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Biomedical subjects

L Mitchell

Publications and source records attributed to L Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

Manmade and natural radionuclides in north east Atlantic shelf and slope sediments: Implications for rates of sedimentary processes and for contaminant dispersion.

Results are presented for a study of manmade and natural radionuclides in north east Atlantic continental shelf and slope sediments to the west of Scotland. The data are interpreted in the context of sediment mixing and accumulation processes and are used to establish the westward extent of contamination of the sediment system. Offshore shelf and slope sediments were found to have post-glacial sedimentation rates of the order of 1 cm ky(-1) but nearshore sediments had much higher accumulation rates of the order of 0.1 cm y(-1). Surface mixed layer depths of up to 6 cm were observed and non-local mixing affected most of the slope sediments, resulting in advective transport of surface sediment to depths of up to 10 cm. Biodiffusion coefficients for offshore shelf and slope sediments were dominantly in the range 10(-8) to 10(-9) cm2 s(-1). The study confirmed that seawater contaminated with Sellafield waste radionuclides is dominantly entrained to the east of 7 degrees W and, consistent with this, higher levels of Sellafield derived radionuclides were confined to nearshore sediments, with lower levels to the west of 7 degrees W. 238Pu/(239,240)Pu data indicated that Sellafield contributed 75-91% of the total plutonium in coastal sediment but only about 4-8% of the total in slope sediments. By analogy, it can be concluded that a similar situation will apply to other contaminants in seawater entering the north east Atlantic via the North Channel.

Atlantic Ocean↗
PubMed2006

Specialist dermatology clinics for organ transplant recipients significantly improve compliance with photoprotection and levels of skin cancer awareness.

BACKGROUND: Organ transplant recipients (OTRs) have 100-fold increased risk of developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation is the main risk factor and there is evidence that lack of dermatological surveillance may be responsible for poor levels of knowledge and photoprotection among OTRs. OBJECTIVES: This study evaluated whether routine consultation in a specialist OTR dermatology clinic improves understanding of skin cancer risk and compliance with photoprotection measures. METHODS: A cross-sectional questionnaire-based study was performed in a specialist OTR dermatology clinic at Bart's and the London NHS Trust, London, U.K. The subjects were 399 white-skinned patients under surveillance in a renal transplant clinic, who were sent a postal questionnaire from the renal transplant clinic. The main outcome measures were responses to the questionnaire regarding photoprotective practices and skin cancer risk awareness. RESULTS: Two hundred and ninety-two of 399 (73%) responded, of whom 89% had previously attended the specialist dermatology clinic. Ninety-six per cent recalled receiving photoprotection advice at least once (85% from dermatologists); 92% reported use of sunscreen; 88% specifically dressed to photoprotect themselves; 96% directly avoided sun exposure during summer; 68% were aware that an increased risk of skin cancer was the reason that extra photoprotective measures were important after a transplant. Photoprotective measures and level of skin cancer awareness were significantly lower in those responders who had never attended the specialist clinic. No obvious bias was identified among nonresponders. CONCLUSIONS: Skin cancer awareness and compliance with photoprotective measures in our patient population is generally greater than previously reported, suggesting that delivery of educational messages regarding skin cancer may be improved if provided in a specialist dermatological setting.

Cross-Sectional Studies↗
PubMed2006

Star testing: a novel evaluation of intraocular lens optical quality.

BACKGROUND: Despite the importance of optical quality of an intraocular lens (IOL) on visual outcomes following cataract surgery, objective data on their optical quality are not readily available, and manufacturing standards are industry regulated. The star test is a classic test of optical quality based on examination of the Airy disc and expanded diffraction rings of a point source of light, used mainly for telescope and microscope objectives. METHODS: A physical model eye cell allowed star testing of IOLs under conditions similar to the optical environment in which they operate. 18 IOLs were tested and results compared to actual images produced by these lenses in the model eye cell. Quantitative measures of star testing performance were developed. RESULTS: The optical performance of the IOLs varied, some performing very poorly. Most lenses (13/17) performed better in reverse orientation, while aberrations induced by the haptics of foldable IOLs were also detected. There was excellent correlation between actual images formed and star testing parameters. CONCLUSION: Star testing IOLs was a novel biomedical application of a centuries old, inexpensive method. A concerning variation of optical quality was found, suggesting IOL optical performance data should be more readily available. Independent, authority mandated IOL optical quality standards should be developed, and results readily available to ophthalmologists.

