic patients but in no normal volunteers. This factitious elevation could be predicted from a retention time for haemoglobin F of more than 1.15 min, the normal retention time being 1.08-1.15 min. Haemoglobinopathy laboratories need to be alert to the possibility of this erroneous result.

Chromatography, High Pressure Liquid↗

Methylphenidate regulates activity regulated cytoskeletal associated but not brain-derived neurotrophic factor gene expression in the developing rat striatum.

Methylphenidate (MPH) is a psychostimulant drug used to treat attention deficit hyperactivity disorder in children. To explore the central effects of chronic MPH, we investigated the expression of an effector immediate early gene, activity regulated cytoskeletal associated (arc), and the neurotrophin, brain-derived neurotrophic factor (bdnf) in the brain of immature and adult rats following repeated MPH. Prepubertal (postnatal day (PD) 25-38) and adult (PD 53-66) male rats were injected once daily for: a) 14 days with saline or MPH (2 or 10 mg/kg; s.c.) or b) 13 days with saline followed by a single dose of MPH (2 or 10 mg/kg; s.c.). To determine possible long-term effects of MPH, prepubertal rats were allowed a drug-free period of 4 weeks following the 14 days of treatment, and then were given a challenge dose of MPH. We demonstrated, for the first time, that an acute injection of MPH increased levels of activity-regulated cytoskeletal protein (ARC) and arc mRNA in the prepubertal rat striatum and cingulate/frontal cortex. This response was significantly attenuated by chronic MPH. The desensitization in arc expression observed in prepubertal rats persisted in the adult striatum following a later MPH challenge. In contrast to these data we observed little effect of MPH on bdnf expression. We also developed an effective, non-stressful technique to treat freely moving immature rats with oral MPH. Consistent with the results described above, we observed that oral MPH (7.5 and 10 mg/kg) also increased arc expression in the prepubertal rat striatum. However, unlike the effects of injected MPH, repeated oral MPH (7.5 mg/kg) did not alter the normal arc response. This result raises the important possibility that oral doses of MPH that reproduce clinically relevant blood levels of MPH may not down-regulate gene expression, at least in the short term (14 days). We confirmed, using mass spectrometry, that the oral doses of MPH used in our experiments yielded blood levels within the clinical range observed in children. The novel oral administration paradigm that we describe thus provides a clinically relevant animal model to further explore the effects of chronic drug exposure on central gene expression in the developing rat brain.

Administration, Oral↗

Risk assessments for forest trees: the performance of the ozone flux versus the AOT concepts.

Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury.

Betula↗

High friction from a stiff polymer using microfiber arrays.

High dry friction requires intimate contact between two surfaces and is generally obtained using soft materials with an elastic modulus less than 10 MPa. We demonstrate that high-friction properties similar to rubberlike materials can also be obtained using microfiber arrays constructed from a stiff thermoplastic (polypropylene, 1 GPa). The fiber arrays have a smaller true area of contact than a rubberlike material, but polypropylene's higher interfacial shear strength provides an effective friction coefficient of greater than 5 at normal loads of 8 kPa. At the pressures tested, the fiber arrays showed more than an order of magnitude increase in shear resistance compared to the bulk material. Unlike softer materials, vertical fiber arrays of stiff polymer demonstrate no measurable adhesion on smooth surfaces due to high tensile stiffness.

Journal Article↗

Staggered ladder spectra.

We exactly solve a Fokker-Planck equation by determining its eigenvalues and eigenfunctions: we construct nonlinear second-order differential operators which act as raising and lowering operators, generating ladder spectra for the odd- and even-parity states. The ladders are staggered: the odd-even separation differs from even-odd. The Fokker-Planck equation corresponds, in the limit of weak damping, to a generalized Ornstein-Uhlenbeck process where the random force depends upon position as well as time. The process describes damped stochastic acceleration, and exhibits anomalous diffusion at short times and a stationary non-Maxwellian momentum distribution.

Journal Article↗

The relationship between the lactate turnpoint and the time at VO2max during a constant velocity run to exhaustion.

