Search PubMed⌕ Search

Biomedical subjects

S Clarke

Publications and source records attributed to S Clarke.

At least 37 records · Page 2Linked to original sources
PubMed2004

Randomized clinical trial of the effects of immediate enteral nutrition on metabolic responses to major colorectal surgery in an enhanced recovery protocol.

BACKGROUND: The effects of immediate postoperative enteral nutrition on postoperative nitrogen balance and insulin resistance were studied in patients subjected to an enhanced-recovery protocol. METHODS: Eighteen patients undergoing major colorectal surgery in an enhanced-recovery protocol were randomized to immediate postoperative enteral feeding for 4 days with either complete or hypocaloric nutrition. Nitrogen balance and changes in glucose kinetics, substrate utilization (indirect calorimetry) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured. Values are mean(s.e.m.). RESULTS: Mean postoperative urinary nitrogen losses were low (10.7(1.0) versus 10.5(0.7) g per day for complete versus hypocaloric nutrition) and insulin resistance was insignificant (-20(7) versus -27(11) per cent), with no difference between groups. Complete enteral feeding was given without hyperglycaemia (blood glucose concentration 5.8(0.4) versus 5.0(0.4) mmol/l) and resulted in nitrogen balance (+0.1(0.8) versus -12.6(0.6) g nitrogen per day; P < 0.001). CONCLUSION: This enhanced-recovery protocol was associated with minimal postoperative insulin resistance and nitrogen losses after surgery. Immediate postoperative enteral nutrition was provided without hyperglycaemia and resulted in nitrogen balance.

Blood Glucose↗
PubMed2004

A homemade model for training in cricothyrotomy.

We describe a simple, homemade model for teaching cricothyrotomy. It can easily be constructed from materials found in every anaesthetic room and is cheap, portable and usable several times before requiring replacement. We also describe evaluation of the model in a two-part study. First, 20 anaesthetic trainees, both with and without prior experience of percutaneous cricothyrotomy/tracheotomy, cannulated the 'trachea' using two percutaneous airway sets (Ravussin jet ventilation catheter[VBM] and Mini-Trach II Seldinger[Portex]), then scored the model for realism and usefulness for training. Next, 20 further trainees used the Mini-Trach II Seldinger on both the homemade model and a commercially available cricothyrotomy/tracheotomy trainer (Pharmabotics), scoring both models as before. In the first part of the study, trainees found the homemade model a useful substitute for practice of percutaneous techniques and teaching. In the second part, both models were rated well, with similar scores. The homemade model is an easily assembled alternative to more expensive models. Both experienced and inexperienced trainees find practising on such models useful.

Airway Obstruction↗
PubMed2004

Iron status and haematological changes in adolescent female inpatients with anorexia nervosa.

OBJECTIVES: (i) To investigate the incidence of iron deficiency (both latent iron deficiency and iron deficiency anaemia) in post menarchal female adolescent patients hospitalized with anorexia nervosa. (ii) To observe changes in iron status during refeeding. METHODS: During the study period all post menarchal female patients admitted to the adolescent unit with anorexia nervosa were invited to participate. Ferritin, serum iron, transferrin and transferrin saturation were measured on admission and discharge. Haemoglobin, haematocrit, weight, and body mass index were monitored weekly. RESULTS: All 12 eligible patients participated in the study. Four patients had elevated ferritin levels on admission. Ten of the 12 showed a statistically significant fall in serum ferritin at time of discharge compared with admission (P = 0.004). One of 12 patients had a low serum iron at presentation. All 12 had normal serum iron levels at discharge. Nine of the 12 subjects had a higher serum iron at discharge which was statistically significant (P = 0.046). There was no significant change in haemoglobin levels when comparing admission and discharge levels. Nine of the 12 patients however, transiently developed anaemia, at some stage during treatment. CONCLUSIONS: Iron deficiency is uncommon at both presentation and after nutritional rehabilitation in post menarchal adolescent females with anorexia nervosa. This is most likely due to increased iron storage secondary to the contraction of the circulating blood volume and reduced iron losses from (secondary) amenorrhoea. The fall in ferritin observed during treatment is due to haemopoiesis necessary to fill the increased blood volume associated with weight gain. This also results in normalization of the haemoglobin and haematocrit.