Acrylic Resins↗
PubMed2004

The need to redefine non-cystic fibrosis bronchiectasis in childhood.

BACKGROUND: Non-cystic fibrosis (CF) bronchiectasis has previously been reported to be rare and progressive in children living in western societies. METHOD: A clinical and radiological review was undertaken of 93 children with non-CF bronchiectasis defined by high resolution computed tomographic (HRCT) scanning presenting to a tertiary paediatric respiratory centre since 1996. RESULTS: Cases constituted 9.6% of all new referrals. Male to female ratio was 2:1. Median age at symptom onset was 1.1 years (range 0-16) and of HRCT diagnosis was 7.2 years (1.6-18.8). The most common referral diagnosis of asthma was refuted in 39 of 45 cases. Associations were previous pneumonic illness (30%), immunocompromise (21%), obliterative bronchiolitis (9%), congenital lung abnormality (5%), chronic aspiration (3%), eosinophilic oesophagitis (2%), familial syndrome (2%), primary ciliary dyskinesia (1%), and right middle lobe syndrome (1%). 8% had two associated diagnoses and 18% were idiopathic. There was agreement between the chest radiograph and HRCT scan for diagnosis and lobe affected in only five cases (5%). A repeat HRCT scan in 18 cases at a minimum interval of 18 months showed total resolution of the changes in six, improvement in one, progression in five, and was unchanged in six. CONCLUSIONS: Radiologically defined non-CF bronchiectasis in children is not uncommon. Diagnostic delay is a problem. The most common association is a previous pneumonia. Chest radiography is of little diagnostic value, but resolution is possible on HRCT scanning. Bronchiectasis is currently defined as a condition which is both permanent and progressive. This term is not necessarily appropriate for all paediatric patients for whom we suggest an alternative nomenclature.

Adolescent↗
PubMed2003

Clinical and electrophysiological differences between patients with arrhythmogenic right ventricular dysplasia and right ventricular outflow tract tachycardia.

AIMS: Radiofrequency catheter ablation is considered first line treatment for symptomatic patients with right ventricular outflow tract tachycardia (RVOT). The role of ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more limited. As such, differentiating between the two conditions is essential. METHODS AND RESULTS: This study compared non-invasive findings, magnetic resonance images (MRI), invasive electrophysiological characteristics, results of ablation and long-term outcome in 50 consecutive patients with RVOT (33) or ARVD (17). Structural abnormalities were uniform in the ARVD group; in addition 18 (54%) of the RVOT tachycardia group had MRI abnormalities. At electrophysiological study the tachycardia in the ARVD group displayed features of re-entry in over 80%, but behaved with a triggered automatic basis in 97% with RVOT. Ablation was complete or partial success in 12 (71%) patients with ARVD and ventricular tachycardia (VT) recurred in eight (48%). In the RVOT patients, ablation was a complete success in 97% with recurrent VT in 6%. Long-term success in the RVOT patients was 95% in both patients with and without MRI abnormalities. CONCLUSIONS: Electrophysiological characterization can differentiate ARVD from RVOT. The finding of abnormalities on MRI does not have any bearing on arrhythmia mechanism, acute or long-term success of RFA.

Adolescent↗
PubMed2003

Hepatic and intestinal cytochrome P450 and conjugase activities in rats treated with black tea theafulvins and theaflavins.

Theaflavins and theafulvins, a fraction of thearubigins, were isolated from aqueous infusions of black tea, and their effects on the hepatic and intestinal cytochrome P450 system, and on the glutathione S-transferase, epoxide hydrolase, glucuronosyl transferase and sulphotransferase enzyme systems were investigated in rats following oral intake for four weeks. Neither theafulvins nor theaflavins influenced cytochrome P450 activity in the liver as exemplified by the O-dealkylations of methoxy-, ethoxy- and pentoxyresorufin, the hydroxylations of lauric acid and p-nitrophenol, and the N-demethylation of erythromycin; similarly, hepatic xenobiotic conjugation systems were unaffected. In the intestine, both polyphenolic fractions markedly suppressed the O-deethylation of ethoxyresorufin and this was accompanied by a decrease in the CYP1A1 apoprotein levels. Probing intestinal microsomes with antibodies to CYP2E1 revealed the presence of a single band in the cytochrome P450 region whose intensity was lower in the polyphenol-treated animals. Immunoblot analysis utilising antibodies to CYP3A showed that the treatment with theafulvins and theaflavins reduced the apoprotein levels. A single band in the cytochrome P450 region was evident when the intestinal microsomes were probed with antibodies to CYP4A1 but the level of expression was not affected by the treatment with the black tea polyphenols. Finally, treatment of the rats with theaflavins had no effect on any of the intestinal conjugating enzymes studied, but treatment with theafulvins led to inhibition of glucuronosyl transferase activity.

