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Biomedical subjects

L Fairbanks

Publications and source records attributed to L Fairbanks.

At least 19 recordsLinked to original sources

Lactate threshold does not influence metabolic responses during exercise in cyclists.

The purpose of this study was to compare plasma markers of metabolic stress and other physiological parameters during prolonged endurance exercise of different intensity in trained subjects possessing a "high" or "low" lactate threshold (LT) expressed as a percentage (%) of peak power output (PPO). Fifteen trained male cyclists completed an incremental exercise test for determination of PPO and the LT (% PPO). Each subject then completed a 90-min and 20-min exercise trial at an intensity representing 75 and 85 % of PPO, respectively. Blood lactate (La), as well as plasma hypoxanthine (Hx) and uric acid (UA) were measured during each exercise trial. The responses in two groups, one (n = 8) with a LT approximately 65 % PPO (LT (low)), the other group (n = 7) with a LT approximately 75 % (LT (high)) (p < 0.01), were then compared. With the exception of UA, La and Hx increased significantly (p < 0.01) throughout each exercise trial compared to rest. However, there were no significant differences in each trial between the two groups of cyclists. There were also no significant differences in the other physiological parameters in each exercise trial between the subjects in LT (low) and LT (high). This study demonstrates that in trained cyclists homogeneous in terms of PPO, plasma markers of metabolic demand during prolonged exercise are not influenced by the LT when measured in an incremental exercise test.

Adult↗

Evaluation of uridine metabolism in human and animal spermatozoa.

The objective of this study was to elucidate the role of uridine for spermatozoa, since this pyrimidine nucleoside was found in millimolar concentration in human seminal plasma. Here, the degradative activity of uridine-phosphorylase [EC 2.4.2.3] and the salvage activity of uridine kinase [EC 2.7.1.48] were detected in human spermatozoa. HPLC analysis depicted the uptake of exogeneous 14C-labelled adenine, but not of uridine and of hypoxanthine, into nucleotide pools of boar spermatozoa. On addition of uridine, the computer-assisted semen analysis (CASA) of human cells revealed a reduction of the percentage of motile spermatozoa in contrast to an elevation of some velocity parameters. It is concluded that exogeneous uridine could function as suppressor for early capacitation and as a substrate for phosphorolysis, if ribose is needed, rather than to satisfy a demand for intracellular pyrimidine nucleotides.

Adenine↗

Neuropsychological function in nondemented carriers of presenilin-1 mutations.

BACKGROUND: Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD). OBJECTIVE: To investigate these observations by the study of persons at risk for autosomal dominant forms of AD. METHODS: Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE epsilon4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs. RESULTS: MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE epsilon4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores. CONCLUSIONS: This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE epsilon4 allele did not demonstrate large influences on neuropsychological performance.

Adolescent↗

How reliable is the allopurinol load in detecting carriers for ornithine transcarbamylase deficiency?

The allopurinol test aims to distinguish carriers and noncarriers for ornithine transcarbamylase (OTC) deficiency. We have evaluated the reliability of the test in at-risk females of known genotype. Results based on urine orotidine and/or orotic acid measurement were compared in terms of sensitivity and specificity. Retrospectively, we analysed the results of allopurinol tests in 42 women (22 confirmed heterozygotes and 20 noncarriers) from 23 pedigrees at risk of being carriers for OTC deficiency. Using a cut-off of 2 standard deviations above the mean of controls, the highest sensitivity (91%) was given by orotidine alone or in combination with orotic acid, but specificity was only 70% and 65%, respectively. We conclude that the value of the allopurinol test for detecting OTC carriers in at-risk females is limited. This needs to be recognized when counselling families. The test still has a role as a safe, quick, noninvasive screen of individuals at risk, but test results in possible carriers should be interpreted with caution. In the absence of other supportive evidence, confirmation by mutation analysis is required.

Adult↗

Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population.

