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Biomedical subjects

K Martin

Publications and source records attributed to K Martin.

At least 37 records · Page 2Linked to original sources
PubMed2002

Patients' and carers' preferences in two models of care for acute exacerbations of COPD: results of a randomised controlled trial.

BACKGROUND: Patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) were randomised to either hospital at home (HaH) or inpatient management, and patient and carer preferred site of management and satisfaction with care received in the two arms was determined. METHODS: Emergency admissions with an acute exacerbation of COPD were randomised to inpatient care or HaH care. After discharge an independent observer administered a questionnaire to both patients and carers on the preferred site of care and scored satisfaction with the care received. RESULTS: Of 60 patients recruited, 30 were randomised to receive HaH care. Retrospective patient preference for HaH care was 96.3% in the domiciliary arm and 59.3% in the conventional arm; carer preference figures were 85.7% and 42.9%, respectively. There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm (p=0.001 and p=0.01, respectively). Patients recorded equal satisfaction with care in the two arms (88.1% in the conventional arm, 91.7% in the domiciliary arm); carer scores were 91.3% and 91.9%, respectively. CONCLUSIONS: The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm. Since patients had to be willing to be looked after at home, both patients' and carers' perceptions of the benefits of HaH care were reinforced by their experience. HaH care of acute exacerbations of COPD is the preferred option in suitable patients.

Acute Disease↗
PubMed2002

Candidate genes colocalized to linkage regions in inflammatory bowel disease.

BACKGROUND/AIMS: The genes encoding for tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor receptor (EGFR) and the vitamin D receptor (VDR) are colocalized to inflammatory bowel disease-associated linkage regions on chromosomes 6, 7 and 12. An association study of these gene polymorphisms with ulcerative colitis or Crohn's disease and a stratification according to disease phenotypes was performed in order to identify genetically homogenous subgroups. PATIENTS AND METHODS: 119 healthy, unrelated controls, 95 patients with Crohn's disease and 93 patients with ulcerative colitis were genotyped for the (G to A) -308 TNF-alpha promoter polymorphism on chromosome 6, the codon 497 EGFR polymorphism on chromosome 7 and the TaqI polymorphism of the VDR gene on chromosome 12. After genotyping, patients were stratified according to the respective disease phenotype. RESULTS: A disequilibrium in the distribution of the VDR genotypes was found in patients with ulcerative colitis compared to controls (p = 0.024). In fistulizing and fibrostenotic Crohn's disease the 'TT' genotype was significantly reduced compared with other phenotypes (p = 0.006), whereas the 'tt' genotype was found more frequently (p = 0.04). The frequency of the WT allele of the EGFR gene was significantly higher in ulcerative colitis (p = 0.04) than in controls. Further significant differences, concerning the associations of the different polymorphisms and disease susceptibility or clinical phenotypes, were not observed. CONCLUSIONS: Regardless of the disease phenotype, the associations between the polymorphisms and inflammatory bowel disease investigated herein are modest, even after stratification for the disease phenotypes. Hence, these polymorphisms are unlikely to confer the reported linkage between inflammatory bowel disease and chromosomes 6, 7 and 12.

Adult↗
PubMed2002

Detection of diluted gene expression alterations using cDNA microarrays.

The use of DNA microarrays has spanned numerous disciplines of life science research. Despite the volume of studies utilizing this technology, no consensus exists on basic issues such as the determination of significantly altered genes in a given experiment, often leading to either false-negative or false-positive data. In this report, we study the effect of dilution of biological alterations on the detection level of gene expression differences using cDNA microarrays. We propose that subtle alterations in transcript levels of genes below the 2-fold level should be considered when replicate hybridizations are performed, because these subtle gene expression changes may be due to a robust response in few cells. We measured the effect of dilution of gene expression and found that differences in gene expression between the two cell lines assayed (HaCaT and MCF-7) were detected even after a 20-fold dilution factor. These results better our understanding of biological alterations that comprise a relatively small percentage of an assayed organ and help in the interpretation of gene expression data.

Cell Line↗
PubMed2001

[Cardiac neuroses].