Animals↗
PubMed2003

Lercanidipine vs lacidipine in isolated systolic hypertension.

This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.

Aged↗
PubMed2003

Do Thoroughbred and Standardbred horses have similar increases in pulmonary vascular pressures during exertion?

To test the hypothesis that the pulmonary vascular pressures of Thoroughbred and Standardbred horses behave similarly during exertion. Measurements were made on 5 Thoroughbred and 5 Standardbred horses on a treadmill at rest and during 3-minute exercise intervals at speeds predicted to produce 75%, 90%, and 100% maximal heart rate. Left forelimb acceleration, heart rate, esophageal pressure, and pulmonary artery pressure were measured continuously. Pulmonary capillary and wedge pressures were measured during intermittent occlusion of the pulmonary artery. Breathing rate and gait frequency were the fundamental frequencies of the esophageal pressure and limb acceleration signals respectively. The ratio of speed:gait frequency gave stride length. The effects of exertion and breed were evaluated using two-way analysis of variance. Exertion produced significant increases in pulmonary artery (P = 0.001), capillary (P = 0.002), and wedge (P = 0.005) pressures. No significant effect of breed was detected on pulmonary artery pressure, but at exertion pulmonary capillary and wedge pressures were 15% (P = 0.03) and 23% (P = 0.04) greater in Thoroughbreds, respectively. Treadmill speed was approximately 12% greater (P = 0.04), stride length was approximately 25% greater (P = 0.0003), gait frequency was approximately 10% less (P = 0.006), breathing rate was approximately 10% less (P = 0.001), and heart rate was approximately 6% less (P = 0.06) for Thoroughbreds. There was no effect of breed on inspiratory or expiratory esophageal pressure although mean esophageal pressure was approximately 2 mmHg greater (P = 0.03) in exercising Standardbreds. In conclusion, pulmonary capillary and wedge pressures are greater in Thoroughbreds than in Standardbreds at similar fractions of maximal heart rate. This is compatible with the higher incidence of exercise-induced pulmonary hemorrhage observed in Thoroughbreds.

Analysis of Variance↗
PubMed2001

Characterization of the active sites in decay-accelerating factor.

Decay-accelerating factor (DAF) is a complement regulator that dissociates autologous C3 convertases, which assemble on self cell surfaces. Its activity resides in the last three of its four complement control protein repeats (CCP2-4). Previous modeling on the nuclear magnetic resonance structure of CCP15-16 in the serum C3 convertase regulator factor H proposed a positively charged surface area on CCP2 extending into CCP3, and hydrophobic moieties between CCPs 2 and 3 as being primary convertase-interactive sites. To map the residues providing for the activity of DAF, we analyzed the functions of 31 primarily alanine substitution mutants based in part on this model. Replacing R69, R96, R100, and K127 in the positively charged CCP2-3 groove or hydrophobic F148 and L171 in CCP3 markedly impaired the function of DAF in both activation pathways. Significantly, mutations of K126 and F169 and of R206 and R212 in downstream CCP4 selectively reduced alternative pathway activity without affecting classical pathway activity. Rhesus macaque DAF has all the above human critical residues except for F169, which is an L, and its CCPs exhibited full activity against the human classical pathway C3 convertase. The recombinants whose function was preferentially impaired against the alternative pathway C3bBb compared with the classical pathway C4b2a were tested in classical pathway C5 convertase (C4b2a3b) assays. The effects on C4b2a and C4b2a3b were comparable, indicating that DAF functions similarly on the two enzymes. When CCP2-3 of DAF were oriented according to the crystal structure of CCP1-2 of membrane cofactor protein, the essential residues formed a contiguous region, suggesting a similar spatial relationship.

Amino Acid Sequence↗
PubMed2001

MRI changes in multiple sclerosis following treatment with lofepramine and L-phenylalanine.

