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Biomedical subjects

Peter Thomas

Publications and source records attributed to Peter Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2005

Re-admission to intensive care: identification of risk factors.

BACKGROUND AND PURPOSE: The re-admission of patients to intensive care is associated with increased morbidity, mortality, loss of morale for patients and family, and increased health costs. The aim of the present study was to identify factors which place patients at a higher risk of re-admission to intensive care. METHOD: A prospective study of patients who were re-admitted to a 22-bed tertiary level intensive care facility within a 12 month period. Data were kept on every patient re-admitted to intensive care, including standard demographic data, initial admission diagnosis, co-morbidities, re-admission diagnosis, mobility on discharge, secretions, airway, chest X-ray, PaCO2, PaO2, PaO2/FiO2 and time of discharge. Subjects included 74 patients who had been re-admitted to intensive care in 12-month period and a comparison group of patients who were not re-admitted to intensive care. A cross-tabs procedure was initially used to estimate maximum likelihood. Significant factors with an alpha value of <0.10 were entered into a backward conditional binary logistic regression to determine independent factors. RESULTS: The overall percentage of patients who were re-admitted to intensive care compared with total admissions was 7.7%. Significant independent factors for re-admission were found to be age >65 years (p<0.05), colonization (p<0.001), weakness (p<0.001), co-morbidities of cardiac and/or respiratory disease (p<0.001) and depression (p<0.001). CONCLUSIONS: A certain profile of patients has been established who are at increased risk of re-admission to intensive care. These patients could be provided with increased intervention and surveillance on discharge from intensive care.

Age Factors↗
PubMed2005

Biomechanical and allergological characteristics of a biodegradable poly(D,L-lactic acid) coating for orthopaedic implants.

A poly(D,L-lactic acid) surface coating (PDLLA) has been developed to optimize interactions at the implant-tissue interface. Mechanical and allergological characteristics were evaluated in the present study to elucidate possible indications and limitations prior to clinical application. Implants of stainless steel and Ti-6Al-4V and Co-Cr-Mo alloys were coated with PDLLA, and mechanical stability was studied during intramedullary implantation into rat and human cadaver bones and during dilation of coronary artery stents. Elongation resistance was examined on AlMgSi alloy specimens. Furthermore, proliferation of peripheral blood mononuclear cells of nickel-allergic donors and controls and interleukin-4 and interferon-gamma levels were measured in the presence of coated/uncoated implants and after stimulation with phytohemagglutinin or NiSO4. PDLLA remained stable on the implants with a minimum of 96% of the original coating mass and tolerated lengthening of at least 8%. Further lengthening was followed by microcracking and cohesive failure within the coating. PDLLA exerted no suppressive effect upon spontaneous and pan-T-cell mitogen inducible T-cell proliferation. Furthermore, specific proliferation to nickel in cells of nickel-allergic blood donors and production of interleukin-4 and IFN-gamma were not influenced by the coating. PDLLA coating proved high mechanical stability on different orthopaedic implants and did not influence in vitro T-cell reactivity towards specific biomaterials.

Adult↗
PubMed2005

GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release.

Heterotrimeric G proteins and seven-transmembrane-spanning (7TM) receptors are implicated in rapid estrogen signaling. The orphan 7TM receptor GPR30 is linked to estrogen-mediated activation of adenylyl cyclase, release of epidermal growth factor (EGF)-related ligands, and specific estrogen binding. GPR30 acts independently of estrogen receptors, ERalpha and ERbeta, and probably functions as a heptahelical ER. 7TM receptors elicit signals that stimulate second messengers, and convey intracellular signals via EGF receptors. Identification of GPR30 as a Gs-coupled 7TM receptor that triggers release of heparin-binding EGF establishes its role in cell signaling cascades initiated by estrogens, and explains their capacity to activate second messengers and promote EGF-like effects. Thus, estrogen can signal by the same mechanism as various other hormones, through a specific 7TM receptor.

Adenylyl Cyclases↗
PubMed2005

An in-service evaluation of hip protector use in residential homes.

