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J M Wilkinson

Publications and source records attributed to J M Wilkinson.

At least 19 recordsLinked to original sources
PubMed1999

Electron contamination and build-up doses in conformal radiotherapy fields.

The dose in the build-up region depends upon the primary photon beam, backscattered radiation from the patient and contamination radiation from outside the patient. In this paper, a model based on measured data is proposed which allows the build-up dose for arbitrarily shaped treatment fields to be determined. The dose in the build-up region is assumed to comprise a primary photon component and a contamination component that is a function of the field size and shape. This contamination component, for modelling purposes, is subdivided into contributions that correspond to elements of 1 cm by 1 cm cross-sectional area at the plane of the isocentre. The magnitude of these components has been obtained by fitting measured data to an exponential function. The exponent was found to vary linearly with depth for energies between 4 MV and 20 MV. The coefficient decreased linearly with depth at 4, 6 and 8 MV, but exhibited a broad build-up region at 20 MV. The primary component, in the build-up region, could be approximated by a 100 - (100 - PSD) e(-mu d) function, where PSD is the primary surface dose. The values obtained during the fitting procedure were used to calculate dose in the build-up region for arbitrarily shaped fields. Good agreement was found in each case.

Electrons↗
PubMed1998

A high-performance liquid-chromatographic assay for amphotericin B in a hydrophilic colloidal paste base.

A stability-indicating high-performance liquid-chromatographic (HPLC) assay has been developed for amphotericin B (AmB) in a paste, containing AmB, tobramycin (or gentamicin) sulphate, colistin sulphate, liquid paraffin and Orabase. Extraction of AmB was performed by partitioning the antibiotic between N,N-dimethylformamide (DMF) and cyclohexane, which led to precipitation of the polymeric materials and extraction of the liquid paraffin into the cyclohexane and AmB into the DMF. Analysis by HPLC of the latter layer gave a linear relationship between concentration and peak area response for the AmB over the range 5.0 x 10(-4) to 7.5 x 10(-3)% (w/v) (r = 0.9995) with a relative standard deviation of +/- 1.46% (n = 8). The efficiency of extraction was 1006 +/- 2.4% (n = 5).

Amphotericin B↗
PubMed1998

Rectangular edge synchronization for intensity modulated radiation therapy with dynamic multileaf collimation.

The implementation of intensity modulated radiotherapy by dynamic multileaf collimator control involves the use of interpreter software which creates leaf trajectory plans for each leaf pair. Interpreter software for use with an Elekta SL15 linear accelerator and dedicated multileaf collimator has been written and tested. In practice the ideal trajectory plans often predict contact between leaves from opposing leaf banks, but this is prohibited by control software on the Elekta system as it could lead to mechanical damage. If the modulation within the geometric limits of a shaped field is not to be compromised then strategies to avoid leaf contact result in additional unwanted doses outside the geometric edge. The magnitude of any such additional dose can be reduced to acceptable levels by a technique which we have called rectangular edge synchronization. The performance of interpreter software which incorporates rectangular edge synchronization has been compared with that of potentially more efficient software which does not. The option containing the rectangular edge synchronization algorithm was shown to work consistently well at high monitor unit rates, and without incurring leaf contacts, under a wide range of test conditions. It therefore provides a sound basis for using intensity modulation to replace mechanical wedges, to simulate customized patient shape compensators, or to implement the results of inverse treatment planning processes that require superimposed intensity modulated beams.

Algorithms↗
PubMed1998

Surgical stabilisation of the lower limb in osteogenesis imperfecta using the Sheffield Telescopic Intramedullary Rod System.

The Sheffield Expanding Intramedullary Rod System was developed after experiencing problems with existing rod systems in the management of osteogenesis imperfecta. Between 1986 and 1996 we treated 74 bones in the lower limb in 28 children at a median follow-up of 5.25 years. We have reviewed 24 children with a total of 60 rods. Before surgery, all children had had multiple fractures of the lower limb. At review eight patients had experienced no further fractures, but three had suffered five or more subsequently. Before initial stabilisation, 15 children had never walked, and only three (13%) used walking as their main means of mobility. After surgery, half of those who showed motor arrest were able to walk (p = 0.016). The number of patients able to walk, with or without aids, increased to 17 (p = 0.0001). We have experienced no evidence of epiphyseal damage after the procedure, and complication rates requiring rod exchange have been low (7%).

