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The neuropsychological correlates of borderline personality disorder and suicidal behaviour.

OBJECTIVE: In subjects with borderline personality disorder (BPD), compared with subjects who attempted suicide, to review neuropsychological (NP) function that may predispose to suicidal behaviour along a continuum of high and low lethality. METHOD: We undertook electronic searches of MEDLINE, PsycINFO, EMBASE, Biosos Reviews, and Cinhal. The searches were restricted to English-language publications from 1985 onward. The search terms borderline personality disorder, suicide, suicide attempt, self-harm behaviour, neuropsychological, executive function (EF), neurocognitive, and neuropsychological function produced 29 neuropsychology studies involving BPD and 7 neuropsychology studies of suicide attempters, regardless of psychiatric diagnosis. RESULTS: Of the BPD studies, 83% found NP impairment in one or more cognitive domains, irrespective of depression, involving specific or generalized deficits linked to the dorsolateral prefrontal and orbitofrontal regions. The functions most frequently reported (in 71% to 86% of BPD studies) are response-inhibitory processes affecting executive function performance that requires speeded attention and visuomotor skills. Decision making and visual memory impairment are also most frequently affected; 60% to 67% of BPD studies report attentional impairment, verbal memory impairment, and visuospatial organizational impairment. Least affected processes in BPD appear to involve spatial working memory, planning, and possibly, IQ. The similarities in NP deficits found in BPD and suicide-attempt studies involve decision making and Trails performances. BPD studies, however, reflect more frequent impairment on the Stroop Test and Wisconsin Card Sort Test performance than the suicide-attempt studies, whereas verbal fluency appears to be more frequently impaired in those attempting suicide. CONCLUSIONS: Impaired EF and disinhibitory processes, as indicated by verbal fluency, Trails, and Stroop performance, primarily associated with dorsolateral prefrontal cortical regions may represent a dominant executive pathway to suicide attempt. A primary motivational inhibitory pathway involving conflictual, affective, and reflexive decision-making processes associated with orbitofrontal brain regions, in combination with significant cognitive rigidity, may influence the repetitive expression of self-harm or low-lethality suicidal behaviour. The hypothesis of a specific trait-like cognitive vulnerability for suicidal behaviour involving dysregulatory, disinhibiting pathways awaits confirmation.

Attention↗

Neurobehavioral testing of subjects exposed residentially to groundwater contaminated from an aluminum die-casting plant and local referents.

Residents adjoining a die-casting plant had excessive headaches, numbness of hands and feet, dizziness, blurred vision, staggering, sweating, abnormal heart rhythm, and depression, which led to measurements of neurobehavioral performance, affective status, and the frequency of symptoms. They had all been exposed via well water and proximity to the plant to volatile organic chemicals (VOC) and to polychlorinated biphenyls (PCBs). The 117 exposed women and men and 46 unexposed referents were studied together for simple and choice visual reaction time, body sway speed, blink reflex latency, color discrimination, Culture Fair (a nonverbal nonarithmetic intelligence test), recall of stories, figures, and numbers, cognitive and psychomotor control (slotted pegboard and trail making A and B), long-term memory, profile of mood states (POMS), and scores and frequencies of 34 symptoms. Choice reaction time, sway speed, and blink latency were impaired in both sexes of the exposed group and trail making B was impaired in exposed women. The POMS scores and frequencies of 30 of 34 symptoms were elevated in both sexes, compared to referents. Recall, long-term memory, psychomotor speed, and other cognitive function tests were reduced in exposed subjects and in the referents as compared to national referents. Neurophysiological impairment, and cognitive and psychomotor dysfunction and affective disorders, especially depression and excessive frequency of symptoms, were associated with the use of wells contaminated with VOCs, TCE and PCBs.

Adolescent↗

Cognitive function in patients with insulin-dependent diabetes mellitus during hyperglycemia and hypoglycemia.

