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Biomedical subjects

T Nichols

Publications and source records attributed to T Nichols.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mortality in people taking selegiline: observational study.

OBJECTIVE: To evaluate mortality among patients with Parkinson's disease receiving different treatment. DESIGN: Cohort study based on computerised medical records. SETTING: UK General Practice Research Database. SUBJECTS: 12 621 patients aged between 35 and 90 years who had received a prescription for an antiparkinsonian drug, whether or not a diagnosis of Parkinson's disease had been recorded. Patients prescribed an antipsychotic drug before or at the same time as their first antiparkinsonian drug or before age 35 were excluded to avoid including drug-induced Parkinsonism. MAIN OUTCOME MEASURE: Death from any cause. RESULTS: 1720 deaths occurred during 14 000 person-years of observation. There was a non-significant 11% (95% confidence interval 0% to 23%) increase in the risk of death associated with taking selegiline either alone or in combination with levodopa. The death rate was higher among younger patients (aged under 80 years) and those with a recorded diagnosis of Parkinson's disease taking selegiline alone. CONCLUSIONS: The results are compatible with a small excess mortality in people taking selegiline and suggest a larger excess in patients under 80 years of age and those with a confirmed diagnosis of Parkinson's disease taking selegiline without levodopa.

Adult↗
PubMed1998

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain.

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.

Adult↗
PubMed1997

PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia.

Changes in regional cerebral blood flow (rCBF), associated with performance of an auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R schizophrenic patients and eight pair-wise matched normal controls. Four positron emission tomography (PET) scans, using the [15O]-H2O technique, were acquired: two while subjects fixated a cross hair and two while performing a verbal free-recall supraspan memory task. Task performance showed typical patterns of recency and primacy effects in both groups; however, patients performed more poorly than controls on the primary (working) memory aspect of the task. Regions showing rCBF changes overlapped in both groups and were similar to those seen in previous studies of normals; however, patients had smaller increases in rCBF than controls in frontal and superior temporal cortical regions bilaterally. Our results suggest that remitted patients with schizophrenia demonstrate impairments of capacity-limited information processing, which may be related to metabolic dysfunction within a distributed network of brain structures, including the prefrontal and temporal cortical regions; however, dysfunction limited to the frontal cortex cannot be ruled out by the results of this experiment.

Adult↗
PubMed1997

Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance.

OBJECTIVE: Attentional deficits are a prominent aspect of cognitive dysfunction in schizophrenia. The anterior cingulate gyrus is proposed to be an important component of frontal attentional control systems. Structural and functional abnormalities have been reported in this region in schizophrenia, but their relationship to attentional deficits is unknown. The authors investigated the function of the anterior cingulate gyrus and the related neural systems that are associated with selective attention in patients with schizophrenia. METHOD: While subjects performed multiple blocks of a single-trial Stroop task, [15O]H2O positron emission tomography scans were obtained. Fourteen patients with schizophrenia were compared with 15 normal subjects matched for age, gender, and parental education. RESULTS: The patients with schizophrenia responded at the same rate but made more errors in color naming during the color-incongruent condition. Consistent with the authors' hypothesis, patients with schizophrenia showed significantly less anterior cingulate gyrus activation while naming the color of color-incongruent stimuli. CONCLUSIONS: Patients with schizophrenia fail to activate the anterior cingulate gyrus during selective attention performance. This finding adds to the understanding of the functional significance of the structural and metabolic abnormalities in schizophrenia that have been previously reported in this region of the brain.

Adult↗
PubMed1997

A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis.

OBJECTIVES: The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis. METHODS: Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit. RESULTS: At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated. CONCLUSIONS: The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone.

Administration, Oral↗
PubMed1996

Alterations in functional neuroanatomical connectivity in Alzheimer's disease. Positron emission tomography of auditory verbal short-term memory.

Conscious recall of past events which have specific temporal and spatial contexts, termed episodic memory, is mediated by a system of interrelated brain regions. In Alzheimer's disease (AD) this system breaks down, resulting in an inability to recall events from the immediate past. Studies of normal human auditory-verbal short-term memory suggest that the brain system underlying these processes has distinct components, and the present study utilized the methods of functional brain mapping to determine the nature and extent of the breakdown that occurs in AD. Using subtraction techniques of PET-acquired images of regional cerebral blood flow we demonstrate that AD patients show a compensatory hyperactivation of various regions of cerebral cortex normally involved in these tasks, as well as activation of cortical areas not activated by normal elderly subjects. These results provide clear evidence of functional plasticity in the AD patient's brain even if those changes do not result in normal memory function.