Adolescent↗
PubMed2004

Topography of cortico-striatal connections in man: anatomical evidence for parallel organization.

Tracing studies in non-human primates support the existence of several parallel neuronal circuits involving cerebral cortex, basal ganglia and thalamus. Distinct functional loops were proposed to underlie multiple aspects of normal and pathological behaviour in man. We present here the first anatomical evidence for separate corticostriatal systems in humans. Neural connections of the sensorimotor and prefrontal cortex to the striatum were studied in one human brain using the Nauta method for anterogradely degenerating axons. Axons originating from a lesion in the left sensorimotor cortex, including the face area, were found to terminate in the superolateral part of the ipsilateral putamen, forming a narrow band in its posterior part. Inside the band, the distribution of degenerating axons was inhomogeneous; high-density clusters of approximately 2.5 mm in diameter were separated by regions with less dense cortical projections. Axons originating from a small lesion in the fundus of the right superior frontal sulcus were found in the upper part of the ipsilateral caudate nucleus. The existence of discrete and anatomically segregated terminal patches originating from distinct cortical regions suggests parallel organization of cortico-striatal connections in man.

Aged↗
PubMed2003

Simian immunodeficiency virus Nef gene regulates the production of 2-LTR circles in vivo.

The replication dynamics of simian immunodeficiency virus (SIVmac32H-C8), attenuated through discrete genetic disruption of the nef gene, were compared with the wild-type parental clone (SIVmac32H-J5) using quantitative molecular methods. The primary viraemia of both infections were similar during the first week, but peaked on Day 10 at higher levels for wild-type virus. Viral RNA levels differed most markedly at Day 14. The frequency and levels of viral DNA species, detectable as gag provirus or circular 2-LTR episomes, differed depending on the virus and the lymphoid compartment sampled. 2-LTR circles persisted for prolonged periods in the peripheral blood but were never detected in any SIVmac32H C8-infected tissue, even if positive by gag PCR. Paradoxically, the converse was observed following wild-type infection. 2-LTR circles disappeared from the peripheral blood by Day 42 postinfection but persisted in lymphoid tissues. These findings are discussed in terms of nef and the role and stability of 2-LTR circle forms in vivo.

Animals↗
PubMed2003

Endoscopic balloon dilatation of esophageal strictures in infants and children: 17 years' experience and a literature review.

PURPOSE: Whereas endoscopic balloon dilatation (EBD) of benign esophageal strictures is an established mode of therapy in adults, this has not been accepted universally in the pediatric population. The aim of this study is to report the safety, efficacy, and long-term results of EBD for children in the authors' center. METHODS: Between 1986 and 2002, a total of 77 children (median age, 1.8 years; range, 2 months to 20 years) were treated by EBD for various causes: 2 had achalasia, and 75 had esophageal strictures (postesophageal atresia repair, 63; reflux esophagitis, 7; postfundoplication, 2; caustic injury, 3). Dilatations were performed using flexible endoscopy and fluoroscopic screening under general anesthesia. RESULTS: A total of 260 dilatations were carried out with the mean number of EBD per patient being 3.4 (range, 1 to 19). A mean period of 5 months (maximum, 28 months) for each patient was required. Four complications of esophageal perforations (1.5%) were observed, but only one required surgical repair because of persistent leakage. The remaining patients have undergone long-term follow-up (median follow-up, 6.6 years), and all are asymptomatic. CONCLUSIONS: This large series has shown that EBD can provide a safe and effective mean of relieving esophageal strictures with good long-term results.

Adolescent↗
PubMed2003

Region selective up-regulation of micro-, delta- and kappa-opioid receptors but not opioid receptor-like 1 receptors in the brains of enkephalin and dynorphin knockout mice.

