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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 19 recordsLinked to original sources
PubMed2006

Interpretation of ante-mortem stature estimates in South Africans.

When human skeletal remains of unknown individuals are analysed, the estimation of ante-mortem stature forms a key part of the report. However, for many people it may be difficult to judge the height of their missing relative in metric values. In this paper, we report on the statures of 2052 black, 483 coloured and 880 white South Africans of both sexes, measured during the last few years. It is shown that the statures of whites are significantly higher than those of the other two groups. The statures of the black and coloured groups are similar. It is proposed that the stature estimates provided in forensic reports are interpreted as tall, medium or short, based on whether they fall in the upper 25%, middle 50% or lower 25% of the distribution for the specific population.

Adolescent↗
PubMed2006

Retention time for corticosteroid-sparing systemic immunosuppressive agents in patients with inflammatory eye disease.

BACKGROUND: Multiple immunosuppressive drugs have been used to manage inflammatory eye disease when control cannot be achieved by corticosteroid alone. However, although clinical studies support the effectiveness of most of these agents, comparative studies have not been undertaken. Retention time, a measure of the duration of treatment with any given drug, is a crude indicator of drug effectiveness and tolerability that facilitates such a comparison. The retention time was compared for corticosteroid-sparing immunosuppressive agents in patients attending our tertiary referral inflammatory eye disease clinic. METHODS: The clinical records of all patients attending an inflammatory eye disease clinic at the Casey Eye Institute over a 1-year period (2003) were reviewed. From these records, we collected the following clinical data: age; sex; ocular diagnosis; and use of steroid-sparing systemic immunosuppression, including drugs, duration of treatment and, if ceased, reasons for cessation. Cox regression analysis, adjusted for clustering, was used to compare other drugs against methotrexate. RESULTS: 107 of 302 (35%) patients seen at the inflammatory eye disease clinic in 2003 had a total of 193 current or past prescriptions for systemic steroid-sparing immunosuppressive agents. The treated group, most of whom had uveitis, included 32 men and 75 women, aged 5-86 years. Most commonly prescribed were methotrexate (66 uses, 34%), ciclosporin (37 uses, 19%), azathioprine (26 uses, 13%), mycophenolate mofetil (22 uses, 11%) and cyclophosphamide (15 uses, 8%). Patients were retained significantly less on ciclosporin (p = 0.004), azathioprine (p = 0.04), mycophenolate mofetil (p = 0.04) and cyclophosphamide (p<0.001) compared with methotrexate. Reasons for cessation included adverse events, lack of effectiveness, success or remission, cost and desire for fertility. CONCLUSIONS: In patients with inflammatory eye disease, methotrexate may offer a superior combination of effectiveness and tolerability over other commonly used corticosteroid-sparing immunosuppressive agents. In this study, there was a twofold risk of not being retained on azathioprine, mycophenolate mofetil and ciclosporin and a fourfold risk of not being retained on cyclophosphamide compared with methotrexate.

Adolescent↗
PubMed2006

Anatomical hemispherectomy.

INTRODUCTION: Anatomical hemispherectomy is frequently employed in the surgical management of pediatric patients with medically refractory epilepsy. MATERIALS AND METHODS: In this chapter, we review the historical evolution of this surgical procedure, outline the indications and the criteria for selecting surgical candidates and describe the important pre-operative evaluation of the surgical candidates. DISCUSSION: We provide a detailed description of our surgical technique, anesthesiological considerations, and post-operative care plan. Ultimately we analyze the most common complications associated with this procedure. CONCLUSION: Anatomical hemispherectomy performed in carefully selected pediatric patients with medically intractable epilepsy can be a safe and efficacious surgical procedure.

Epilepsy↗
PubMed2006

Active metabolite from Tamiflu solution is bioequivalent to that from capsule delivery in healthy volunteers: a cross-over, randomised, open-label study.