BACKGROUND: The establishment of a hip protector service has allowed us to study eligibility, acceptability and compliance with use, reasons for non-use, and the effect of dementia, confusion, incontinence and risk of falling. METHODS: All residents in all residential homes in Poole were assessed at baseline. All eligible residents were offered 1 week's trial of protectors and those who wished to continue were given a set of protectors. Compliance was assessed at 3, 6 and 12 months. Percentages shown for compliance exclude those who died, were transferred, had lost data or in whom follow-up was not yet completed. RESULTS: Over 18 months, 873 residents from 47 homes were identified (mean age 88 years, female:male 4.5:1). Of these, 745 were considered eligible to wear protectors (86%) and 535 agreed to wear them after 1 week (72%). Compliance over 12 months was 78%. Most wearers wore protectors every day. At 3 months, 83% of demented compared to 73% of not demented residents (P = 0.023), 86% of always confused, 77% of sometimes confused and 72% of never confused (P < 0.009) and 82% of incontinent compared to 73% of continent residents (P = 0.024) were wearing hip protectors. There was a positive linear trend between the risk of falling and compliance (P = 0.048). CONCLUSIONS: The results suggest that there is a 48% chance of a resident wearing the protectors after 1 year. The higher compliance among those with dementia, confusion, incontinence and at high risk of falling supports the concept that hip protectors are worn by those at greatest risk of fracture.

Accidental Falls↗
PubMed2005

Physicians with disabilities and the physician workforce: a need to reassess our policies.

People with disabilities make up about 20% of the population, yet only a tiny fraction of matriculants to medical school have disabilities. Attempts to define core technical standards and competencies have not kept pace with technological changes, diverse specialization, and changing practice options. This has resulted in the inappropriate exclusion of some people with disabilities. Medical schools determine how any qualified applicant, regardless of physical or cognitive ability, can be effectively accommodated and counseled in achieving the most appropriate medical career. A serious effort to redefine the technical standards and core competencies of the 21st century medical education at the undergraduate and graduate levels would likely resolve many of the troubling questions regarding medical students with disabilities. We have made some recommendations to organized medicine for constructing an agenda to address these issues.

Attitude to Health↗
PubMed2005

Molecular characterization of three forms of putative membrane-bound progestin receptors and their tissue-distribution in channel catfish, Ictalurus punctatus.

Membrane-bound progestin receptors (mPR) were recently cloned and characterized as a new class of steroid receptors that transduce cell-signals through alteration of MAP kinase- and cAMP-dependent pathways. To further develop our understanding of this new class of steroid receptors, we characterized the cDNAs and genes of thealpha, beta and gamma forms of the channel catfish mPRs (IpmPR). The predicted alpha and beta proteins have 49% sequence identity, whereas they only have 30% and 27% identities, respectively, with the gamma form. Furthermore, IpmPRalpha and IpmPRbeta genes have similar structures featuring intronless coding regions, while IpmPRgamma gene is composed of 8 exons and 7 introns. The 5'-flanking region of each IpmPR gene differs, but each contains putative transcriptional regulatory elements of factors known to influence reproductive physiology and endocrine disruption, for example, responsive elements for cAMP and steroids and the recognition sites for steroidogenic factor-1 and for the aryl hydrocarbon receptor. The IpmPRalpha gene was detected in all the tissues tested with relatively greater expression in brain, pituitary, muscle and testis. The expression of IpmPRbeta was much lower than that of IpmPRalpha and the transcript was predominantly observed in brain, pituitary, ovary and testis. In contrast, the IpmPRgamma transcript was mainly detected in gill, ventral aorta, intestine, and trunk kidney. In conclusion, all the structural features of the IpmPRs strongly suggest that the closely related alpha and beta forms are distantly related to the gamma form. Additionally, regulatory features of the 5'-flanking regions and the differences in tissue-specific expression of each IpmPR gene suggest that they are involved in different endocrine functions in catfish.