Cardiac neurosis is defined as heart complaints for which no organic cause can be found. Other common terms are "cardiac anxiety neurosis", "cardiac anxiety disorder", "cardiac phobia", "functional heart complaints" and "somatoform autonomous functional disorders of the cardiovascular system" (ICD-10). Although cardiac neurosis is rarely diagnosed, it is estimated that approximately 30 bis 40% of patients with cardiovascular disorders are actually suffering from functional complaints. Predisposing to the development of cardiac neurosis are insufficient internalization processes during childhood, leading to an insoluble autonomy dependency conflict. Cardiac neurosis is treated with drugs and psychotherapy.

Diagnosis, Differential↗
PubMed2001

Effect of vaccination on experimental infection with Bordetella bronchiseptica in dogs.

OBJECTIVE: To determine comparative efficacy of vaccines administered IM and intranasally, used alone or sequentially, to protect puppies from infection with Bordetella bronchiseptica and determine whether systemic or mucosal antibody response correlated with protection. DESIGN: Randomized controlled trial. ANIMALS: 50 specific-pathogen-free Beagle puppies. PROCEDURE: In 2 replicates of 25 dogs each, 14-week-old puppies that were vaccinated against canine distemper virus and parvovirus were vaccinated against B bronchiseptica via intranasal, IM, intranasal-IM, or IM-intranasal administration or were unvaccinated controls. Puppies were challenge exposed via aerosol administration of B bronchiseptica 2 weeks after final vaccination. Clinical variables and systemic and mucosal antibody responses were monitored for 10 days after challenge exposure. Puppies in replicate 1 were necropsied for histologic and immunohistochemical studies. RESULTS: Control puppies that were seronegative before challenge exposure developed paroxysmal coughing, signs of depression, anorexia, and fever. Vaccinated puppies (either vaccine) that were seronegative before challenge exposure had fewer clinical signs. Puppies that received both vaccines had the least severe clinical signs and fewest lesions in the respiratory tract. Vaccinated dogs had significantly higher concentrations of B bronchiseptica-reactive antibodies in serum saliva before and after challenge. Antibody concentrations were negatively correlated with bacterial growth in nasal cavity and pharyngeal samples after challenge exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Parenterally and intranasally administered vaccines containing B bronchiseptica may provide substantial protection from clinical signs of respiratory tract disease associated with infection by this bacterium. Administration of both types of vaccines in sequence afforded the greatest degree of protection against disease.

Administration, Intranasal↗
PubMed2001

Ageing of murine small intestinal stem cells.

Most organs of the body comprise populations of cells that are committed to specialized functions and that are renewed from small numbers of uncommitted progenitor or 'stem' cells. Stem cells are of central importance in the study of ageing because any senescent decline in the number or functional competence of stem cells will impair the capacity for renewal and turnover of committed cells, with potentially serious consequences for tissue homeostasis. The intestinal epithelium represents an excellent model system for the study of stem cells. Its spatial and hierarchical organisation allows the study of the function or characteristic of a given cell according to its position within the crypt. Hence, the stem cells which are located at the 4th-5th cell position from the bottom can be studied together with their daughter cells, as they divide and differentiate while migrating along the crypt-villus axis. The ability of the stem cells to undergo apoptosis and the capacity to regenerate the epithelium following injury were investigated in mice of different ages. Stem cells from older animals showed an increased apoptotic response following exposure to low doses of ionising radiation. The regenerative capacity was estimated by measuring the crypt survival levels and the growth rate of surviving crypts after high doses of irradiation. Surviving crypts in the older mice, suggesting an impairment in the damage recognition/response mechanisms, were both fewer and smaller than in young mice. The growth rate of surviving crypts was determined by measuring the crypt area and the number of cells/crypt at various times after 14 Gy irradiation. There was a growth delay of between half and one day in the older mice, and they subsequently grew more slowly. The number of cells susceptible to regenerate a crypt was also estimated. Surprisingly, they appear to be more numerous in the older mice. These studies indicate important age-related alterations in the capacity of the stem cells to regenerate the crypts after radiation-induced damage. The molecular bases of these changes are currently being investigated. Preliminary data showed alteration in the level of p53 and p21 expression, suggesting an age-related defect in the capacity to recognize damage and initiate apoptosis or repair.