Child↗
PubMed1998

Functional characterization of PM6/13, a beta3-specific (GPIIIa/CD61) monoclonal antibody that shows preferential inhibition of fibrinogen binding over fibronectin binding to activated human platelets.

We report the characterization of a monoclonal antibody (MAb) PM6/13 which recognises glycoprotein IIIa (GPIIIa) on platelet membranes and in functional studies inhibits platelet aggregation induced by all agonists examined. In platelet-rich plasma, inhibition of aggregation induced by ADP or low concentrations of collagen was accompanied by inhibition of 5-hydroxytryptamine secretion. EC50 values were 10 and 9 microg/ml antibody against ADP and collagen induced responses respectively. In washed platelets treated with the cyclooxygenase inhibitor, indomethacin, PM6/13 inhibited platelet aggregation induced by thrombin (0.2 U/ml), collagen (10 microg/ml) and U46619 (3 microM) with EC50 = 4, 8 and 4 microg/ml respectively, without affecting [14C]5-hydroxytryptamine secretion or [3H]arachidonate release in appropriately labelled cells. Studies in Fura 2-labelled platelets revealed that elevation of intracellular calcium by ADP, thrombin or U46619 was unaffected by PM6/13 suggesting that the epitope recognised by the antibody did not influence Ca2+ regulation. In agreement with the results from the platelet aggregation studies, PM6/13 was found to potently inhibit binding of 125I-fibrinogen to ADP activated platelets. Binding of this ligand was also inhibited by two other MAbs tested, namely SZ-21 (also to GPIIIa) and PM6/248 (to the GPIIb-IIIa complex). However when tested against binding of 125I-fibronectin to thrombin stimulated platelets, PM6/13 was ineffective in contrast with SZ-21 and PM6/248, that were both potent inhibitors. This suggested that the epitopes recognised by PM6/13 and SZ-21 on GPIIIa were distinct. Studies employing proteolytic dissection of 125I-labelled GPIIIa by trypsin followed by immunoprecipitation with PM6/13 and analysis by SDS-PAGE, revealed the presence of four fragments at 70, 55, 30 and 28 kDa. PM6/13 did not recognize any protein bands on Western blots performed under reducing conditions. However Western blotting analysis with PM6/13 under non-reducing conditions revealed strong detection of the parent GPIIIa molecule, of trypsin treated samples revealed recognition of an 80 kDa fragment at 1 min, faint recognition of a 60 kDa fragment at 60 min and no recognition of any product at 18 h treatment. Under similar conditions, SZ-21 recognized fragments at 80, 75 and 55 kDa with the 55 kDa species persisting even after 18 h trypsin treatment. These studies confirm the epitopes recognised by PM6/13 and SZ-21 to be distinct and that PM6/13 represents a useful tool to differentiate the characteristics of fibrinogen and fibronectin binding to the GPIIb-IIIa complex on activated platelets.

Antibodies, Monoclonal↗
PubMed1998

Chronic appendicitis: does it exist?

The typical presentation of acute appendicitis is well known. A few patients, however, have had an atypical clinical course suggestive of recurrent appendiceal inflammation, which has been confirmed by appendectomy. Therefore, in the evaluation of a patient with abdominal pain, a history of similar episodes should not preclude a diagnosis of appendicitis.

Abdominal Pain↗
PubMed1997

High-performance liquid chromatographic method for the determination of nelfinavir, a novel HIV-1 protease inhibitor, in human plasma.

Nelfinavir mesylate, a potent and orally bioavailable inhibitor of HIV-1 protease (Ki=2 nM), has undergone Phase III clinical evaluation in a large population of HIV-positive patients. A high-performance liquid chromatography analytical method was developed to determine the pharmacokinetic parameters of the free base, nelfinavir, in these human subjects. The method involved the extraction of nelfinavir and an internal standard, 6,7-dimethyl-2,3-di-(2-pyridyl)quinoxaline, from 250 microl of human plasma with a mixture of ethyl acetate-acetonitrile (90:10, v/v). The analysis was via ultraviolet detection at 220 nm using a reversed-phase C18 analytical column and a mobile phase consisting of 25 mM monobasic sodium phosphate buffer (adjusted to pH 3.4 with phosphoric acid)-acetonitrile (58:42, v/v) that resolved the drug and internal standard peaks from non-specific substances in human plasma. The method was validated under Good Laboratory Practice (GLP) conditions for specificity, inter- and intra-assay precision and accuracy, absolute recovery and stability. The mean recovery ranged from 92.4 to 83.0% for nelfinavir and was 95.7% for the internal standard. The method was linear over a concentration range of 0.0300 microg/ml to 10 microg/ml, with a minimum quantifiable level of 0.0500 microg/ml for nelfinavir.