BACKGROUND: To determine the impact of glycemic control, gender, and other relevant parameters on cognitive function during exposure to different blood glucose levels in patients with insulin-dependent diabetes mellitus (IDDM), we examined neuropsychologic function during experimentally induced periods of hyperglycemia and hypoglycemia. METHODS: We studied 20 men and 22 women, aged 18 to 44 years, with IDDM duration of 3 to 14 years and HbA1 values ranging from 5.8% to 18.0% (nondiabetic range 5.4% to 7.4%). We used a controlled experimental setting involving tests of sensory perceptual processing, simple motor abilities, attention, learning and memory, language, and spatial and constructional abilities at plasma glucose levels of 2.2, 5.6, 8.9, 14.4, and 21.1 mmol/L. Patients were blind to the glucose level. Tests used at each glucose level included reaction time (simple and choice), digit vigilance, trail making part B, word recall, digit sequence learning, and verbal fluency. RESULTS: All aspects of neuropsychologic function were diminished at 2.2 mmol/L when compared with basal levels of performance at 8.9 mmol/L, whereas no alterations were observed at 14.4 or 21.1 mmol/L. Tests involving associative learning, attention, and mental flexibility were the most affected during hypoglycemia. Glycemic control was not correlated with neuropsychologic function at any glucose level. Women demonstrated less of an impairment in neuropsychologic function than men at 2.2 mmol/L. CONCLUSIONS: Cognitive function in IDDM patients was generally well-preserved even at substantially elevated blood glucose levels. Deficits in all relevant areas of cognitive function occurred during hypoglycemia (2.2 mmol/L), irrespective of prior glycemic control, and women with IDDM were less cognitively impaired than men with IDDM during hypoglycemia.

Adult↗

Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome.

Continuous positive airway pressure (CPAP) is the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS); it is usually given with the aim of improving daytime cognitive function, mood, and sleepiness. However, its efficacy has not been validated by controlled trials. We have carried out a randomised, placebo-controlled, crossover study of objective daytime sleepiness, symptoms, cognitive function, and mood in a consecutive series of 32 SAHS patients with a median apnoea plus hypopnoea frequency of 28 (range 7-129) per hour slept. Patients were treated with 4 weeks each of CPAP and an oral placebo, which they were told might improve upper airway muscle function during sleep. Assessments on the last day of each treatment included a multiple sleep latency test and tests of symptom scores, mood profiles, and cognitive performance. The patients had significantly less daytime sleepiness on CPAP than during the placebo period (mean sleep latency 7.2 [SE 0.7] vs 6.1 [0.7] min, p = 0.03). There were also improvements with CPAP in symptom ratings (2.1 [0.2] vs 4.3 [0.3], p < 0.001), mood (p < 0.05 for several measures), and cognitive performance, which showed improved vigilance (obstacles hit in Steer Clear "driving" test 76 [5] vs 81 [6], p < 0.01), mental flexibility (trail-making B time 66 [5] vs 75 [5] s, p < 0.05), and attention (p < 0.05). Objectively monitored CPAP use averaged only 3.4 (0.4) hours per night, but this study provides evidence of improved cognitive performance even at this low level of CPAP compliance.

Affect↗

Congestive heart failure and cognitive functioning amongst older adults.

BACKGROUND: Congestive heart failure is associated with decline in quality of life and, possibly, cognitive functions such as memory and attention. AIMS: The present study was designed to investigate the presence of cognitive impairment amongst patients with congestive heart failure (CHF). We hypothesised that CHF patients would have lower scores than elderly controls on general measures of cognitive functioning. METHODS AND RESULTS: We examined a sample of 50 consecutive patients admitted to hospital with CHF functional class III/IV and a convenience sample of 30 older adults assessed at the outpatient service of geriatric medicine of a teaching hospital in São Paulo, Brazil. All subjects were interviewed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), as well as the neuropsychological battery of the CAMDEX (CAMCOG), Mini-Mental State Examination (MMSE), Trail Making A and B, Digit Span, Digit Symbol, and Letter Cancellation Test. All CHF patients had left ventricular ejection fraction (EF) below 45% and all controls above 65%. The cognitive performance of CHF patients was significantly worse than controls for all cognitive assessments. Twenty-seven of 50 CHF patients had a MMSE total score lower than 24, compared with only 10/30 controls (p=0.073). Similarly, 36/49 and 9/30 CHF subjects and controls respectively had CAMCOG scores below 80 (p<0.001). Cognitive scores were significantly associated with EF, which was the most robust predictor of cognitive impairment according to the CAMCOG in a logistic regression model. CONCLUSION: Our results indicate that CHF is associated with significant levels of cognitive impairment and show that mental performance is, at least partly, a consequence of EF. Physicians should be prepared to assess the mental state of patients, as poor cognitive functioning may interfere with treatment compliance and management plan.