Amino Acid Sequence↗
PubMed2005

Influence of caffeine on frequency of hypoglycemia detected by continuous interstitial glucose monitoring system in patients with long-standing type 1 diabetes.

OBJECTIVE: The aim of this study was to investigate the effect of caffeine (in doses equivalent to normal daily ingestion) on rates and severity of hypoglycemia in patients with long-standing type 1 diabetes to determine the relationship between caffeine, autonomic function, and hypoglycemia. RESEARCH DESIGN AND METHODS: Using a double-blinded randomized study, we investigated the effect of caffeine versus placebo in 19 patients with long-standing type 1 diabetes using continuous glucose sensing technology and simultaneous assessment of autonomic function using Holter monitoring. RESULTS: Caffeine reduced the duration of nocturnal hypoglycemia with a mean duration of 49 minutes (range 0-235) versus 132 (0-468) minutes (P = 0.035). The reduction in duration of nighttime hypoglycemia was due to a decline in the number of episodes of moderate hypoglycemia at the expense of mild hypoglycemic episodes (P = 0.04). There was no overall correlation between reduced heart rate variability (a marker of autonomic dysfunction) and hypoglycemic events (r(s) = 0.12, P = 0.62). CONCLUSIONS: Our results suggest that caffeine is associated with a significant reduction in nocturnal hypoglycemia. The reduction in nocturnal hypoglycemia was not linked to the concomitant rise in parasympathetic activity associated with caffeine.

Adult↗
PubMed2005

Expression of hepatocyte growth factor and its receptor c-met, correlates with severity of pathological injury in experimental alcoholic liver disease.

Expression of hepatocyte growth factor (HGF) and its receptor, c-met is up-regulated in various forms of liver injury. This study evaluated the relationship between HGF and c-met expression and pathological changes in experimental alcoholic liver disease. Rats (5 per group) were fed ethanol and a diet containing saturated fat corn oil or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In a second set of experiments, Kupffer cells, endothelial cells and hepatocytes were isolated from rats in each group. Pathological evaluation and analysis of HGF and c-met expression were performed in liver and the different cell types. Increased expression of HGF and c-met expression was detected in the liver of rats showing necroinflammatory changes. The Kupffer and endothelial cells were primarily responsible for the increase in HGF, c-met expression was seen only in hepatocytes. Thus, up-regulation of HGF and c-met occurred in the presence of the necrosis and inflammation suggesting that HGF may be acting to protect against liver injury or accelerate the regenerative process.

Animals↗
PubMed2005

"I can't breathe"--assessment and emergency management of acute dyspnoea.

BACKGROUND: Acute dyspnoea is a distressing symptom that can suddenly affect any age group. OBJECTIVE: The article provides an approach to the identification of causes and initial management of acute dyspnoea based on history, physical assessment, appropriate triage and investigation. DISCUSSION: Successful management includes rapid assessment of the extent of the disease process, with emphasis on maintenance or protection of airway integrity and identification of impending respiratory failure. All general practice surgeries must have the appropriate equipment available, and staff trained in its use, to provide immediate relief to any patient who presents with dyspnoea. Urgent transfer from the general practice setting to a more specialised centre is usually necessary.

Acute Disease↗
PubMed2004

Identification of 17,20beta,21-trihydroxy-4-pregnen-3-one as an oocyte maturation-inducing steroid in black porgy, Acanthopagrus schlegeli.

