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Biomedical subjects

A J Baker

Publications and source records attributed to A J Baker.

At least 19 recordsLinked to original sources
PubMed2006

Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats.

BACKGROUND: Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats. METHODS: Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)]. RESULTS: Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus. CONCLUSION: Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension.

Adrenergic beta-2 Receptor Antagonists↗
PubMed2006

Ischemic preconditioning depends on age and gender.

UNLABELLED: The goal of this study was to determine if an ischemic preconditioning (IPC) protocol improved post-ischemic functional recovery of female mouse hearts. A previous study found that IPC did not occur in hearts from 10-week-old females. We studied Langendorff-perfused hearts from both 10- and 18-week-old mice (males and females). Hearts were subjected to 45 min ischemia and 45 reperfusion (I/R); IPC involved pretreatment with 3 min ischemia. We measured hemodynamics, infarct size and levels of the phosphorylated prosurvival kinase Akt (p-Akt). Similar to a previous study, for 10- week-old mice we found that the IPC protocol appreciably improved recovery of LV developed pressure (LVDP) for hearts from males but not females. However, for 18-week-old mice we found that the IPC protocol doubled the recovery of LVDP for both males and females. For both ages, hearts from females had greater recovery of LVDP and higher levels of p-Akt compared to males. CONCLUSIONS: These findings are consistent with growing evidence that preconditioning induced by ischemia or other interventions can occur in hearts from females. However, for hearts from females, preconditioning depends on age. Moreover, consistent with previous studies, hearts from females have greater inherent resistance to ischemic injury, possibly involving increased signaling via p-Akt.

Age Factors↗
PubMed2004

Distinct patterns of Trypanosoma cruzi infection in Leontopithecus rosalia in distinct Atlantic coastal rainforest fragments in Rio de Janeiro--Brazil.

Previous studies on infection of Trypanosoma cruzi in the Poço das Antas Biological Reserve population of wild free-ranging Leontopithecus rosalia have shown the presence of genotype T. cruzi II, associated in Brazil with human disease. Herein, this study has been extended, the infection being evaluated in L. rosalia of 3 different tamarin populations, inhabiting distinct forest areas located in the same Atlantic Coastal Rainforest. Edentata, Marsupialia, Rodentia and Chiroptera were examined exclusively in the Poço das Antas Biological Reserve. Excluding Chiroptera, T. cruzi infection was found in all orders. Biochemical and molecular characterization demonstrated that golden lion tamarins maintained stable infections by T. cruzi II. The isolates from the other mammals corresponded to T. cruzi I, suggesting independent transmission cycles occurring among the sylvatic mammals inside Poço das Antas Biological Reserve. Significant differences in the infection patterns presented by the 3 populations of wild and captive-born golden lion tamarins were noticed. In Poço das Antas a considerably higher number of positive haemocultures from tamarins with positive serological titres was observed in comparison to those obtained from other areas. The implications for conservation and public health of an active sylvatic cycle in the Atlantic Coastal Rainforest of Rio de Janeiro are discussed.

Animals↗
PubMed2004

Trauma recidivism in a large urban canadian population.

BACKGROUND: Prevention of trauma might be achieved by risk factor modification. Identification of such risk factors can be pursued by various means. Trauma recidivists may possess and highlight risk factors. Accordingly, trauma recidivists were analyzed as a method to elucidate trauma risk factors. METHODS: A retrospective analysis of 13,057 trauma patients in Toronto was conducted. Forty-two recidivists were identified, and their first admission was compared with a control group of 84 non-recidivists. RESULTS: The rate of trauma recidivism was 0.38% overall. Trauma recidivists were more likely to be from the inner city, male, homeless, suffering from chronic medical conditions. In addition, psychiatric conditions, an alcoholism history or any alcohol at the time of injury, intentionally injured, or engaged in criminal activity were also significantly more common in recidivists (p <0.05). CONCLUSION: Risk factors for major trauma can be identified by analyzing recidivists in a large urban Canadian population.

Accident Proneness↗
PubMed2004

Fatty liver disease in children.

NAFLD/NASH is now recognised as an increasing clinical problem in children and adolescents. Risk factors include obesity, insulin resistance, and hypertriglyceridaemia. Drug hepatoxicity and genetic or metabolic diseases that can cause hepatic steatosis must be excluded. Affected children are usually asymptomatic although a few may complain of malaise, fatigue, or vague recurrent abdominal pain. Liver biopsy is the gold standard for diagnosis, and is important in determining disease severity and prognosis. The natural history of childhood NASH may be progressive liver disease for a significant minority. Long term follow up studies in this population are still lacking. The mainstay of treatment is weight reduction. The use of pharmacological therapy, though promising, ideally needs further evaluation in well designed randomised controlled studies in children.