The bioavailability of oseltamivir phosphate and oseltamivir carboxylate were assessed in healthy volunteers when delivered as a solution of the active pharmaceutical ingredient (API) compared with the commercial capsule formulation. The 90% confidence intervals (CIs) for the ratios of the two treatments (capsule versus solution) were within the reference region [0.80-1.25] for area under the curve (AUC(0-infinity): [0.94-0.99]) and maximum observed plasma concentrations (C(max): [0.93-1.08]). Thus, the two formulations were bioequivalent for oseltamivir carboxylate. For pandemic stockpiling of Tamiflu, governments can therefore choose between the capsule formulation alone, the API alone, or quantities of both.

Administration, Oral↗
PubMed2006

Modification of the Woodruff-Stamper assay demonstrates binding of Toxoplasma gondii tachyzoites to retinal vascular endothelium.

In the human host, infection with the protozoan parasite, Toxoplasma gondii, most commonly involves the eye and/or the brain. Previous work indicates a relative susceptibility of the human retinal vascular endothelium to infection with the T. gondii tachyzoite, which may contribute to this tissue localization. To facilitate the investigation of potential adhesive interactions between parasite and endothelium in the retina, we have modified the Woodruff-Stamper assay, originally described to study lymphocytic-endothelial binding. Vascular endothelium was identified in sections of human retina by Alexa Fluor 594-tagged anti-von Willebrand factor antibody. Binding of yellow fluorescent protein-expressing tachyzoites to endothelium under conditions of flow, simulated by rotation on an orbital shaker, was quantified in a masked fashion using imaging software. We observed multiple yellow spots in contact with Alexa Fluor 594-positive retina, indicating binding of T. gondii tachyzoites to retinal vascular endothelium. This modification of the Woodruff-Stamper assay provides an opportunity to evaluate potential host receptors for T. gondii on the retinal vascular endothelium. In addition, the assay suggests a methodology that could be used to examine adhesion of other microbes to microvasculature in different tissues.

Animals↗
PubMed2006

Management of intracranial meningeal hemangiopericytomas: outcome and experience.

Hemangiopericytomas represent rare intracranial tumors that have a tendency to recur locally and have the unique characteristic of giving extracranial metastases. Our current communication reviews a series of patients diagnosed with hemangiopericytoma who were treated in our facility. Eleven patients with a mean age of 51.2 years underwent follow-up for a mean time of 7.1 years. Their neuroimaging preoperative evaluation included plain skull X-rays, head CT scans, brain MRI, angiograms, and (1)HMRS. Preoperative embolization of the tumor was employed in 6/11 patients. All patients underwent craniotomy for tumor resection and postoperative radiation treatment was employed on all but one. Grade I resection was accomplished in 6/11 (54.5%), grade III in 4/11 (36.4%), and grade IV in 1/11 (9.1%). Local recurrence was detected in 3/11 (27.3%) at a mean period of 5 (range 2-7.5) years. Extracranial metastatic disease was documented in 4/11 (36.4%) patients at a mean of 4.9 (range 2.5-7) years after the initial diagnosis. The GOS score was: 7/11 (63.6%) scored 5, while 4/11 (36.4%) died at a mean time of 5.5 (range 3-8) years after the initial diagnosis. Intracranial hemangiopericytomas management requires aggressive surgical resection, postoperative radiation treatment, and extensive follow-up to rule out local recurrences and delayed extracranial metastases.

Adult↗
PubMed2006

The role of supracervical hysterectomy in benign disease of the uterus.

The aim of this study was to investigate the type of hysterectomy that gynaecological surgeons and female hospital staff would choose for benign disease of the uterus, and to investigate the most influential factors in that choice. We performed a prospective survey of 369 gynaecological surgeons and 370 female staff members of a large teaching hospital. Our survey found that 88% of UK gynaecological oncologists and 50% of US gynaecological oncologists responding would perform a supracervical hysterectomy (SCH) over a total abdominal hysterectomy (TAH) for benign disease of the uterus. A total of 72% of the female staff surveyed would choose a SCH for benign disease of the uterus. In conclusion, our study has given gynaecological and prospective patient approval to support the idea of replacing total hysterectomy with supracervical hysterectomy for benign disease of the uterus.