Aged↗
PubMed1996

Functional connectivity in auditory-verbal short-term memory in Alzheimer's disease.

Alzheimer's disease (AD) patients show normal patterns of regional cerebral blood flow during performance of subspan verbal memory tasks, but appear to allocate new brain regions when performing supraspan recall tasks. To understand the relationships among these interconnected brain regions, their functional connectivity was considered using principal components analysis (PCA). AD patients and controls were scanned in four conditions: visual fixation only and visual fixation with one-word recall, three-word recall, and eight-word recall. When applied to the data from the three recall task conditions (i.e., eliminating fixation), PCA revealed a significant first component accounting for 75.8% of the variance in the control data and 66.8% of the variance in the patient data. The one-word recall condition had a high positive component score, and the eight-word condition a high negative score. The correlations of individual voxels on this factor (i.e., spatial modes) were very similar between the patients and the controls. The overall similarity in the results of the PCAs between the patients and the controls suggests that they have similar functional connectivity. This would suggest that, at least in the early course of the dementia, the functional CNS organization of verbal memory systems remains normal.

Aged↗
PubMed1996

Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease.

Conscious recall of past events that have specific temporal and spatial contexts, termed episodic memory, is mediated by a system of interrelated brain regions. In Alzheimer's disease (AD) this system breaks down, resulting in an inability to recall events from the immediate past. Using subtraction techniques with PET-acquired images of regional cerebral blood flow, we demonstrate that AD patients show a greater activation of regions of cerebral cortex normally involved in auditory-verbal memory, as well as activation of cortical areas not activated by normal elderly subjects. These results provide clear evidence of functional plasticity in the AD patient's brain even if those changes do not result in normal memory function, and provide insights into the mechanism by which the AD brain attempts to compensate for neurodegeneration.

Aged↗
PubMed1996

An experimental model for testing von Willebrand factor function: successful SLA-matched crossed bone marrow transplantations between normal and von Willebrand pigs.

To assess the relative in vivo roles of von Willebrand factor (vWF) of different origins, we performed crossed bone marrow transplantations (BMTs) among normal pigs and pigs with the von Willebrand disease(vWF). The two groups were fully compatible immunologically according to typing by swine leukocyte antigen (SLA). After total-body irradiation (8-10 Gy), all pigs received 0.5X10(9) to 10(10)/kg mononuclear bone marrow cells without any immunosuppression. The nadir of aplasia occurred between days 5 and 7 after irradiation (white blood cell [WBC] count 0.6X10(9)/L, platelet [Plt] count 76X10(9)/L. Three weeks after the graft, WBC and Plt counts had returned to normal levels. Animals were followed for at lease 50 days, during which no bone marrow rejection occurred; no evidence of graft-vs-host disease (GVHD) was observed. Each BMT was confirmed by karyotype analysis. In the six homozygous pigs with vWD grafted with normal marrow, platelet vWF antigen (vWFAg) and platelet vWF activity rose from <3 to 450 U/dl with a normal multimeric pattern; plasma vF increases slightly. No correction of bleeding time was observed. In the five normal pigs grafted with bone marrow form pigs with vWD, platelet vWFAg and platelet vWF activity decreased from >100 U/dl to undetectable levels; bleeding time and plasma vWFAg remained unchanged. A derivative of normal porcine plasma, a concentrate containing factor VIII and vWF, was infused into a homozygous vWD pig before and after BMT from a normal pig. Co correction of bleeding time was obtained, even though plasma nd platelet vWFAg levels were normal. W concluded that crossed BMT among SLA-identical pigs is a feasible model of studying the synthesis and the roles of vWF in hemostasis and thrombosis.

Animals↗
PubMed1986

Characterization of the binding and internalization of tetanus toxin in a neuroblastoma hybrid cell line.