The identity of the maturation-inducing steroid (MIS) in black porgy, Acanthopagrus schlegeli, a marine protandrous teleost, is unknown. Previous studies demonstrated that two teleost MISs, the progestins 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) and 17,20beta-dihydroxy-4-pregnen-3-one (DHP) can induce maturation of black porgy oocytes in vitro. The purpose of the present study was to identify the major progestin produced during oocyte maturation (OM) in black porgy and investigate whether its secretion increases during this process. Females were injected twice with a LHRH analog to induce OM. Ovarian follicles undergoing OM were incubated in vitro with tritiated [3H]pregnenolone precursor and the tritiated products were extracted, purified, and identified by HPLC, TLC, acetylation, and recrystallization. Significant amounts of tritiated products were biosynthesized from [3H]pregnenolone that co-migrated with 20beta-S but not with DHP on HPLC and TLC. Similar TLC profiles were obtained with the tritiated products isolated from the HPLC/TLC 20beta-S fraction and standard 20beta-S after the acetylation reaction. The identity of the tritiated products as 20beta-S was confirmed by recrystallization. 20beta-S had a slightly higher potency than DHP in the inducing in vitro final oocyte maturation. Plasma 20beta-S concentrations increased significantly during the oocyte maturation after injection with a LHRH analog. The present data suggest that 20beta-S is the MIS in black porgy.

Acetylation↗
PubMed2004

Disruption of rapid, nongenomic steroid actions by environmental chemicals: interference with progestin stimulation of sperm motility in Atlantic croaker.

Several nongenomic steroid actions, like genomic ones, can be disrupted by estrogenic xenobiotics (xenoestrogens), but the extent and sensitivity of this alternative mechanism of steroid action to chemical interference remain unclear. The effects of environmentally realistic concentrations of a broad range of organic contaminants on the nongenomic action of a progestin (17,20beta,21-trihydroxy-4-pregnen-3-one or 20beta-S) to upregulate Atlantic croaker sperm motility were examined in an in vitro bioassay. Pretreatment of sperm for 10 min in vitro with estrogenic compounds (estradiol-17beta, o,p'-DDT derivatives, zearalenone, bisphenol A, 2',3',4',5'-PCB-4-OH, kepone, chlordane, methoxyclor) and nonestrogenic organic compounds (p,p'-DDT derivatives, atrazine, Aroclor 1254, naphthalene, benzene) at concentrations ranging from 0.01 to 10 microM did not decrease the percent of motile sperm, but all of them partially or completely blocked the response to 20beta-S. Most of the compounds impaired this endocrine mechanism at a concentration of 0.1 microM (approximately 30-40ppb), whereas o,p'-DDT and atrazine were effective at lower concentrations. The antagonistic actions of o,p'-DDT were partially reversed with 10-fold higher concentrations of 20beta-S, which is consistent with a hormone receptor-mediated mechanism of DDT action. The finding that low concentrations of a wide range of organic environmental contaminants can interfere with a rapid, nongenomic steroid action suggests that this mechanism of endocrine disturbance is of toxicological importance.

Animals↗
PubMed2004

Carcinoembryonic antigen induction of IL-10 and IL-6 inhibits hepatic ischemic/reperfusion injury to colorectal carcinoma cells.

Tumor cells cause ischemia/reperfusion (I/R) injury as they arrest within the hepatic microvasculature with the production of nitric oxide (NO) and reactive oxygen species (ROS) that kill both host liver and implanting tumor cells. Carcinoembryonic antigen (CEA) both facilitates the survival of experimental metastasis to nude mouse liver by weakly metastatic human colorectal carcinomas (CRCs) and induces the release of the proinflammatory cytokine IL-6. We hypothesized that CEA also stimulates the release of the antiinflammatory cytokine IL-10 causing inhibition of the toxicity of hepatic I/R injury and indirect stimulation of tumor cell colonization of the liver. Intravenous injection of CEA produced more than 1 ng/ml of IL-10 in the systemic circulation within 1 hr which subsided by 8 hr. The IL-10 response is specific to CEA since the pentapeptide sequence in CEA that binds to the CEA receptor stimulated isolated Kupffer cells to produce IL-10. IL-10, but not IL-6, increased the survival of weakly metastatic CRC cocultured with ischemic-reoxygenated liver fragments but did not affect the survival of CRC exposed to oxidative stress in the absence of any host cells. CEA, IL-6 and IL-10 pretreatment reduced expression of iNOS but only CEA and IL-10 strongly inhibited NO and total reactive species production by ischemic-rexoygenated liver. IL-6 was toxic to CRC exposed to oxidative stress while IL-10 did not have a direct effect on CRC. Thus, CEA stimulates production of IL-10 that may enhance metastasis by promoting the ability of circulating CRC cells to survive the I/R injury of implantation.