Attitude of Health Personnel↗
PubMed2005

The Coping with Asthma Study: a randomised controlled trial of a home based, nurse led psychoeducational intervention for adults at risk of adverse asthma outcomes.

BACKGROUND: Morbidity and mortality associated with severe asthma might be reduced by interventions that address psychosocial factors contributing to adverse outcomes. A study was undertaken to assess the effectiveness of a 6 month home based psychoeducational intervention delivered by a respiratory nurse specialist for adults at risk of adverse asthma outcomes. METHODS: A pragmatic randomised controlled trial was performed in 92 adults registered with hospital or primary care asthma clinics. All had previous hospital admissions and/or were on British Thoracic Society step 4-5 treatment and had failed to attend clinic appointments or were considered to have poor adherence to other aspects of their agreed management. Patients were visited in their homes for assessment and, where appropriate, intervention. The main outcomes measured were symptom control, asthma specific quality of life, and generic health status. RESULTS: At the 6 month primary time point there were no significant differences between usual care and intervention groups in mean symptom control, physical functioning, or mental health scores (differences (with 95% CI) -0.35 (-1.83 to 1.13), 3.10 (-11.42 to 17.63), 0.42 (-10.22 to 11.07), respectively). Small effects on asthma specific quality of life up to 12 months (e.g. adjusted difference at 12 months 0.13 (95% CI 0.02 to 0.25)) and short term effects on generic health status, which mirrored improvements in aspects of self-care observed at the end of the intensive phase of the intervention, were apparent only from fully adjusted analyses. CONCLUSIONS: A home based intervention provided by a nurse receiving psychological supervision may have effects on quality of life but is overall of limited long term benefit to adults at risk of adverse asthma outcomes.

Adaptation, Psychological↗
PubMed2005

Corneal graft rejection occurs despite Fas ligand expression and apoptosis of infiltrating cells.

BACKGROUND/AIMS: Constitutive expression of Fas ligand (CD95L) protects the eye against cell mediated immune responses by inducing apoptosis in infiltrating Fas bearing T cells. This study was designed to examine Fas ligand expression on acutely rejecting rat corneal grafts and to investigate the kinetics of induction of apoptosis in infiltrating leucocytes. METHODS: Orthotopic penetrating corneal transplantation was performed between genetically disparate inbred rats. Fas ligand expression and the phenotype of infiltrating leucocytes were examined by immunohistochemistry. Apoptotic nuclei were visualised in sections of normal rat cornea, rejecting allografts, and time matched isografts by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling (TUNEL) and quantified by video image analysis. Staining with Hoechst dye 33258 was used to confirm the presence of apoptotic nuclei. RESULTS: Fas ligand was expressed on corneal endothelial and epithelial cells during acute corneal graft rejection. At all time points examined, including as early as the fifth postoperative day, the cells infiltrating both corneal isografts and allografts were TUNEL positive. By the 15th postoperative day, over 90% of all nuclei, many of which were T cells, were apoptotic. CONCLUSION: Expression of Fas ligand is not downregulated on the cornea during allograft rejection and infiltrating leucocytes in both isografts and allografts die rapidly in situ. Despite the death of the cells believed to be responsible for rejection, isografts survive indefinitely whereas allografts are irreparably damaged.

Acute Disease↗
PubMed2005

A systematic review to examine the impact of psycho-educational interventions on health outcomes and costs in adults and children with difficult asthma.