Adolescent↗
PubMed2003

Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience.

BACKGROUND: The role of interleukin-2 receptor antibodies as rescue therapy in steroid-resistant rejection (SRR) has not been studied. We evaluated the safety and efficacy of an interleukin-2 receptor antibody, basiliximab (Simulect, Novartis, East Hanover, NJ), in treating SRR in pediatric liver transplant recipients. METHODS: This was a prospective study of seven pediatric liver transplant recipients with biopsy-proven SRR who would have otherwise received OKT3 or antithymocyte globulin. The primary immunosuppression consisted of cyclosporine (Neoral, Novartis), azathioprine, and prednisolone in four patients and tacrolimus and prednisolone in three patients who had undergone retransplantation for chronic rejection (n=2) and hyperacute rejection (n=1). Four patients had received two cycles of high-dose steroids, and three patients had received a single cycle; all had been converted to tacrolimus, followed by the addition of mycophenolate mofetil. RESULTS: The median time from transplant to SRR was 30 days (range, 8 days-23 months). Five children received two doses of basiliximab (10 mg, 3-7 days apart), and two children received a single dose. Aspartate aminotransferase levels normalized in three children 12, 21, and 30 days after basiliximab treatment. Aspartate aminotransferase levels decreased without normalizing in two children, but there was no further evidence of cellular rejection on repeat biopsies. All five children are rejection-free with a median follow-up of 22 months (range, 5-32 months). Biochemical abnormalities persisted in the remaining two children, and both developed chronic rejection. There were no immediate side effects associated with basiliximab. Two patients were treated empirically for possible cytomegalovirus infection 21 and 57 days after basiliximab treatment, with no evidence of cytomegalovirus disease. CONCLUSION: Five of seven pediatric liver transplant recipients with SRR experienced successful outcomes with basiliximab treatment without major side effects, indicating that it is a safe alternative to OKT3 and other antilymphocyte antibodies.

Antibodies, Monoclonal↗
PubMed2003

Nutritional support in critically ill children.

BACKGROUND & AIMS: Enteral nutrition is the feeding method of choice during critical illness, but in some cases as few as 25% are fed appropriately. The aim was to retrospectively review the administration of nutrition to critically ill children. METHODS: The notes of 95 children over the age of 1 year who were in PICU>or=3 days were reviewed and information related to the delivery of nutrition was obtained. RESULTS: Fifty-nine per cent were fed within 24h of admission. Enteral nutrition was administered 54% of the time, 10% required parenteral nutrition and 9.5% received no nutritional support. Children only received a median 58.8 (range 0-277)% of their energy requirements, which could not be optimised until the 10th intensive care day. Energy intake was greater when supplemented with parenteral nutrition. Parenteral nutrition administration was interrupted 3 times while enteral nutrition was stopped 264 times, mainly to allow other clinical procedures to take place. For 75% of the study time, children had abnormal bowel patterns. Seventy-nine per cent were constipated for 3-21 days and 43% had diarrhoea of unknown aetiology. CONCLUSION: This was a retrospective study to describe the efficiency of nutritional support in critically ill children. We have shown that it is possible to administer enteral nutrition safely. However, the difference between desirable intake and actual intake achieved suggests that a more pro-active approach should be adopted.

Adolescent↗
PubMed2003

Disjunct distribution of highly diverged mitochondrial lineage clade and population subdivision in a marine bivalve with pelagic larval dispersal.

