Biomedical subjects

J A Bell

Publications and source records attributed to J A Bell.

At least 19 recordsLinked to original sources

PubMed2006

C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis.

Campylobacter jejuni is a globally distributed cause of human food-borne enteritis and has been linked to chronic joint and neurological diseases. We hypothesized that C. jejuni 11168 colonizes the gastrointestinal tract of both C57BL/6 mice and congenic C57BL/6 interleukin-10-deficient (IL-10(-/-)) mice and that C57BL/6 IL-10(-/-) mice experience C. jejuni 11168-mediated clinical signs and pathology. Individually housed mice were challenged orally with C. jejuni 11168, and the course of infection was monitored by clinical examination, bacterial culture, C. jejuni-specific PCR, gross pathology, histopathology, immunohistochemistry, and anti-C. jejuni-specific serology. Ceca of C. jejuni 11168-infected mice were colonized at high rates: ceca of 50/50 wild-type mice and 168/170 IL-10(-/-) mice were colonized. In a range from 2 to 35 days after infection with C. jejuni 11168, C57BL/6 IL-10(-/-) mice developed severe typhlocolitis best evaluated at the ileocecocolic junction. Rates of colonization and enteritis did not differ between male and female mice. A dose-response experiment showed that as little as 10(6) CFU produced significant disease and pathological lesions similar to responses seen in humans. Immunohistochemical staining demonstrated C. jejuni antigens within gastrointestinal tissues of infected mice. Significant anti-C. jejuni plasma immunoglobulin levels developed by day 28 after infection in both wild-type and IL-10-deficient animals; antibodies were predominantly T-helper-cell 1 (Th1)-associated subtypes. These results indicate that the colonization of the mouse gastrointestinal tract by C. jejuni 11168 is necessary but not sufficient for the development of enteritis and that C57BL/6 IL-10(-/-) mice can serve as models for the study of C. jejuni enteritis in humans.

Animals↗

PubMed2006

Dysregulation of muscle fatty acid metabolism in type 2 diabetes is independent of malonyl-CoA.

AIMS/HYPOTHESIS: An elevated lipid content within skeletal muscle cells is associated with the development of insulin resistance and type 2 diabetes mellitus. We hypothesised that in subjects with type 2 diabetes muscle malonyl-CoA (an inhibitor of fatty acid oxidation) would be elevated at baseline in comparison with control subjects and in particular during physiological hyperinsulinaemia with hyperglycaemia. Thus, fatty acids taken up by muscle would be shunted away from oxidation and towards storage (non-oxidative disposal). MATERIALS AND METHODS: Six control subjects and six subjects with type 2 diabetes were studied after an overnight fast and during a hyperinsulinaemic (0.5 mU kg(-1) min(-1)), hyperglycaemic clamp (with concurrent intralipid and heparin infusions) designed to increase muscle malonyl-CoA and inhibit fat oxidation. We used stable isotope methods, femoral arterial and venous catheterisation, and performed muscle biopsies to measure palmitate kinetics across the leg and muscle malonyl-CoA. RESULTS: Basal muscle malonyl-CoA concentrations were similar in control and type 2 diabetic subjects and increased (p<0.05) in both groups during the clamp (control, 0.14+/-0.05 to 0.24+/-0.05 pmol/mg; type 2 diabetes, 0.09+/-0.01 to 0.20+/-0.02 pmol/mg). Basal palmitate oxidation across the leg was not different between groups at baseline and decreased in both groups during the clamp (p<0.05). Palmitate uptake and non-oxidative disposal were significantly greater in the type 2 diabetic subjects at baseline and during the clamp (p<0.05). CONCLUSIONS/INTERPRETATION: Contrary to our hypothesis, the dysregulation of muscle fatty acid metabolism in type 2 diabetes is independent of muscle malonyl-CoA. However, elevated fatty acid uptake in type 2 diabetes may be a key contributing factor to the increase in fatty acids being shunted towards storage within muscle.