Aged↗

Neurotoxicity from airborne chemicals around a superfund site.

A pilot investigation had shown that 88 people living within 2.4 km of a waste chemical disposal and oil-reprocessing facility which operated from 1966 to 1983 had reduced neurobehavioral performance compared to 66 regional referents. A geographic model of dispersal predicted less effect with greater distance from the distilling. To explore this gradient and the boundaries of the adverse effects, we tested 408 residents in random proportional samples of concentric zones from the center out to 4.8 km that were divided by compass octants. Reaction times, balance, blink reflex latency, color discrimination, Culture Fair, pegboard, and Trail Making A and B were measured. Patients completed a Profile of Mood States, frequency of 33 symptoms, and medical, occupational, and exposure histories. Distance and direction from the site and duration of residence were examined for effect on each test score by stepwise linear regression. Exposed subjects' had diminished reaction time, balance, color score, and scores for Culture Fair, pegboard, and Trail Making A and B compared to referents. Functional impairment was not correlated with distance or direction from the site but subjects with short durations of residence had better function on one test. Combinations of these factors were not predictive.

Adult↗

[The neuropsychological test battery for elderly people].

OBJECTIVE: To establish a Chinese T-score norm of neuropsychological test battery for the elderly (NTBE). METHODS: 903 normal elderly people over 60 years old from Shanghai, Beijing, Hebei, Jiangsu, Hubei, Hunan, Zhejiang, Shandong and Liaoning were evaluated by using NTBE which includes tests of auditory verbal learning, sorting, cancellation, language, motor, visual function, construction, trail making 1 and 2, etc. RESULTS: Age and education greatly affected the score of NTBE, but gender did not. Based on these facts, the 903 normal subjects were divided into 12 subgroups, according to the age and the years of education they had received. The raw scores of NTBE were transformed to standard score and normalized standard score, and then these scores were transformed to a total T score (Mean = 100, SD = 10). Using another normal elderly sample (n = 474) to analysis, the correlation between the raw scores and the total T score was significant. Using NTBE to diagnose 110 mild cognitive impairment (MCI) and 63 Alzheimer's disease (AD) patients, the sensitivity and specificity were 66% and 91% for MCI, and 79% and 96% for AD. CONCLUSION: The T norm of the NTBE is suitable for Chinese elderly, and can be a useful instrument for diagnosing mild cognitive impairment and Alzheimer's disease.

Aged↗

Cognitive functions in severe congestive heart failure before and after an exercise training program.

BACKGROUND: Congestive heart failure is associated with cognitive impairment, particularly of attentional skills. We assessed, in a hypothesis-generating study, the effect of an exercise training program on cognitive functions among patients with severe congestive heart failure. METHODS: Patients with severe congestive heart failure (n=20; New York Heart Association functional class III; left ventricular ejection fraction < or =35%) were evaluated before and following a standardized and supervised exercise training program (x2/week for 18 weeks; exercise group), while 5 additional patients did not undergo an exercise training program (control group). A battery of cognitive tests was used to assess cognitive functions. Physical performance was assessed by the 6-min walk test and the modified Bruce exercise test, cardiac index and systemic vascular resistance using thoracic electrical bioimpedance, and cerebral vasomotor reactivity to hypercapnia by means of the breath-holding index using transcranial Doppler. RESULTS: Time of completion of the trail making A (105+/-116 to 75+/-52; p=0.02) and B (169+/-100 to 119+/-65; p=0.002) tests, and of the Stroop part A (40+/-13 to 37+/-13; p=0.04) was shorter in patients completing the exercise training program, but not in control patients, while the other neuropsychological measures remained unchanged in both groups. Cerebral vasomotor reactivity to hypercapnia remained diminished (breath-holding index 0.64+/-0.27 vs. 0.68+/-0.37) despite significant improvements in exercise capacity (6-min walk test 308+/-87 to 423+/-91 m, p<0.001; modified Bruce exercise test 5.6+/-3.8 to 9.8+/-3.4 min, p<0.001). CONCLUSIONS: Patients with severe congestive heart failure undergoing an exercise training program improve in some measures of cognitive functions that are limited to general attention and psychomotor speed. Based on these preliminary findings, further evaluations are designed within the framework of a larger controlled clinical trial.

