Search PubMed⌕ Search

Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 271 records · Page 15Linked to original sources
PubMed2000

Functional MR imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer's disease and in cognitively able elderly volunteers.

BACKGROUND AND PURPOSE: Alzheimer's disease is associated with progressive visuospatial dysfunction. This study used functional MR (fMR) imaging with an eye movement paradigm to investigate differences in visuospatial cognition between patients with probable Alzheimer's disease (pAD) and cognitively able elderly volunteers. METHODS: Using established, although imperfect, clinical criteria, patients with pAD (n = 18) and cognitively able elderly volunteers (n = 10) were selected for study. All patients underwent echo-planar fMR imaging at 1.5 T. The visually guided saccade paradigm consisted of alternating periods (30 s) of central fixation and visually guided saccades to a target appearing randomly along the horizontal meridian. Activation maps were derived using a voxelwise t test, comparing the signal intensities between the two steady-state conditions. The activation patterns were characterized by Talairach coordinates, activation volumes, and laterality ratios (LRs). RESULTS: Statistically significant differences existed between the activation patterns of the patients with pAD and those of the volunteers. In contrast to the control group, a left-dominant parietal activation pattern and enhanced prefrontal cortical activation were observed in most patients with pAD. CONCLUSION: Within the limitations of the imperfect clinical standard of reference, the reduction in right parietal activation producing the left-dominant LR for the intraparietal sulcus may reflect the progressive dysfunction in spatial attention associated with Alzheimer's disease, considering the known parietal lobe involvement in this function and the disease. The high specificity of a positive intraparietal sulcal LR measured by fMR imaging may have a role in detecting and monitoring Alzheimer's disease.

Aged↗
PubMed2000

Could repeat prescriptions identify patients needing extended medical review? An exploratory study.

INTRODUCTION: New Medicare Benefit Schedule care planning items require general practitioners (GPs) to identify their patients with chronic medical conditions and multidisciplinary care needs. This paper investigates the use of long term repeat prescriptions to identify general practice patients who meet these criteria. METHODS: Twenty-nine GPs in urban, rural and inner city locations recruited 10 consecutive patients on repeat prescriptions for 12 months for medical (not primarily psychiatric) conditions. These patients reported their disease, service and morbidity (SF-36) profiles. GP attender profiles were compared with chronic disease self help group members (n = 44), an ACT community sample (n = 555) and a national GP consultation survey sample (n = 31,575). RESULTS: GP patients reported common chronic disease profiles, high levels of specialist, hospital and medication usage, with infrequent use of allied health professionals and self help groups. They reported considerable physical and psychosocial morbidity comparable to or worse than other groups. DISCUSSION: GP patients requesting repeat prescriptions may have substantial physical, psychological and social needs that might be met using a multidisciplinary team approach with allied health professionals and self help groups. CONCLUSION: GPs can use long term repeat prescriptions to identify a chronic disease cohort who could benefit from health care planning under the new Medicare Benefit Schedule funding arrangements.

Adult↗
PubMed2000

Effect of composition of ruminally-infused short-chain fatty acids on net fluxes of nutrients across portal-drained viscera in underfed ewes.

Four ewes, each fitted with a rumen cannula and with catheters in the mesenteric artery and portal and mesenteric veins, received continuous intrarumen infusions of water or of short-chain fatty acids (SCFA). SCFA infusions were isoenergetic (83 kJ/h) and provided rumen molar proportions (acetate:propionate:butyrate) of 70:20:10, 50:40:10 or 50:20:30. The rumen SCFA production rate with the basal diet was 90.0, 23.1 and 8.8 mmol/h for acetate, propionate and butyrate respectively. Portal net fluxes indicated that 74, 67 and 22-30% of infused acetate, propionate and butyrate respectively, reached the portal vein. Portal net release of beta-hydroxybutyrate increased with SCFA infusions, irrespective of the amount of butyrate infused. Portal net release of lactate decreased with high-butyrate infusion. Portal net uptake of glucose increased with the SCFA infusions. In ewes infused with water, a portal net uptake of total amino acids (AA) was observed. SCFA infusions decreased the uptake of nonessential AA (glutamate, glycine, but not glutamine) and increased the net release of tyrosine and essential AA (isoleucine, leucine). Portal net fluxes of AA were similar with both high-acetate and high-propionate infusions. Lower net uptake of glutamine and net release of most essential AA and some nonessential AA were observed with the high-butyrate infusion. Energetic summation of portal net release was not significantly different between the three SCFA infusions, although it tended to be lower with high-butyrate infusion. This may be related to the higher trophic effect of butyrate on the digestive mucosa.

