Search PubMed⌕ Search

Biomedical subjects

C Holmes

Publications and source records attributed to C Holmes.

At least 19 recordsLinked to original sources
PubMed2001

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗
PubMed2001

Visual hallucinations are associated with lower alpha bungarotoxin binding in dementia with Lewy bodies.

Patients with dementia with Lewy bodies (DLB) commonly experience psychotic symptoms, most notably visual hallucinations. Previously, it has been shown that visual hallucinations in DLB are associated with reduced cortical choline acetyltransferase activity, a marker of cholinergic innervation, but not with predominantly postsynaptic muscarinic M1 receptor binding. In the present investigation, nicotinic acetylcholine receptor (nAChR) levels in the temporal cortex (Brodmann's areas [BA] 20 and 36) were measured in a group of 24 prospectively assessed DLB patients; comparisons were made between groups with or without visual and auditory hallucinations and delusional misidentification. Visual hallucinations and delusional misidentification were associated with lower [(125)I]alpha bungarotoxin binding in areas 36 and 20 (P<.05), but not with changes in [(3)H]epibatidine binding. There were no significant associations with auditory hallucinations. [(3)H]epibatidine, but not [(125)I]alpha bungarotoxin, binding for all DLB cases was reduced compared to controls (P<.001). Loss of cortical alpha 7 nicotinic receptors may contribute to hallucinations and delusional misidentification in DLB, with implications for treatment and understanding the mechanisms of psychotic symptoms in dementia.

Aged↗
PubMed2001

On-line sulfur isotope analysis of organic material by direct combustion: preliminary results and potential applications.

Sulfur isotopes have received little attention in ecology studies because plant and animal materials typically have low sulfur concentrations (< 1 wt.%) necessitating labor-intensive chemical extraction prior to analysis. To address the potential of direct combustion of organic material in an elemental analyzer coupled with a mass spectrometer, we compared results obtained by direct combustion to results obtained by sulfur extraction with Eschka's mixture. Direct combustion of peat and animal tissue gave reproducibility of better than 0.5/1000 and on average, values are 0.8/1000 higher than values obtained by Eschka extraction. Successful direct combustion of organic material appears to be a function of sample matrix and sulfur concentration. Initial results indicate that direct combustion provides fast, reliable results with minimal preparation. Pilot studies underway include defining bear diets and examining fluctuations between freshwater and brackish water in coastal environments.

Ecosystem↗
PubMed2001

Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation.

This study investigated possible associations between selected polymorphisms in the dopamine receptor genes DRD1 and DRD3 with the presence of psychotic phenomena or aggressive behaviour in a community based cohort of 134 patients with late onset Alzheimer's disease. An association was found between the presence of psychotic symptoms and aggressive behaviour and the DRD1 polymorphism and between the presence of psychosis, but not aggression, and the DRD3 polymorphism. Specifically, carriers of the DRD1 B2 allele were more likely to be aggressive or experience hallucinations whereas homozygous carriers of the DRD3 1 allele were more likely to experience delusions.

Age of Onset↗
PubMed2001

Probabilistic risk assessment of cotton pyrethroids: III. A spatial analysis of the Mississippi, USA, cotton landscape.

Estimates of potential aquatic exposure concentrations arising from the use of pyrethroid insecticides on cotton produced using conventional procedures outlined by the U.S. Environmental Protection Agency's Office of Pesticide Programs Environmental Fate and Effects Division seem unrealistically high. Accordingly, the assumptions inherent in the pesticide exposure assessment modeling scenarios were examined using remote sensing of a significant Mississippi, USA, cotton-producing county. Image processing techniques and a geographic information system were used to investigate the number and size of the water bodies in the county and their proximity to cotton. Variables critical to aquatic exposure modeling were measured for approximately 600 static water bodies in the study area. Quantitative information on the relative spatial orientation of cotton and water, regional soil texture and slope, and the detailed nature of the composition of physical buffers between agricultural fields and water bodies was also obtained. Results showed that remote sensing and geographic information systems can be used cost effectively to characterize the agricultural landscape and provide verifiable data to refine conservative model assumptions. For example, 68% of all ponds in the region have no cotton within 360 m and 92% of the ponds have no cotton within 60 m. Only 2% of ponds have cotton present in all directions around the ponds and within 120 m. These are significant modifications to conventional pesticide risk assessment exposure modeling assumptions and exemplify the importance of using landscape-level risk assessments to better describe the Mississippi cotton agricultural landscape. Incorporating spatially characterized landscape information into pesticide aquatic exposure scenarios is likely to have greater impact on the model output than many other refinements.