The present investigation examined the relationship between the running velocity at the lactate turnpoint (vLTP) and the time at which VO2max can be sustained (TVO2max) during a continuous run to exhaustion at the minimal running velocity that elicits VO2max (vVO2max). Seven moderately-trained endurance runners undertook three tests on a treadmill. The first test was to determine vVO2max; the second to determine the time to exhaustion during a constant velocity run at vVO2max (Tlim vVO2max) and TVO2max; and the third to determine the vLTP. Pearson's correlation coefficient was used to determine the association between the vLTP (%vVO2max; i.e. the relative vLTP) and TVO2max, and between other selected physiological variables. Correlations between the relative vLTP and TVO2max, expressed as a percentage of T(lim vVO2max (the relative TVO2max; r=0.82), and between TVO2max and Tlim vVO2max (r=0.89), were significant at the p<0.05 level. All other correlations between selected measured physiological variables were found to be statistically insignificant. The main finding of this present study is that the relative vLTP demonstrated a significant positive correlation with the relative TVO2max. The physiological mechanism by which the lactate turnpoint may influence the relative TVO2max has not been elucidated, but may be due to a combination of decreasing the time to attain VO2max and increasing Tlim vVO2max. The present investigation has demonstrated that the lactate turnpoint may influence the relative time at which VO2max can be sustained during a continuous run to exhaustion at vVO2max, although further research is required to substantiate these findings.

Adult↗

Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group.

BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. OBJECTIVES: To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these, 51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15 patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48-h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS: Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed-site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.

Adolescent↗

Comparison of early postoperative rehabilitation outcome following total knee arthroplasty using different surgical approaches and instrumentation.

PURPOSE: To assess early postoperative rehabilitation outcome following computer-assisted total knee arthroplasty (TKA) or standard instrumentation TKA using a medial parapatellar or subvastus approach. METHODS: A prospective controlled trial of 70 consecutive patients undergoing TKA with a low contact stress rotating platform prosthesis was conducted. Patients were randomised to receive surgery with either computer navigation or standard instrumentation. A medial parapatellar or subvastus approach was used according to the surgeons' preference. Outcome measures included preoperative knee function, intra-operative factors, and postoperative rehabilitation. RESULTS: Duration of surgery was significantly longer when using computer navigation; however, operating time decreased with greater experience. A higher incidence and duration of early postoperative quadriceps dysfunction was associated with computer-assisted TKA through the medial parapatellar approach than through the subvastus approach or TKA performed with standard instrumentation. No patient who received surgery through the subvastus approach had a lag of more than 20 degrees, at 48 hours postoperatively, regardless of the instrumentation used. CONCLUSION: Computer-assisted TKA through a medial parapatellar approach was associated with delayed recovery of the quadriceps during early postoperative rehabilitation. This was due to the additional quadriceps dissection required to place the femoral tracking array. The subvastus approach is therefore recommended for computer-assisted TKA.

Aged↗

Organ doses from prostate radiotherapy and associated concomitant exposures.

In addition to the therapeutic exposure, a course of radiotherapy will involve the additional (concomitant) irradiation of the patient using CT, simulator or portal imaging systems, for localization of the target volume and subsequent verification of treatment delivery. The number of concomitant exposures is likely to increase as the developing technical capabilities for conformal, image-guided radiotherapy make target and critical organ definition an increasingly important aspect of radiotherapy. Estimation of doses and risks to critical organs in the body from all sources is thus necessary to provide the basis for adequate justification of the exposures as required by ICRP. In this paper, doses to selected organs and tissues for which ICRP have identified fatal cancer probabilities have been measured using a realistic anthropomorphic phantom loaded with thermoluminescent dosemeters and irradiated using a treatment protocol for radical radiotherapy of the prostate. Independently, doses to the same organs and tissues have been measured from concomitant CT and portal imaging exposures given for localization and verification purposes. Although negligible in comparison with the target dose, realistic numbers of concomitant exposures give a small but significant contribution to the total dose to most organs and tissues outside the target volume. Generally, this is in the range 5-10% of the total organ dose, but can be as high as 20% for bone surfaces. These data may be used to estimate concomitant doses from any combination of CT and portal imaging and may help in the justification process, especially when additional verification exposures may be required during treatment.

Dose-Response Relationship, Radiation↗

Criteria and other methodological considerations in the evaluation of time at V.O2max.