The enzyme inosine triphosphate pyrophosphatase (ITPase) catalyses the pyrophosphohydrolysis of ITP to IMP. ITPase deficiency is a clinically benign autosomal recessive condition characterised by the abnormal accumulation of ITP in erythrocytes. A deficiency of ITPase may predict adverse reactions to therapy with the thiopurine drug 6-mercaptopurine and its prodrug azathioprine. In this study, we examine the frequencies of ITPA polymorphisms in 100 healthy Japanese individuals. The allele frequency of the 94C > A variant in the Japanese sample was 0.135 (Caucasian allele frequency 0.06). The IV2 + 21A > C polymorphism was not found in Japanese (Caucasian allele frequency 0.130). Allele frequencies of the 138G > A, 561G > A and 708G > A polymorphisms were 0.57, 0.18 and 0.06 respectively in the Japanese population, and with the exception of the 138G > A polymorphism, similar to allele frequencies in Caucasians.

Alleles↗

Genetic determinants of the pre- and post-azathioprine therapy thiopurine methyltransferase activity phenotype.

Thiopurine drug therapy has been reported to lead to a variable increase in red cell TPMT activity that may alter effective dose and therapeutic outcome. The aim of this study was to correlate Variable Number Tandem Repeat (VNTR) in the promoter region of the TPMT gene with induction of red cell TPMT activity in patients treated with azathioprine (AZA). In 58 patients, TPMT activity measured at 3 months was not significantly induced on average above pre-therapy levels. Individual patients showed variation in TPMT activity pre- and post-AZA therapy, however changes in TPMT activity were not predicted by VNTR configuration. In conclusion, TPMT promoter VNTRs are unlikely to play a significant role in changes in TPMT activity in response to AZA therapy.

Alleles↗

Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.

OBJECTIVES: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer's disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. METHODS: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer's Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. RESULTS: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. CONCLUSION: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.

Activities of Daily Living↗

Endogenous estradiol in elderly individuals: cognitive and noncognitive associations.

OBJECTIVE: To investigate an association between endogenous estradiol (E(2)) levels and cognition and behavior in elderly individuals. PATIENTS: We studied 135 community-based men and women aged 52 to 85 years in urban Bangkok, Thailand; 72 had dementia and 63 did not. MATERIALS AND METHODS: Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria after appropriate investigations. Blood samples for assay were collected in the morning after 6 hours of fasting. Levels of E(2) were measured by radioimmunoassay (double antibody technique). The Thai version of the Mini-Mental State Examination was used to assess cognition; the Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms; and the Functional Assessment Questionnaire was used to assess instrumental activities of daily living. RESULTS: There was no correlation between age and level of E(2) in either men or women. Individuals with lower estrogen levels had more behavioral disturbances (men: r = -0.467, n = 45; P =.001; women: r = -0.384, n = 90; P<.001) and worse cognition (men: r = 0.316, n = 45; P =.03; women: r = 0.243, n = 90; P =.02) and function (men: r = -0.417, n = 45; P =.004; women: r = -0.437, n = 90; P<.001). The threshold level of endogenous E(2) in elderly individuals for the risk of developing dementia was less than 15 pg/mL (<55 pmol/L) in men and less than 1 pg/mL (<4 pmol/L) in women. CONCLUSION: Lower E(2) levels are correlated with poor cognitive, behavioral, and functional status in older individuals.

Aged↗

Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning.

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurological symptomatology including ataxia, developmental delay and spasticity. Patients usually die in the first or second decade of life due to recurrent infections. The only curative treatment is bone marrow transplantation (BMT). We describe a 22-month-old girl who underwent BMT from her HLA-identical brother. Conditioning consisted of busulfan and fludarabine only, resulting in low toxicity and prompt engraftment. At 18 months after BMT, the girl has developed normal immunological functions, and her neurological status has improved.

Antineoplastic Combined Chemotherapy Protocols↗

Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency.

OBJECTIVE: The objective was to evaluate the cognitive, behavioral, and neurodevelopmental function in patients with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) and to compare the findings with those of a case control group of patients without ADA-SCID. STUDY DESIGN: Case-matched pairs of patients with ADA-SCID (n = 11) and patients without ADA-SCID who had undergone bone marrow transplantation were recruited. Subjects were assessed by age-appropriate standard tests of intelligence, behavior, and neurodevelopment. RESULTS: Cognitive ability was not significantly different between the 2 groups, but patients with ADA-SCID showed a significant inverse correlation between deoxyadenosinetrisphosphate levels at diagnosis and IQ (P =.048). Behavioral assessment showed that patients with ADA-SCID functioned in the pathologic range on all domains, whereas mean scores for the control group were within normal limits. Behavioral impairment in patients with ADA-SCID also showed a significant positive correlation with age (P =.026). CONCLUSIONS: Cognitive function in ADA deficiency is adversely affected by the severity of metabolic derangement at the time of diagnosis. In addition, patients with ADA-SCID have significant behavioral abnormalities after transplantation. These defects are not due to the transplant procedure but reflect the systemic nature of ADA deficiency. These findings have important implications for future medical and nonmedical management strategies.

