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Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 37 records · Page 2Linked to original sources
PubMed2004

Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests.

BACKGROUND: HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy ((1)H-MRS), but how these abnormalities relate to brain function is unclear. METHODS: Metabolite concentrations in five brain regions of 20 HIV-infected and 13 control children were measured, and these findings were correlated with age, log(10) plasma viral load, CD4 count, and neuropsychological scores. RESULTS: Compared with control subjects, HIV patients had decreased choline concentration [Cho] in left frontal white matter (LFW) (-12%; p = 0.04); those with high viral load (>5,000 HIV RNA copies/mL) had decreased right basal ganglia (RBG) [Cho] (-15%; p = 0.005), and [Cr] (-13%; p = 0.02). Patients with high viral load also had higher [Cho] in the midfrontal gray matter (MFG) (+25%; p = 0.002) and lower myo-inositol [Ins] in the RBG (-18%; p = 0.04) than patients with low HIV viral load. N-Acetyl aspartate concentration ([NAA]) correlated with age in right frontal white matter (RFW) (r = 0.59, p = 0.04), LFW (r = 0.66, p = 0.02), and right hippocampus (RHIP) (r = 0.69, p = 0.02) only in control subjects. In contrast, [Ins] correlated with age in both RFW and LFW (r = 0.71, p = 0.0006; r = 0.65, p = 0.006) only in the HIV patients. Log(10) plasma viral load correlated positively with [Ins] in RFW (r = 0.54, p = 0.02) and [Cho] in MFG (r = 0.49, p = 0.04). Compared with control subjects, HIV patients had poorer spatial memory (p = 0.045) and delayed spatial memory correlated with [Cho] in RHIP (r = 0.68, p = 0.02). CONCLUSIONS: These data suggest that normal brain development may be affected in children infected with HIV at birth, particularly evidenced by the lack of age-related increases in the neuronal marker [NAA]. Early, aggressive treatment of infants with HIV before development of encephalopathy is warranted.

Adolescent↗
PubMed2004

Anti-hyperalgesic effect of octreotide in patients with irritable bowel syndrome.

BACKGROUND: Octreotide has been found to be beneficial in the treatment of chronic pain, although the mechanisms underlying its therapeutic effect are incompletely understood. AIMS: To assess the effect of octreotide on perceptual responses to rectal distension in irritable bowel syndrome patients and healthy controls at baseline and following the experimental induction of rectal hyperalgesia. METHODS: In study 1, rectal perception thresholds for discomfort were determined in seven irritable bowel syndrome patients and eight healthy controls on three separate days using a computer-controlled barostat. Subjects received saline, low-dose and high-dose octreotide in a random double-blind fashion. In study 2, perceptual responses to rectal distension were obtained in nine irritable bowel syndrome patients and seven controls before and after repetitive high-pressure mechanical sigmoid stimulation. RESULTS: Octreotide increased the discomfort thresholds in irritable bowel syndrome patients, but not in controls, without changing rectal compliance. Repetitive sigmoid stimulation resulted in decreased rectal discomfort thresholds in the patient group only. In irritable bowel syndrome patients, octreotide prevented the sensitizing effect of repetitive sigmoid stimulation on rectal discomfort thresholds. CONCLUSIONS: Octreotide effectively increased discomfort thresholds in irritable bowel syndrome patients, but not in controls, at baseline and during experimentally induced rectal hyperalgesia. These findings suggest that octreotide exerts primarily an anti-hyperalgesic rather than analgesic effect on visceral perception.

Adult↗
PubMed2004

Methamphetamine and AIDS: 1HMRS studies in a feline model of human disease.

Potential interactions between psychostimulant drugs and infection with feline immunodeficiency virus (FIV) on brain metabolism were evaluated. Four groups of cats were studied: control, FIV positive, methamphetamine (MA) exposed, and FIV positive plus MA exposed. Frontal gray matter, frontal white matter, and caudate brain extracts were studied with proton magnetic resonance spectroscopy (1HMRS). In the frontal white matter, FIV-infected cats showed decreases in creatine and choline, while MA-treated cats had elevated gamma-aminobutyric acid (GABA). The decreased glutamate in FIV cats normalized with MA exposure. FIV and MA both affect brain metabolites individually and combined. 1HMRS is useful for evaluating the effects of FIV and drug abuse in the brain.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Increased frontal white matter diffusion is associated with glial metabolites and psychomotor slowing in HIV.

Diffusion-weighted imaging (DWI) measures brain water diffusion that is sensitive to microscopic brain injury. A total of 11 HIV seropositive patients were compared to 14 seronegative subjects using DWI, proton magnetic resonance spectroscopy (1H MRS), and neuropsychological tests. The apparent diffusion coefficient (ADC) was significantly increased in the HIV patients, primarily in the frontal white matter (FWM; +5%, p=0.01). Diffusivity correlated positively with the glial marker myo-inositol (r=0.5, p=0.008) and negatively with cognitive performance (NPZ-8 composite score; r=-0.43, p=0.05). These findings suggest increased brain water diffusion may reflect increased glial activation or inflammation, which in turn, may contribute to the cognitive deficits in HIV patients.

