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Biomedical subjects

K Fleming

Publications and source records attributed to K Fleming.

At least 37 records · Page 2Linked to original sources

Patterns and associates of hyperphagia in patients with dementia.

This study examined patterns and associates of excessive eating (hyperphagia) in a community-based registry of patients with dementia. From patients enrolled in the Mayo Clinic Alzheimer's Disease Patient Registry (n = 439), 39 were identified with excessive eating reported on the Behavior Symptom Checklist at some time during their illness. They were matched for age, gender, duration of disease, and Global Deterioration Scale (GDS) score to "normal eaters." Annualized weight change was determined based on weight from the 6 months before the evaluation to weight 6 months after the evaluation. Annualized weight change scores were not significantly different between excessive eaters and normal eaters nor between wanderers and nonwanderers. In cross-sectional analysis, univariate modeling suggested age at onset, GDS, and Mini-Mental State Examination score to be significant predictors of excessive eating. Using multivariate logistic model with backward elimination, only age of onset and GDS were retained as associates of excess eating. Rater type also emerged as a significant predictor for excessive eating with family raters reporting this behavior in 16% of patients compared to 5% for other raters. In chi-square analyses excessive eating was associated with greater frequency of wandering, unpredictable behavior, inappropriate dressing, inappropriate bodily concerns, and threatening self-harm. Associates of excess eating were subsequently examined separately in wandering and nonwandering excessive eaters. Logistic modeling suggested that among nonwanderers, patients who were younger but more severely demented were likely to have reported excessive eating. These results suggest hyperphagia to be present in approximately 10% of a community-based cohort of patients with dementia and associated with increasing functional decline. Excessive eating does not appear to arise from memory dysfunction, but for wanderers may result from needing increased caloric intake because of increased activity levels. Thus, for wandering excessive eaters, it may be appropriate to endure the eating to ensure appropriate caloric intake. Nonwandering excessive eaters were younger, had greater dementia severity, and had more unpredictable behavior. They may have dementia with prominent frontal lobe involvement and may respond to any food stimulus respective of hunger. Restricting food exposure may be an effective management intervention for them.

Aged↗

Visuospatial working memory in patients with schizophrenia.

Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The "scratch pad's" passive visual store--responsible for the temporary retention of visual material--was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem--specialized for retaining the temporal properties--was explored through visual block span. To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia.

Adult↗

Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: a comparison of the alkaline phosphatase and immunofluorescent techniques.

BACKGROUND: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. METHOD: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. PATIENTS: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. RESULTS: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. CONCLUSION: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient, related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

Adult↗

Antineutrophil cytoplasmic antibodies in chronic liver diseases: prevalence, titre, specificity and IgG subclass.