Adenosine Deaminase↗

Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome.

OBJECTIVE: To evaluate the circulating concentrations of the neuroactive steroids in response to an i.v. L-tryptophan (L-TP) challenge across the menstrual cycle in women with premenstrual syndrome (PMS) and in controls. METHOD: An i.v. L-TP challenge was administered eight times during 1 month to five women with prospectively documented PMS and five age- and body mass-matched controls. Progesterone, allopregnanolone pregnenolone and 3alpha-5alpha-tetrahydrocorticosterone were assessed 15 and 0 min before, and at 30, 60 and 90 min after the challenge, across the menstrual cycle. RESULTS: In response to L-TP challenge, only allopregnanolone concentrations were significantly increased across the cycle and this increase was of a greater magnitude in women with PMS. Pregnenolone and 3alpha-5alpha-tetrahydrocorticosterone concentrations were not affected in women with PMS or controls after L-TP challenge. CONCLUSIONS: The data provide evidence for possible interaction between the serotonergic system and the neuroactive steroid, allopregnanolone. Women with PMS demonstrated a more significant increase in allopregnanolone concentrations in response to L-TP challenge, which could be due to an initial low basal serotonergic tone in the luteal phase in the PMS group.

Adult↗

Neuroendocrine response to an intravenous L-tryptophan challenge in women with premenstrual syndrome.

OBJECTIVE: To evaluate the neuroendocrine responses to an intravenous L-tryptophan challenge across the menstrual cycle in women with premenstrual syndrome (PMS) and controls. DESIGN: Controlled clinical study. SETTING: The Clinical Research Center of an academic research environment. PATIENT(S): Women with PMS and healthy volunteers. INTERVENTION(S): An intravenous L-tryptophan challenge was administered two times a week during 1 month to five subjects with prospectively documented PMS and five age- and body mass-matched controls. MAIN OUTCOME MEASURE(S): Whole-blood serotonin, cortisol, and prolactin levels were assessed at the baseline and at 30, 50, 60, 70, 80, and 90 minutes after the challenge. RESULT(S): Whole-blood serotonin response to the L-tryptophan challenge was blunted in the luteal phase of the menstrual cycle in subjects with PMS compared with controls. Cortisol levels differed between groups and cycle phases only at the baseline, with higher baseline cortisol levels during the luteal phase in women with PMS, whereas baseline and postchallenge prolactin levels did not differ between groups. CONCLUSION(S): The present results support previously reported findings of alterations in tryptophan handling in women with PMS. The elevated baseline luteal phase cortisol concentrations in subjects with PMS warrants further investigation.

Adult↗

Cognitive, mood, and functional evaluations using touchscreen technology.

We describe the design and development of the Cognitive Evaluation Protocol (CEP), a computer software program for evaluating cognitive and functional capacities and mood. The program is self-administered by subjects using touchscreen monitors for input. Stimuli in CEP subtests are randomized to reduce the effects of learning on repeated assessments. Findings demonstrate that a) minimum instruction is required for touchscreen use, even for computer-naive subjects; c) both normative subjects and psychiatric patients respond positively to self-administered evaluations; and c) CEP can be used for within-subject repeated evaluations with minimal distortion of results due to practice effects. The CEP Report Generator provides immediate printed performance results and creates a database for long-term digital storage and information use.

Affect↗

Memory, attention, function, and mood among patients with chronic posttraumatic stress disorder.