Mitochondrial DNA sequence data for 295 individuals of the marine bivalve Macoma balthica (L.) were collected from 10 sites across the European distribution, and from Alaska. The data were used to infer population subdivision history and estimate current levels of gene flow. Inferred historical biogeography was expected to be congruent with colonization of the Atlantic Ocean from the Pacific Ocean after the opening of the Bering Strait 3.5 Ma. In addition, the last glacial maximum, about 18000 years ago, was expected to have been responsible for most of the present-day distribution of molecular variation within Europe, because the area must have been recolonized after confinement to France and the south of the British Isles during the last glacial maximum. Current gene flow was hypothesized to be high, because the larvae of M. balthica spend 2-5 weeks drifting in the water column. The geographical distribution of one highly diverged haplotype clade was found to be disjunct and was encountered exclusively in samples from the Baltic Sea and Alaska. A molecular clock calibration for marine bivalve cytochrome-c-oxidase I dates this clade as having split off from the other haplotypes 9.8-39 Ma. Multiple colonizations of the Atlantic Ocean from the Pacific by M. balthica may explain the strong differences found between Baltic Sea and other European populations of this species. The sympatric occurrence of the highly diverged mitochondrial lineages in western parts of the Baltic Sea points to secondary admixture. With the use of coalescent analysis, population divergence times for French vs. other non-Baltic European populations ('Atlantic population assemblage') were estimated at a minimum of about 110000 years ago, well before the last glacial maximum 18000 years ago. Signatures of population divergence of M. balthica that appear to have originated during the Pleistocene have thus survived the last glacial maximum. Some of the populations within the Atlantic assemblage are currently isolated, while others appear to be connected by gene flow. Apparently, populations of this species can remain highly subdivided in spite of the potential for high gene flow, implying that their population and evolutionary dynamics can be independent.

Alaska↗
PubMed2002

Association between cerebrospinal fluid interleukin-6 concentrations and outcome after severe human traumatic brain injury.

Acute inflammation plays a significant role in the pathophysiology of traumatic brain injury (TBI). However, the specific relationships between inflammatory mediators and patient outcome following TBI have not been fully established. In this study, we measured plasma and cerebrospinal fluid interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations in 36 patients, following severe TBI. Patients were monitored with continuous measurements of somatosensory-evoked potentials (SSEP) to derive an established surrogate outcome measurement, the 96-h evoked potential (SSEP96). Clinical outcomes were assessed at 3 months using the Glasgow Outcome Scale (GOS). Peak cerebrospinal fluid (CSF) IL-1 and IL-6 concentrations were significantly higher than those observed in the plasma [median 6.5 pg/mL (range 1.4-25.0) vs. 3.0 (0.8-7.6) for IL-1, and 650 (130-7,214) vs. 253 (52-1,506) for IL-6, p < 0.001 for both]. Peak CSF IL-6 levels correlated with SSEP96 (r = 0.42; p = 0.0133), and peak CSF IL-6 levels were higher with improved GOS (p = 0.024). Multiple regression analysis identified that age (p = 0.0072), pupillary abnormality (p = 0.021), the presence of mass lesion (p = 0.023), and peak CSF IL-6 concentrations (p = 0.026) were all statistically significant predictors of clinical outcome following TBI. These results suggest that peak CSF IL-6 concentrations correlate with improved outcome following TBI. This finding helps to characterize the inflammatory reaction associated with TBI and may help to develop improved treatment strategies for patients with TBI.

Adolescent↗
PubMed2002

Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat.

This study describes a new method used to evaluate axonal physiological dysfunction following fluid percussion induced traumatic brain injury (TBI) that may facilitate the study of the mechanisms and novel therapeutic strategies of posttraumatic diffuse axonal injury (DAI). Stimulated compound action potentials (CAP) were recorded extracellularly in the corpus callosum of superfused brain slices at 3 h, and 1, 3, and 7 days following central fluid percussion injury and demonstrated a temporal pattern of functional deterioration. The maximal CAP amplitude (CAPA) covaried with the intensity of impact 1 day following sham, mild (1.0-1.2 atm), and moderate (1.8-2.0 atm) injury (p < 0.05; 1.11 +/- 0.10, 0.82 +/- 0.11, and 0.49 +/- 0.08 mV, respectively). The CAPA in sham animals were approximately 1.1 mV and did not vary with survival interval (3 h, and 1, 3, and 7 days); however, they were significantly decreased at each time point following moderate injury (p < 0.05; 0.51 +/- 0.11, 0.49 +/- 0.08, 0.46 +/- 0.10, and 0.75 +/- 0.13 mV, respectively). The CAPA at 7 days in the injured group were higher than at 3 h, and 1 and 3 days. H&E and amyloid precursor protein (APP) light microscopic analysis confirmed previously reported trauma-induced axonal injury in the corpus callosum seen after fluid percussion injury. Increased APP expression was confirmed using Western blotting showing significant accumulation at 1 day (IOD 913.0 +/- 252.7; n = 3; p = 0.05), 3 days (IOD 753.1 +/- 159.1; n = 3; p = 0.03), and at 7 days (IOD 1093.8 = 105.0; n = 3; p = 0.001) compared to shams (IOD 217.6 +/- 20.4; n = 3). Thus, we report the characterization of white matter axonal dysfunction in the corpus callosum following TBI. This novel method was easily applied, and the results were consistent and reproducible. The electrophysiological changes were sensitive to the early effects of impact intensity, as well as to delayed changes occurring several days following injury. They also indicated a greater degree of attenuation than predicted by APP expression changes alone.