As part of a large, randomized placebo-controlled trial of inpatients with multiple sclerosis (MS), a subsample of 15 underwent cerebral MRI at baseline and 6-months (eight on lofepramine and l-phenylalanine; seven on placebo). Unlike the placebo group, the active group showed a significant reduction in lesion number visible on T1-weighted scans (p < 0.05). The lateral ventricular volume increased, on average, by 1020 mm3 in the untreated group and 600 mm3 in the treated group. In the treated patients the ventricular size change correlated with both change in Gulick MS-related symptoms scale scores (rs = 0.71, p = 0.07) and Gulick MS-related activities of daily living scale scores (rs = -0.83, p = 0.02). It is concluded that treatment with lofepramine and l-phenylalanine is associated with significant MRI changes.

Adult↗
PubMed2001

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

Activated Protein C Resistance↗
PubMed2001

Elevated blood pressure predicts the risk of acute rejection in renal allograft recipients.

BACKGROUND: Acute rejection (AR) is a strong predictor of renal allograft survival. Recent advances in immunosuppression have reduced considerably the incidence of AR. Still, approximately 25% of patients have AR early post-transplant, and the factors that predispose to AR have not been fully clarified. METHODS: The study includes 1641 adults, recipients of first cadaveric (CAD, N = 1195) or living related renal grafts (LRD, N = 446), transplanted in one institution. The variables associated with the occurrence of AR during the first year post-transplant were identified. RESULTS: By univariate analyses, AR was associated with the following variables: younger (P < 0.001); heavier (P = 0.003); and African American recipients (P = 0.002); CAD transplants (P = 0.001); higher number of HLA mismatches (P = 0.001); delayed graft function (DGF, P = 0.001); higher levels of serum creatinine post-transplant (P = 0.003); and higher levels of systolic and/or diastolic blood pressure (BP) post-transplant (P < 0.001). Higher BP levels were also associated with earlier AR episodes (P < 0.0001). By multivariable analysis AR was significantly associated with recipient age, number of HLA mismatches, DGF, pre-PRA and systolic BP. Analysis of BP measured weekly post-transplant indicated that elevated BP levels, even three weeks prior to the AR episode, were significantly associated with AR. For every level of BP, the use of BP medications was associated with a lower incidence of AR (P < 0.0001). Furthermore, the use of calcium channel blockers was also associated with lower incidence of AR (P = 0.001). Of note, 81% of recipients whose BP increased after the transplant had AR. In contrast, 22% of patients whose BP declined post-transplant had AR. CONCLUSIONS: Elevated BP levels post-transplant identify patients at high risk of AR independently of graft function. Treatment of BP and reduction of BP levels appears to be associated with a decreased risk of AR. We hypothesize that high BP may be an indicator of a particular type of allograft damage, perhaps ischemic, that may predispose to AR.

Acute Disease↗
PubMed2001

Fluoride-releasing elastomeric modules reduce decalcification: a randomized controlled trial.

OBJECTIVE: To determine whether fluoride releasing elastomeric modules reduced the incidence of decalcification around orthodontic brackets during a complete course of orthodontic treatment. DESIGN: A randomised controlled, split mouth design. SETTING: The study was carried out in the orthodontic department of Newcastle-upon-Tyne Dental Hospital, UK. SUBJECT AND METHODS: 21 consecutive patients (126 teeth) undergoing fixed appliance therapy were studied. A split mouth technique was adopted to examine the upper labial segment, where one side (left or right) was randomly assigned to the experimental group, and the opposite side served as a control throughout their course of orthodontic treatment. INTERVENTIONS: The control teeth were ligated to the archwire using conventional modules. The experimental teeth were ligated to the archwire using Fluoride releasing elastomeric modules. OUTCOME MEASURES: Standardised photographs were taken of the upper labial segment before and after completion of orthodontic treatment, and the degree of decalcification assessed in each tooth quadrant, using a modification of the Enamel Defect Score. RESULTS: Decalcification was found to occur in both treatment groups, though to a significantly greater degree on the control side (p = 0.002). The fluoride module side showed significantly fewer serious decalcified lesions than the control (p = 0.013). No patients withdrew from the study. CONCLUSIONS: It would appear that the use of fluoride releasing elastomeric modules reduces the degree of decalcification experienced during orthodontic treatment.

Fluorides↗
PubMed2001

A randomized controlled trial to investigate brackets bonded with a hydrophilic primer.

