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Biomedical subjects

J Carter

Publications and source records attributed to J Carter.

At least 55 records · Page 3Linked to original sources

Creating a DIN to tackle drug-related deaths in the community.

Brighton and Hove has one of the highest rates of drug-related deaths in the UK. The deceased commonly have had contact with a number of organizations isolated from each other. The aim of this study was to explore aspects of drug addiction in Brighton as the first stage in the creation of a local Drug addiction Intervention Network (DIN) and to make recommendations about improving the effectiveness of medical contacts so that modifiable risk factors could be addressed appropriately and consistently. The coroner's records of the drug-related deaths in 1998 for Brighton and Hove were cross-referenced with computerized records of the Accident & Emergency department of the local hospital and the police station. Of the 36 drug misusers who died during the year, most were male, mean age 34 years. Alcohol was a common comorbid finding. Seventy-eight per cent were known to the A&E department and 62% had been arrested locally during 1997 or 1998. Such retrospective data can only give limited information. We, therefore, performed a prospective survey. It was carried out by the forensic medical examiner (FME) in 1997-1998, interviewing 41 arrestees to give a profile of the criminally involved drug misusers. With the information obtained, the A&E doctors and FMEs were able to review the medical advice given and establish a protocol for the transfer of severely intoxicated arrestees.

Journal Article↗

Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica.

Chronic inhalation of crystalline silica can produce lung tumors in rats whereas this has not been shown for amorphous silica. At present the mechanisms underlying this rat lung tumor response are unknown, although a significant role for chronic inflammation and cell proliferation has been postulated. To examine the processes that may contribute to the development of rat lung tumors after silica exposure, we characterized the effects of subchronic inhalation of amorphous and crystalline silica in rats. Rats were exposed for 6 h/day, on 5 days/week, for up to 13 weeks to 3 mg/m(3) crystalline or 50 mg/m(3) amorphous silica. The effects on the lung were characterized after 6.5 and 13 weeks of exposure as well as after 3 and 8 months of recovery. Exposure concentrations were selected to induce high pulmonary inflammatory-cell responses by both compounds. Endpoints characterized after silica exposure included mutation in the HPRT gene of isolated alveolar cells in an ex vivo assay, changes in bronchoalveolar lavage fluid markers of cellular and biochemical lung injury and inflammation, expression of mRNA for the chemokine MIP-2, and detection of oxidative DNA damage. Lung burdens of silica were also determined. After 13 weeks of exposure, lavage neutrophils were increased from 0.26% (controls) to 47 and 55% of total lavaged cells for crystalline and amorphous silica, with significantly greater lavage neutrophil numbers after amorphous silica (9.3 x 10(7) PMNs) compared to crystalline silica (6.5 x 10(7) PMNs). Lung burdens were 819 and 882 microg for crystalline and amorphous silica, respectively. BAL fluid levels of LDH as an indicator of cytotoxicity were twice as high for amorphous silica compared to those of crystalline silica, at the end of exposure. All parameters remained increased for crystalline silica and decreased rapidly for amorphous silica in the 8-month recovery period. Increased MIP-2 expression was observed at the end of the exposure period for both amorphous and crystalline silica. After 8 months of recovery, those markers remained elevated in crystalline silica-exposed rats, whereas amorphous silica-exposed rats were not significantly different from controls. A significant increase in HPRT mutation frequency in alveolar epithelial cells was detected immediately after 13 weeks of exposure to crystalline, but not to amorphous silica. A significant increase in TUNEL staining was detected in macrophages and terminal bronchiolar epithelial cells of amorphous silica-exposed rats at the end of the exposure period; however, crystalline silica produced far less staining. The observation that genotoxic effects in alveolar epithelial cells occurred only after crystalline but not amorphous silica exposure, despite a high degree of inflammatory-cell response after subchronic exposure to both types of silica, suggests that in addition to an inflammatory response, particle biopersistence, solubility, and direct or indirect epithelial cell cytotoxicity may be key factors for the induction of either mutagenic events or target cell death.

Administration, Inhalation↗

Thermal lattice boltzmann simulation for multispecies fluid equilibration

The equilibration rate for multispecies fluids is examined using thermal lattice Boltzmann simulations. Two-dimensional free-decay simulations are performed for effects of velocity shear layer turbulence on sharp temperature profiles. In particular, parameters are so chosen that the lighter species is turbulent while the heavier species is laminar-and so its vorticity layers would simply decay and diffuse in time. With species coupling, however, there is velocity equilibration followed by the final relaxation to one large co- and one large counter-rotating vortex. The temperature equilibration proceeds on a slower time scale and is in good agreement with the theoretical order of magnitude estimate of Morse [Phys. Fluids 6, 1420 (1963)].