Adult↗

PubMed2006

Effect of safflower oil, flaxseed oil, monensin, and vitamin E on concentration of conjugated linoleic acid in bovine milk fat.

Conjugated linoleic acid (CLA) refers to a mixture of conjugated octadecadienoic acids of predominantly ruminant origin. The main isomer in bovine milk fat is the cis-9, trans-11 CLA. Interest in CLA increased after the discovery of its health-promoting properties, including potent anticarcinogenic activity. Two experiments were conducted to evaluate dietary strategies aimed at increasing the concentration of CLA in bovine milk fat. Both experiments were organized as a randomized complete block design with a repeated measures treatment structure. In Experiment 1, 28 Holstein cows received either a control diet or one of 3 treatments for a period of 2 wk. The control diet consisted of 60% forage (barley silage, alfalfa silage, and alfalfa hay) and 40% concentrate on a dry matter (DM) basis, fed as a total mixed ration (TMR). The concentrate was partially replaced in the treatment groups with 24 ppm of monensin (MON), 6% of DM safflower oil (SAFF), or 6% of DM safflower oil plus 24 ppm of monensin (SAFF/M). Average cis-9, trans-11 CLA levels in milk fat after 2 wk of feeding were 0.45, 0.52, 3.36, and 5.15% of total fatty acids for control, MON, SAFF, and SAFF/M, respectively. In Experiment 2, 62 Holstein cows received either a control diet or one of 5 treatment diets for a period of 9 wk. The control diet consisted of 60% forage (barley silage, alfalfa silage, and alfalfa hay) and 40% concentrate on a DM basis, fed as a TMR. The concentrate was partially replaced in the treatment groups with 6% of DM safflower oil (SAFF), 6% of DM safflower oil plus 150 IU of vitamin E/kg of DM (SAFF/E), 6% of DM safflower oil plus 24 ppm of monensin (SAFF/M), 6% of DM safflower oil plus 24 ppm of monensin plus 150 IU of vitamin E/kg of DM (SAFF/ME), or 6% of DM flaxseed oil plus 150 IU of vitamin E/kg of DM (FLAX/E). Average cis-9, trans-11 CLA levels during the treatment period were 0.68, 4.12, 3.48, 4.55, 4.75, and 2.80% of total fatty acids for control, SAFF, SAFF/E, SAFF/M, SAFF/ME, and FLAX/E, respectively. The combination of safflower oil with monensin was particularly effective at increasing milk fat CLA. The addition of vitamin E to the diet partially prevented the depression in milk fat associated with oilseed feeding, but had no significant effect on the concentration of CLA in milk.

Animal Feed↗

PubMed2005

Parasitemia in an immunocompetent horse experimentally challenged with Sarcocystis neurona sporocysts.

Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of horses in Americans. Most cases are attributed to infection of the central nervous system with Sarcocystis neurona. Parasitemia has not been demonstrated in immunocompetent horses, but has been documented in one immunocompromised foal. The objective of this study was to isolate viable S. neurona from the blood of immunocompetent horses. Horses used in this study received orally administered S. neurona sporocysts (strain SN 37-R) daily for 112 days at the following doses: 100/day for 28 days, followed by 500/day for 28 days, followed by 1000/day for 56 days. On day 98 of the study, six yearling colts were selected for attempted culture of S. neurona from blood, two testing positive, two testing suspect and two testing negative for antibodies against S. neurona on day 84 of the study. Two 10 ml tubes with EDTA were filled from each horse by jugular venipuncture and the plasma fraction rich in mononuclear cells was pipetted onto confluent equine dermal cell cultures. The cultures were monitored weekly for parasite growth for 12 weeks. Merozoites grown from cultures were harvested and tested using S. neurona-specific PCR with RFLP to confirm species identity. PCR products were sequenced and compared to known strains of S. neurona. After 38 days of in vitro incubation, one cell culture from a horse testing positive for antibodies against S. neurona was positive for parasite growth while the five remaining cultures remained negative for parasite growth for all 12 weeks. The Sarcocystis isolate recovered from cell culture was confirmed to be S. neurona by PCR with RFLP. Gene sequence analysis revealed that the isolate was identical to the challenge strain SN-37R and differed from two known strains UCD1 and MIH1. To our knowledge this is the first report of parasitemia with S. neurona in an immunocompetent horse.