OBJECTIVE: To compare the clinical failure rates of brackets bonded using a prototype hydrophilic primer, designed to be insensitive to moisture, with brackets bonded with a conventional primer. DESIGN: Single centre randomised controlled clinical study. Thirty-three patients were bonded using a split mouth technique: randomly allocating the hydrophilic primer to one side of the mouth and a conventional primer to the other. SETTING: Hospital orthodontic department, Bradford, UK. SUBJECTS: Orthodontic patients requiring fixed appliances. MAIN OUTCOME MEASURES: The site and time to bond failure was recorded for each bracket that failed over 6 months. RESULTS: Using survival analysis, there was an increased risk of bracket failure when bonded with the hydrophilic primer compared with the conventional primer (hazard ratio = 2.2, 95% confidence interval: 1.1 to 4.5, P = 0.01). CONCLUSIONS: This hydrophilic primer cannot be recommended for routine clinical use.

Adolescent↗
PubMed2001

Development and application of a quantitative, specific assay for Cryptosporidium parvum oocyst detection in high-turbidity environmental water samples.

Chlorine-resistant Cryptosporidium parvum oocysts in drinking water play an important role in the epidemiology of cryptosporidiosis. Current methods of detecting these organisms in water are insensitive, labor-intensive, highly subjective, and severely limited by sample turbidity. We describe here an alternative technique utilizing electrochemiluminescence (ECL) technology for detecting C. parvum oocysts in environmental water samples. This method is quantitative, reproducible, and requires only minimal sample processing. Currently, the ECL assay can detect as few as one oocyst in one milliliter of concentrated test sample with sample turbidity of up to 10,000 nephelometric turbidity units. Water and sewer samples collected during a cryptosporidiosis outbreak were tested by ECL assay. Cryptosporidium parvum oocysts were found in the source water at the time of outbreak, and a sharply decreasing level of oocysts in sewer samples was observed over a three-month period following the outbreak.

Animals↗
PubMed2001

Early and periodic screening, diagnosis, and treatment examination completion rates for Oklahoma Medicaid managed care: 1995-1998.

Although quality medical care is a goal of all health care providers, finding a means by which to take that idea from the abstract to the measurable is often an arduous task. The Oklahoma Health Care Authority and the Oklahoma Foundation for Medical Quality confronted that challenge when examining the state of Oklahoma's Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) examination completion rates. Focused on measuring processes of care, the Oklahoma Health Care Authority (OHCA) and the Oklahoma Foundation for Medical Quality (OFMQ) used chart abstraction to track EPSDT examination rates for SoonerCare Plus Medicaid managed care recipients from 1995 through 1998. During the abstractions, an examination was interpreted as an EPSDT screen if a comprehensive health and development history plus a comprehensive unclothed physical examination were recorded. Examination rates have improved from 1995 when there was a documented 17.6% completion rate. The 1998 documented rate of completion was 60.0%. Trend analysis shows significant improvement over the four-year period. The results also suggest the necessity for continued improvement in the provision of documented EPSDT examinations to individuals in Medicaid managed care plans in Oklahoma.

Adolescent↗
PubMed2000

A common measure of disease-gene associations for case-control and tdt studies.

PURPOSE: Associations between a disease and a candidate gene can be evaluated in case-control studies, or using the transmission/disequilibrium test (TDT) in data from studies of case-parent trios. Consequently, data for a given disease-gene association are often available from both case-control and "TDT studies." The present investigation was undertaken to identify a measure of the magnitude of a disease-gene association that could be estimated using data from either type of study.METHODS: The magnitude of a disease-gene association detected using the TDT can be estimated by the frequency (T) with which heterozygous parents transmit the putative, high-risk allele to affected offspring. To derive an expression for T that could be solved using data from a case-control study, T was first rewritten as a function of the relative frequencies of the genotypes, at the candidate gene, among the affected offspring of a heterozygous parent. By application of Bayes' theorem, this equation was reduced to a form that could be solved using case-control data.RESULTS: T can be expressed as a function of the genotypic probabilities among individuals with the disease of interest and the frequency of the high-risk allele in the general population, which can be estimated from cases and controls, respectively. Hence, estimates of T can be derived from the data available in a case-control study.CONCLUSIONS: The parameter T, which provides a measure of the magnitude of a disease-gene association, can be estimated from either case-control or TDT data and, therefore, provides a means by which to compare results from these two types of studies. As in other areas of epidemiology, comparison of a quantitative measure of the magnitude of an association, as well as the direction and statistical significance of the association, should greatly aid in the interpretation of the overall body of literature on a particular disease-gene association, and may help to clarify seemingly discrepant results.

Journal Article↗