Journal Article↗

An experience with transvaginal sonography in gynaecologic tumour surveillance.

Surveillance of gynaecologic cancer patients treated with a curative intent involves frequent presentations by the patient for a targeted history, detailed general and pelvic examination, including Pap smear. One of the aims of such surveillance is to detect potentially curable recurrences early to allow the initiation of further therapy, hopefully to attain eradication of the recurrent tumour. Six cases are presented where the prudent use of transvaginal sonography (TVS) was found to be useful in the exclusion of recurrent tumour in patients with symptoms; early diagnosis in patients who were asymptomatic; confirmation of disease in those with symptoms; to evaluate patients with obliterated upper vaginas due to therapy, and follow-up of those with confirmed recurrence as a form of disease marker.

Aftercare↗

Surgery and post-operative radiotherapy for early stage cervical cancer.

The use of post-operative radiotherapy in the treatment of cervical cancer is controversial. The aim of this study was to document the results and toxicity of adjuvant irradiation in patients with Stage 1B and 2A cervical cancer. We performed a retrospective review of all patients treated with post-operative radiotherapy at Royal Prince Alfred Hospital between 1986 and 1993. Patient, tumour and treatment factors and late toxicity were recorded. Relapse-free and overall survival were calculated. Eighty-one patients form the study population. The median follow-up was 6.1 years. Fifty-eight patients (72%) had stage 1B cervical cancer and 23 (28%) stage 2A. The 5 year relapse-free and overall survival were 78% and 80% respectively. Six patients (7%) had late toxicity requiring inpatient medical treatment and 6 patients (7%) required surgery. The survival was comparable to other series reported in the literature. There was an incidence of 14% late toxicity requiring medical or surgical intervention which is greater than with hysterectomy or pelvic irradiation alone. Clinical prognostic factors should be used to select patients for either surgery or radiotherapy alone to minimise the increased toxicities associated with a combination of surgery and radiotherapy.

Adenocarcinoma↗

The London handicap scale: a re-evaluation of its validity using standard scoring and simple summation.

OBJECTIVE: To assess the validity of the London handicap scale (LHS) using a simple unweighted scoring system compared with traditional weighted scoring METHODS: 323 patients admitted to hospital with acute stroke were followed up by interview 6 months after their stroke as part of a trial looking at the impact of a family support organiser. Outcome measures included the six item LHS, the Dartmouth COOP charts, the Frenchay activities index, the Barthel index, and the hospital anxiety and depression scale. Patients' handicap score was calculated both using the standard procedure (with weighting) for the LHS, and using a simple summation procedure without weighting (U-LHS). Construct validity of both LHS and U-LHS was assessed by testing their correlations with the other outcome measures. RESULTS: Cronbach's alpha for the LHS was 0.83. The U-LHS was highly correlated with the LHS (r=0.98). Correlation of U-LHS with the other outcome measures gave very similar results to correlation of LHS with these measures. CONCLUSION: Simple summation scoring of the LHS does not lead to any change in the measurement properties of the instrument compared with standard weighted scoring. Unweighted scores are easier to calculate and interpret, so it is recommended that these are used.

Disability Evaluation↗

Inter-rater reliability of the Frenchay activities index in patients with stroke and their careers.

OBJECTIVE: To measure the inter-rater reliability of the interview-administered version of the Frenchay Activities Index (FAI). DESIGN: Comparison of FAI score on the same person when administered by two raters (mean time between interviews 15.2 days). SUBJECTS: Fifty-nine Oxfordshire residents who either had had a stroke (n = 35) or were the main carer (n = 24). RESULTS: The 95% limits of agreement for the FAI totals were -9.9 to +8.4. The kappa statistic for nine of the 15 items showed a good level of agreement between the two research interviews (0.64-0.80). The other six items showed fair or moderate strength of agreement (0.26-0.52). Three items showed significant differences between the two raters p < 0.05 (Wilcoxon's sign paired rank sum test). The mean difference between the total scores was -0.76 (95% confidence interval from -1.98 to 0.46). Spearman's rho correlation coefficient for FAI totals of rater B against A was r(59) = 0.93 (p < 0.001). CONCLUSION: The FAI is a reliable tool for measuring outcome following stroke. Suggestions are made to strengthen the reliability, and consequently the validity of the measure.

Activities of Daily Living↗

The development of funding policies for hospices: is casemix-based funding an option?