Anti-HIV Agents↗
PubMed1997

Monoclonal antibodies recognizing the N- and C-terminal regions of talin disrupt actin stress fibers when microinjected into human fibroblasts.

We have characterized a panel of 6 monoclonal antibodies raised against human platelet talin by Western blotting, immune precipitation, and immunofluorescence, and shown that antibodies TA205 and TD77 disrupt actin stress fibers and focal adhesions, and inhibit cell motility when microinjected into human fibroblasts. Using a series of chick talin fusion proteins spanning the entire length of the molecule, we have mapped the epitopes recognized by these antibodies to the conserved N- and C-terminal regions of the protein. TA205 bound to an epitope contained within residues 139-433, a region which overlaps an F-actin binding site, and which shows homology with the ezrin/radixin/moesin family of cytoskeletal proteins. The epitope recognized by TD77 was located within the C-terminal region of the protein (residues 2269-2541) which also contains an F-actin binding site homologous to that in the yeast actin-binding protein SIa2p. To investigate the possibility that TD77 disrupts actin stress fibers by binding directly to the C-terminal actin binding site, additional talin fusion proteins were generated and analyzed for TD77 and actin binding. Fusion proteins containing residues 2269-2541, 2304-2541, and 2304-2463 all cosedimented with F-actin, whereas TD77 did not recognize the latter fusion protein. These results show that the C-terminal actin-binding site is distinct from the region recognized by the anti-functional antibody TD77, raising the possibility that it binds to a novel functionally important ligand-binding site in the talin molecule.

Actins↗
PubMed1997

Identification of new HLA class I region genes by sample sequencing.

Although many human major histocompatibility genes have been identified, relatively few have been localized to the class I region. We searched for new class I region genes by sample sequencing, a process in which short stretches of random genomic sequence are generated from cosmids and then compared with sequences deposited in nucleotide databases. Four class I region cosmids were isolated for sample sequencing by screening a chromosome 6 specific cosmid library with probes derived from specific class I region genes or with overlapping class I region yeast artificial chromosomes. Cosmids were sonnicated to produce fragments of 0.5 - 1 kilobases, subcloned, and sequenced using an automated sequencer. Sequences were then compared with nucleotide sequences deposited in the GenBank databases using the BLASTN algorithm. A number of potential new class I region genes were identified, including a cDNA with similarity to the tre oncogene, the trans-activating factor SC1 (TCF19), and a member of the interferon inducible 1 - 8 gene family. These observations suggest that sample sequencing is an efficient method for identifying new class I region genes, which can be applied to other regions of the genome and to other species, and support previous observations that the class I region contains a variety of genes other than those encoding HLA antigens.

Base Sequence↗
PubMed1997

Diagnostic dilemmas in dysphagia aortica.

OBJECTIVE: Dysphagia aortica describes swallowing difficulty caused by external compression from a tortuous or aneurysmal aorta. We present 5 cases in which dysphagia to solids accompanied a localised high pressure barrier (HPB) on manometry suggestive of dysphagia aortica, and explore other investigation modalities useful to confirm the diagnosis. METHODS: Four females and 1 male with a median age of 56 years (range 47-58) were investigated. All underwent investigation with endoscopy, chest radiography, CT scanning, barium swallow, and video solid bolus swallow in addition to oesophageal manometry and 24 h ambulatory pH monitoring. RESULTS: Median basal pressure rise at the mid oesophageal HPB was 45 mmHg (range 40-80). In addition to the HPB, 4 patients had manometric abnormalities of swallow activity and 2 patients had significant gastroesophageal reflux disease (GORD). Contrast enhanced computed tomography and barium swallow were normal in all cases. Video bolus swallow showed pronounced obstruction to transit at the aortic arch in 2 cases and excluded significant dysphagia aortica in 2 others. CONCLUSIONS: Dysphagia aortica commonly coexists with motility disorders and GORD. Video solid bolus swallow allowed us to determine the clinical significance of a manometric HPB in 4 out of 5 patients suspected on dysphagia aortica where standard evaluation would have failed. We recommend its use in those patients with a manometric HPB suggestive of dysphagia aortica in whom standard barium swallow is normal.