OBJECTIVES: Prior research has highlighted the importance of psychosocial factors in 'difficult' asthma. This study aimed to review the content, effectiveness and cost-effectiveness of psycho-educational interventions designed to address these factors in patients with severe and difficult asthma. DATA SOURCES: Thirty-two electronic databases and other sources were searched for studies of educational, self-management, psychosocial and multifaceted interventions. REVIEW METHODS: Abstracts were screened in duplicate, against prior definitions, to identify eligible interventions targeted to patients with forms of or risk factors for difficult asthma. Studies were classified by patient group (child, adult) and graded along two dimensions related to study design and relevance in terms of the degree to which they were judged to have targeted difficult asthma. Detailed data were extracted from studies meeting a minimum design and relevance threshold. Characteristics of studies were tabulated and results qualitatively synthesised. Where sufficiently similar studies reported adequate data about comparable outcomes, quantitative syntheses of results were undertaken using a random effects approach to calculate pooled relative risks (RR) or standardised mean differences (SMD), with 95% confidence intervals (CI). RESULTS: Searches identified over 23,000 citations. After initial screening and removal of duplicates, 4240 possibly relevant abstracts were assessed. Papers associated with 188 studies were initially obtained and classified. Fifty-seven studies including control groups and those that were judged to have at least 'possible' targeting of difficult asthma (35 in children, 21 in adults, 1 in both) were selected for in-depth review. The delivery, setting, timing and content of interventions varied considerably even within broad types. Reporting of interventions and methodological quality was often poor, but studies demonstrated some success in targeting and following up at-risk patients. Studies reporting data suitable for calculation of summary statistics were of higher quality than those that did not. There was evidence from these that, compared to usual or non-psycho-educational care, psycho-educational interventions reduced admissions when data from the latest follow-ups reported were pooled across nine studies in children (RR = 0.64, CI = 0.46-0.89) and six studies with possible targeting of difficult asthma in adults (RR = 0.57, CI = 0.34-0.93). In children, the greatest and only significant effects were confined to individual studies with limited targeting of difficult asthma and no long-term follow-up. Limited data in adults also suggested effects may not extend to those most at risk. There was no evidence of pooled effects of psycho-educational interventions on emergency attendances from eight studies in children (RR = 0.97, CI = 0.78-1.21) and four in adults (RR = 1.03, CI = 0.82-1.29). There were overall significant reductions in symptoms, similar in different sub-groups of difficult asthma, across four paediatric studies that could be combined (SMD = -0.45, CI = -0.68 to -0.22), but mixed results across individual adult studies. A few individual studies in children showed mainly positive effects on measures of self-care behaviour, but with respect to all other outcomes in adults and children, studies showed mixed results or suggested limited effectiveness of psycho-educational interventions. No studies of psychosocial interventions were included in any quantitative syntheses and it was not possible to draw clear conclusions regarding the relative effectiveness of educational, self-management and multifaceted programmes. Data on costs were very limited. Of the two well-designed economic evaluations identified, both of multifaceted interventions, one in children suggested an additional cost of achieving health gain in terms of symptom-free days. Provisional data from the other study suggested that in adults the significantly increased costs of providing an intervention were not offset by any short-term savings in use of healthcare resources or associated with improvements in health outcomes. CONCLUSIONS: There was some evidence of overall positive effects of psycho-educational interventions on hospital admissions in adults and children, and on symptoms in children, but limited evidence of effects on other outcomes. The majority of research and greatest effects, especially in adults, were confined to patients with severe disease but who lacked other characteristics indicative of difficult asthma or likely to put them at risk. A lack of good-quality research limited conclusions about cost-effectiveness. Although psycho-educational interventions may be of some benefit to patients with severe disease, there is currently a lack of evidence to warrant significant changes in clinical practice with regard to the care of patients with more difficult asthma. Further research is needed to: (1) standardise reporting of complex interventions; (2) extend and update this review; (3) improve identification of patients at risk from their asthma; (4) develop and test appropriate outcome measures for this group; and (5) design and evaluate, via the conduct of high-quality pragmatic RCTs, more powerful psycho-educational interventions that are conceptualised in terms of the ways in which psychosocial factors and asthma interact.

Adult↗
PubMed2004

Assessment of welfare of the child in HIV positive couples.