Animals↗

PubMed2004

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma.

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.

Adenocarcinoma↗

PubMed2004

Identification of carcinoma cells in peripheral blood samples of patients with advanced breast carcinoma using RT-PCR amplification of CK7 and MUC1.

We have undertaken a pilot study to attempt to identify circulating carcinoma cells in a series of patients with advanced breast carcinoma, using reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA of epithelial specific antigens. Using this method to amplify mRNA of MUC1 and cytokeratin 7 (CK7) the sensitivity of the technique was demonstrated by means of diluted concentrations of "spiked MCF7" cells in whole blood, showing a detection limit of 1 in 10(6) (CK7) and 1 in 10(5) (MUC1). Positive results were obtained from the peripheral blood of all nine female patients with advanced breast cancer for CK7 and eight of the nine patients for MUC1. CK7 was however detected in five of 11 healthy controls (eight females, three males) and MUC1 in one of the 11 controls. None of the control group were positive for both CK7 and MUC1, in contrast to eight of the nine patients with advanced breast carcinoma who were positive for both markers. The RT-PCR method thus appears sufficiently sensitive to identify circulating tumour cells in peripheral blood samples from patients with advanced breast carcinoma. However a high proportion of false-positive results was seen in the control population. More extensive investigation is required before the technique is likely to be of benefit clinically.

Adult↗

PubMed2004

Phenotypic similarities in bilateral breast cancer.

Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.

Adult↗

PubMed2003

Prognostic significance of BRCA1 expression in sporadic breast carcinomas.

BRCA1 is a tumour suppresser gene frequently mutated in familial breast cancer and thought to influence the progression of sporadic breast cancer. Decreased BRCA1 mRNA and protein expression has been identified in breast cancer cell lines and sporadic breast tumours. Here the prognostic significance of reduced BRCA1 protein expression is investigated in primary operable breast cancer. Immunohistochemical analysis was used to determine the level of BRCA1 protein expression in 100 breast cancers. BRCA1 expression was compared with known prognostic factors and survival to investigate its prognostic significance. BRCA1 nuclear expression was reduced by varying amounts in breast carcinomas. A progressive loss of BRCA1 expression correlated well with higher histological grade (p = 0.002) and an excess of medullary/atypical medullary/grade 3 ductal carcinomas (p = 0.0001). When adjusted for grade, patients with loss of BRCA1 expression had a significantly longer disease-free survival time. Loss of BRCA1 expression associated with high-grade breast tumours suggests that BRCA1 may play an important role in the pathogenesis of sporadic breast cancer.

Adult↗

PubMed2003

Expression of p27kip1 in breast cancer and its prognostic significance.

p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p<0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful.

Adult↗

PubMed2003

Short communication: Postruminal infusion of conjugated linoleic acids negatively impacts milk synthesis in Holstein cows.

In view of the potential of rumen-protected conjugated linoleic acid (CLA) as a means to increase the CLA content of bovine milk, a study was undertaken to evaluate the effect of synthetic CLA on milk production and composition. Four Holstein cows received abomasal infusion of: 1) control, no lipid infusion, 2) 150 g/d of synthetic CLA, 31.7% cis-9, trans-11; 30.4% trans-10, cis-12, 3) 150 g/d of safflower oil, and 4) 150 g/d of tallow. Infusion was carried out for 20 to 22 h/d for 11-d periods in a 4 x 4 Latin square design. The milk fat concentration of cis-9, trans-11 and trans-10, cis-12 isomers of CLA was significantly increased with infusion of CLA. However, CLA infusion had other unexpected effects on milk production and composition. Milk yield dropped significantly during the period of CLA infusion. Furthermore, as well as the typical depression in milk fat reported with trans-10 isomers of CLA, other negative effects specific to CLA infusion were observed including a drop in lactose concentration and yield, a drop in protein yield, and an elevated somatic cell count. The important difference between synthetically produced CLA and CLA produced naturally in the cow is the much higher proportion of trans-10 isomers of CLA in the former. The results of this study suggest that the extent of enrichment possible for trans-10 isomers of CLA, and hence the usefulness of synthetic CLA for this purpose, may be limited because of unacceptable effects on milk yield and composition.