AIM: Many previous studies have examined the time limit at which an individual can maintain VO(2max) (T(lim) VO(2max)) during high-intensity continuous and intermittent runs to exhaustion. The main purpose of the present study was to examine the effects of employing different criteria used in previous investigations during T(lim) VO(2max) evaluation. METHODS: Seven moderately trained competitive runners completed 2 running tests to exhaustion, during which metabolic data was obtained from breath-by-breath gas analysis. The 1(st) test was an incremental test to evaluate VO(2max) and the minimal running velocity at which VO(2max) was elicited (v VO(2max)). The 2(nd) test was a continuous single velocity test at v VO(2max) from which the time to attain VO(2max) (TA VO(2max)) and T(lim) VO(2max) were subsequently evaluated. Time at VO(2max) was evaluated employing 6 specific criteria. Intra-individual differences in T(lim) VO(2max) values due to applying the different criteria were analysed using a one-way ANOVA, with significant differences between pairs identified using Tukey's HSD posthoc test. Significance was set at p<0.05. RESULTS: A one-way ANOVA demonstrated that significant differences (F=4.03, p=0.005) existed between T(lim) VO(2max) values generated by employing the six different criteria. CONCLUSIONS: The present study provides support that employing different criteria in the evaluation of T(lim) VO(2max), such as those used in previous investigations, leads to significantly different T(lim) VO(2max) values. However, the practical implications of these measurement differences require further investigation.

Adult↗

Aggregation of inertial particles in random flows.

We consider the trajectories of particles suspended in a randomly moving fluid. If the Lyapunov exponent of these trajectories is negative, the paths of these particles coalesce, so that particles aggregate. Here we give a detailed account of a method [B. Mehlig and M. Wilkinson, Phys. Rev. Lett. 92, 250602 (2004)] for calculating this exponent: it is expressed as the expectation value of a random variable evolving under a stochastic differential equation. We analyze this equation in detail in the limit where the correlation time of the velocity field of the fluid is very short, such that the stochastic differential equation is a Langevin equation. We derive an asymptotic perturbation expansion of the Lyapunov exponent for particles suspended in three-dimensional flows in terms of a dimensionless measure of the inertia of the particles, epsilon, and a measure of the relative intensities of potential and solenoidal components of the velocity field, Gamma. We determine the phase diagram in the epsilon-Gamma plane.

Journal Article↗

Methylphenidate differentially regulates c-fos and fosB expression in the developing rat striatum.

Methylphenidate (MPH, Ritalin) is a psychostimulant drug used in very young children with attention deficit hyperactivity disorder (ADHD). To explore the central effects of MPH, we compared repeated MPH treatments on c-fos and fosB expression in the striatum of immature and adult rats. Prepubertal (PD25-38) or adult (PD53-66) male rats were treated once daily for: (a) 14 days with either saline or MPH (2 or 10 mg/kg) or (b) 13 days with saline followed by a single dose of MPH (2 or 10 mg/kg) on day 14. To determine long-term effects of MPH, another group of prepubertal rats was allowed a drug-free period of 4 weeks following the initial 14 days of treatment, and received a challenge dose of MPH at adulthood. All rats were sacrificed 2 h post-injection on the final day. Expression of c-fos and fosB was quantified by densitometric analysis of cFOS and FOSB-immunoreactivity (-ir). We demonstrated that FOSB-ir was increased by a single dose of MPH in the prepubertal and adult striatum, and this effect was further elevated by chronic MPH in prepubertal rats, in contrast to the inhibitory effect of MPH (2 and 10 mg/kg) on cFOS-ir. In adult rats, repeated MPH down-regulated cFOS-ir only at the higher dose (10 mg/kg), while fosB expression remained at levels comparable to acute MPH. The reduction in cFOS-ir observed in prepubertal rats given repeated MPH (10 mg/kg) persisted in the adult striatum following MPH challenge at adulthood. Our results suggest that (1) repeated MPH treatment differentially regulates c-fos and fosB expression in the immature and adult brain; (2) MPH-induced changes in gene expression may be enduring, and (3) the immature brain is more sensitive to the stimulant effects of MPH than the adult. Thus, our findings have implications for the long-term use of MPH in ADHD.

Age Factors↗

Methylphenidate regulates c-fos and fosB expression in multiple regions of the immature rat brain.

