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W L Sibbitt

Publications and source records attributed to W L Sibbitt.

At least 19 recordsLinked to original sources
PubMed2006

Accumulation of acetyl groups following cycling: a 1H-MR spectroscopy study.

Using in vivo proton magnetic resonance spectroscopy (1H-MRS), a new peak resonating at 2.13 ppm post-exercise has been attributed in the literature to the acetyl groups of acetylcarnitine. Since this peak is inconsistently generated by various submaximal exercise regimens, this study aimed at (a) verification of the previous chemical assignment, (b) determination of exercise conditions necessary for its induction, and (c) documentation of the recovery kinetics through 60 minutes following exercise. Ten healthy males (31 +/- 4 yr) cycled continuously for 45 minutes with intensity alternating between 50% (3 min) and 110% (2 min) of ventilatory threshold (VT). 1H-MR spectra were acquired from the vastus lateralis before and for 60 minutes following exercise. The peak at 2.13 ppm was not quantifiable at rest in any subject. However, it was present in all subjects following intense exercise (p < 0.0001), and expressed the chemical characteristics of an acetyl-containing compound. The estimated concentration, accumulation with high-intensity exercise, the presence as a single peak at 2.13 ppm, and the chemical shift were all consistent with the chemical and biophysical characteristics of acetyl groups associated with acetylcarnitine. This study provides further evidence that acetyl groups are robustly generated by intense exercise, and that the accumulation of acetyl groups in healthy subjects is dependent on the degree of exercise intensity. 1H-MRS may be used for the noninvasive study of muscle metabolism during exercise and recovery and may have special applications for studying the generation and transport of acetyl compounds, including acetylcarnitine.

Acetylation↗
PubMed2001

Gerstmann syndrome in systemic lupus erythematosus: neuropsychological, neuroimaging and spectroscopic findings.

Gerstmann syndrome (GS) comprises four interlaced neuropsychological symptoms including finger agnosia, right-left confusion, agraphia, and acalculia. While GS is commonly associated with focal lesions to the region of the left angular gyrus, it has also been associated with numerous diffuse etiologies including atrophy, alcoholism, carbon monoxide poisoning, lead intoxication and anaphylactic shock. Thus, a vigorous debate has emerged as to whether GS represents a syndrome arising from general brain decline or a distinct and localizing lesion. We report a right-handed patient who developed neuropsychological dysfunction secondary to systemic lupus erythematosus (SLE). Neuropsychological evaluation found the patient to exhibit symptoms consistent with the GS tetrad, as well as general cognitive decline. Magnetic resonance imaging revealed a distinct focal lesion of the left parieto-occipital white matter underlying the angular gyrus as well as diffuse atrophy. (1)H-magnetic resonance spectroscopy revealed substantial metabolic derangement in a voxel placed within the visible lesion, although substantial metabolic derangement was observed in regions remote from the focal pathology. Thus, GS in this first case in SLE would appear to comprise a focal neurological tetrad of disorders within a more general pattern of cognitive decline and metabolic derangement.

Adult↗
PubMed2001

Cigarette smoking, alcohol consumption, and the risk of systemic lupus erythematosus: a case-control study.

OBJECTIVE: To investigate the effects of cigarette smoking and alcohol consumption on the development of systemic lupus erythematosus (SLE). METHODS: We interviewed 125 patients with SLE and 125 controls in a case-control study. Demographically similar controls randomly selected from outpatient clinics were matched to SLE cases for sex and age. Clinical data, including cigarette smoking, drinking habits, and other demographic variables, were collected by an interview-administered questionnaire. RESULTS: To minimize bias associated with reactive habits induced by disease, cigarette smoking before the diagnosis of SLE was the primary variable for subsequent analysis. Analysis of the data by multivariate conditional logistic regression revealed that both cigarette smoking before SLE diagnosis and ex-smoking before SLE diagnosis significantly increased the risk of development of SLE (OR 6.69, 95% CI 2.59, 17.28, p < 0.001; and OR 3.62, 95% CI 1.22, 10.70, p = 0.02, respectively). This association remained even when statistically controlling for the effects of family history and education, indicating an independent effect. Alcohol did not place an individual at increased risk nor did it have a protective role. CONCLUSION: The results of this study provide further evidence that cigarette smoking may be an associated risk factor for the development of SLE.