BACKGROUND/AIMS: Antineutrophil cytoplasmic antibodies are reported in patients with chronic liver disease, but controversy exists about their prevalence and specificity. We aimed to find the prevalence and specificity of antineutrophil cytoplasmic antibodies in chronic liver diseases by determination of antineutrophil cytoplasmic antibody titre and IgG subclass. METHODS: One hundred and eight-four sera were studied: 63 primary sclerosing cholangitis, 28 autoimmune hepatitis, 34 primary biliary cirrhosis, 12 alcoholic liver disease, five large duct obstruction, four haemochromatosis, one chronic cholestatic syndrome, one cryptogenic cirrhosis and 36 normal individuals. Antineutrophil cytoplasmic antibodies were detected on alcohol-fixed neutrophils using an alkaline phosphatase technique. The IgG subclass of antineutrophil cytoplasmic antibodies was determined using monoclonal antibodies: HP 6001 for IgG1, HP 6002 for IgG2, HP 6050 for IgG3 and SK 44 for IgG4 (Sigma Immunochemicals). RESULTS: Antineutrophil cytoplasmic antibodies were detected in 65% of primary sclerosing cholangitis patients at a serum dilution of 1:5, dropping to 49% at 1:50. For autoimmune hepatitis, antineutrophil cytoplasmic antibodies were detected in 49% at 1:5, dropping to 11% at 1:50. Only 6% of primary biliary cirrhosis patients were antineutrophil cytoplasmic antibody-positive at 1:5, dropping to 3% at 1:50. All other controls were antineutrophil cytoplasmic antibody negative at 1:5. The presence of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis correlated with involvement of the intra- and extrahepatic biliary tree (p = 0.016, Fisher's exact test), but no other clinical parameters. Determination of the IgG subclass of antineutrophil cytoplasmic antibody in 33 primary sclerosing cholangitis and 11 autoimmune hepatitis patients revealed a predominance of IgG1 in both groups (94% and 82% of all IgG antineutrophil cytoplasmic antibodies, respectively), with a similar distribution of IgG2, IgG3 and IgG4 antineutrophil cytoplasmic antibodies between the groups. CONCLUSIONS: Antineutrophil cytoplasmic antibodies are specific to the autoimmune liver diseases, particularly primary sclerosing cholangitis and autoimmune hepatitis. Titres are highest in primary sclerosing cholangitis, with a diagnostic sensitivity of 49% and specificity of 89% at 1:50, making it a useful serological marker for this disease. The lack of correlation with any marker of activity and the association of antineutrophil cytoplasmic antibody with extent of biliary tract involvement suggest that antineutrophil cytoplasmic antibodies arises as a result of the disease or related process rather than being a cause of it. The detection of antineutrophil cytoplasmic antibodies in autoimmune hepatitis, together with a similar IgG subclass distribution of primary sclerosing cholangitis and autoimmune hepatitis antineutrophil cytoplasmic antibodies, may reflect similar mechanisms of immune regulation and a possible overlap syndrome. Future identification of the antigens against which this antineutrophil cytoplasmic antibody are directed should help to clarify this point, as well as allowing the development of a more sensitive and specific serological test for diagnostic purposes.

Adult↗

Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm.

Recent studies of schizophrenia have implicated deficits in processes related to working memory, but the cognitive features of these deficits have been incompletely characterized. We used a modified Brown-Peterson paradigm to compare working memory in patients with schizophrenia and in normal control subjects. Distractor conditions differed in processing demand, increasing in complexity from no distractor to counting backwards (serial threes). We found significant effects of group, of distractor condition, and of a group x distractor condition interaction. The significant interaction was the result of a more rapid decline in the performance of schizophrenic patients with concurrent articulation. In addition, the schizophrenic group also made significantly more intrusion errors. The study suggests that schizophrenic patients exhibit dysfunction of the verbal working memory system due to a diminution in its overall processing resources.

Adult↗

The Healthy Eating Index: design and applications.

OBJECTIVE: To develop an index of overall diet quality. DESIGN: The Healthy Eating Index (HEI) was developed based on a 10-component system of five food groups, four nutrients, and a measure of variety in food intake. Each of the 10 components has a score ranging from 0 to 10, so the total possible index score is 100. METHODS/SUBJECTS: Data from the 1989 and 1990 Continuing Survey of Food Intake by Individuals were used to analyze the HEI for a representative sample of the US population. STATISTICAL ANALYSES PERFORMED: Frequencies, correlation coefficients, means. RESULTS: The mean HEI was 63.9; most people scored neither very high nor very low. No one component of the index dominated the HEI score. People were most likely to do poorly in the fruit, saturated fat, grains, vegetable, and total fat categories. The HEI correlated positively and significantly with most nutrients; as the total HEI increased, intake for a range of nutrients also increased. DISCUSSION/CONCLUSIONS: The HEI is a useful index of overall diet quality of the consumer. The US Department of Agriculture will use the HEI to monitor changes in dietary intake over time and as the basis of nutrition promotion activities for the population.

Adolescent↗

Backward masking performance during and after manic episodes.