Adolescent↗
PubMed2004

Practice-induced changes of brain function during visual attention: a parametric fMRI study at 4 Tesla.

A parametric functional MRI (fMRI) study with three levels of task difficulty was performed to determine the effect of practice and attentional load on brain activation during visual attention tasks. Brief practice during repeat fMRI scanning (20 min) did not change performance accuracy or reaction times (RT), but decreased activation bilaterally in the inferior, middle, and superior frontal gyri, superior temporal gyrus, thalamus, and cerebellum. Increased attentional load decreased performance accuracy but not RT, and increased activation bilaterally in the inferior, posterior, and superior parietal cortices, thalamus, cerebellum, and frontal gyri. These changes suggest that practice decreases dependency on thalamus, cerebellum, and the frontal cortices for controlled task processing possibly due to increased efficiency of the attentional network. Since short-term practice-effects in the prefrontal cortex may be similar to attentional load-effects, studies of attentional load need to take practice effects into account.

Adult↗
PubMed2004

A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age.

OBJECTIVE: Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment. METHODS: Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls. RESULTS: Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter. CONCLUSIONS: The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.

AIDS Dementia Complex↗
PubMed2004

Using chaotic interrogation and attractor nonlinear cross-prediction error to detect fastener preload loss in an aluminum frame.

Structural health monitoring is an important field concerned with assessing the current state (or "health") of a structural system or component with regard to its ability to perform its intended function appropriately. One approach to this problem is identifying appropriate features obtained from time series vibration responses of the structure that change as structural degradation occurs. In this work, we present a novel technique adapted from the nonlinear time series prediction community whereby the structure is excited by an applied chaotic waveform, and predictive maps built between structural response attractors are used as the feature space. The structural response is measured at several points on the structure, and pairs of attractors are used to predict each other. As the dynamics of the structure change due to damage, the prediction error rises. This approach is applied to detecting the preload loss in a bolted joint in an aluminum frame structure.

Journal Article↗
PubMed2004

Review article: epidemiology and quality of life in functional gastrointestinal disorders.

The epidemiology and health-related quality of life associated with functional gastrointestinal disorders are reviewed, with particular emphasis on irritable bowel syndrome and functional dyspepsia. The literature supports the significant world-wide prevalence of functional gastrointestinal disorders, including irritable bowel syndrome (IBS), functional dyspepsia and chronic constipation. An increased female prevalence has been demonstrated in most studies in patients with IBS and chronic constipation, but not functional dyspepsia. The female to male ratio appears to be greater in the health care-seeking population than in community populations. However, some differences in the reported general prevalence and gender-related prevalence of functional gastrointestinal disorders may be due to cultural factors and study methodology. A significant health care burden is associated with IBS, with increased out-patient services, abdominal and pelvic surgeries, and gastrointestinal- and non-gastrointestinal-related physician visits and health care costs. Health-related quality of life is impacted significantly in patients with functional gastrointestinal disorders, such as functional dyspepsia and IBS, compared with the general healthy population, as well as patients with other chronic medical conditions, such as gastro-oesophageal reflux disease and asthma. Impaired health-related quality of life has been demonstrated, in particular, in patients with moderate to severe disease seen in referral settings. The health-related quality of life appears to improve in treatment responders, or correlates with symptom improvement, with at least some treatment modalities studied in functional gastrointestinal disorders, but further studies are needed. Predictors of health-related quality of life in patients with functional gastrointestinal disorders include psychosocial factors, such as early adverse life events, and symptoms related to visceral perception, e.g. pain and chronic stress. The presence of extra-intestinal symptoms appears to have a major if not greater impact on health care visits, excess health care costs and health-related quality of life in patients with functional gastrointestinal disorders.

Adult↗
PubMed2003

Robotic surgery: identifying the learning curve through objective measurement of skill.

BACKGROUND: The incorporation of new devices into surgical practice often requires that surgeons acquire and master new skills. We studied the learning curve for intracorporeal knot tying in robotic surgery. METHODS: We developed an objective scoring system to evaluate knot tying and tested eight attending surgeons during 3 weeks of training on a surgical robot. Each performed intracorporeal knot tying tasks both before and after robotic skills training. These performances were compared to their laparoscopic knots and analyzed to determine and define skill improvement. RESULTS: Baseline laparoscopic knot completion took 140 sec (range, 47-432), with a mean composite score of 77 (100 possible), whereas robotic knot tying took 390 sec, with a mean composite score of 40. After initial robotic training, times decreased by 65% to 139 sec and scores increased to 71. With more training, completion times and composite scores were improved and errors were reduced. CONCLUSION: Like any new technology, surgical robotics requires dedicated training to achieve mastery. Initially, even experienced laparoscopists may register an inferior performance. However, after adequate training, surgeons can exceed their laparoscopic performance, completing intracorporeal knots better and faster using robotics.