Adult↗
PubMed2000

Myths of neuropsychology: intelligence, neurometabolism, and cognitive ability.

Recently, Dodrill (1999) revised a previously described "Myth of neuropsychology" (1997) to state: "Just as below average performances on neuropsychological tests are found when intelligence is below average, to that same degree above average performances on neuropsychological tests are expected when intellectual abilities are above average." This study addresses the relationship between intellectual and neuropsychological performance in the context of Magnetic Resonance Spectroscopy (MRS) measurements of the neurometabolite N-acetylaspartate (NAA). When subjects were stratified by Full Scale IQ (Average, High Average, Superior) they differed significantly in terms of total neuropsychological performance [F(2,47) = 17.63; p <.001] and the neuronal marker NAA [F(2,47) = 3.25; p <.05]. Regression analysis across groups demonstrated that FSIQ and NAA were independently related to Total z-score [F(1,47) = 29.43; p <.0001] and accounted for over half the variance (r(2) of model =.56). The concurrent relationship of FSIQ and NAA to total neuropsychological performance suggests that the relationship between measures sensitive to intellectual ability and neuropsychological performance is real, and does not reflect arbitrary psychometric or scaling properties of the WAIS-III.

Adult↗
PubMed2000

Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study.

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique insight into brain cellular metabolism following traumatic brain injury (TBI). The aim of the present study was to assess change in neurometabolite markers of brain injury during the recovery period following TBI. We studied 19 TBI patients at 1.5, 3, and 6 months postinjury and 28 controls. We used 1H-MRS to quantify N-acetylaspartate (NAA), creatine (Cre), choline (Cho), and myoinositol (mIns) in occipitoparietal gray matter (GM) and white matter (WM) remote from the primary injury focus. Neuropsychological testing quantified cognitive impairment and recovery. At 1.5 months, we found cognitive impairment (mean z score = -1.36 vs. 0.18,p < 0.01), lower NAA (GM: 12.42 mM vs. 13.03, p = 0.01; WM: 11.75 vs. 12.81, p < 0.01), and elevated Cho (GM: 1.51 vs. 1.25, p < 0.01; WM: 1.98 vs. 1.79, p < 0.01) in TBI patients compared with controls. GM NAA at 1.5 months predicted cognitive function at outcome (6 months postinjury; r = 0.63, p = 0.04). GM NAA continued to fall by 0.46 mM between 1.5 and 3 months (p = 0.02) indicating continuing neuronal loss, metabolic dysfunction, or both. Between 3 and 6 months, WM NAA increased by 0.55 mM (p = 0.06) suggesting metabolic recovery. Patients with poorer outcomes had elevated mean GM Cho at 3 months postinjury, suggesting active inflammation, as compared to patients with better outcomes (p = 0.002). 1H-MRS offers a noninvasive approach to assessing neuronal injury and inflammation following TBI, and may provide unique data for patient management and assessment of therapeutic efficacy.

Adolescent↗
PubMed1999

Biochemical markers of cognition: a proton MR spectroscopy study of normal human brain.

In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.

Adult↗
PubMed1999

Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain.

Proton magnetic resonance spectroscopy (1H-MRS) offers a unique non-invasive approach to measurement of N-acetylaspartate (NAA) and choline (Cho), putative markers of neuronal and glial integrity. Previous studies revealed that these neurochemicals predict cognitive impairment in diseased subjects, although little is known about their relationship to cognitive functioning in healthy people. We measured the concentrations of NAA and Cho in the left occipitoparietal white matter of 26 healthy adults and compared them with intellectual performance assessed by the Wechsler Adult Intelligence Scale-3. We found that NAA (b = 0.6, p < 0.01) and Cho (b = -0.42, p < 0.01) were independently associated with the Full-Scale Intelligence Quotient. Together, these metabolites accounted for a large proportion of the variance in intelligence (r2 = 0.45). Possible mechanisms underlying these correlations, such as mitochondrial function and myelin turnover, are discussed. 1H-MRS is a sensitive new tool to assess the neuronal underpinnings of cognitive function non-invasively.

Adult↗
PubMed1999

Automated T2 quantitation in neuropsychiatric lupus erythematosus: a marker of active disease.