In a longitudinal design, 16 inpatients with bipolar mood disorder and 16 normal control participants were administered measures of backward masking. Bipolar inpatients were assessed while actively manic and again following manic episode. Clinical state was determined from ratings on an expanded version of the Brief Psychiatric Rating Scale. Two backward masking paradigms were used: (a) a staircase method, which yielded a critical interstimulus interval, and (b) set interstimulus intervals, which provided a masking function. Bipolar patients performed significantly worse than the normal controls at both sessions, but the Group X Session interaction was nonsignificant with both masking procedures. The masking performance deficit for the manic patients was not related to the presence of psychotic symptoms but seemed to be partially associated with lithium treatment. The results indicate that the impaired masking performance of manic patients is not strictly limited to the period of the manic episode.

Adolescent↗

Adhesion molecule expression in primary sclerosing cholangitis and primary biliary cirrhosis.

There are conflicting reports regarding intercellular adhesion molecule-1 (ICAM-1) expression in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Expression of adhesion molecules ICAM-1, lymphocyte adhesion molecule-1 (LFA-1), vascular cell adhesion molecule (VCAM), and E-selectin was examined together with HLA-DR in 16 liver biopsy specimens showing PSC and 12 specimens showing PBC. These were compared with biopsy specimens showing large duct obstruction (n = 7), chronic active hepatitis (n = 4), alcoholic liver disease (n = 4), and normal liver histological results (n = 5). ICAM-1 was detected on biliary epithelium in five of seven PSC specimens of histological stage 3 or 4, but not in nine early PSC specimens or in specimens from disease controls. In PBC, ICAM-1 was positive on three of 12 cases, two stage 2, and one stage 3. Nine of 16 PSC specimens (three of nine early, six of seven late disease) and six of 10 PBC specimens (three early, three late disease) were positive for HLA-DR. LFA-1 stained infiltrating inflammatory cells in PSC, PBC, and disease controls. In conclusion, ICAM-1 expression on biliary epithelium in PSC occurs mainly in late stage disease and therefore may be secondary to previous events inducing inflammation rather than of primary pathogenic importance. ICAM-1 expression in PBC is less common and not clearly associated with a particular disorder. Previous reports of ICAM-1 prevalence may have been biased towards end stage, pre-transplantation biopsy specimens.

Cell Adhesion Molecules↗

Neuropsychological effects of amphetamine may correlate with personality characteristics.

Although the stimulant properties of amphetamine are well established, its effects on cognitive test performance in unfatigued normal adults are poorly documented. Seventeen healthy individuals received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study. Neurocognitive tests, motor tests, and behavioral observations were performed. Personality information, based on the Tridimensional Personality Questionnaire (TPQ) was also gathered to explore a relationship between personality factors and response to the stimulant. With the exception of two measures of reaction time, there were no overall changes in performance on measures of memory or other cognitive functions. There was decreased reaction time on the continuous performance task (CPT) and increased accuracy of performance under minimal delay conditions in the spatial delay response task while subjects were receiving amphetamine. In addition, the novelty-seeking subscale was found to correlate with a measure of verbal memory. Individuals with higher scores on the novelty-seeking scale deteriorated under amphetamine, while those who had lower scores improved. These results suggest that some cognitive abilities of persons who may have relatively high dopaminergic tone are disrupted by amphetamine, while those with relatively low dopaminergic tone may have their performance enhanced.

Administration, Oral↗

Anonymous HIV testing: the impact of availability on demand in Arizona.

The purpose of this study was to evaluate the impact of anonymous testing availability on human immunodeficiency virus (HIV) test demand in Arizona. Testing patterns before and after the introduction of anonymous testing were compared. Client knowledge of new test policy and delay in testing until an anonymous option was available were assessed. Test numbers among men who have sex with men showed a statistically significant increase after introduction of an anonymous testing option. Arizona continues to maintain anonymous testing availability. Public health agencies should consider how test policy may influence people's HIV test decisions.

AIDS Serodiagnosis↗

Inappropriate expression of blood group antigens in hepatic allografts.