Animals↗
PubMed2001

Delta 32 mutation of the chemokine-receptor 5 gene in inflammatory bowel disease.

The gene encoding chemokine receptor 5 (CCR5) is colocalized to the microsatellite marker D3S1573, which was linked with inflammatory bowel disease. Genetic heterogeneity in inflammatory bowel disease might be defined by a combination of the p-ANCA status and immunoregulatory genes. One hundred and twenty healthy unrelated controls, 101 patients with Crohn's disease, and 99 patients with ulcerative colitis were genotyped for the Delta 32 mutation of the CCR5 gene. The presence of p-ANCA was determined by the use of indirect immunofluorescence. After genotyping, patients were stratified according to p-ANCA status. The frequency of the Delta 32 mutation was not significantly different in controls and patients with Crohn's disease or ulcerative colitis (P 0.207 or more). Moreover, the frequency of the mutation was not significantly different in patients with inflammatory bowel disease after stratification for the p-ANCA status (P 0.482). Regardless of the p-ANCA status, Crohn's disease and ulcerative colitis are not associated with the Delta 32 mutation of the CCR5 gene.

Adult↗
PubMed2001

Polymorphisms of the ICAM-1 gene are associated with inflammatory bowel disease, regardless of the p-ANCA status.

The intercellular adhesion molecule-1 (ICAM-1) is of paramount importance for the initiation and propagation of various inflammatory conditions. An increased frequency of allele R241 of the ICAM-1 gene was previously described in p-ANCA-negative as compared to p-ANCA-positive ulcerative colitis and vice versa in Crohn's disease. One hundred sixteen healthy unrelated controls, 121 patients with ulcerative colitis, and 96 patients with Crohn's disease were genotyped for two polymorphisms of the ICAM-1 gene (R/G241, exon 4; and K/E469, exon 6), employing dot-blot hybridization and stratified according to their p-ANCA status. When compared with the control group the frequency of the allele R241 (P = 0.024) and the heterozygous genotype R/G241, P = 0.032) were significantly increased in ulcerative colitis, whereas the homozygous genotype G/G241 was found less frequently (P = 0.022). The heterozygous genotype K/E469 was observed less frequently (P = 0.001 and 0.037, resp.) than the homozygous genotype E/E469, which was more frequent in Crohn's disease and ulcerative colitis (P = 0.002 and 0.012, respectively). Further significant differences concerning the allele or genotype distribution were not observed. After stratification for the p-ANCA status significant differences concerning the frequencies of both the R241 and the E469 alleles were not detected when p-ANCA-positive inflammatory bowel disease and p-ANCA-negative inflammatory bowel disease were compared. Ulcerative colitis and Crohn's disease are associated with polymorphisms of the ICAM-1 gene, which might therefore represent a functional candidate gene. However, the observed associations are independent of the p-ANCA status.

Alleles↗
PubMed2001

Effects of acetaminophen on monoaminergic systems in the rat central nervous system.

Although acetaminophen is a well established analgesic, its mechanism of action is still unknown. We investigated whether this drug could affect central monoaminergic neurotransmission in rats. Significant increases in serotonin (5-HT) levels were found in the posterior cortex, hypothalamus, striatum, hippocampus and brain stem, but not spinal cord, 45 min after per os administration of 200-400 mg/kg of acetaminophen. However, this treatment altered neither the levels of 5-hydroxyindoleacetic acid nor the accumulation of 5-hydroxytryptophan after blockade of aromatic L-amino acid decarboxylase. On the other hand, a decrease in both the levels of the dopamine (DA) metabolite, dihydroxyphenylacetic acid, and the accumulation of dihydroxyphenylalanine were noted in the striatum of acetaminophen-treated rats. Finally, acetaminophen administration significantly increased noradrenaline (NA) levels in the posterior cortex. In vitro studies showed that acetaminophen (1 mM) enhanced K+-evoked overflow of [3H]5-HT, but not [3H]DA and [3H]NA, previously taken up in brain slices, and exerted no direct effect on monoamine oxidase A, tyrosine hydroxylase and catechol-O-methyl-transferase activities. These results indicate that acetaminophen affects central monoaminergic neurotransmission, thereby suggesting that monoamines (especially 5-HT) might participate in its analgesic action.

