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Biomedical subjects

C Fox

Publications and source records attributed to C Fox.

At least 55 records · Page 3Linked to original sources

Effect of hip prostheses on radiotherapy dose.

A small but growing proportion of patients requiring radiotherapy for prostate cancer have one or two hip prostheses which may shadow the target and affect the dose distribution. Approximately 10 such patients are treated at the Illawarra Cancer Care Centre per year. Hence a study was undertaken to examine the accuracy of various treatment methods that involve some of the treatment fields travelling through the prosthesis. A fixed-field measurement showed a dose reduction of 52% in the shadow of the prosthesis. A Monte Carlo simulation confirmed an increase in dose on the distal surface of the prosthesis of 35%. Of more clinical relevance, however, is the dose distribution due to the overall combined field treatment. Using a power law correction benchmarked against thermoluminescent dosimeters and Gafchromic film, three different beam set-ups for patient treatment were planned and the dose variation analysed. A four-field brick technique gave a dose variation across the target volume of +/- 15% whereas a dual arc technique gave a dose variation of only +/- 5%. A four-field oblique technique gave a dose variation of only +/- 2% across the target volume but the oblique field technique included extra dose to the rectum.

Biocompatible Materials↗

Improving the epilepsy service: the role of the specialist nurse.

There is currently a wide variation in the level of service provided for patients with epilepsy across the UK. Evidence is becoming available to suggest that improvements in local service provision may be achieved through the intervention of a specialist nurse. Using practical examples, this article explores the roles of the epilepsy specialist nurse, and examines how they may benefit patients and improve services. Functions such as liaison, patient assessment and management, counselling, provision of information, education, and audit are considered. It is hoped that the improved co-ordination and management of epilepsy services, that is achieved through specialist nurse intervention, will lead to improved patient outcomes and increased cost-effectiveness.

Epilepsy↗

Nutritional factors affecting serum phenylalanine concentration during pregnancy for identical twin mothers with phenylketonuria.

UNLABELLED: The effect of energy, protein, fat, and phenylalanine on serum phenylalanine concentrations during pregnancy for a set of identical twins with phenylketonuria (PKU) was examined. Blood samples were collected one to two times per week. The subjects completed a 3-d food record prior to each blood collection. The effect of the factors on serum phenylalanine levels was evaluated statistically using time-series analysis. Dietary intakes of the nutrients evaluated were similar for the subjects. For one subject, there were highly significant effects of energy, protein, and fat on serum phenylalanine levels. In contrast, these nutrients had no significant effect on serum phenylalanine for the other subject. Dietary phenylalanine had no significant effect on serum phenylalanine for either twin. CONCLUSIONS: There was no effect of phenylalanine intake and no consistent effect of energy, protein, or fat on serum phenylalanine. Other dietary or environmental factors or a combination of factors may impact serum phenylalanine levels of pregnant women with PKU.

Adult↗

Appropriate insulin regimes for type 2 diabetes: a multicenter randomized crossover study.

OBJECTIVE: To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment. RESEARCH DESIGN AND METHODS: A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol. RESULTS: HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens. CONCLUSIONS: These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

Blood Glucose↗

The cortical endoplasmic reticulum (ER) of the mouse egg: localization of ER clusters in relation to the generation of repetitive calcium waves.

The endoplasmic reticulum (ER) of the mature mouse egg consists of a fine tubular network and pronounced accumulations in the cortex. The ER was visualized both in intact eggs and with in vitro preparations of the cortex using the fluorescent lipophilic dye, DiI. Immunofluorescent labeling of the ER in isolated cortical preparations demonstrated that the ER clusters contain inositol 1,4, 5-trisphosphate (IP(3)) receptors, indicating an important involvement in sperm-induced Ca(2+) transients, which are triggered by IP(3). We imaged the ER during fertilization and the subsequent Ca(2+) transients and found that the clusters remained intact throughout this period. Recovery of fluorescence after photobleaching established that the ER clusters are continuous with the reticular ER network and that these structures remain stable and continuous throughout the time of fertilization-induced Ca(2+) transients; continuity also remained during IP(3) injection. These results indicate that, in contrast to echinoderm eggs, the ER of mouse eggs does not become disrupted when it releases Ca(2+)at fertilization. The localization and apparent stability of the cortical ER clusters may be important in generating Ca(2+) oscillations, which are characteristic of fertilized mammalian eggs. Imaging of intracellular Ca(2+) revealed that Ca(2+) transients originate in the hemisphere of the egg that contains abundant ER clusters, thus the mouse contains a stable cortical pacemaker responsible for generating Ca(2+) waves.