We examined the expression of blood group antigens of the ABO, Lewis and Kell antigen systems using monoclonal antibodies and immunohistochemical study on 42 liver allograft specimens from 33 patients who underwent liver transplantation between 1986 and 1991 to learn whether altered blood group antigen expression might have a bearing on the immunopathogenesis of transplant rejection. Specimens were obtained at intervals of 0 days to 3 yr after transplant; they yielded the following histological diagnoses; time zero (n = 4), acute rejection (n = 4), pure cholestasis (n = 4), biliary obstruction (n = 4), early chronic rejection (n = 4), end-stage chronic rejection (n = 15) and miscellaneous late posttransplant biopsies (n = 7). Aberrant expression of blood group antigens was observed in 5 of 15 patients with chronic rejection. Two transplants into the same group O patient showed aberrant expression of AB antigens on hepatocytes, with a canalicular pattern, in group O-transplanted livers. In all three cases in which a group O liver was transplanted into a group A recipient and histological signs of chronic rejection were present, antibody staining showed acquisition of recipient blood phenotype by the donor liver bile ducts, endothelium or both. Aberrant expression of ABO antigens was seen only in chronic rejection. In seven cases we noted canalicular staining of periportal hepatocytes with the Lewis antibodies, normally confined to ducts and ductules. This was associated with severe cholestasis in six of the seven cases and may have represented early ductular metaplasia. These changes in carbohydrate cell surface phenotype may play a role in regulation of hepatic allograft susceptibility to immune-mediated damage.

Adolescent↗

Human papillomavirus type 6-induced condylomata: an unusual complication of intertrigo.

A 79-year-old virgo intacta presented with a 20-year-history of intertrigo, and a 3-month history of superimposed warty masses beneath both breasts and in the groin and perianal areas. There was no evidence of immunosuppression. Histology of the warty lesions showed squamous papillomata, with evidence of wart virus infection. Human papillomavirus (HPV) type 6 was identified by in situ DNA hybridization, in the submammary lesions. This is an unusual manifestation of both intertrigo and wart virus infection. HPV-6 is classically found in anogenital warts. We assume that these warts were acquired by a non-venereal route and/or by congenital infection some 78 years ago. We suggest that it is the warm, moist environment, rather than the specific site, which encourages HPV-6 to flourish.

Aged↗

Inappropriate expression of blood group antigens on biliary and colonic epithelia in primary sclerosing cholangitis.

The distribution of carbohydrate antigens of the ABO, Lewis, and Kell systems was examined in biliary and colonic epithelial of 11 patients with primary sclerosing cholangitis (PSC) using a panel of 11 monoclonal antibodies. Controls consisted of 27 liver biopsy specimens (11 normal, six alcoholic liver disease, five extrahepatic obstruction, and five primary biliary cirrhosis) and 24 colonic biopsy specimens (six normal, four Crohn's disease, and 14 ulcerative colitis). There was inappropriate staining with anti-A (four of six, 66%) and anti-B (nine of 11, 81%) in biliary epithelium of PSC patients compared with normal and disease controls. Expression of Lewis antigens was increased in patients with cholestatic liver disease. Ninety one per cent of PSC patients showed a similar pattern of inappropriate staining by anti-A and anti-B antibodies in colonic epithelium compared with 33% of normal and 42% of inflammatory bowel disease controls. There is inappropriate expression of A and B carbohydrate antigens in biliary and colonic epithelium in PSC. Whether these oncofetal antigens are implicated in the pathogenesis of this condition is discussed.

Adult↗

Left turning (swivel) in manic patients.

Nineteen bipolar inpatients in manic episodes and 19 normal control subjects were tested on a two-button task which required turning (swiveling) 180 degrees to collect coin-reinforcers. Significantly more right-handed (8/16) manic patients turned left (consistently 16 times to collect reinforcement) than right-handed normal controls (1/15), most of whom turned consistently right 16 times. Right-handed manic patients were also significantly slower with both hands on a motor sequencing task (Pin Test) than the normal controls. Left hemi-spatial preference may be linked to asymmetric striatal dopaminergic activity common to all psychoses.