Acetates↗
PubMed1999

Primary association of a TNF gene polymorphism with susceptibility to multiple sclerosis.

The associations of three promoter polymorphisms in the tumor necrosis factor (TNFA) gene have been studied in 238 patients and 324 control subjects. A significant correlation was found between MS susceptibility and the TNFA-376 polymorphism. This association was independent of the human leukocyte antigen (HLA) class II association and the combined inheritance of HLA-DRB1*1501 and the TNFA-376A allele more than additively increased susceptibility to MS.

Alleles↗
PubMed1999

Changes in the expression of myometrial ryanodine receptor mRNAs during human pregnancy.

Uterine contraction is triggered by a rise in intracellular free Ca(2+) concentration ([Ca2+]i), and although ryanodine-sensitive Ca(2+) release channels (RyRs) play a key role in the regulation of [Ca(2+)](i) in skeletal and cardiac muscle, much less is known about their role in smooth muscle. In this study, we investigated the expression of RyR mRNAs (ryr1-3) during human pregnancy by examining myometrial samples (n=18) taken, with informed consent and ethical approval, from non-pregnant patients undergoing hysterectomy, and patients undergoing elective caesarean section (at term, prior to or following the onset of labour). Ca(2+) release channel expression was determined both qualitatively and quantitatively, using reverse transcription-polymerase chain reaction (RT-PCR) analysis, RNase protection assays, and in situ mRNA hybridisation. RT-PCR analysis demonstrated that all three ryr genes, as well as the gene encoding the type I inositol 1,4,5-trisphosphate receptor (InsP(3)RI), are expressed in human myometrium. Quantitation by RNase protection assays showed that ryr3 and InsP(3)RI mRNAs are the most abundant, while ryr2 mRNA is barely detectable. In situ mRNA hybridisation confirmed that ryr3 and InsP(3)RI mRNAs are both localised to myometrial smooth muscle cells. The expression of ryr2 and ryr3 mRNA is down-regulated at the end of pregnancy compared to non-pregnant myometrium, indicating that ryanodine-sensitive Ca(2+) release channels are differentially expressed. The relative conservation of ryr1 expression is consistent with a role for Ca(2+) release from ryanodine-sensitive stores in the mechanism of uterine contractility during labour.

Adolescent↗
PubMed1999

Interaction with amylopectin influences the ability of granule-bound starch synthase I to elongate malto-oligosaccharides.

This paper examines the properties in soluble form of two isoforms of starch synthase. One of these, granule-bound starch synthase I (GBSSI), is responsible for the synthesis of amylose inside the amylopectin matrix of the starch granule in vivo. The other, starch synthase II (SSII), is involved in amylopectin synthesis. Both isoforms can use amylopectin and malto-oligosaccharide as substrates in vitro. As well as acting as a substrate for GBSSI, amylopectin acts as an effector of this isoform, increasing the rate at which it elongates malto-oligosaccharides and promoting a processive rather than distributive mode of elongation of these compounds. The affinity of GBSSI for amylopectin as an effector is greater than its affinity for amylopectin as a substrate. The rate and mode of elongation of malto-oligosaccharides by SSII are not influenced by amylopectin. These results suggest that specific interaction with amylopectin in the matrix of the starch granule is a unique property of GBSSI and is critical in determining the nature of its products.

Amylopectin↗
PubMed1999

[When and how to research anxiety disorders in children?].

From the epidemiological evidence, anxiety disorders appear frequent in childhood and adolescence. Because anxiety has normal adaptative forms through development, the identification of pathology may sometimes pose difficulty. Child and adolescent anxiety disorders are defined in modern classifications with diagnostic criteria nearby of those used for adulthood. Behavioural symptoms of anxiety often alert relatives or teachers of the children. This paper reviews the main behavioural signs found in anxiety disorders (shyness, school refusal, sleep disorders, somatic distress, slowness, domestic tyranny).

Adaptation, Psychological↗
PubMed1999

Characterization of sheep brain ryanodine receptor ATP binding site by photoaffinity labeling.