Active neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by brain edema as measured by manual quantitative magnetic resonance (MR) relaxometry. An automated image processing method was developed to segment gray matter (GM), while minimizing the effects of confounding factors, specifically cerebral atrophy and volume averaging artifacts. Twenty patients with SLE (10 major, 10 minor), matched for atrophy, were studied. We compared T2 calculated for GM segmented by manual and automated methods. Both methods demonstrated a marked increase in GM T2 in patients with major NPSLE (P < 0.001), confirming the presence of cerebral edema. The results from each method were highly correlated, (r = 0.64, P = 0.002). The automated method effectively identifies GM, minimizes volume averaging artifacts, and produces results similar to the manual method. This method markedly decreases analysis time and will make quantitative relaxometry a valuable contribution to the clinical management of NPSLE.

Adult↗
PubMed1999

Neuropsychiatric systemic lupus erythematosus.

The systemic lupus erythematosus (SLE) patients with neuropsychiatric complaints requires a comprehensive and timely diagnostic approach. Despite the obvious difficulties in diagnosing neuropsychiatric SLE, the neurologic complications of SLE can be approached in a careful, logical manner with gratifying results.

Algorithms↗
PubMed1999

Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between neurochemical markers of brain injury and brain dysfunction associated with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n = 12) were studied using magnetic resonance spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and Cho/Cre. Neurocognitive testing results were expressed as a composite z score. Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and disease injury by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index. RESULTS: Neurochemical measures of brain injury were correlated with neurocognitive testing z scores: NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71, p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between neurometabolite ratios and SLEDAI did not reach significance. CONCLUSION: Brain function is closely correlated with brain injury assessed noninvasively by proton magnetic resonance spectroscopy. This important finding further supports the use of magnetic resonance spectroscopy to evaluate brain injury in SLE.

Adult↗
PubMed1998

Structural and neurochemical markers of brain injury in the migraine diathesis of systemic lupus erythematosus.

OBJECTIVE: To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity. METHODS: Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS). RESULTS: Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatric manifestations, or end-organ involvement compared to patients without migraine (p > 0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache (p > 0.05). CONCLUSIONS: Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.

Adolescent↗
PubMed1998

Brain injury and neurometabolic abnormalities in systemic lupus erythematosus.

PURPOSE: To investigate with statistical analysis the relationship between brain injury measured with magnetic resonance (MR) imaging and that measured with proton (hydrogen-1) MR spectroscopy. MATERIALS AND METHODS: Forty-two patients (34 female, eight male; mean age +/- SD, 38.7 years +/- 13.1; age range, 6-60 years) with systemic lupus erythematosus (SLE) were examined with H-1 MR spectroscopy to measure N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels in normal-appearing white matter and with MR imaging to detect anatomic abnormalities. RESULTS: Results of linear regression analysis revealed an association between the NAA/Cr ratio and anatomic abnormalities (P = .03). However, only small focal lesions were independently related to NAA/Cr ratio changes (P = .04). Results of a similar analysis showed associations between the Cho/Cr ratio and anatomic abnormalities (P = .002). An elevated Cho/Cr ratio and cerebral infarction were independently associated (P = .02), as were a decreased Cho/Cr ratio and severe cortical atrophy (P = .02). CONCLUSION: Cerebrovascular abnormalities underlie diffuse cerebral injury in SLE, with small vessel injury (i.e., small focal lesions) primarily associated with a decreased NAA/Cr ratio and medium vessel injury (i.e., infarct) primarily associated with an increased Cho/Cr ratio. Statistical integration of H-1 MR spectroscopic and MR imaging findings over large data sets provides insights into the relevance of individual MR imaging-visible brain abnormalities in SLE. This statistical approach may be applicable to other systemic diseases complicated by brain injury.

Adolescent↗
PubMed1998

Neurometabolite markers of cerebral injury in the antiphospholipid antibody syndrome of systemic lupus erythematosus.