Adult↗

Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment. A prospective study.

Corticosteroids often induce a variety of psychiatric symptoms, such as alterations of mood, neuropsychological deficits and even psychotic states. To date, only a few studies have specifically addressed behaviour as well as cognitive functioning in patients under steroid treatment. Fifty ophthalmologic patients participated in this prospective study. They received methylprednisolone or fluocortolone at doses of 119 +/- 41 mg/day in the beginning and 75 +/- 22 mg after 8 days of treatment. Psychopathology and neuropsychological functioning were examined before and after steroid therapy, mood was self-rated on days 0, 3, 5 and 8. No marked psychopathological abnormalities such as psychosis, dementia or delirious states were observed. However, a significant proportion of patients suffered from an organic mood disorder, 26-34% experienced a hypomanic syndrome, 10-12% a depressive syndrome. Most neuropsychological tests did not reveal significant effects of steroid treatment. Performance of Word Fluency and Trail Making A improved, while the Auditory-Verbal-Learning and the Digit-Symbol showed a worsening. Psychopathological and neuropsychological effects were not significantly correlated.

Administration, Oral↗

Psychomotor performance and monoamine function in bipolar and unipolar affective disorders.

BACKGROUND: Affective disorders are associated with prominent psychomotor abnormalities that may be related to changes in arousal or motivation due to altered catecholamine function. METHODS: We investigated relationships between performance on psychomotor tests of motor speed (reaction time and tapping speed) and visual tracking (trail making and dot placement) and catecholamine system function including cerebrospinal fluid (CSF) or urinary concentrations of catecholamines or their metabolites. Subjects were medicine-free inpatients with unipolar depression or with manic, depressive, or mixed episodes of bipolar disorder, and healthy controls matched by gender and stratified by age. RESULTS: Unipolar and bipolar depressed patients were impaired in motor speed, dexterity, and visual tracking, whereas manic and mixed patients did not differ from controls. Tapping speed correlated positively with CSF 3-methoxy-4-hydroxyphenylglycol in healthy controls and with CSF homovanillic acid in bipolar depressed subjects. Increased catecholamine function correlated with slowing in all other measures for patients with bipolar disorder. Relationships between catecholamines and psychomotor function were weaker in unipolar depressed subjects. Psychomotor function was related to severity of depression in bipolar, but not in unipolar, patients. CONCLUSIONS: These data suggest that catecholamine systems are associated with increased arousal and psychomotor impairment in patients with bipolar disorder. Similar behavioral changes have different neurotransmitter relationships in unipolar disorder.

Adult↗

Neurobehavioral effects of formaldehyde and solvents on histology technicians: repeated testing across time.

Neurobehavioral functions were studied by periodic testing of 318 histology technicians and by a single session testing 494 of such technicians from 1982 through 1986. Tests included immediate recall of stories, of drawings, and of number series from the Wechsler Memory Scale, block designs from the Wechsler Adult Intelligence Scale (WAIS), slotted pegboard, trail making A and B, embedded figures, number writing on the fingers, visual simple and two-choice reaction times, balance (speed of body sway), and the profile of mood state (POMS) score. Mean test scores of four initial "first test" groups were not different from 1982 to 1986. Immediate recall of stories and drawings improved on the first retest as did the block design score. Other test scores showed insignificant variation over the 4 years, including memory for numbers forward and backward, trails A and B, number writing on fingers, radius of body sway, and choice reaction time. Only placing of pegs in the pegboard took longer. POMS score was lower in the second year in naive subjects and decreased from 39 to 13 in those retested. Variations in results of neurobehavioral tests given at intervals across 4 years were small. No cumulative effects of occupational exposures or of aging were found. However, small decreases may have been offset by increases due to test familiarity or learning.

Adult↗

The role of functional and molecular imaging in cancer drug discovery and development.