Action Potentials↗
PubMed2002

Intestinal permeability and absorptive capacity in children with portal hypertension.

BACKGROUND: Portal hypertension may affect intestinal function leading to malnutrition in children with liver disease. The aim was to determine whether children with portal hypertension with or without liver disease had impaired absorptive capacity and intestinal barrier function (intestinal permeability) and to ascertain whether these abnormalities related to changes in body composition. METHODS: Twenty-six children with portal hypertension were divided according to aetiology into: Group 1 intrahepatic (n = 15) and Group 2 prehepatic (n = 11). Thirty-five children acted as controls. Carbohydrate absorption and intestinal permeability were assessed using a sugar absorption/permeability test and a variety of anthropometric measurements were obtained. RESULTS: 3-O-methyl-D-glucose, D-xylose and L-rhamnose excretion were significantly reduced in both patient groups compared to controls (P < or = 0.008) and the differential urinary excretion of melibiose/rhamnose (intestinal permeability) was significantly increased in Group 1 only (P < 0.05). Anthropometric measurements showed low Z scores in both groups, but there was no significant (P > 0.05) difference between them. There was no significant correlation between urinary excretion of sugars. anthropometric measurements and energy intake. CONCLUSIONS: Increased portal pressure reduces the absorptive capacity of the small intestine, while liver disease itself leads to increased intestinal permeability.

Adolescent↗
PubMed2001

Calcineurin-inhibitor related nephrotoxicity- reversibility in paediatric liver transplant recipients.

AIM: To study the efficacy of mycophenolate mofetil (MMF) as renal rescue in paediatric liver transplant recipients with calcineurin-inhibitor- (CI) related nephrotoxicity. METHODS: Pediatric liver transplant recipients with stable graft function and a glomerular filtration rate (GFR) <80 ml/min/1.73 m2 were enrolled. MMF was introduced at 20 mg/kg/day and increased to 40 mg/kg/day after 1 week. CI dose was then reduced 6 weeks to achieve blood levels 25% of baseline. GFR was reassessed after 6 and 12 months. RESULTS: Fourteen children with a median (range) interval from transplant of 57 (4-111) months were studied. Their median (range) GFR in ml/min/1.73 m2 increased from a baseline of 52 (31-71), to 69 (38-111) and 73 (35-98) at 6 and 12 months, respectively (P=0.00014). Side effects of MMF include leucopaenia in two and backache in one, two of whom discontinued MMF. Acute allograft rejection occurred in three children. All 14 are well with a median (range) follow-up of 24 (14-38) months from MMF introduction. CONCLUSION: MMF allows the recovery of renal function from CI related nephrotoxicity in more than 70% of paediatric liver transplant recipients with renal impairment.

Adolescent↗
PubMed2001

Hyperaccumulation of Zn by Thlaspi caerulescens can ameliorate Zn toxicity in the rhizosphere of cocropped Thlaspi arvense.

The metal hyperaccumulating plant Thlaspi caerulescens is effective in depleting plant-available metals from the soil. We hypothesized that this reduction of toxic metals in the rhizosphere of T. caerulescens would increase the growth of less metal-tolerant plants with their roots permitted to intermingle and develop coincident rhizospheres. The extent of rhizosphere interaction between T. caerulescens and a coplanted nonaccumulator species, Thlaspi arvense, was controlled using barriers. Two media with elevated concentrations of water-extractable Zn were prepared by enriching one soil with zinc oxide (ZnO) or zinc sulfide (ZnS). The shoot mass of T. arvense was increased by 30% when its roots were permitted to intermingle with those of T. caerulescens in the ZnO treatment. The concomitant 2-3-fold reduction in shoot Zn concentration in T. arvense confirmed that its improved growth was associated with reduced uptake and phytotoxicity of Zn. Thlaspi arvense also showed increased growth and reduced metal uptake when cocropped with T. caerulescens in the ZnS treatment. We conclude that the strong Zn accumulation by T. caerulescens might enhance the establishment and development of surrounding less-tolerant species on soils that are naturally- or anthropogenically-enriched with metals.

Biological Availability↗
PubMed2001

Complete mitochondrial DNA genome sequences of extinct birds: ratite phylogenetics and the vicariance biogeography hypothesis.