Abomasum↗

PubMed2002

Partial coherence laser interferometry vs conventional ultrasound biometry in intraocular lens power calculations.

AIMS: The purpose of the study was to compare optical biometry based on partial coherence laser interferometry (PCLI) principle to conventional ultrasound biometry in the accuracy of intraocular lens (IOL) power calculations. The role of partial coherence laser interferometry in pseudophakic axial length measurement was analysed in the study. METHODS: In a prospective randomised clinical trial, 100 patients undergoing phacoemulsification cataract surgery were randomised to undergo biometry by either partial coherence laser interferometry (IOL Master) or the applanation ultrasound technique. The IOL material, design and the IOL formula were standardized. The mean error and mean absolute error were calculated and compared using paired t-tests. RESULTS: One hundred patients were included in this prospective randomised trial, of whom 50 patients underwent optical biometry and 50 patients had biometry by applanation ultrasound. The mean age of patients in the PCLI group was 67 +/- 6 yrs as compared to 71 +/- 8 yrs in the ultrasound group (P > 0.05). The preoperative mean axial length was 23.47 +/- 1.1 mm in the PCLI group (range 20-27.6 mm) and 23.43 +/- 1.2 mm in the ultrasound group with a range of 20.1-27 mm (P > 0.05). The mean absolute error (MAE) in the PCLI group was 0.52 +/- 0.32 D (upper and lower 95% CI 0.62 and 0.42 respectively). The MAE in the ultrasound group was 0.62 +/- 0.4 D (upper and lower CI 0.73 and 0.50 D respectively). Eighty-seven per cent of patients were within +/- 1 D in the PCLI group as compared to 80% in the ultrasound group (P = 0.24). The MAE of axial length difference with optical biometry was 0.13 mm +/- 0.13 SD (range -0.42 to 0.78 mm) in the PCLI group and 0.19 +/- 0.13 mm in the ultrasound group. There was a mean shortening of the eye length in the PCLI group postoperatively. Optical biometry improved the post op refraction by 16% on retrospective IOL power calculations. Eight per cent failed biometry with IOL Master (dense cataracts (4%) and fixation instability due to macular degeneration (4%)). CONCLUSION: The non contact optical biometry using the partial coherence laser interferometry principle improves the predictive value for postoperative refraction and is a reliable tool in the measurement of intraocular distances in pseudophakic eyes.

Adult↗

PubMed2002

Neuroendocrine differentiation and prognosis in breast adenocarcinoma.

AIMS: Neuroendocrine differentiation has been detected, and its prognostic value studied, in a number of common human carcinomas. To date there are few detailed studies examining its relevance in breast carcinoma. In this study we evaluate the frequency and prognostic importance of neuroendocrine differentiation in breast adenocarcinoma. METHODS AND RESULTS: The presence of neuroendocrine differentiation, defined as positive reactivity for three markers, neuron-specific enolase (NSE), chromogranin A and/or synaptophysin, has been evaluated in 99 patients with primary operable breast cancer using standard immunocytochemical techniques. A consecutive cohort of patients were selected from the Nottingham/Tenovus series. Comprehensive patient and tumour records have been maintained, and patients were followed up according to a defined protocol. Eighteen cases were positive for NSE, 10 for chromogranin A and 13 for synaptophysin. Eleven percent were positive with more than one neuroendocrine marker. No significant association was found between neuroendocrine differentiation and tumour size, grade, stage or the prevalence of vascular invasion. There was no significant difference in either overall or disease-free survival between patients with or without neuroendocrine differentiation. CONCLUSIONS: In this study we confirm that neuroendocrine differentiation can be identified in a subset (10-18%) of human breast carcinomas. This phenomenon appears to have no relationship to established prognostic factors or patient outcome.