Animals↗

Lymph node architecture preceding and following 6 months of potent antiviral therapy: follicular hyperplasia persists in parallel with p24 antigen restoration after involution and CD4 cell depletion in an AIDS patient.

OBJECTIVES: To evaluate changes in architecture, viral RNA, and viral protein over 6 months in lymph nodes from retroviral-naïve HIV-infected persons before and after commencing highly active antiretroviral therapy (HAART). METHODS: Nine antiretroviral-naïve HIV-infected persons had lymph nodes excised at baseline and at 2 and 6-8 months after beginning a four-drug combination regimen containing zidovudine, lamivudine, nevirapine, and indinavir. Two patients had AIDS. Lymph nodes were examined by immunohistochemical staining for Gag p24 HIV, CD3, CD21, CD20, HAM 56, and Ki67 antigens and by in-situ hybridization (ISH) for HIV RNA and H3-histone RNA. RESULTS: Eight of nine baseline lymph nodes showed follicular hyperplasia and germinal center and paracortical mononuclear cell activation. At 2 months, the lymph nodes from seven patients, including the AIDS patients, showed more follicular hyperplasia and activation than their baseline specimens but with decreased mononuclear cell activation. By 6 months, seven lymph nodes were less hyperplastic and activated than their corresponding 2 month specimens. Combined ISH/immunohistochemical staining of baseline lymph nodes revealed productively infected T (CD3) and B (CD20) cells and macrophages (HAM56+). HIV RNA-positive mononuclear cells were infrequent at 2 months, and rare at 6 months. HIV RNA was still associated with follicular dendritic cells (FDC) at 2 months, but not at 6 months. HIV p24-positive antigen in germinal centers persisted through all 6, and the one 8 month specimens. The baseline lymph nodes from one of the AIDS patients was involuted and T cell depleted, whereas the follow-up lymph nodes were hyperplastic with normal T cell levels. CONCLUSION: Follicular hyperplasia and cell activation, possibly caused by persistent viral protein in germinal centers, may help explain why HIV viremia rebounds so rapidly after the interruption of HAART. Restoration of architecture may follow the treatment of patients with AIDS who initially had involuted and CD4 cell-depleted lymph nodes.

Acquired Immunodeficiency Syndrome↗

Infection of HIV-1 transgenic mice with Mycobacterium avium induces the expression of infectious virus selectively from a Mac-1-positive host cell population.

Infection of HIV-1-transgenic mice with Mycobacterium avium, a common opportunistic pathogen in AIDS patients, was shown to result in increased tissue expression of viral specific transcripts. Moreover, by coculturing splenocytes from the transgenic animals with human T cells it was possible to demonstrate that the elevation in HIV-1 mRNA triggered by M. avium infection reflects increased production of infectious virions. Viral immune activation was also shown to correlate with a marked elevation of p24 in supernatants of ex vivo-cultured tissues and, more importantly, in systemic increases in the HIV-1 protein in plasma. Interestingly, these tissue and systemic p24 responses were found to be differentially regulated. Thus, while in vitro p24 production by cultured splenocytes increased concurrently with bacterial loads during the first 6 wk of infection, levels of the Ag in plasma actually decreased. In situ localization experiments together with FACS analysis of HIV-1-expressing splenocytes indicated that virus production is restricted largely to cells of the monocyte/macrophage lineage. Indeed, in vitro p24 expression by cells from noninfected transgenic mice was up-regulated by polyclonal stimulation of macrophages but not T cells. Together these results underscore the importance of the macrophage reservoir in persistent virus expression and establish a convenient and relevant animal model for studying the factors responsible for immune activation of HIV-1 induced by mycobacterial as well as other common coinfections encountered by AIDS patients.

Animals↗

Diabetes and hypertension: an era of clarity or confusion?

In light of recent data from the UKPDS and HOT trials, it appears that intensive combination therapies are essential in the treatment of patients with diabetes and hypertension. Appropriate treatment strategies, based on effective BP reductions, will usually require two or more different antihypertensives and the addition of lipid-lowering agents. There is also an urgent need to update existing guidelines and perhaps even provide specific guidelines for the treatment and long-term management of patients with diabetes and hypertension.

Antihypertensive Agents↗

How much risk does a woman with active epilepsy pose to her newborn child in the puerperium? A pilot study.