BACKGROUND: Demand for assisted conception amongst HIV-infected couples is rising in parallel with increased efficacy of antiretroviral medication which has improved life expectancy and reduced vertical transmission risk. There are no published data on welfare of the child assessment in HIV positive couples undergoing assisted conception. METHODS: We assessed welfare of the child in 131 (i.e. total number seen, not treated) couples, where one or both partners were infected with HIV and referred to the infertility clinic at Chelsea and Westminster Hospital since 1999. In total, 59 couples received sperm washing treatment (male partner infected) resulting in 17 healthy babies, and 14 couples were treated in the female positive programme (5 concordant and 9 discordant for HIV) resulting in three healthy babies. RESULTS: Issues surrounding welfare of the child were commonly encountered in this series and were significant enough to withhold treatment in five cases. Many were relationship issues surrounding acquisition of infection, fear of infection in the negative partner or child (n = 1), poor prognosis (multiple drug resistance) (n=3) or disability related to infection (n = 1). CONCLUSIONS: Welfare of the child in HIV infected couples must be carefully considered in specialist centres with experienced counsellors. Issues surrounding treatment are complex and require close liaison with HIV specialists and involvement of the couple.

Child Welfare↗
PubMed2004

Management of uveitis.

Uveitis is a group of inflammatory eye diseases that cause substantial visual disability and present challenges to diagnosis and treatment. Immune-mediated subtypes of uveitis must be distinguished from infections and malignant forms of the disease, and systemic associations of an ocular inflammation must be recognized. Clinical examination, rather than screening by a series of laboratory and radiological investigations, is generally the key to making the correct diagnosis. Treatment of many forms of immune-mediated uveitis involves immunosuppressive agents, which may be administered locally or systemically. The introduction of biological agents and novel methods for drug delivery are providing further therapeutic options for patients with recalcitrant disease. This review focuses on the common specific forms of uveitis, and describes current and potential future treatment practices.

Humans↗
PubMed2004

The effect of intermittent maternal fasting on human fetal breathing movements.

In order to determine the effect of maternal fasting on human fetal breathing movements (FBM), 63 healthy pregnant women with singleton uncomplicated pregnancies of 30 weeks' gestation or more, and who were fasting during Ramadan, were recruited. Maternal blood glucose level and fetal movements were recorded during and after fasting. Statistical comparison of samples before and after a meal was made using Wilcoxon's signed-ranks test. Maternal glucose level during fasting (5.1 +/- 0.5 mmol/l) was significantly (P = 0.01) lower than after breakfast (5.3 +/- 1.0 mmol/l). There was a significant association between maternal glucose levels and numbers of days faster (P = 0.01). The time needed to detect breathing movements was significantly longer (P = 0.005) during fasting than postprandial. The continuous variety of fetal breathing movement was significantly (P = 0.02) less during fasting compared to postprandial. It is concluded that intermittent maternal fasting is associated with a significant alteration in the frequency and pattern of human FBM.

Adult↗
PubMed2004

The application of the fluoride reactivation process to the detection of sarin and soman nerve agent exposures in biological samples.

The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus), in blood from in vivo exposed rhesus monkeys (Macaca mulatta), and in spiked human plasma and purified human albumin. Guinea pig exposures ranged from 0.05 to 44 LD50, and reactivated nerve agent levels ranged from 1.0 ng/mL in plasma obtained from 0.05 LD50 sarin-exposed guinea pigs to an average of 147 ng/g in kidney tissue obtained from two 2.0 LD50 soman-exposed guinea pigs. Positive dose-response relationships were observed in all low-level, 0.05 to 0.4 LD50, exposure studies. An average value of 2.4 ng/mL for reactivated soman was determined in plasma obtained from two rhesus monkeys three days after a 2 LD50 exposure. Of the five types of guinea pig tissue studied, plasma, heart, liver, kidney and lung, the lung and kidney tissue yielded the highest amounts of reactivated agent. In similar tissue and with similar exposure procedures, reactivated soman levels were greater than reactivated sarin levels. Levels of reactivated agents decreased rapidly with time while the guinea pig was alive, but decreased much more slowly after death. This latter chemical stability should facilitate forensic retrospective identification. The high level of reactivated agents in guinea pig samples led to the hypothesis that the principal source of reactivated agent came from the agent-carboxylesterase adduct. However, there could be contributions from adducts of the cholinesterases, albumin and fibrous tissue, as well. Quantitative analysis was performed with a GC-MS system using selected ion monitoring of the 99 and 125 ions for sarin and the 99 and 126 ions for soman. Detection levels were as low as 0.5 ng/mL. The assay was precise and easy to perform, and has potential for exposure analysis from organophosphate nerve agents and pesticides in other animal species.