Methylphenidate (Ritalin, MPH) is a common psychostimulant used to treat childhood attention-deficit hyperactivity disorder (ADHD). Little is known about the long-term developmental effects on gene expression and behavior, which may occur with extended MPH use. We reported previously that the striatum is a major target of MPH, consistent with human MRI studies. In the present study, we tested the hypothesis that MPH is likely to have widespread effects in extra-striatal regions of the brain. We used the expression of two immediate early genes, c-fos and fosB, as probes to map the response of the immature rat brain to single (1 day) versus repeated (14 days) MPH treatment (2 or 10 mg/kg; s.c.) from postnatal day 25 to 38. Consistent with previous reports, the striatum is a major target of acute MPH action, as indicated by elevated levels of cFOS-immunoreactivity (-ir). Increases in c-fos expression were also seen in the nucleus accumbens, cingulate/frontal cortex and piriform cortex, and Islands of Calleja. FosB expression was elevated only in the striatum following a single stimulation. Chronic MPH treatment (10 mg/kg/day for 14 days) resulted in an attenuation of c-fos expression in the striatum and Islands of Calleja. However, levels of cFOS-ir remained elevated in the nucleus accumbens and frontal cortex. In contrast to the inhibitory effect of repeated MPH exposure on c-fos expression, FOSB-ir was further elevated in the striatum, and an increase was observed in the cingulate/frontal and piriform cortices. Thus, chronic MPH differentially regulated expression of c-fos and fosB in several brain regions. Our data suggest that MPH may exert its stimulant effects at multiple sites in the immature brain, which has implications for long-term treatment in children.

Analysis of Variance↗

Morphology of the kidney in the West African caecilian, Geotrypetes seraphini (Amphibia, Gymnophiona, Caeciliidae).

This study deals with the morphology and ultrastructure of the mesonephros in adult caecilians of the species Geotrypetes seraphini. Based on serial sections in paraffin and araldite, nephrons are reconstructed and the cellular characteristics of different nephron segments described. The long and slender mesonephric kidneys of G. seraphini are broadest caudally and taper toward the front, where the organs are divided into smaller segmental divisions. Two nephron types can be distinguished on the basis of their connections to the coelom and their position within the nephric tissue: ventral nephrons connect to the coelom via a ciliated peritoneal funnel, whereas medial nephrons lack this connection. Both nephron types are composed of a filtration unit, the Malpighian corpuscle, and a renal tubule, which can be divided into six morphologically distinct segments: neck segment, proximal tubule, intermediate segment, early distal tubule, late distal tubule, and collecting tubule. Collecting tubules merge and form a branch system that opens into collecting ducts. Collecting ducts empty into the Wolffian duct. Proximal tubules of nephrons in the frontal divisions are morphologically different from the proximal tubules of more caudal kidney regions. Distal tubule subdivision is only clearly recognizable at the electron microscopic level. The length of each nephron segment is calculated from a ventral nephron with a total length of approximately 3.8 mm, and the course of the segments within the nephric tissue is reported. The number of nephrons was estimated at 1,700 units in each kidney. The segmentation and ultrastructure of the mesonephric nephrons in G. seraphini are discussed in relation to nephron descriptions from other caecilians and we further discuss the evolutionary origin of the amphibian nephron.

Africa, Western↗

Associations with Vitamin D deficiency in "at risk" Australians.

In a study of 185 elderly living in assisted care and 192 frail aged living in the community in the Sydney metropolitan area, nursing home residents were found to be at a 3-fold and hostel dwellers at a 2-fold risk of Vitamin D [25(OH)D] deficiency (<25 nmol/L) compared to self care residents. Middle Eastern people were found to be at 4-fold risk and Vietnamese a 3-fold risk of deficiency compared to their Australian counterparts. In recently arrived Chinese immigrants, Vitamin D deficiency, was found in 28%, and marginal levels (<37 nmol/L) in 60%, compared to the 34 and 76% found in our nursing home population, and 25 and 57% in hostel care residents. Of the Middle Eastern elderly, 58% were deficient and 83% marginal; although only 18% of Vietnamese were deficient, 68% had marginal Vitamin D status. Other factors associated with Vitamin D deficiency were mobility and sun exposure in assisted care, and low dietary Vitamin D and calcium intake, reduced exercise levels and high % body fat levels in the immigrant groups.

Aged↗