Studies of pharmacokinetics (which is what the body does to the drug) and pharmacodynamics (which is what the drug does to the body) are essential components of the modern process of cancer drug discovery and development. Defining the precise relationship between pharmacokinetics and pharmacodynamics is critical. It is especially important to establish a well understood pharmacological "audit trail" that links together all of the essential parameters of drug action, from the molecular target to the clinical effects. The pharmacological audit trail allows us to answer two absolutely crucial questions: (1) how much gets there; and (2) what does it do? During the pre-clinical drug discovery phase, it is essential that pharmacokinetic/pharmacodynamic (PK/PD) properties are optimized, so that the best candidate can be selected for clinical development. As part of contemporary mechanistic, hypothesis-testing clinical trials, construction of the pharmacological PK/PD audit trail facilitates rational decision-making. However, PK/PD endpoints frequently require invasive sampling of body fluids and tissues. Non-invasive molecular measurements, e.g. using MRI or spectroscopy, or positron emission tomography, are therefore very attractive. This review highlights the need for PK/PD endpoints in modern drug design and development, illustrates the value of PK/PD endpoints, and emphasises the importance of non-invasive molecular imaging in drug development. Examples cited include the use of PK/PD endpoints in the development of molecular therapeutic drugs such as the Hsp90 molecular chaperone inhibitor 17AAG, as well as the development of SR-4554 as a non-invasive probe for the detection of tumour hypoxia.

Antineoplastic Agents↗

Executive dysfunction and clinical outcome in chronic alcoholics.

BACKGROUND: The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients' alcohol-specific and/or alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics' functional outcome. METHODS: We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty-two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge. RESULTS: The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices. CONCLUSIONS: The BADS total profile score is related to alcohol-nonspecific outcome but not to alcohol-specific outcome.

Alcoholism↗

Clinical treatment reverses attentional deficits in congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is associated with cognitive deficits, particularly of memory and attention. The present study aims to clarify whether clinical treatment can reverse the attentional deficits of patients with CHF. METHODS: A convenience sample of 50 patients with CHF functional class IV and 30 elderly controls were recruited from a teaching hospital in Brazil. Participants received a clinical and cognitive examination that included the Mini-Mental State Examination (MMSE), Cambridge Cognitive Examination of the Elderly (CAMCOG), Digit Span, Digit-Symbol Substitution, and Letter Cancellation test. The cognitive performance of CHF patients was reassessed 6 weeks after the introduction of clinical treatment. RESULTS: Twenty-seven CHF subjects had MMSE<24, compared to only 10 of the controls (p = 0.07). CHF patients also had lower CAMCOG scores (mean = 71.8) than controls (mean = 82.0; p < 0.01). Digit Span, Digit Symbol and Letter Cancellation scores were lower for patients with CHF than controls (p < 0.01). Similarly patients with CHF took longer to complete the Trail Making A (p = 0.07) and B (p < 0.01). CAMCOG scores and left ventricular ejection fraction were moderately correlated (rho = 0.4, p < 0.01). Nineteen patients were lost for follow-up (11 deceased). Clinical treatment was associated with significant improvement of cognitive scores, particularly on the Digit Symbol (p < 0.01) and Letter Cancellation Tests (p < 0.01). Digit Span, Digit Symbol, Letter Cancellation and Trail Making scores of treated CHF patients and controls were similar (p > 0.10). CONCLUSIONS: CHF is associated with deficits in attention and psychomotor speed. These deficits improve with clinical treatment.

Journal Article↗

Executive functions and speed of mental processing in elderly patients with frontal or nonfrontal ischemic stroke.

Impairments in executive functions have been related to aging and frontal lobe lesions. Aging also causes slowing of mental processing. We examined whether ischemic stroke in the frontal brain area results in dysexecutive syndrome, or whether the frontal stroke causes increased slowing of mental processing. Neurological, radiological and neuropsychological examinations were carried out 3 months post-stroke on 250 ischemic stroke patients (55-85 years) and on 39 healthy control subjects. Of the patients, 62 had frontal and 188 had nonfrontal lesions. The neuropsychological examination comprised several cognitive domains, including tests considered to measure executive functions. The frontal group was slower than the nonfrontal group in tasks measuring speed of mental processing which were time-limited (Trail Making A, Stroop dots and fluency). They were also inferior in the Digit Span backwards task. There were no differences between the groups in other cognitive domains, nor in some tests which are considered to be measures of executive functions (e.g. WCST). Impairments in executive functions were evident in both the frontal and the nonfrontal groups compared with the controls, but no dysexecutive syndrome specifically related to frontal lesions was found. Frontal stroke related mainly to the slowing of mental processing.

Age Factors↗

Correlates of trait impulsiveness in performance measures and neuropsychological tests.