Animals↗
PubMed2004

Regulation of cytokine production in carcinoembryonic antigen stimulated Kupffer cells by beta-2 adrenergic receptors: implications for hepatic metastasis.

Elevated Carcinoembryonic antigen (CEA) levels in the serum indicate a poor prognosis for colorectal cancer patients. Induction of proinflammatory cytokines by CEA interaction with Kupffer cells has been proposed as a mechanism for hepatic metastasis formation. Studies show that the cytokine response in circulating and peritoneal macrophages is regulated by beta-adrenergic receptor signals, though little information is available regarding Kupffer cells. We investigated the relationship between beta-adrenergic receptor stimulation and the response of Kupffer cells to CEA. Comparisons between unstimulated and CEA stimulated rat Kupffer cells, using cDNA arrays, showed up-regulation (>4 fold) of the beta2-adrenergic receptor mRNA. Peak up-regulation occurred after 30 min with a decline at 1 h. We examined the effects of the specific beta2-adrenergic receptor agonist terbutaline on cytokine production by CEA stimulated rat Kupffer cells. Pre-treatment of Kupffer cells with terbutaline followed by CEA caused a significant increase in IL-6 and IL-10 production, but a significant reduction in TNF-alpha production (>3 fold). mRNA levels reflected those of the ELISA assays for IL-6 and IL-10 but not for TNF-alpha. For IL-6 and TNF-alpha, these changes were serum independent, while IL-10 was serum dependent. This response is different from LPS treated Kupffer cells where all three cytokines showed serum dependency. Overall, these data suggest that Kupffer cell stimulation by CEA is under beta-adrenergic receptor control and induction of the beta-receptor is an early event following CEA binding to its receptor. Control of TNF-alpha production is negatively affected by terbutaline, while that of IL-6 and IL-10 is positively controlled suggesting that very different beta-adrenergic receptor signaling pathways are involved.

Adrenergic beta-Agonists↗
PubMed2004

Preventing childhood obesity by reducing consumption of carbonated drinks: cluster randomised controlled trial.

OBJECTIVE: To determine if a school based educational programme aimed at reducing consumption of carbonated drinks can prevent excessive weight gain in children. DESIGN: Cluster randomised controlled trial. SETTING: Six primary schools in southwest England. PARTICIPANTS: 644 children aged 7-11 years. INTERVENTION: Focused educational programme on nutrition over one school year. MAIN OUTCOME MEASURES: Drink consumption and number of overweight and obese children. RESULTS: Consumption of carbonated drinks over three days decreased by 0.6 glasses (average glass size 250 ml) in the intervention group but increased by 0.2 glasses in the control group (mean difference 0.7, 95% confidence interval 0.1 to 1.3). At 12 months the percentage of overweight and obese children increased in the control group by 7.5%, compared with a decrease in the intervention group of 0.2% (mean difference 7.7%, 2.2% to 13.1%). CONCLUSION: A targeted, school based education programme produced a modest reduction in the number of carbonated drinks consumed, which was associated with a reduction in the number of overweight and obese children.

Body Mass Index↗
PubMed2004

A randomised controlled study of the efficacy of hypromellose and Lacri-Lube combination versus polyethylene/Cling wrap to prevent corneal epithelial breakdown in the semiconscious intensive care patient.