Animals↗
PubMed2000

Cardiac sympathetic denervation in Parkinson disease.

BACKGROUND: In Parkinson disease, orthostatic hypotension can result from L-dopa treatment or from sympathetic neurocirculatory failure. The latter is detected by abnormal blood pressure responses to the Valsalva maneuver and can be associated with loss of functional cardiac sympathetic nerve terminals. OBJECTIVE: To determine the frequency of cardiac sympathetic denervation in Parkinson disease, with or without sympathetic neurocirculatory failure, and its association with disease duration, severity, and L-dopa treatment DESIGN: Intergroup comparisons in resting patients. SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PATIENTS: 29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers. MEASUREMENTS: Beat-to-beat blood pressure responses to the Valsalva maneuver, interventricular septal 6-[18F]fluorodopamine-derived radioactivity, cardiac extraction fraction of [3H]norepinephrine, appearance rate of norepinephrine in coronary sinus plasma (cardiac norepinephrine spillover) and venous-arterial differences in levels of dihydroxyphenylglycol (DHPG) and endogenous L-dopa. RESULTS: Of the 29 patients with Parkinson disease, 9 with sympathetic neurocirculatory failure and 11 without had low septal 6-[18F]fluorodopamine-derived radioactivity (2861 +/- 453 Bq/mL per MBq/kg and 5217 +/- 525 Bq/mL per MBq/kg, respectively). All 6 patients with Parkinson disease and decreased 6-[18F]fluorodopamine-derived radioactivity who underwent right-heart catheterization had a decreased cardiac extraction fraction of [3H]norepinephrine and virtually no cardiac norepinephrine spillover or venous-arterial increments in plasma levels of DHPG and L-dopa. Sympathetic neurocirculatory failure and decreased 6-[18F]fluorodopamine-derived radioactivity were unrelated to disease duration, disease severity, or L-dopa treatment CONCLUSIONS: Many patients with Parkinson disease-including all those with sympathetic neurocirculatory failure-have evidence of cardiac sympathetic denervation. This suggests that loss of catecholamine innervation in Parkinson disease occurs in the nigrostriatal system in the brain and in the sympathetic nervous system in the heart

Adult↗
PubMed2000

Mouth protection in sport in Scotland--a review.

The oral health strategy for Scotland, which was published in 1995, recommends that dentists promote the use of mouth protection in sport to reduce the risk of injury. There is compulsory mouthguard use in some sports including ice-hockey, fencing, boxing, lacrosse and some forms of autocycling. In cricket, face protection appears to be compulsory for batsmen only. The use of mouth protection in the martial arts is compulsory at international level but, in the UK, the rule does not seem to be always enforced at club level. Players of contact sports, such as rugby and hockey, are considered to be more at risk of dentoalveolar injury and the governing bodies of these sports recommend that players at all levels wear mouth protection but have not made it mandatory.

Adolescent↗
PubMed2000

Air-wood coupling and the Swiss-cheese violin.

Some problems with the conventional formalism for describing the coupling of fluid vibrations to those of an enclosing shell are examined. An alternative ("dynamic") basis for expanding the normal modes, in which the "pure shell modes" include incompressible motion of the fluid, is proposed. This new approach is applied to Hutchins's "Swiss-cheese violin," the behavior of whose air modes for the case of a rigid shell have been calculated by Shaw. Measurements are presented of various response functions of this instrument as a function of both frequency and the number of open rib holes. These results show the predicted "mode veering" behavior, and can be easily matched to theory with the assumption of plausible parameters.

Acoustic Stimulation↗
PubMed2000

Delusions associated with elevated muscarinic binding in dementia with Lewy bodies.