Adenocarcinoma↗

PubMed2002

Crystine: fibrous biomolecular material from protein crystals cross-linked in a specific geometry.

Cysteine substitutions were engineered on the surface of maltose binding protein to produce crystine fibers, linear polymers of folded protein formed within a crystal. Disulfide bond formation between adjacent protein molecules within the lattice was monitored by X-ray crystallography. The cross-linked crystals were resistant to dissolution in water or neutral buffer solutions, even though the cross-linking was one-dimensional. However, crystine fibers were observed by transmission electron microscopy to dissociate from the crystals in acidic solutions. Some fibers remained associated as two-dimensional bundles or sheets, with a repeat unit along the fibers consistent with the packing of the individual protein molecules in the crystal. Neutralization of the acidic solutions caused the fibers to re-associate as a solid. Crystine threads were drawn out of this solution. In scanning electron microscopy images, many individual fibers could be seen unwinding from the ends of some threads. Crystine fibers are a new type of biomolecular material with potential applications wherever the use of proteins in a fibrous form is desirable, for example, the incorporation of enzymes into cloth or filtration material.

Carrier Proteins↗

PubMed2002

3D back shape in normal young adults.

In today's climate of evidence based medicine, there is an increasing emphasis on objective assessment to monitor treatment effectiveness. Although spinal posture and back shape are commonly assessed by clinicians, current practice is based on subjective findings and unreliable objective tools. Numerous management protocols aim to improve both posture and shape, however data related to normal back shape is quite scarce. The aim of this study was to investigate normal back shape in young adults, in order to produce normative values against which deformity could be defined. The Integrated Shape Imaging System (ISIS) was used to measure the three-dimensional back shape. A convenience sample of 48 normal adults, aged 18-28 volunteered to participate in this study. A small minority of individuals showed no curve (8%), 55% showed a single curve and the rest showed a double one. Right spinal asymmetry was more frequent than the left (77% to 52%). Mean values and 95% confidence intervals were 14.1 degrees (11.7 degrees-16.5 degrees) for upper Lateral asymmetry, 5.6 degrees (3.3 degrees - 7.9 degrees) for lower lateral asymmetry, 24.9mm (20.6mm -29.2mm) for thoracic kyphosis and 14.9mm (12.5mm -17.2mm) for lumbar lordosis. Increasing upper lateral asymmetry correlated with decreasing thoracic kyphosis (p=0.01). Maximum skin surface angle correlated positively with only upper lateral asymmetry (p<0.0001). Similar topographical interrelationships have been demonstrated in scoliosis. It is important that clinicians in relevant disciplines objectively assess all three dimensions of back shape, as our research shows that changes in one plane are associated with changes in the other two planes.

Adolescent↗

PubMed2001

E-cadherin as a prognostic indicator in primary breast cancer.

Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal antibody HECD-1 (Zymed Laboratories Inc.). In normal epithelial cells E-CD was strongly expressed at cell-cell boundaries. 66% of the breast cancers examined had reduced intensity of E-CD expression with 74% having significant reductions in the proportion of E-CD-positive tumour cells. Using a combined intensity/proportion score, significant associations were found between E-CD expression and tumour type (P </= 0.001). ER status (P = 0.026) and histological grade (P = 0.031). Expression of E-CD was not found to be related to recurrence, distant metastases, lymph node stage, vascular invasion, primary tumour size, prognostic group or survival. Thus E-CD expression in human breast cancer appears to have minimal prognostic value, but may have a role as a phenotypic marker.

Adult↗

PubMed2001

Analysis of segregation data from selfed progeny of allopolyploids.