BACKGROUND AND PURPOSE: To determine the neurometabolic patterns of brain injury in systemic lupus erythematosus with antiphospholipid antibody syndrome (SLE-aPLS). METHODS: Forty-nine SLE patients (12 SLE-aPLS) and 23 control subjects were studied using magnetic resonance imaging and spectroscopy. N-Acetylaspartate/creatine (NAA/Cre) and choline/Cre (Cho/Cre) were measured in normal-appearing tissue. IgG and IgM antiphospholipid antibodies (aPL) were measured by enzyme-linked immunosorbent assay. RESULTS: Stroke, epilepsy, and elevated IgG-aPL were more common in SLE-aPLS patients than in SLE patients (P<0.001). NAA/Cre was lower (P<0.05) and Cho/Cre higher (P<0.001) in SLE-aPLS patients than in SLE patients without aPLS. Regression models showed NAA/Cre was most related to injury seen by imaging (P<0.01), disease duration (P<0. 05), and prior neuropsychiatric SLE (NPSLE) (P=0.07). Reduced NAA/Cre was more closely related to IgG-aPL (P<0.01) than the presence of stroke or aPLS. When adjusted for all factors, Cho/Cre was most associated with the presence of aPLS (P=0.05). CONCLUSIONS: SLE and SLE-aPLS are actually a clinical continuum describing brain injury in SLE, with SLE-aPLS being characterized by increased aPL, NPSLE, stroke, epilepsy, and disturbed neurochemistry. An elevated IgG-aPL level is a potent risk factor for brain injury as measured by NAA/Cre in SLE that is independent of stroke and aPLS. However, thrombotic phenomena and the presence of aPL (aPLS) are most closely associated with increased Cho/Cre in SLE. These results suggest that aPLs exacerbate SLE, resulting in increased thrombotic and nonthrombotic brain injuries. Spectroscopy detects brain injury in SLE and may permit better understanding of the neurological consequences of SLE and SLE-aPLS.

Adult↗
PubMed1998

Proton MR spectroscopic measurement of neurometabolites in hepatic encephalopathy during oral lactulose therapy.

BACKGROUND AND PURPOSE: MR imaging and MR spectroscopy are increasingly being used to determine response to pharmacologic therapy. Hepatic encephalopathy (HE) is characterized by abnormal cerebral metabolites, yet the response to lactulose and other anti-HE measures is still primarily determined by using arbitrary categorical clinical rating scales, rather than MR spectroscopy. The purpose of this study was to determine whether MR spectroscopy could demonstrate relevant neurometabolic changes associated with lactulose therapy and thereby provide further support for the use of MR spectroscopy in clinical trials. METHODS: Ten control subjects and 23 patients with grades I to III HE were studied by proton MR spectroscopy with imaging parameters of 2000/26 (TR/TE). Metabolic ratios were calculated for myo-inositol (mI)/creatine (Cre), choline (Cho)/Cre, (glutamine + glutamate) (Glx)/Cre, N-acetylaspartate (NAA)/Cre, and (Cho + mI)/Glx. A time series design trial was used in which eight patients with HE were compared before and after lactulose therapy (60 mL by mouth three times per day). RESULTS: Relative to control subjects, HE was characterized by 43%, 64%, and 5% reductions, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre. In comparison, Glx/Cre was increased by 75% and NAA/Cre was not changed. Therapy with lactulose was associated with increases of 29%, 37%, and 7%, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre, as well as respective decreases of 15% and 42%, respectively, in Glx/Cre and HE grade. NAA/Cre did not change with lactulose therapy. CONCLUSION: MR spectroscopy detects neurometabolic changes associated with pharmacologic therapy for HE. The metabolic ratios ml/Cre and (Cho + mI)/Glx are the most sensitive measures of lactulose effect. These data support the expanded use of MR spectroscopy as an adjunctive technique in pharmaceutical development and clinical trials for HE.

Administration, Oral↗
PubMed1998

Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome.