Adult↗

Probe-detection times during the reading of easy and difficult text.

Two experiments were conducted to determine the effects of text difficulty on cognitive capacity demands. In Experiment 1, subjects read easy and difficult text when a secondary task was either present or absent. Text was presented one word at a time, and rereading was prevented by erasing each word after it had been read. Prior studies have indicated that cognitive capacity demands decrease as text difficulty increases (e.g., Britton, Westbrook, & Holdredge, 1978). In contrast to this, the main results of Experiment 1 revealed shorter visual-probe-detection times during the reading of easy text than during the reading of difficult text. Analyses of word-reading times showed that difficult text was read slower than easy text, irrespective of probe application. Experiment 2 compared visual-probe detection with auditory-probe detection. The results again showed shorter probe reaction times during the reading of easy text than during the reading of difficult text, irrespective of probe type. There were, however, effects of probe type on the reading time of words following the visual probe. The results were taken as evidence that the reading of difficult text requires more capacity than the reading of easy text and that probes may incur modality-specific and modality-independent capacity demands.

Adult↗

In situ hybridization studies of adenoviral infections of the lung and their relationship to follicular bronchiectasis.

We have used a probe against the adenovirus genome to study cultured epithelial cells specifically infected with various types of adenovirus and Graham 293 cells, which contain few copy numbers of a fraction of the adenovirus genome. We have also examined lung tissue obtained from three cases of acute adenovirus pneumonia, two cases of adenovirus pneumonia that had passed through the acute phase, and nine cases of follicular bronchiectasis. Our purpose was to determine whether the probe was effective in detecting a wide variety of adenovirus types, to determine whether it could detect adenovirus in lung tissue that had been fixed and stored in paraffin blocks for several years, and to test the hypothesis that adenovirus was an important cause of follicular bronchiectasis. The results show that the probe was able to detect adenovirus from Genera B1, B2, C, D, and E with a sensitivity of 5 to 10 copies/cell. The probe also detected adenovirus in 14 of 14 slides from three cases of acute disease, but failed to obtain a positive result in the cases examined after an acute infection or in any of the cases of follicular bronchiectasis. We conclude that the in situ hybridization technique is useful in the investigation of active adenovirus infection of the lung. The failure to show that the virus persisted in the chronic respiratory disease that follows adenovirus infection, or that it was present in cases of follicular bronchiectasis could be due to either a true absence, or to its presence in a latent form that is below the level of sensitivity of this technique.

Adenoviridae Infections↗

Anti-neutrophil nuclear antibody in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis.

We have previously described circulating autoantibodies to a portal tract antigen in patients with primary sclerosing cholangitis. In this study the antigen has been shown by double-labelling studies to be specifically located in the nuclei of tissue neutrophils. Using isolated peripheral blood neutrophils and an immunoperoxidase technique, anti-neutrophil nuclear antibody (ANNA) was found in the serum of 84% of patients with primary sclerosing cholangitis (PSC: n = 32) with a median titre of 1/1000 and a peak titre of 1/500,000. ANNA was also detected in 86% of patients with inflammatory bowel disease alone (IBD: n = 76) with a median titre of 1/10 and a peak titre of 1/10,000. In contrast, only 12% of controls had ANNA, and in none was the titre greater than 1/10. In PSC the ANNA titre correlated with the serum aspartate transaminase concentration, suggesting that it is related to disease activity. In IBD the titre of ANNA was significantly higher in patients with recently active disease. There was no significant difference between the titres seen in ulcerative colitis and Crohn's disease. ANNA was not associated with neutropaenia. The results provide further evidence of involvement of autoimmune mechanisms in inflammatory bowel disease and primary sclerosing cholangitis.

Adolescent↗