The role of endogenous opioid peptides and receptors has recently been investigated using knockout mice. Although the affinities of opioid peptides for opioid receptors has been known for many years there is still some uncertainty over which receptor is the endogenous target for each peptide. To address this issue we have studied using quantitative autoradiography the levels of all four opioid receptor subtypes (micro, delta, kappa and opioid receptor-like 1 [ORL1]) in brains sectioned from enkephalin and dynorphin knockouts, as well as from double knockouts. Because receptor up-regulation has been observed when its cognate ligand-peptide is genetically ablated, regional changes in receptor binding in knockout mice may reflect areas where the peptide ligand is tonically active at its receptor or played a role in receptor regulation. In addition, the study aimed to correlate previously observed behaviour in these animals with receptor modulation. Marked region-specific up-regulation of the micro, delta, and kappa opioid receptors but not ORL1 receptors was observed in proenkephalin and prodynorphin knockouts. In proenkephalin knockouts this was most pronounced for the micro- and delta-receptor and in prodynorphin knockouts for the kappa-receptor. Combinatorial double knockouts did not show any changes in addition to those observed in single knockouts. The largest changes were observed in limbic regions and our results suggest that proenkephalin peptides are tonically active at micro and delta-receptors predominantly in these areas. Prodynorphin peptides appear to regulate mostly the kappa-receptor but they are also modulators of micro- and delta-receptors.

Animals↗
PubMed2003

Controlled biological response on blends of a phosphorylcholine-based copolymer with poly(butyl methacrylate).

Phosphorylcholine (PC)-based polymers have been used in a variety of medical device applications to improve biocompatibility. Here, solutions containing poly(butyl methacrylate) (PBMA) and 2-methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA(2)) copolymer were spin-coated onto glass coverslips at various ratios ranging from 5:1 to 1:0 for each of the two components, respectively. The resulting blend coatings were shown to be phase-separated on the nanometre-scale by atomic force microscopy, the PC copolymer within the blend being preferentially expressed at the surface. The adsorption of two key blood proteins, fibrinogen and albumin were investigated using surface plasmon resonance as an indicator of biocompatibility. The adsorption of protein to a biomaterials' surface can then stimulate further biological responses. This study therefore, also investigates the materials ability to elicit an inflammatory response by studying the adhesion of human mononuclear cells to the material surface. The materials ability to support the adhesion and growth of other tissue cells was also evaluated, looking specifically at the adhesion and proliferation of rabbit corneal epithelial cells. Results suggest that the adsorption of proteins and the adhesion of both corneal epithelial cells and mononuclear cells are dependent on the composition of the PBMA:MPC-co-LMA(2) copolymer.

Adsorption↗
PubMed2003

MEAD (part I)--a mathematical model of the long-term dispersion of radioactivity in shelf sea environments.

A mathematical model (MEAD) that simulates the transport of radioactivity in shelf-sea environments is presented. In the model it is assumed that the radioactivity can be present in three phases and transport both within and between the phases is captured. The set-up of the model for the Irish Sea is described and results from a simple discharge scenario are presented for (137)Cs and (239)Pu. From these results it appears that MEAD provides a good representation of the transport of radionuclides in the Irish Sea.

Forecasting↗
PubMed2003

Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain.