The 1993 health reforms, with their emphasis on the purchasing of defined amounts or units of service, have led to the implementation of casemix-based funding for the acute medical and surgical services of the public hospitals. Despite growing interest in New Zealand in casemix-based funding for non-acute services such as palliative care, the nature of this service and the characteristics of its patient population pose particular difficulties for the development and implementation of casemix. This paper examines the feasibility of implementing casemix-based funding for hospice/palliative care services and discusses the development of casemix classification systems for palliative care. Problems associated with implementing casemix-based funding are considered including: the dual funding of hospices, the multi-agency nature of palliative care service provision and the need for the Health Funding Authority to identify and specify the hospice services it is willing to fund. While it is concluded that these problems will impede the introduction of casemix-based funding of hospice care, they highlight important issues that the hospice movement must address if it is to ensure its future within the new health environment.

Diagnosis-Related Groups↗

Purification of a highly modified RNA-aptamer. Effect of complete denaturation during chromatography on product recovery and specific activity.

To evaluate RNA-aptamers as potential drug candidates, efficient and scaleable purification protocols are needed. Because aptamers are highly structured and rigid molecules, denaturation during the purification process is a critical aspect to obtain a pure and active product. A two-step chromatographic procedure was developed to purify a synthetic anti-VEGF aptamer at the preparative scale. A reversed-phase chromatographic step was optimized with a highly hydrophobic ion pairing reagent, followed by ion-exchange chromatography in which heat and a chaotropic salt were used. Because of the presence of 2'-modified ribose, denaturation conditions had to be optimized in both chromatographic steps to achieve a fully active molecule.

Chromatography, High Pressure Liquid↗

Whole abdominal radiotherapy following second-look laparotomy for ovarian carcinoma.

AIM: The safety and efficacy of whole abdominal radiotherapy was evaluated as salvage or consolidation treatment for ovarian cancer patients treated with primary surgery and chemotherapy, followed by second-look laparotomy (SLL). Overall survival and acute and late toxicity of treated patients were assessed. METHODS: Patients were recruited between April 1981 and June 1994. All patients had SLL performed at Royal Prince Alfred Hospital after completion of primary chemotherapy. Data collected included demographic details, diagnosis, tumor stage, histology, grade, adjuvant chemotherapy, and radiotherapy. Radiation dose and fractionation, field size, boost volume and dose, failure to complete treatment and treatment interruptions, renal dose, and acute and late toxicity were recorded. RESULTS: Fifty-one patients were evaluated; the median age was 51 years. Median follow-up for patients still alive was 62 months. Prior to 1988, chemotherapy comprised oral chlorambucil, with or without cisplatin (n = 25), while after this date all patients (n = 26) received primary cisplatin-based therapy. A radiation dose of 22. 5 Gy over 22 fractions was planned to the whole abdomen followed by a pelvic boost of 22 Gy in 11 fractions. Radiotherapy was completed in 37 (73%) patients. Treatment interruptions were necessary in 12 (24%) patients. Thrombocytopenia, neutropenia, nausea, vomiting, and diarrhea were the main causes of incomplete or interrupted treatment. Late bowel toxicity was seen in 6 (12%) patients, 2 of whom required laparotomy to relieve obstruction. There were no treatment-related deaths. Seven of the 51 patients are alive and free of disease, 2 died from other causes, and 2 are alive with evidence of recurrent or progressive disease. Mean follow-up time for surviving patients is 78.5 months. Overall survival at 2, 5, and 10 years was 65, 27, and 10%, respectively. Residual disease after primary surgery, smaller preirradiation tumor residuum, and completion of radiotherapy were independently associated with improved overall survival. CONCLUSION: In this poor-prognosis group of patients, a combined approach of surgery, chemotherapy, and radiotherapy, while associated with acceptable toxicity, may not afford a prolongation of survival.

Abdomen↗

Distribution of topiramate in a medical examiner's case.

Topimarate (Topamax) is a novel antiepileptic drug. Its mode of action is multifactorial and involves blockage of voltage-dependent sodium channels. The drug was detected in a 15-year-old epileptic who died soon after switching seizure prescriptions. Topimarate was recovered by basic extraction with ethyl acetate and analyzed by gas chromatography-mass spectrometry using selected ion monitoring. Ions monitored were m/z 324 and m/z 110 for topiramate and m/z 98 for the internal standard mepivacane. The drug was quantitated in blood, vitreous humor, bile, stomach content, and liver: the concentrations were 8.9, 12.4, and 10.9 mg/L, 31 mg/total content, and 29 mg/kg, respectively. Topiramate was detected in urine but not quantitated. Other drugs identified in this case were 0.45 mg/L nordiazepam and 0.05 mg/L oxazepam in blood. No alcohol was detected in any of the specimens. The cause of death was seizure disorder with upper respiratory infection. The manner of death was determined as natural. To our knowledge, this is the first report of the presence of topiramate in postmortem specimens.

Adolescent↗