Performance measures of impulsiveness offer great promise for assessing this trait in clinical and experimental studies. However, little is known about their relative superiority or inferiority to standard cognitive performance measures as correlates of this trait. In this study, 58 healthy volunteers completed a self-rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of neuropsychological tests. The test battery included measures of reaction time, attention, memory, fluency, and executive function, as well as two performance measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings correlated moderately with a number of these test scores, but many correlations became non-significant after adjustment for age and education. Correlations with the Go-No Go task, verbal fluency, executive function measures (Trails B), and tasks requiring decision-making against time (Choice Reaction Time, Reaction Time to Paired Words and Paired Faces Memory Tasks, and response bias on the Continuous Performance Test) remained significant. Performance on the Go-No Go task was the strongest correlate of self-rated impulsiveness. The findings suggest that once general demographic or ability factors are accounted for, specialized performance tasks requiring decision-making and response organization under time pressure provide the most effective means of assessing this behavioral trait.

Adult↗

Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: To assess cognitive function in patients with chronic fatigue syndrome (CFS) and multiple sclerosis (MS) and to evaluate the role of depressive symptoms in cognitive performance. DESIGN: Case-control. All subjects were given a neuropsychological battery, self-report measures of depression and fatigue, and a global cognitive impairment rating by a neuropsychologist "blinded" to clinical diagnosis. Patients with MS and CFS were additionally evaluated with a Structured Clinical Interview for DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition) disorders. SETTING: Institutional and private neurological practices and the community at large. PATIENTS: Twenty patients with CFS diagnosed in accord with the Centers for Disease Control and Prevention-revised criteria who had cognitive complaints; 20 patients with clinically definite MS who were ambulatory and were matched for fatigue severity, age, and education to CFS subjects; and 20 age- and education-matched healthy controls. RESULTS: Patients with CFS had significantly elevated depression symptoms compared with patients with MS and healthy controls (P < .001) and had a greater lifetime prevalence of depression and dysthymia compared with MS subjects. Patients with CFS, relative to controls, performed more poorly on the Digit Symbol subtest (P = .023) and showed a trend for poorer performance on logical memory (P = .087). Patients with MS compared with controls had more widespread differences of greater magnitude on the Digit Span (P < .004) and Digit Symbol (P < .001), Trail Making parts A (P = .022) and B (P = .037), and Controlled Oral Word Association (P = .043) tests. Patients with MS also showed a trend of poorer performance on the Booklet Category Test (P = .089). When patients with CFS and MS were directly compared, MS subjects had lower scores on all measures, but the differences reached significance only for the Digit Span measure of attention (P = .035). CONCLUSIONS: Patients with CFS compared with MS have more depressive symptoms but less cognitive impairment. Relative to controls, a subset of CFS subjects did poorly on tests of visuomotor search and on the logical memory measure of the Wechsler Memory Scale-revised. Poor performance of logical memory in CFS appears to be related to depression, while visuomotor deficits in CFS are unrelated. Cognitive deficits in patients with MS are more widespread compared with those in patients with CFS and are independent of depressive symptoms.

Adult↗

Optimizing the correlation between results of testing in vitro and therapeutic outcome in vivo for fluconazole by testing critical isolates in a murine model of invasive candidiasis.

The trailing growth phenomenon seen when determining the susceptibilities of Candida isolates to the azole antifungal agents makes consistent endpoint determination difficult, and the M27-A method of the National Committee for Clinical Laboratory Standards addresses this problem by requiring an 80% reduction in growth after 48 h of incubation. For some isolates, however, minor variations of this endpoint criterion can produce up to 128-fold variations in the resulting MIC. To investigate the significance of this effect, isolates of Candida that exhibited various forms of trailing growth when tested against fluconazole were identified. The isolates were examined in a murine model of invasive candidiasis and were ranked by their relative response to fluconazole by using both improvement in survival and reduction in fungal burden in the kidney. The resulting rank order of in vivo response did not match the MICs obtained by using the M27-A criterion, and these MICs significantly overestimated the resistance of three of the six isolates tested. However, if the MIC was determined after 24 h of incubation and the endpoint required a less restrictive 50% reduction in growth, MICs which better matched the in vivo response pattern could be obtained. Minor variations in the M27-A endpoint criterion are thus required to optimize the in vitro-in vivo correlation for isolates that demonstrate significant trailing growth when tested against fluconazole.

Animals↗