The opioid receptor-like 1 receptor is a novel member of the opioid receptor family and its endogenous peptide ligand has been termed nociceptin and orphanin FQ. Activation of the opioid receptor-like 1 receptor by nociceptin/orphanin FQ in vivo produces hyperalgesia when this peptide is given supraspinally but analgesia at the spinal level. Nociceptin/orphanin FQ also reverses stress-induced analgesia, suggesting that the peptide has anti-opioid properties. Nociceptin/orphanin FQ knockout mice show alterations in pain sensitivity and stress responses and display increased morphine dependence, suggesting an interaction of the nociceptin/orphanin FQ system with classical opioid receptor function. To determine if the behavioural phenotype of nociceptin/orphanin FQ knockout mice reflects changes in either opioid receptor-like 1 or classical opioid receptor expression, we have carried out quantitative autoradiography of the opioid receptor-like 1, mu-, delta- and kappa-opioid receptors in the brains of these animals. Receptor density was measured on coronal sections from wild-type, heterozygous and homozygous mice using [(3)H]nociceptin, [(3)H][D-Ala(2)-N-methyl-Phe(4)-Gly(5) ol] enkephalin, [(3)H]deltorphin-I, or [(3)H](-)-N-methyl-N-[7-(1-pyrrodinyl)-1-oxospiro[4,5]dec-8-yl]-4-benzofuranacetamide to label opioid receptor-like 1, mu-, delta- and kappa-receptors, respectively. A region-specific up-regulation of the opioid receptor-like 1 receptor (up to 135%) was seen in brains from homozygous mice. Mu-Receptors also showed significant differences between genotypes whilst changes in delta- and kappa- receptors were minor. In conclusion the region-specific up-regulation of the opioid receptor-like 1 receptor indicates a tonic role for nociceptin/orphanin FQ in some brain structures and may suggest the peptide regulates the receptor expression in these regions. The changes in the opioid receptor-like 1 receptor may relate to the anxiogenic phenotype of these animals but the observed change in mu-receptors does not correlate with altered morphine responses.

Animals↗
PubMed2003

Patterns of calcium-binding proteins in human inferior colliculus: identification of subdivisions and evidence for putative parallel systems.

The subdivisions of human inferior colliculus are currently based on Golgi and Nissl-stained preparations. We have investigated the distribution of calcium-binding protein immunoreactivity in the human inferior colliculus and found complementary or mutually exclusive localisations of parvalbumin versus calbindin D-28k and calretinin staining. The central nucleus of the inferior colliculus but not the surrounding regions contained parvalbumin-positive neuronal somata and fibres. Calbindin-positive neurons and fibres were concentrated in the dorsal aspect of the central nucleus and in structures surrounding it: the dorsal cortex, the lateral lemniscus, the ventrolateral nucleus, and the intercollicular region. In the dorsal cortex, labelling of calbindin and calretinin revealed four distinct layers.Thus, calcium-binding protein reactivity reveals in the human inferior colliculus distinct neuronal populations that are anatomically segregated. The different calcium-binding protein-defined subdivisions may belong to parallel auditory pathways that were previously demonstrated in non-human primates, and they may constitute a first indication of parallel processing in human subcortical auditory structures.

Adult↗
PubMed2003

DTI mapping of human brain connectivity: statistical fibre tracking and virtual dissection.

Several approaches have been used to trace axonal trajectories from diffusion MRI data. If such techniques were first developed in a deterministic framework reducing the diffusion information to one single main direction, more recent approaches emerged that were statistical in nature and that took into account the whole diffusion information. Based on diffusion tensor MRI data coming from normal brains, this paper presents how brain connectivity could be modelled globally by means of a random walk algorithm. The mass of connections thus generated was then virtually dissected to uncover different tracts. Corticospinal, corticobulbar, and corticothalamic tracts, the corpus callosum, the limbic system, several cortical association bundles, the cerebellar peduncles, and the medial lemniscus were all investigated. The results were then displayed in the form of an in vivo brain connectivity atlas. The connectivity pattern and the individual fibre tracts were then compared to known anatomical data; a good matching was found.

Algorithms↗
PubMed2003

Assessing limiting factors to the acceptance of antiretroviral therapy in a large cohort of injecting drug users.