Tetanus toxin is known to bind neuronal tissue selectively. To study the interactions of this potent neurotoxin in an intact cell system, the binding of 125I-tetanus toxin was characterized in a neuroblastoma retina hybrid cell line, N18-RE-105. The binding of 125I-tetanus toxin to membranes prepared from N18-RE-105 cells showed many similarities to the interactions of 125I-toxin with rat synaptic membranes. The binding was decreased with increasing temperature, ionic strength, and pH. 125I-Toxin bound to membranes with high affinity: KD = 0.62 +/- 0.05 nM; Bmax = 196 +/- 45 pmol/mg protein. Quantitative thin-layer chromatography and acid-degradation analysis revealed that N18-RE-105 cells contained polysialogangliosides GD1a and GT1b in high concentrations. An assay was developed to quantitate surface-bound and internalized 125I-tetanus toxin by exploiting the observation that surface-bound 125I-toxin is susceptible to pronase digestion. When cells were incubated with 125I-tetanus toxin at 0 degree C, all of the bound 125I-toxin could be degraded with pronase. In contrast, when the incubations were performed at 37 degrees C, within 10 min about 50% of the total cell-associated 125I-toxin was pronase-resistant. Temperature pulse experiments demonstrated that 125I-tetanus toxin that was bound to cells at 0 degree C rapidly disappeared from the surface when the cells were warmed to 37 degrees C, as revealed by the appearance of pronase-resistant radioactivity. This internalization was sensitive to metabolic inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Control of upper gastrointestinal bleeding with a microcrystalline collagen hemostat.

A microcrystalline collagen hemostat (MCH) widely used in general surgery was tested in the control of bleeding from experimentally produced gastric ulcers. Five dogs had a gastrotomy and were given heparin. Using the standard "ulcer maker," three sets of three ulcers were made in the gastric mucosa of each animal. Blood from each ulcer was collected for a 5-min period to allow for stabilization of bleeding. MCH powder or slurry or no MCH was placed directly on one ulcer of each set in random order. The bleeding rate for the next 10 min was measured. Mean decrements in the bleeding rate for slurry MCH and dry MCH-treated ulcers were 87% and 81%, respectively, compared with 51% for controls, P less than 0.05. Twelve MCH-treated ulcers, but no control ulcer, stopped bleeding completely, P less than 0.01. Preliminary observations show that MCH slurry can be applied through an endoscope and may be hemostatically effective in man. MCH may have a role in the endoscopic control of gastrointestinal bleeding.

Animals↗
PubMed1980

A new selective medium for Streptococcus pneumoniae.

The development and evaluation of a new selective medium for Streptococcus pneumoniae is described. It is shown that the new medium (crystal violet-nalidixic acid-gentamicin agar:CVNG) is highly selective for Strep. pneumoniae in sputum specimens containing other organisms and is also sensitive, being only marginally inhibitory when compared to Columbia blood agar. The advantages of the medium in routine use are presented, based on 206 consecutive sputum specimens. It is concluded that CVNG medum is a useful adjunct to sputum bacteriology, especially in combination with digestion of the sputum samples by Cleland's reagent.

Agar↗
PubMed1979

Caroli's disease. Clinical presentation simulating carcinoma of the pancreas.

A patient with Caroli's disease (intrahepatic biliary duct dilatation), presenting when he was middle-aged with symptoms of painless jaundice and weight loss suggesting carcinoma of the head of the pancreas, is described. The world's literature of Caroli's disease is reviewed and this patient's unusual presentation is put into perspective.

Age Factors↗
PubMed1979

Compartment syndrome of the interosseous muscles: early recognition and treatment.

A compartment syndrome of the interosseous muscles can be a challenging diagnosis as there is generally no neurovascular compromise to the digits involved. The most sensitive clinical sign is pain with passive motion at the metacarpal phalangeal joint of the involved digit. In this report, a 31-year-old man developed a compartment syndrome of the first, second, and third dorsal interosseous muscles following an injection of heroin in the "snuffbox" area. Compartmental tissue pressure measurements were 80, 75, and 55 mmHg respectively, and were a significant aid in the early diagnosis as well as management.

Adult↗
PubMed1979

Pseudosarcoma of the esophagus. Three new cases and review of the literature.

Three newly found patients with an esophageal pseudosarcoma are described. The features of this unusual polypoid tumor are reviewed based on these three patients and 21 additional reported patients. The origin of the sarcomatous element as a metaplastic reaction to the underlying carcinoma is discussed. The exuberant growth may present with obstructive symptoms earlier than the usual carcinoma of the esophagus, permitting curative surgical resection in some patients.

Aged↗