Acetaminophen↗
PubMed2001

Substance P stimulates inhibitory synaptic transmission in the guinea pig basolateral amygdala in vitro.

To determine the physiological role of tachykinin NK1 receptors in the basolateral nucleus of the amygdala (BLN) we have studied the electrophysiological effects of substance P (SP) in the absence and presence of selective tachykinin receptor antagonists in guinea pig brain slices. Recordings were made from two populations of neurones; spiny pyramidal and stellate neurones, both thought to be projection neurones. Activation of NK1 receptors with SP increased the frequency of spontaneous inhibitory postsynaptic potentials in the majority of cells. This effect was blocked by bicuculline or tetrodotoxin, but not ionotropic glutamate receptor antagonists. The enhanced synaptic activity induced by SP was antagonised by the NK1 receptor antagonist L-760,735 but not by the less active enantiomer L-781,773 or the NK3 receptor antagonist L-769,927. Thus in the basolateral nucleus of the guinea pig amygdala, NK1 receptor activation preferentially stimulates inhibitory synaptic activity. Consistent with this observation, immunohistochemistry revealed NK1 receptor immunoreactivity to be largely restricted to a subset of GABA interneurones. These studies support a physiological role for SP in the regulation of pathways involved in the control of emotional behaviour.

Amygdala↗
PubMed2001

Measurement of the speed of sound in ethanol/water mixtures.

Ethanol/water mixtures are used commonly as a propagation medium in test objects to calibrate the measurement facilities of ultrasound (US) imaging systems. The speed of sound c in the mixture should be known, preferably with an accuracy of +/-0.1% where clinical measurements to +/-1% are required. This article describes measurements of c in several ethanol/water mixtures over a range of temperatures using a simple pulse superposition technique, which gives an estimated measurement uncertainty of 0.1%. The measurements show that, at 20 degrees C, a mixture of 9.5 +/- 0.25% ethanol by volume in distilled water is required to give a speed of 1540 +/- 1.5 m s(-1). However, to achieve this accuracy, the temperature of the mixture must be maintained in the range 20 degrees +/- 0.75 degrees C.

Equipment Design↗
PubMed2001

Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension.

Dihydropyridine and nondihydropyridine calcium channel blockers (CCB) differ in pharmacologic characteristics. Few clinical studies distinguish effects of CCB as monotherapy. We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension. Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were randomly assigned to either nifedipine-GITS or verapamil-SR. Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks. Clinic blood pressure (BP), 24-h ambulatory BP, exercise BP, left ventricular mass, systolic and diastolic function by echocardiography, and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline, end of titration, 3 months and 6 months of treatment. Plasma renin activity, atrial natriuretic peptide, norepinephrine, and epinephrine were assayed. Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index. Compared to nifedipine-GITS, verapamil-SR produced a significantly lower resting and peak exercise heart rate. Nifedipine-GITS elicited a lower peak exercise systolic BP. At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels, no longer apparent by 6 months. Plasma norepinephrine was lower with verapamil-SR, also at end titration and at 3 months, but not at 6 months. Plasma epinephrine and plasma renin activity were unchanged by either drug. There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments. Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension. Differences in their hemodynamic profiles and neurohormonal responses are consistent with preclinical pharmacologic characteristics. The clinical implications of their similarities and differences remain to be fully evaluated in outcome studies.

Blood Pressure↗
PubMed2001

MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis.