The ratites have stimulated much debate as to how such large flightless birds came to be distributed across the southern continents, and whether they are a monophyletic group or are composed of unrelated lineages that independently lost the power of flight. Hypotheses regarding the relationships among taxa differ for morphological and molecular data sets, thus hindering attempts to test whether plate tectonic events can explain ratite biogeography. Here, we present the complete mitochondrial DNA genomes of two extinct moas from New Zealand, along with those of five extant ratites (the lesser rhea, the ostrich, the great spotted kiwi, the emu and the southern cassowary and two tinamous from different genera. The non-stationary base composition in these sequences violates the assumptions of most tree-building methods. When this bias is corrected using neighbour-joining with log-determinant distances and non-homogeneous maximum likelihood, the ratites are found to be monophlyletic, with moas basal, as in morphological trees. The avian sequences also violate a molecular clock, so we applied a non-parametric rate smoothing algorithm, which minimizes ancestor-descendant local rate changes, to date nodes in the tree. Using this method, most of the major ratite lineages fit the vicariance biogeography hypothesis, the exceptions being the ostrich and the kiwi, which require dispersal to explain their present distribution.

Animals↗
PubMed2001

Sources of variability in numbers of live births in wild golden lion tamarins (Leontopithecus rosalia).

We examined the effects of several variables on the number of live births in multiparous females in a wild population of golden lion tamarins (Leontopithecus rosalia). Independent variables included the number of infants born to a female the previous breeding season, the number of infants weaned the previous breeding season, the female's age and body mass, the number of adult males and helpers in the group, and the inbreeding coefficient of the offspring. We also tested the hypothesis that trapping and chemical immobilization during pregnancy affected the number of live births. Female body mass was the only statistically significant predictor of the number of live-born infants in the current season when both first and second peaks were included. Characteristics that predicted higher numbers of infants in the first peak of a season were the number of infants born the previous season and the body mass of the female. The greater the number of infants born the previous season, the greater the number of infants born in the first peak of the current season. Factors positively correlated with the number of live births in the second peak within a season included the number of infants born the previous season, as well as the number of available helpers. Due to sample size constraints, the analysis of litters in the second peak did not include body mass of the female as a variable. Inbreeding and handling did not affect the number of live births. We found no evidence that current reproduction negatively impacts future reproduction in this species. We also found no evidence for an age-related reduction in fertility.

Age Factors↗
PubMed2001

Quantification of toluene dioxygenase induction and kinetic modeling of TCE cometabolism by Pseudomonas putida TVA8.

As measured by the toluene-induced bioluminescent response of Pseudomonas putida TVA8 in batch experiments, toluene dioxygenase (Tod) enzyme activities are dependent on toluene concentration between 0 and 30 mg/L. To provide a measure of the Tod activity for use in Michaelis-Menten competitive-inhibition kinetics, a correlation between toluene concentration and induced Tod activity as measured by an induced bioluminescent response of P. putida TVA8 is presented as a nondimensional Tod activity parameter. A packed-bed, radial-flow bioreactor (RFB) using the bioreporter P. putida TVA8A serves as the model system for studying the effect of the enzyme activity parameter on model predictions of vapor-phase toluene oxidation and trichloroethylene (TCE) cometabolism. Mass balances were performed on a differential section of the RFB to describe the radial transport of vapor-phase toluene and TCE through a bulk gas phase and the concomitant biological reaction in a stationary biofilm phase. The finite-element Galerkin weak-statement formulation with first-order basis functions was used to find the optimum solution to the highly nonlinear, coupled equations. For this RFB system with toluene concentrations less than 1 mg/L in the bulk gas phase, the Tod activity parameter enables accurate predictions of steady-state TCE degradation rate (0.27 microg TCE/min).

Kinetics↗
PubMed2001

Serum hyaluronic acid as an early prognostic marker in biliary atresia.

PURPOSE: The aim of this study was to assess whether serum concentrations of hyaluronic acid (HA), measured at diagnosis is an early biochemical marker of prognosis in biliary atresia. METHODS: Serum HA was measured at diagnosis using a radiometric assay in 84 infants with biliary atresia (BA), and related to outcome by 5 years of age. RESULTS: Serum HA was higher in the 29 patients who died or required liver transplant by 5 years of age compared with the 56 who survived to 5 years without transplant (490 +/- 216 microg/L v 262 +/- 163 microg/L; P <.001, 95% confidence intervals of the difference 145 to 311 microg/L). CONCLUSION: High serum concentrations of HA at diagnosis may help to identify at an early stage those patients with BA who have a poor prognosis and will require liver transplant by 5 years of age.

Actuarial Analysis↗