OBJECTIVE: A comprehensive questionnaire was designed to assess the knowledge and understanding of injecting drug users (IDUs) regarding their HIV disease, and to determine any factors that may increase the acceptance of antiretroviral therapy (ART) by this group. RESULTS: Twenty percent of the total IDU cohort attending the GUIDE (GenitoUrinary Medicine and Infectious Diseases) clinic participated in the study. Fifty-two percent had been homeless in the past 5 years and 84% are unemployed. Seventy-two percent of patients did not complete second level education and 10% were illiterate. Fifty-one percent had siblings or parents with a history of injection drug misuse, and 25% had at least one sibling also HIV positive. Forty-seven percent started using drugs before the age of 13 years, and the most common initial drug was heroin (44%). Ninety-five percent had attended for methadone maintenance therapy (MMT), with 39% currently attending for daily therapy. The majority of patients were unable to simply explain or interpret CD4 cell counts (54%) and 'viral loads' (65%). Fifty-seven percent of patients were receiving highly active antiretroviral therapy (HAART). There was a statistically significant association between patients receiving HAART and both attendance at a primary care physician for methadone maintenance therapy (P = 0.005), and weekly take-outs of methadone (P = 0.005). There was also an association between adherence to HAART and attendance at a methadone maintenance clinic (P = 0.04). CONCLUSIONS: This study highlights the chaotic lifestyle and complex social background of the IDU. Such factors were not, however, associated with acceptance of HAART. The primary factor associated with both the acceptance of and adherence to HAART was regular and stable attendance for methadone therapy.

Adolescent↗
PubMed2003

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force.

In 1999, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim to evaluate the existing evidence for the clinical effectiveness of cognitive rehabilitation. This review led to the development of a set of guidelines to be used in the management of adult patients with cognitive disorders due to acquired focal neurological damage.

Advisory Committees↗
PubMed2003

ALIMTA (pemetrexed disodium) as second-line treatment of non-small-cell lung cancer: a phase II study.

BACKGROUND: The purpose of this study was to evaluate ALIMTA (pemetrexed disodium, LY231514), a multi-targeted antifolate with first-line activity against non-small-cell lung cancer (NSCLC), in a second-line setting. PATIENTS AND METHODS: Patients with NSCLC were eligible for this phase II study if they had progressive disease within 3 months after first-line chemotherapy or progression while being treated with first-line chemotherapy. In 81 patients studied, two cohorts of patients were assigned based on whether the first-line therapy had included a platinum regimen. ALIMTA was administered at 500 mg/m2 by 10-min intravenous infusion once every 21 days. RESULTS: The response rate in the 79 evaluable patients with poor prognostic features was 8.9% [95% confidence interval (CI) 2.6% to 15.1%]. The response rate in the platinum-pretreated group was 4.5% and 14.1% in the non-platinum-pretreated group. The median duration of response was 6.8 months (95% CI 3.4-7.8 months, 0% censoring). The median survival time was 5.7 months (95% CI 4.0-8.3 months, 7.6% censoring). The probability of survival for at least 6 months was estimated to be 48%. The median time to disease progression was 2 months (95% CI 1.4-2.8 months, 0% censoring). The principal toxicity was myelosuppression, which was reversible. CONCLUSIONS: ALIMTA is active in a second-line setting in non-platinum-pretreated NSCLC patients progressing within 3 months of first-line chemotherapy. This study demonstrates that it is possible to evaluate new drugs against NSCLC in a second-line setting.

Adult↗
PubMed2003

Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients.

BACKGROUND: The purpose of this study was to report response rates, survival and toxicity in advanced non-small-cell lung cancer (NSCLC) following docetaxel and carboplatin, and to explore potential differences in these end points between Caucasian and Asian patients. PATIENTS AND METHODS: Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore. Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks. Response to treatment and toxicity were graded by standard criteria. The Kaplan-Meier method was used to estimate survival rates, and subgroups compared by the log-rank test. Cox's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome. RESULTS: The response rate was 39% (95% confidence interval 27% to 52%), and 42% in evaluable patients. Response occurred in 65% of Asian and 31% of Caucasian patients (P = 0.01). Ethnicity was the only significant predictor of response in multivariate analysis. The 1-year survival rate was 53%. Performance status (P = 0.021), ethnicity (P = 0.035) and presence of bone or liver metastases (P = 0.011) were independent predictors of overall survival. Neutropenia (grade IV in 73% of patients), febrile neutropenia (26% patients) and diarrhea (grade III/IV in 11% of patients) were the major treatment related toxicities. A high rate (three of six) of febrile neutropenia in Singapore, including one treatment-related death in the initial patients treated, resulted in a reduction in the carboplatin dose to AUC 4.5 at that site. CONCLUSIONS: This regimen is active in advanced NSCLC. The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation.

Adult↗