We report a study of memory, attention, function, and mood among 36 male Vietnam War Veterans suffering from chronic posttraumatic stress disorder (PTSD). PTSD subjects (N = 36) were in good physical health, suffering from moderate depression, and not knowingly suffering from other mental disorders. Control subjects (N = 18) were in good physical health, not knowingly suffering from a mental disorder, and matched with PTSD subject for age, sex, and level of education. Assessment instruments for PTSD subjects included the PostTraumatic Stress Diagnostic Scale (clinician administered), the Hamilton Depression Rating Scale (clinician administered), and the Cognitive Evaluation Protocol (CEP), a touchscreen computer assessment instrument that is self-administered by subjects. CEP was administered twice to PTSD subjects 1 month apart; other instruments were administered at the beginning of the study. Control subjects took CEP once and were administered the Hamilton Depression Rating Scale and the PostTraumatic Stress Diagnostic Scale once. Compared with control subjects, PTSD subjects performed significantly less well on CEP for the three cognitive domains of attention, memory, and function and had highly elevated depression scores. An interaction between depression and memory was found but not with depression and attention. There was no evidence of reduced information processing speed among PTSD subjects. Comparisons between the three assessment instruments showed a high degree of cross-assessment agreement. The findings are consistent with reports that chronic PTSD is associated with compromised memory, attention, and function. The study documents the feasibility of using self-administrated touchscreen computer programs to evaluate and track features of mental disorders.

Affect↗

Quantitative electroencephalographic correlates of psychosis in Alzheimer disease.

OBJECTIVE: We hypothesized that the distinctive neurobiology of Alzheimer disease (AD) with psychosis would be reflected in more severe abnormalities in frontal and temporal regions on quantitative electroencephalography (QEEG). BACKGROUND: Patients with AD and psychosis have more rapid cognitive decline and greater pathologic involvement of frontal and temporal cortex than AD patients without psychotic features. METHOD: We evaluated brain function using QEEG in a group of 44 patients who had a diagnosis of probable or possible AD. All patients were administered the Mini-Mental State Examination and the Neuropsychiatric Inventory to assess psychiatric symptoms, including the presence of hallucinations and delusions. Absolute and relative power in patients with and without psychosis were compared to determine if there were regional or global QEEG differences in these two groups. RESULTS: Patients with psychosis showed greater overall absolute and relative delta power but no regional predominance of slowing compared with those without psychosis. Those with psychosis had a concomitant decrease in relative alpha power. These differences remained after adjustment for different dementia severity in the two groups. CONCLUSIONS: This finding suggests more severe brain dysfunction in patients with psychosis than in those with similar levels of cognitive impairment but without psychosis. The QEEG abnormalities were not regionally specific and involved all areas assessed.

Aged↗

Motor, cognitive, and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson disease.

OBJECTIVE: To evaluate the effects of ventroposterior pallidotomy on motor disability and on behavior and cognition in patients with medically intractable idiopathic Parkinson disease. DESIGN: Detailed motor testing both while receiving and discontinuing levodopa medication, posturography, and neurocognitive and behavioral assessments were performed before and 3 to 6 months after unilateral ventroposterior pallidotomy. SETTING: University-based movement disorder program. PATIENTS: Thirty-two patients without dementia with medically refractory idiopathic Parkinson disease were studied. MAIN OUTCOME MEASURES: Motor function and disability were measured using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and the Schwab and England Activities of Daily Living Scale. Dynamic balance was measured by sway (amplitude and velocity) using the Chattecx Balance System. Detailed cognitive and behavioral assessments were also performed both before and after surgery. RESULTS: Eighty-three percent of patients experienced improvement of their total Unified Parkinson's Disease Rating Scale score at 3 to 6 months after surgery. Significant improvements were also seen in the contralateral Unified Parkinson's Disease Rating Scale motor subscore (78%) as well as in the contralateral Unified Parkinson's Disease Rating Scale total score both during the on and off period (78% and 79%, respectively). The Hoehn and Yahr stage, Schwab and England Activities of Daily Living Scale score, and dynamic balance when standing on foam also improved following unilateral pallidotomy in many patients. Cognitive performance remained relatively unchanged following surgery with the exception of category fluency, which exhibited a modest decline (P < .04). A significant improvement in depression was found on the Beck Depression Inventory. CONCLUSIONS: Ventroposterior pallidotomy significantly improves motor performance and daily level of function in Parkinson disease. Cognition and behavior are not adversely affected in patients without dementia, and a cognitive screening battery is proposed.

Adult↗