MICA and MICB belong to a multicopy gene family located in the major histocompatibility complex (MHC) class I region near the HLA-B gene. They encode for MHC class I molecules, which are induced by stress factors like infection, heat shock or neoplastic transformation and which are mainly expressed on gastrointestinal epithelium. They are recognized by gammadelta T lymphocytes and natural killer (NK) cells. Additionally they are located within a linkage region on chromosome 6p around HLA-B and TNFalpha. Thus the polymorphic MICA and MICB genes are excellent candidate genes for providing the genetic background of inflammatory bowel disease. A strong association of allele A6 of the MICA exon 5 trinucleotide microsatellite polymorphism with ulcerative colitis has been found in Japanese patients. Therefore, we have analysed the MICA exon 5 polymorphism, the MICB intron 1 dinucleotide polymorphism and in addition the tetranucleotide polymorphism C1_4_1, which is located between the MICA gene and the HLA-B gene, in patients of Caucasoid origin with Crohn's disease (n=94) and ulcerative colitis (n=94). In this study we could not find any associations of particular alleles of the MICA, MICB and C1_4_1 polymorphisms with Crohn's disease or ulcerative colitis. We could also not discover any associations of specific two-point or three-point haplotypes with these diseases. Thus it is unlikely that the MICA and MICB genes are involved in causing susceptibility for inflammatory bowel disease, although it cannot be excluded that a weak association could be identified in a larger patient sample.

Colitis, Ulcerative↗
PubMed2001

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.

Adult↗
PubMed2001

Identification of amino acid residues responsible for the alpha5 subunit binding selectivity of L-655,708, a benzodiazepine binding site ligand at the GABA(A) receptor.

L-655,708 is a ligand for the benzodiazepine site of the gamma-aminobutyric acid type A (GABA(A)) receptor that exhibits a 100-fold higher affinity for alpha5-containing receptors compared with alpha1-containing receptors. Molecular biology approaches have been used to determine which residues in the alpha5 subunit are responsible for this selectivity. Two amino acids have been identified, alpha5Thr208 and alpha5Ile215, each of which individually confer approximately 10-fold binding selectivity for the ligand and which together account for the 100-fold higher affinity of this ligand at alpha5-containing receptors. L-655,708 is a partial inverse agonist at the GABA(A) receptor which exhibited no functional selectivity between alpha1- and alpha5-containing receptors and showed no change in efficacy at receptors containing alpha1 subunits where amino acids at both of the sites had been altered to their alpha5 counterparts (alpha1Ser205-Thr,Val212-Ile). In addition to determining the binding selectivity of L-655,708, these amino acid residues also influence the binding affinities of a number of other benzodiazepine (BZ) site ligands. They are thus important elements of the BZ site of the GABA(A) receptor, and further delineate a region just N-terminal to the first transmembrane domain of the receptor alpha subunit that contributes to this binding site.

Amino Acid Sequence↗
PubMed2001

MAPS: a microarray project system for gene expression experiment information and data validation.

SUMMARY: MAPS is a MicroArray Project System for management and interpretation of microarray gene expression experiment information and data. Microarray project information is organized to track experiments and results that are: (1) validated by performing analysis on stored replicate gene expression data; and (2) queried according to the biological classifications of genes deposited on microarray chips.

Computer Communication Networks↗
PubMed2001

Weight loss and exercise walking reduce pain and improve physical functioning in overweight postmenopausal women with knee osteoarthritis.

We conducted an uncontrolled pilot study to determine the effects of a weight loss and walking program on knee pain and physical function in overweight and obese (body mass index; BMI [kg/m] 25-29.9 and BMI > or = 30, respectively) postmenopausal women with knee osteoarthritis (OA). Forty-eight such women completed self-report (Western Ontario and McMaster University Osteoarthritis Index (WOMAC)) and performance-based measures of physical function ("up and go" test, 6-min walk) and enrolled in a 6-month intervention that included weekly nutrition classes and an exercise-walking program. The intervention produced an average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program. There also were significant improvements in the 6-min walk and on VO(2max). Improvements in the timed up and go test and on the WOMAC pain and function scores, however, were restricted only to women who were classified as obese at baseline. These findings suggest that a 6-month weight loss and walking program improves measures of physical functioning and pain in overweight and obese postmenopausal women with knee OA. Among obese women, functional improvement correlated with weight loss, encouraging continued emphasis on weight loss for managing knee OA.

Journal Article↗