BACKGROUND AND PURPOSE: Eosinophilia myalgia syndrome (EMS), a multisystemic disease induced by exposure to L-tryptophan, may result in serious CNS abnormalities. The purpose of this study was to determine the pattern of neurologic characteristics, MR imaging abnormalities, and brain neurometabolites in EMS. METHODS: Sixteen patients with EMS and CNS abnormalities (CNS-EMS) and 12 control subjects underwent evaluation, including medical and neurologic examination, proton MR spectroscopy, and MR imaging. RESULTS: Neurologic findings that were increased in CNS-EMS included minor depression (100%), amnesia (88%), and intermittent confusion (38%), although fatigue (31%), motor disorders (31%), recurrent headache (19%), major depression (13%), and dementia (6%) also occurred, but at a lesser significance. Self-reported disability was markedly increased in CNS-EMS. MR imaging findings included subcortical focal lesions, focal lesions in deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities. MR spectroscopic findings established two distinct spectral patterns: 1) increased choline-containing compounds, decreased N-acetylaspartate, and increased lipid-macromolecules, consistent with inflammatory cerebrovascular disease; and 2) increased glutamine, decreased myo-inositol, and decreased choline, consistent with acute CNS injury or metabolic encephalopathy. CONCLUSION: Neurologic abnormalities, self-reported disability, brain lesions, and MR spectroscopic abnormalities are common in CNS-EMS. The pattern of cerebral lesions and neurometabolites is consistent with widespread inflammatory cerebrovascular disease. However, a subgroup of patients with CNS-EMS have neurometabolic changes consistent with a metabolic encephalopathy identical or similar to hepatic encephalopathy. The neurologic abnormalities in EMS and related hypereosinophilic syndromes should be interpreted cautiously, with the recognition that both cerebrovascular injury and secondary metabolic encephalopathies may be involved.

Adult↗
PubMed1997

Corticosteroid responsive tenosynovitis is a common pathway for limited joint mobility in the diabetic hand.

OBJECTIVE: To test the hypothesis that diabetic tenosynovitis participates in the contractures of the syndrome of limited joint mobility (SLJM). METHODS: Adults with diabetes mellitus were referred for the evaluation of diabetic hand conditions. Patients with SLJM or diabetic trigger finger were studied after Dupuytren's contracture, hand neuropathy, carpal tunnel syndrome, and arthritis were excluded. A time series design was employed in which patients were observed for 3 mo to obtain a baseline, then the planar flexor tendon sheaths were injected with 10 mg of methylprednisolone acetate or 10 mg triamcinolone acetonide and were reassessed at 1, 3, and 12 mo. RESULTS: Response rates, defined by complete resolution of digital contractures and triggering after corticosteroid injection, were 94% (31/33), 76% 28/33), and 61% (17/29) at 1, 3, and 12 mo, respectively, which were all significantly different from preinjection (p < 0.001). Individual response rates for SLJM and trigger finger were similar. No appreciable differences between methylprednisolone acetate and triamcinolone acetonide were observed, although there was a trend for earlier recurrence with methylprednisolone. CONCLUSION: Corticosteroid injection is a safe and effective therapy that should be considered in patients with SLJM or diabetic trigger finger. The excellent response to injection indicates that diabetic tenosynovitis is a common pathway in diabetic hand conditions.

Adrenal Cortex Hormones↗
PubMed1997

Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy.

PURPOSE: To determine the neurometabolism of patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR spectroscopy. METHODS: Thirty-six patients with SLE and eight control subjects were studied with proton MR spectroscopy to measure brain metabolites. Peaks from N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and at 1.3 parts per million (ppm) lipid, macromolecules, and lactate were measured. Patients were classified as having major NPSLE (seizures, psychosis, major cognitive dysfunction, delirium, stroke, or coma) (n = 15) or minor NPSLE (headache, minor affective disorder, or minor cognitive disorder) (n = 21). Patients with major NPSLE were severely ill and hospitalized. RESULTS: SLE patients had lower NAA and increased metabolites at 1.3 ppm than did control subjects (NAA/Cr(SLE) = 1.90 +/- 0.35, NAA/Cr(Control) = 2.16 +/- 0.26; 1.3 ppm/Cr(SLE) = 0.49 +/- 0.41, 1.3 ppm/Cr(Control) = 0.27 +/- 0.05). NAA/Cr in patients with current or prior major NPSLE was lower than in patients without major NPSLE. Increased peaks at 1.3 ppm were present in all SLE subgroups, but particularly in patients with major NPSLE. These resonances were not evident at an echo time of 136, indicating that these signals were not lactate. CONCLUSION: Major NPSLE, past or present, is associated with decreased levels of NAA. Elevated peaks around 1.3 ppm do not represent lactate even in severely ill patients, indicating that global ischemia is not characteristic of NPSLE. Neurochemical markers determined by MR spectroscopy may be useful for determining activity and degree of brain injury in NPSLE.

Adult↗