Aortic Aneurysm, Thoracic↗
PubMed1997

Acute bicaval obstruction as a result of intracapsular haemorrhage in a right atrial myxoma: report of a case.

Right atrial myxomas are rare and presentation is characterised by the gradual onset of one or more of a triad of constitutional, obstructive, or embolic symptoms. We describe a case in which interstitial haemorrhage within a right atrial myxoma resulted in rapid expansion and presentation with features of rapidly progressing bicaval obstruction and atrial flutter. Transthoracic echocardiography failed to detect this tumour; however, transoesophageal echo clearly displayed it and gave information on its attachment and relations which proved to be valuable in the planning of its surgical excision.

Diagnosis, Differential↗
PubMed1997

Middle cerebral artery blood velocity, embolisation, and neurological outcome during carotid endarterectomy: a prospective comparison of the Javid and the Pruitt-Inahara shunts.

OBJECTIVES: To investigate the in vivo haemodynamic performance and neurological outcome of two types of carotid shunt. DESIGN: Randomised single surgeon study of consecutive symptomatic patients. SETTING: 163 consecutive patients undergoing carotid endarterectomy for symptomatic carotid disease were randomised to the Javid or Pruitt shunt. CHIEF OUTCOME MEASURES: Middle cerebral artery velocity (MCAV), preoperatively, during clamping, during shunting and post-restoration of flow, embolic episodes, neurological outcome. MAIN RESULTS: The MCAV preoperatively, at carotid clamping, and postoperatively was the same for both groups (p > 0.15). During shunting the MCAV was significantly lower in the Pruitt group, p < 0.005, 59% of the Javid and 34% of the Pruitt shunts maintained MCAV at preoperative levels p < 0.005, chi 2 = 8.92. The Javid shunt produced significantly more emboli (73% of cases) at declamping than the Pruitt (41%), p < 0.0002, chi 2 = 14.7. Four Javid patients and one Pruitt had disabling thromboembolic strokes; overall thromboembolic stroke rate 3.7%. The difference in stroke rates was not statistically significant (p = 0.14). CONCLUSIONS: The Pruitt shunt was unable to maintain preoperative MCAV in 66% of cases, the Javid shunt had a higher incidence of emboli on declamping. These factors may lead to an increased risk of stroke; however, the numbers required for statistical confirmation would be large.

Adult↗
PubMed1997

Supravesical diversion for incontinence: a long-term follow-up.

OBJECTIVES: To report the long-term follow-up of patients with an ileal conduit urinary diversion, constructed for intractable incontinence in patients with benign disease where the native bladder was left in situ, and to determine the fate of the bladder and the effects on the upper tracts. PATIENTS AND METHODS: Ninety-three patients (mean age at operation 50 years, range 8-78) were followed for a minimum of 2 (mean 5) years after undergoing an ileal conduit urinary diversion. Seventy-one patients (76%) had neurological disease (18 traumatic and 53 non-traumatic) and the single largest group of patients (28) suffered from disseminated sclerosis. Twenty-two patients with no obvious neurological disease underwent the procedure for unmanageable incontinence or intractable bladder symptoms or for interstitial cystitis. The patients were assessed for problems in the bladder remnant, stomal problems and upper tract changes following surgery. RESULTS: Forty-eight patients (52%) had recurrent vesical infections and pyocystis and of these, 23 (48%) required admission for in-patient bladder irrigations. To control recurrent bladder problems, five patients required creation of a vesico-vaginal fistula; this did not suffice in two and they subsequently underwent cystectomy; in total, five patients underwent cystectomy. Twenty-nine patients (31%) had stomal problems, those with the skin being commonest. Parastomal hernia repair was required in 10 (10%) patients and three had further surgery for recurrence. Of 83 patients with normal upper tracts before diversion, post-operative radiological assessment showed upper tract dilatation in 28 (34%) and in 10 (12%) this was bilateral. In one patient with a neuropathic bladder, the ileal diversion resulted regression of the dilated upper tracts. CONCLUSIONS: Supravesical diversion is safe and well tolerated but assessing the long-term follow-up, the incidence of bladder problems in over half these patients and upper tract changes in over a third suggests an indefinite follow-up is mandatory. Despite these problems, most patients are delighted with the outcome of their surgery.