Much attention in the literature has recently been paid to women's issues in epilepsy but most of the literature stops in the delivery room or at the first moment of suckling. Although it is commonly supposed that a woman who continues to have active epilepsy during the puerperium will pose a risk to her child, little assessment of how great a risk this is has been carried out. We present an audit of the puerperal experiences of 187 women with epilepsy counselled before birth in our women's clinic and contrast this with a number of women with epilepsy seen for the first time in the puerperium (and therefore uncounselled). The audit suggests that in counselled women the risk is very low (women with Juvenile Myoclonic Epilepsy may be particularly at risk, as may women with tonic-clonic seizures that occur without warning, plus those with automatisms or who have prolonged post-ictal confusion). Some women with controlled epilepsy prior to conception may lose that control during the puerperium so even women with well controlled epilepsy should adopt precautions in the puerperium. The only baby to die (or be seriously injured) in the puerperium born to a woman with epilepsy was killed in the mother's first seizure.

Accidental Falls↗

Proactive pre-conception counselling for women with epilepsy-is it effective?

We describe the development of a proactive pre-conception counselling service for women with epilepsy based on complete re-investigation of the woman's epilepsy, a policy of withdrawing antiepileptic drugs (AEDs) thought to carry an increased risk of foetal abnormality (and substitution, where indicated, of AEDs thought to carry a lesser risk) and the exhibition of folic acid 5 mg daily plus fulfilment of the woman's educational needs and exploration of her and her partner's wishes. The outcome of the assessment of 90 such women is compared with the outcome of 59 women presenting to our service already pregnant. An audit of the outcomes in the two groups suggests that re-investigation of women pre-conceptually is worthwhile (some women turn out not to have epilepsy or have cerebral lesions best managed before pregnancy) and that foetal morbidity may be reduced by judicious rationalization of medication: folic acid taken before conception may also be protective for the foetus. Proactive pre-conception counselling, however, only works if the woman is prepared to wait (sometimes up to a year) for necessary drug changes to be instituted and is using reliable contraception.

Anticonvulsants↗

Standard effective doses for proliferative tumours.

This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED1) and proliferative standard effective dose two (PSED2) have been calculated for each regimen. Graphs of PSED1 and PSED2 versus potential doubling time (Tp) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED1 or PSED2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue.

Cell Division↗

Long-term benefits for Mäori of an asthma self-management program in a Mäori community which takes a partnership approach.

BACKGROUND: In 1991, an intervention trial of the efficacy of an asthma self-management plan was carried out in partnership with a rural Mäori community. The program relied on Mäori community health workers and other health professionals working in partnership, was delivered through clinics in traditional Mäori community centres and Mäori processes were followed throughout. The plan was shown to be effective in reducing asthma morbidity. OBJECTIVE: To assess whether the long-term benefits of the program extent beyond reduced asthma morbidity and the extent to which any additional benefits may be related to the partnership approach employed by the program. METHOD: Forty-seven (68%) of the original program participants were surveyed in August 1997. Participants were questioned on the program's impact in areas such as cultural development, health service access and lifestyle. RESULTS: In addition to the improvements in asthma morbidity, the program was found to have four key benefits: cultural affirmation; improved access to other health services; a greater sense of control for participants; and positive impacts on the extended family. CONCLUSIONS: The program's benefits extended beyond reduced asthma morbidity and were not due simply to the introduction of the asthma self-management plan but also to the partnership approach employed by the program. IMPLICATIONS: The study provides support for providing public health services for indigenous communities that take a partnership approach, utilise community expertise and are delivered in a way that is consistent with each community's cultural processes.

Adult↗

Plasma leptin concentrations in Pima Indians living in drastically different environments.

OBJECTIVE: Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS: We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS: Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P < 0.0001) and U.S. Pima Indians (r = 0.86, P < 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P < 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P < 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS: These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.

Adult↗

An introduction to the partial credit model for developing nursing assessments.

The partial credit model, which is a special case of the Rasch measurement model, was presented as a useful way to develop and refine complex nursing assessments. The advantages of the Rasch model over the classical psychometric model were presented including the lack of bias in the measurement process, the ability to highlight those items in need of refinement, the provision of information on congruence between the data and the model, and feedback on the usefulness of the response categories. The partial credit model was introduced as a way to develop complex nursing assessments such as performance-based assessments, because of the model's ability to accommodate a variety of scoring procedures. Finally, an application of the partial credit model was illustrated using the Practical Knowledge Inventory for Nurses, a paper-and-pencil instrument that measures on-the-job decision-making for nurses.

Bias↗