Two high Mr protein bands (440 and 420 kDa) in sheep brain microsomal membranes were labeled with the photoaffinity ATP analog, O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (Bz2ATP). The 420 kDa band is labeled by [alpha-32P]-Bz2ATP with about 1000-fold higher affinity than the 440 kDa band. The heavily labeled 420 kDa band is identified as dynein heavy chain based on its partial amino acid sequence, and cross-reactivity with anti-dynein antibodies. The 440 kDa protein is immunologically identified as the type-2 RyR. Bz2ATP binding is obtained in the absence of divalent cations. Bz2ATP and ATP increased the binding of ryanodine to its receptor up to 3-fold, and increased the binding affinity up to 6-fold. Other nucleotides stimulate ryanodine binding with decreasing effectiveness: Bz2ATP > ATP > ADP > AMP > AMP-PNP > GTP > cAMP. With respect to nucleotide specificity, this binding site is similar to the skeletal muscle RyR (type 1). However, the brain RyR may have additional one or more sites with lower affinity with inhibitory effect on ryanodine binding. These results suggest that the major RyR isoform in sheep brain corresponds to the type-2 isoform, and that modulation of ryanodine binding by ATP involves its binding to the RyR protein. The association of dynein with brain microsomal membranes may reflect a linkage of RyR to the cytoskeleton.

Adenosine Triphosphate↗
PubMed1999

Indinavir-based treatment of HIV-1 infected patients: efficacy in the central nervous system.

OBJECTIVE: To study the pharmacokinetic properties and clinical efficacy of the HIV-1 protease inhibitor (PI) indinavir in the central nervous system (CNS). DESIGN: Twenty-five consecutive HIV-1 infected patients on combination therapy that included indinavir, had cerebrospinal fluid (CSF) and plasma samples taken on 32 different occasions, at different times after indinavir administration. CSF and viral load data obtained from these treated patients were compared with those from 36 untreated HIV-1 infected patients of similar immunological and demographic pre-treatment status. METHODS: Concentrations of indinavir were measured in CSF and plasma by high-pressure liquid chromatography with ultraviolet light detection and the data were used in pharmacokinetic modelling. RESULTS: The concentration of indinavir in plasma varied with time over a dose interval by about two orders of magnitude, whereas the concentration in CSF was relatively stable. The median concentration of indinavir in CSF was 210 nmol/l, which is above the 95% inhibitory concentration in vitro. Findings from the pharmacokinetic modelling indicate that indinavir is actively transported out of the CSF (P <0.001 compared with a passive transport-only model). In the PI-treated group there was a reduction in viral load to below 50 copies/ml in most subjects and a normalization of the CSF cell content and IgG-index. CONCLUSIONS: This study has shown that one PI, indinavir, is present in the CSF at therapeutic concentrations, and is likely to contribute to the antiretroviral activities observed within the CNS.

Adult↗
PubMed1999

X-ray structural analysis of compensating mutations at the barnase-barstar interface.

The crystal structure of the barstar mutants (Y29P) and (Y29D, Y30W) as well as that of the complexes of barstar(Y29P) with wild-type barnase and barnase(H102K) have been determined. These barstar mutants compensate for the dramatic loss of barnase-barstar interaction energy caused by a single mutation of the barnase active site His-102 to a lysine. The latter introduces an uncompensated charge in the pocket at the surface of barstar where Lys-102 is located. The analysis of the structures suggests a mechanism for this compensation based on the solvation of the charge of Lys-102. Additional compensation occurs through the formation of a hydrogen bond.

Amino Acid Substitution↗
PubMed1999

Effect of neutron-gamma radiation on dopamine and serotonin metabolism in the rat brain: a regional analysis.

The concentrations of dopamine (DA) and its metabolites and the levels of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of serotonin, were determined in discrete cerebral areas of rats 3 hr after (neutron-gamma) irradiation at 4 and 7 Gy. After the 7 Gy irradiation, no significant effect was observed. After the 4 Gy exposure, the most marked difference between irradiated and control rats was in the levels of DA and its metabolites in the striatum. We observed a decrease of DA, HVA, and DOPAC levels in the striatum and an opposite pattern in the substantia nigra. Whatever the brain area observed, an increase of 5-HIAA levels was noted.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Rapid thinning of parts of the southern greenland ice sheet

Aircraft laser-altimeter surveys over southern Greenland in 1993 and 1998 show three areas of thickening by more than 10 centimeters per year in the southern part of the region and large areas of thinning, particularly in the east. Above 2000 meters elevation the ice sheet is in balance but thinning predominates at lower elevations, with rates exceeding 1 meter per year on east coast outlet glaciers. These high thinning rates occur at different latitudes and at elevations up to 1500 meters, which suggests that they are caused by increased rates of creep thinning rather than by excessive melting. Taken as a whole, the surveyed region is in negative balance.

Journal Article↗
PubMed1999

Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs.

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

Adult↗