Adolescent↗
PubMed1997

Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis.

BACKGROUND & AIMS: Esophagitis healing proportions are often incorrectly called the healing rate. The aim of this study was to compare different drug classes by expressing the speed of healing and symptom relief through a new approach. METHODS: A fully recursive literature search to July 1996 identified 43 articles on gastroesophageal reflux disease (GERD) (7635 patients) meeting strict inclusion criteria: single- or double-blind randomized studies in adults with endoscopically proven erosive or ulcerative esophagitis. For each drug class, linear regression analysis estimated the average percentage of patients who were healed and heartburn free per week. RESULTS: Mean overall healing proportion irrespective of drug dose or treatment duration (< or =12 weeks) was highest with proton pump inhibitors (PPIs; 83.6% +/- 11.4%) vs. H2-receptor antagonists (H2RAs; 51.9% +/- 17.1%), sucralfate (39.2% +/- 22.4%), or placebo (28.2% +/- 15.6%). Correcting for patients without baseline heartburn, the mean heartburn-free proportion was highest with PPIs (77.4% +/- 10.4%) vs. H2RAs (47.6% +/- 15.5%). PPIs showed a significantly faster healing rate (11.7%/wk) vs. H2RAs (5.9%/wk) and placebo (2.9%/wk). PPIs provided faster, more complete heartburn relief (11.5%/wk) vs. H2RAs (6.4%/wk). CONCLUSIONS: More complete esophagitis healing and heartburn relief is observed with PPIs vs. H2RAs and occurs nearly twice as fast. This semiquantitative expression of speed of healing and symptom relief permits comparisons for future economic evaluation and quality-of-life assessments.

Adolescent↗
PubMed1997

Head scatter modelling for irregular field shaping and beam intensity modulation.

Scattered radiation from within the treatment head can contribute significant dose to all parts of a radiotherapy treatment field. A multileaf collimator may be used to create an arbitrarily shaped field, and may also be used, under dynamic control, to modulate the beam intensity over the field. This method of intensity modulation is effectively a superposition of a large number of fields which have the same beam direction, but different shapes, and some of these shapes may have unusually small dimensions, particularly in the direction of the leaf movement. Two models for predicting the head scatter under these conditions have been investigated. These are a first-order Compton scatter approximation from the flattening filter, and an empirical fit to measured data using an exponential function. The first model only considers scatter from the flattening filter and has been applied to field sizes between 2 cm by 2 cm and 10 cm by 10 cm, where agreements are all within 1%. However it is not satisfactory at larger field sizes where small scatter contributions, from scattering sources other than the flattening filter, are integrated over large areas. The second model uses measured data between 4 cm by 4 cm and 30 cm by 30 cm to optimize the exponential function and is used to calculate the head scatter contribution for all field sizes. In this case good agreement is achieved over the full field size range, and hence this is a more generally applicable model. Results are presented for static irregularly shaped fields and intensity modulated beams created using a Philips multileaf collimator.

Biophysical Phenomena↗
PubMed1997

Intracavitary radiotherapy boosting for nasopharynx cancer.

Intracavitary radiotherapy is conceptually an attractive method of boosting dose to nasopharynx cancer whilst sparing sensitive normal tissues. A high dose rate (HDR) microselectron can be used to deliver a brachytherapy boost conveniently, safely, comfortably and effectively. Following external radiotherapy a single outpatient treatment has been given to patients using the remote afterloading system of sources placed in modified paediatric endotracheal tubes. This has been associated with good primary control and no evidence of serious morbidity in eight patients. The main limitation of this method is restriction of its utilization to small volume primary disease.

Brachytherapy↗
PubMed1997

Successful non operative management of late infrainguinal polytetrafluoroethylene vascular graft infection with antibiotics alone: a report of two cases.

Polytetrafluoroethylene (PTFE) prosthetic vascular graft infection is a serious complication of arterial reconstructive surgery. Traditional management is primarily surgical and may result in long hospital stay with significant morbidity and mortality. The authors describe two cases of infected femoropoliteal PTFE grafts which were managed non operatively with antibiotic therapy alone, resulting in early return to normal activities and excellent resolution of infection on Indium labelled leucocyte scanning. The authors suggest that in selected cases antibiotic therapy alone is a valuable tool in the management of infrainguinal PTFE prosthetic sepsis.

Aged↗