OBJECTIVE: To compare the efficacy of two forms of eye care (hypromellose and Lacri-Lube combination vs polyethylene/Cling wrap covers) for intensive care patients. DESIGN: Randomised-controlled trial. SETTING: University affiliated, tertiary referral hospital. PATIENTS AND PARTICIPANTS: One hundred ten patients with a reduced or absent blink reflex were followed through until they regained consciousness, were discharged from the facility during study enrolment, died or developed a positive corneal ulcer or eye infection. INTERVENTIONS: All patients received standard eye cleansing every 2 h. In addition to this, group one ( n=60) received a treatment combining hypromellose drops and Lacri-Lube (HL) to each eye every 2 h. Group two ( n=50) had polyethylene covers only placed over the eye to create a moisture chamber. MEASUREMENTS AND RESULTS: Corneal ulceration was determined using corneal fluorescein stains and mobile slit lamp evaluation, performed daily. No patients had corneal ulceration in the polyethylene cover group, but 4 patients had corneal ulceration in the HL group. CONCLUSIONS: Polyethylene covers are as effective as HL in reducing the incidence of corneal damage in intensive care patients.

Australia↗
PubMed2004

Aroclor 1254 inhibits tryptophan hydroxylase activity in rat brain.

Previous studies have shown that oral exposure of rats to polychlorinated biphenyls (PCBs) results in reduced 5-hydroxytryptamine (5-HT) concentrations in certain brain regions. In the present study, we investigated whether the PCB mixture Aroclor 1254 (0.33 mg/g body weight as a single oral dose) can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, and reduce 5-HT concentrations in selected brain areas. In two separate experiments, Aroclor 1254 exposure consistently reduced TPH activity in the brainstem (7.2 and 8.7%), frontal cortex (17.4 and 14.8%), and hypothalamus (10.7 and 9.4%) without altering the rats' food intake or growth. Moreover, Aroclor 1254 accumulation in the frontal cortex demonstrated a negative correlation with TPH activity (correlation coefficient -0.82). In addition, 5-HT concentrations decreased in the brainstem and frontal cortex after Aroclor 1254 exposure by 9.1 and 19.7%, respectively. These results suggest that the Aroclor 1254-induced decreases in 5-HT concentrations in certain areas of the rat brain are due to inhibition of TPH activity, similar to our recent observations in Atlantic croaker, and that TPH is one of the targets of PCB neurotoxicity in both fish and mammals.

Animals↗
PubMed2004

Biochemical characterization of a membrane androgen receptor in the ovary of the atlantic croaker (Micropogonias undulatus).

Membrane androgen receptors have been biochemically characterized in only a few vertebrate species to date. Therefore, the purpose of the current study was to comprehensively investigate the binding characteristics of a putative membrane androgen receptor in the ovary of the teleost, Atlantic croaker (Micropogonias undulatus). Specific androgen binding to an ovarian plasma membrane fraction was demonstrated using a radioreceptor assay protocol consisting of a short-term incubation with [(3)H]testosterone (T) and subsequent filtration of bound steroid from free steroid. Saturation and Scatchard analyses of T binding to an ovarian plasma membrane fraction indicated the presence of a single, high-affinity (K(d) = 15.32 +/- 2.68 nM [mean +/- SEM]), low-capacity (B(max) = 2.81 +/- 0.31 pmol/mg protein), androgen-binding site. Specific androgen binding to the receptor was readily displaceable, and the association and dissociation kinetics were rapid (half-time = 3.7 +/- 1.7 and 4.7 +/- 0.2 min, respectively). Competitive binding assays showed that 5alpha-dihydrotestosterone, T, and 11-ketotestosterone had relative binding affinities (RBAs) of 193%, 100%, and 13%, respectively, whereas none of the C(18) or C(21) steroids tested bound with high affinity except for progesterone (RBA = 191%). This androgen-binding moiety with high affinity for progesterone is unlikely to mediate the physiological actions of progestins in croaker, because it has low binding affinity for fish progestin hormones. Androgen-binding sites were also detected in membrane fractions of the brain, liver, kidney, and drumming muscle, whereas little or no binding was detected in the trunk muscle, heart, gills, or intestine. Receptor levels increased 10-fold during ovarian recrudescence, reaching maximum levels in fully mature ovaries, which suggests a likely physiological role for this receptor during the reproductive cycle of female croaker. It is concluded that the androgen-binding moiety identified in the plasma membrane fraction of Atlantic croaker ovarian tissue fulfils all the criteria for its designation as a steroid receptor.

Animals↗