Animals↗
PubMed2004

Pharmacokinetic studies of intramuscular midazolam in guinea pigs challenged with soman.

Studies have demonstrated that benzodiazepine compounds are effective at antagonizing seizure activity produced by the organophosphate (OP) cholinesterase inhibitor soman. In this present study we have investigated the pharmacokinetics of midazolam and its associated effects on electroencephalographic (EEG) activity following intramuscular (i.m.) injection to soman-exposed guinea pigs (Crl:(HA)BR). Prior to experiments, the animals were surgically implanted with EEG leads to monitor seizure activity. For the study, animals were administered the following pretreatment/OP/treatment regimen. Pyridostigmine bromide (0.026 mg/kg, i.m.) was given 30 min prior to soman (56 micrograms/kg, 2 x LD50; subcutaneously, s.c.), followed in one minute by atropine sulfate (2 mg/kg, i.m.) and pralidoxime chloride (25 mg/kg, i.m.). All animals receiving this regimen developed seizure activity. Midazolam 0.8 mg/kg, i.m., was administered 5 min after onset of seizure activity. Based on EEG data, animals were categorized as either seizure-terminated or seizure not-terminated at 30 min following anticonvulsant administration. Serial blood samples were collected for the plasma midazolam analysis; the assay was accomplished with a gas chromatograph/mass spectrometer. The mean time to seizure termination was 8.8 +/- 1.6 min. The mean time-plasma concentration data were fit to standard pharmacokinetic models. The following parameter estimates were determined from the model-fit for seizure terminated and not-terminated animals respectively: apparent volumes of distribution (Vd) were 1.4 and 1.7 l/kg; area under the time-concentration curves (AUC), 15,990 and 15,120 ng.min/ml; times to maximal plasma concentration (Tmax), 1.66 and 2.91 min and maximal plasma concentrations (Cmax) 535.1 and 436.6 ng/ml. These data indicate that i.m. injection of midazolam is effective at terminating ongoing soman-induced seizure activity. Additionally, the relatively short Tmax and latency to seizure termination demonstrate the rapidity of drug absorption and action respectively.

Animals↗
PubMed2004

Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Abortion, Induced↗
PubMed2004

Returning to the same area of hair surfaces before and after treatment: a longitudinal AFM technique.

We report the use of longitudinal (aspect ratio > 1 : 1) scanning atomic force microscopy as an aid in returning to the same area of hair fibres after bleaching, treatment with a commercial shampoo or the application of a 'leave-on' conditioner product. The bleaching treatment used in this study was not found to affect the cuticular architecture and lateral force microscopy (LFM) also showed little difference after treatment, reflecting the homogeneity of the newly revealed surfaces. After treatment with a commercial shampoo, the hair sample again showed very little difference in topography or lateral force characteristics. Hair treated with the leave-on conditioner product also showed no major topographical changes. LFM traces, however, showed regions between the ghost edge, marking the original position of the scale edge before cuticular erosion, and the existing scale edge, to have higher frictional properties than distal regions of the cuticle. A thin film of the leave-on product thus seems to form in this region and extends from the foot of the scale edge.

Europe↗