The relation between disturbances of cholinergic neurotransmission and delusions (DELs) has not been investigated in degenerative dementias such as dementia with Lewy bodies (DLB). A cohort of dementia patients were assessed with standardized clinical evaluations (including the Columbia University Scale for Psychopathology in Alzheimer's Disease), which were repeated annually until death. DLB was confirmed neuropathologically in 21 patients. Neurochemical evaluation included M1 receptor autoradiography (pirenzepine binding), biochemical measurement of choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) histochemistry in brain regions hypothesized to be involved in the genesis of psychosis. Compared with 11 age-matched controls, CHAT and pirenzepine levels were most extensively reduced in the temporal and parietal neocortex of DLB patients. In Brodmann area 36, DELs were significantly associated with elevated pirenzepine binding (131.0 vs 93.5, t = 2.7), whereas visual hallucinations were associated with significant reductions in ChAT (1.7 vs 2.5, t = 2.5). There were no significant associations with other areas or with cholinesterase. Although DELs and visual hallucinations were both linked with disturbances in cholinergic neurotransmission, the nature of the associations was different. Upregulation of the postsynaptic muscarinic receptor may be central in the genesis of DELs, with important treatment implications.

Aged↗
PubMed2000

Effects of bicarbonate/lactate solution on peritoneal advanced glycosylation end-product accumulation.

Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However, B/L solution failed to lower pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at 2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was significantly higher in the Lac and B/L groups than in the control group. Intraperitoneal volume was significantly higher in the B/L group than in the Lac group; D2/D glucose and D2P2 urea did not differ between the two groups. In conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L solution showed a small but statistically significant protective effect against decreasing ultrafiltration as compared with Lac solution. The B/L solution attenuated peritoneal AGE accumulation compared with conventional solution, but did not affect peritoneal pentosidine levels. These findings indicate that biochemical kinetics of various AGE peptides are not unique, but multivalent.

Animals↗
PubMed1999

Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer's disease.

BACKGROUND: High cerebrospinal fluid (CSF) norepinephrine (NE) concentrations in aging and Alzheimer's disease (AD) could reflect decreased NE clearance from central nervous system (CNS) extracellular fluid or increased release of NE into CNS extracellular fluid. Measuring CSF concentrations of the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), an estimate of NE clearance, and the NE precursor dihydroxyphenylacetic acid (DOPA), an estimate of NE biosynthesis, can help differentiate these mechanisms. METHODS: NE, DHPG, and DOPA were determined by HPLC in CSF and plasma obtained following yohimbine, clonidine, and placebo. Ten AD, 10 older, and 11 young subjects were studied. RESULTS: CSF DOPA following yohimbine was higher in older and AD than in young subjects. CSF DHPG did not differ among groups. Plasma DOPA following yohimbine was higher in AD than in young subjects. CONCLUSIONS: During alpha-2 adrenoreceptor blockade in both aging and AD, there are increased responses of CNS NE biosynthesis and release with unchanged CNS NE clearance. This pattern is consistent with partial loss of CNS noradrenergic neurons with compensatory activation of remaining CNS noradrenergic neurons. Given the marked loss of locus coeruleus (LC) noradrenergic neurons in AD, achievement of high CSF NE suggests particularly prominent compensatory activation of remaining LC neurons in this disorder.

Adrenergic alpha-Agonists↗
PubMed1999

CYP2D6 polymorphisms in Alzheimer's disease, with and without extrapyramidal signs, showing no apolipoprotein E epsilon 4 effect modification.

BACKGROUND: Allelic variation at the CYP2D6 gene has been reported to be associated with Parkinsons' disease (PD) and Lewy body dementia (LBD), but not with Alzheimer's disease (AD). AD has been associated with apolipoprotein E (apoE) epsilon 4 allele loading. METHODS: We examined CYP2D6 and apoE polimorphisms in a sample of 259 patients with dementia, 210 of whom had a diagnosis of AD, and 107 healthy controls. RESULTS: We found that the allelic frequency in our AD sample did not vary from that in the controls. The debrisoquine hydroxylase poor metabolize phenotype was not more prevalent among AD cases than among controls in contrast to that reported for PD and LBD. We also found that CYP2D6 status does not modify the risk effect for AD conferred by apoE epsilon 4 alleles. CONCLUSIONS: These findings provide some support to the notion that, at a genetic level, at least at this locus, AD could be distinct from PD and LBD.

Age of Onset↗
PubMed1999

Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space.

We have prepared an atlas of the human cerebellum using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux. Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules. A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical-pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum.