This paper discusses the inference of parental genotype based on segregation data from selfed progeny of allopolyploids when there is incomplete information about genotypes and when alleles are codominant or null. The distinct alleles that are present in a genotype are assumed to be known, but not the frequency with which they occur. These assumptions may be appropriate when genotypes are deduced from DNA or protein banding patterns on electrophoretic gels. A computer program, SELF, is described that can generate all possible parental genotypes and rank them on the basis of their agreement with the progeny data. The program caters for tetraploids, hexaploids and octoploids. The methods are illustrated using data from a study of the inheritance of isoenzymes in selfed progeny of octoploid strawberry cultivars.

Alleles↗

PubMed2001

A rapid troponin-I-based protocol for assessing acute chest pain.

In a prospective randomized open trial with 30-day follow-up, we compared a troponin-I-based protocol to 'standard management' for the diagnosis and risk stratification of patients with acute non-ST-elevation chest pain. Patients with acute chest pain (n=400) were randomized to standard diagnostic tests and management, or a protocol based on the admission ECG and the troponin-I result 6 h after onset of chest pain. Low-risk patients were discharged early from CCU; high-risk patients were treated with medical therapy or referred for in-patient angiography as appropriate. We measured length of CCU stay, and followed all patients for major adverse cardiac events (MACE) of death, non-fatal myocardial infarction (MI), or urgent revascularization during the admission and for 30 days post-discharge. The troponin protocol allowed earlier discharge in the low-risk group (10 vs. 30 h, p<0.001) with no excess of adverse events compared to standard management (3% vs. 5%, p=0.32). It identified a group of patients at moderate risk of cardiac events (15% MACE rate during admission and 30-day follow-up), and a high-risk group (75% MACE rate) more accurately than did standard management. The prognostic power of troponin testing in combination with the admission ECG was higher than with either test used alone. The protocol improved the efficiency of low-risk patient management, and improved patient risk stratification. This study adds to the evidence favouring troponin evaluation as part of the management of acute coronary syndromes.

Adult↗

PubMed2001

Contribution of the hyperpolarization-activated current (I(h)) to membrane potential and GABA release in hippocampal interneurons.

Intrinsic GABAergic interneurons provide inhibitory input to the principal neurons of the hippocampus. The majority of interneurons located in stratum oriens (s.o.) of the CA1 region express the hyperpolarization-activated cation current known as I(h). In an effort to elucidate the role of this current in regulating the baseline excitability of these neurons and its participation in the regulation of the release of GABA onto CA1 pyramidal neurons, we utilized whole cell electrophysiological recordings from both populations of cells. In voltage-clamp experiments, hyperpolarization of the interneuron membrane initiated a large inward current with an estimated activation threshold of 51.6 +/- 7.6 mV and a half-maximal voltage of -73.0 +/- 7.0 mV. This current was blocked by bath application of the I(h) inhibitors ZD 7288 (50 microM) or cesium (2 mM). Current-clamp experiments at the interneuron resting membrane potential (-61.3 +/- 1.2 mV) revealed a significant hyperpolarization, a decrease in the rate of spontaneous action potential discharge, an increase in the cellular input resistance, and the elimination of rebound afterdepolarizations during blockade of I(h) with ZD 7288 (50 microM). The hyperpolarizing effect of ZD 7288 was also substantially larger in interneurons clamped near -80 mV using current injection through the pipette. In addition to neurons exhibiting I(h), recordings were obtained from a small population of s.o. interneurons that did not exhibit this current. These cells demonstrated resting membrane potentials that were significantly more negative (-73.6 +/- 5.5 mV) than those observed in neurons expressing I(h), suggesting that this current contributes to more depolarized membrane potentials in these cells. Recordings from postsynaptic pyramidal neurons demonstrated that blockade of I(h) with ZD 7288 caused a substantial reduction (approximately 43%) in the frequency of spontaneous action potential-dependent inhibitory postsynaptic currents (IPSCs), without altering their average amplitude. However, miniature action-potential-independent IPSC frequency, amplitude, and decay kinetics were unaltered by ZD 7288. These data suggest that I(h) is active at the resting membrane potential in s.o. interneurons and as a result contributes to the spontaneous activity of these cells and to the tonic inhibition of CA1 pyramidal neurons in the hippocampus.

Animals↗