Cerebellum↗
PubMed1999

A test of the "epinephrine hypothesis" in humans.

-According to the "epinephrine hypothesis," circulating epinephrine taken up by sympathetic nerves is coreleased with norepinephrine during sympathetic stimulation and binding of coreleased epinephrine to presynaptic beta-adrenoceptors augments exocytotic release of norepinephrine, contributing to high blood pressure. This study examined whether infusion of a physiologically active amount of epinephrine affects subsequent vascular responses and the estimated rate of entry of norepinephrine into regional venous plasma (norepinephrine spillover). Each of 3 experiments included intravenous infusion of 3H-norepinephrine, measurements of forearm vascular resistance, and intra-arterial infusion of epinephrine (3 ng/min per deciliter forearm volume). In experiment 1, subjects underwent lower body negative pressure (LBNP-25 mm Hg) before and after intra-arterial epinephrine; in experiment 2, LBNP and intra-arterial yohimbine before and after intra-arterial epinephrine; and in experiment 3, intravenous nitroprusside before and after intra-arterial epinephrine. In all subjects, intra-arterial epinephrine produced ipsilateral pallor and decreased forearm vascular resistance. Ipsilateral venous epinephrine increased by 10-fold. Epinephrine did not affect forearm vasoconstrictor responses to LBNP or vasodilator responses to intra-arterial yohimbine or intravenous nitroprusside; did not affect venous norepinephrine levels or norepinephrine spillover during LBNP, yohimbine, LBNP during yohimbine, or nitroprusside; and did not increase venous epinephrine levels during any of these manipulations. Loading of forearm sympathetic terminals with epinephrine therefore does not augment subsequent neurogenic vasoconstriction or norepinephrine release in the human forearm in response to sympathetic stimulation. The findings are inconsistent with the epinephrine hypothesis.

Adrenergic alpha-Antagonists↗
PubMed1999

Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer's disease.

OBJECTIVE: The literature reports considerable variation in the rates of psychiatric morbidity for patients with dementia with Lewy bodies. The authors intended to clarify the frequency of psychiatric morbidity in dementia with Lewy bodies and how it differs from probable Alzheimer's disease. METHOD: The study incorporated two groups--a clinical case register cohort (98 with dementia with Lewy bodies; 92 with Alzheimer's disease) and 80 (40 with dementia with Lewy bodies: 40 with Alzheimer's disease) prospectively studied, neuropathologically confirmed cases. Diagnoses were made by using the McKeith et al. consensus criteria for dementia with Lewy bodies and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Neuropathological diagnoses were made by using the consensus criteria for dementia with Lewy bodies and the Mirra et al. protocol for Alzheimer's disease. RESULTS: The occurrence of psychiatric symptoms was reported over 1 month. Hallucinations, depression, delusions, and delusional misidentification were all significantly higher for patients with dementia with Lewy bodies. The differences in frequency between dementia with Lewy bodies and Alzheimer's disease for auditory and visual hallucinations were especially pronounced for patients with mild cognitive impairment. The presence of psychiatric symptoms at presentation was a better discriminator between dementia with Lewy bodies and Alzheimer's disease than occurrence over the course of dementia. CONCLUSIONS: Delusional misidentification and hallucinations in the early stages of dementia may improve differentiation between patients with dementia with Lewy bodies and those with Alzheimer's disease and have important treatment implications.

Aged↗
PubMed1999

Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies.

BACKGROUND: Following the success of the NINCDS-ADRDA criteria for Alzheimer's disease, groups interested in vascular dementia and dementia with Lewy bodies have now adopted similar criteria. AIMS: To assess whether the validity of these criteria are influenced by the prevalence of mixed pathologies or by the prevalence rate. METHOD: A community based post-mortem study. RESULTS: Mixed pathologies were common (33.8%). The high specificities obtained for the CDLB and NINDS-AIREN criteria (1.00 and 0.95, respectively) were associated with low sensitivities (0.22 and 0.43, respectively). Low prevalence and the presence of mixed pathologies had a deleterious effect on positive predictive values. CONCLUSIONS: Current clinical diagnostic criteria are good at detecting pathology per se but not at detecting pure pathology. A large proportion of subjects from the general population fulfilling probable CDLB, probable NINCDS-ADRDA or probable NINDS-AIREN will have mixed pathologies.

Adult↗