Adult↗
PubMed2003

Increased glial metabolites predict increased working memory network activation in HIV brain injury.

Deficits in attention and working memory are common in human immuno deficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy ((1)H MRS) and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. To evaluate the model that attentional deficits in early HIV brain disease are related to brain inflammation, (1)H MRS and fMRI were performed in 14 HIV-positive subjects [acquired immunodeficiency syndrome (AIDS) dementia complex stage 1 or less]. Increasing attentional load on three working memory tasks was assessed with fMRI, and the concentrations of brain metabolites were measured with (1)H MRS in the frontal gray and white matter, and basal ganglia. Metabolite concentrations were correlated with fMRI blood oxygenation level-dependent (BOLD) signals, using a random-effects linear regression model in SPM99. Several positive correlations were observed between the BOLD signal strength in the working memory network (posterior parietal cortex and lateral prefrontal cortex) and the concentrations of frontal white matter and basal ganglia metabolites that are predominant in glial cells (choline-containing compounds, myo-inositol, and total creatine). In contrast, BOLD signals in the working memory network were not correlated with the concentration of N-acetyl compounds, which are markers of neuronal viability, or with metabolite concentrations in the frontal gray matter. These findings are consistent with previous results that mild HIV brain injury is associated with increased glial activation without major involvement of neuronal abnormalities. We propose that the inflammatory glial abnormalities reduce the efficiency of neural processing, and necessitate compensatory increases in attention in patients, and associated BOLD signals, to perform a given task. The same mechanism may also contribute to cognitive dysfunction in other brain diseases that involve inflammation.

AIDS Dementia Complex↗
PubMed2003

Novel strategy for identification of candidate cytotoxic T-cell epitopes from human preproinsulin.

We describe a strategy for identifying ligands of human leukocyte antigen (HLA) class I molecules based on a peptide library-mediated in vitro assembly of recombinant class I molecules. We established a microscale class I assembly assay and used a capture ELISA to quantify the assembled HLA-peptide complexes. The identity of the bound ligands was then deduced by mass spectrometry. In this method, HLA complexes assembled in vitro in the presence of components of a mixture of peptides were immunoprecipitated and the bound peptide(s) identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. This process of epitope extraction is robust and can be used with complex mixtures containing in excess of 300 candidate ligands. A library of overlapping peptides representing all potential octamers, nonamers and decamers from human preproinsulin was synthesized using unique library chemistry. Peptides from the library were used to initiate assembly of recombinant HLA-B8, HLA-B15 and HLA-A2, facilitating the identification of candidate T-cell epitopes from preproinsulin.

Epitopes, T-Lymphocyte↗
PubMed2003

Androgens modulate beta-amyloid levels in male rat brain.

As a normal consequence of aging, men experience a significant decline in androgen levels. Although the neural consequences of age-related androgen depletion remain unclear, recent evidence suggests a link between low androgen levels and the development of Alzheimer's disease (AD). Here, we test the hypothesis that androgens act as endogenous modulators of beta-amyloid protein (Abeta) levels. To investigate this possibility, brain and plasma levels of Abeta were measured in male rats with varying hormonal conditions. Depletion of endogenous sex steroid hormones via gonadectomy (GDX) resulted in increased brain levels of Abeta in comparison to gonadally intact male rats. This GDX-induced increase in Abeta levels was reversed by DHT supplementation, demonstrating a functional role for androgens in modulating brain levels of Abeta. These findings suggest that age-related androgen depletion may result in accumulation of Abeta in the male brain and thereby act as a risk factor for the development of AD.

Amyloid beta-Peptides↗
PubMed2003

Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than nonresponders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Real-time PCR assay for quantitative mismatch detection.

We describe here a quantitative real-time PCR assay for the detection of single-base-pair differences that does not require fluorescently labeled gene-specific probes or complicated primer combinations. Following PCR or RT-PCR of a gene segment that may contain allele-specific differences, 100 pg amplified product are used for a real-time PCR with allele-specific primers and SYBR Green. The use of HEPES buffer at a pH of 6.95 together with AmpliTaq DNA polymerase results in a threshold difference between the correct template and the mismatched template of as many as 20 cycles, depending on the mismatch. Correct matches can be detected in an excess of mismatched template at least at the 0.01 level for the six primer-template matches versus mismatches tested: GC vs. A.C, AT vs. G.T, GC vs. C.C, GC vs. G.G, AT vs. C.T, and GC vs. G.A. Because the initial amplification is separate from real-time detection, conditions can be independently optimized for each step, making the assay particularly suitable for the detection of allele-specific expression in single cells.

Animals↗
PubMed2002

Improving accuracy in identifying the gastroesophageal junction during laparoscopic antireflux surgery.

BACKGROUND: Proper construction of an effective fundoplication to control reflux depends on accurate identification of the gastroesophageal junction (GEJ). In laparoscopic surgery, the accuracy of this GEJ determination is unknown. METHODS: In 40 consecutive laparoscopic antireflux procedures, the GEJ location was determined independently by endoscopy and laparoscopy, and the differences were measured. After this was completed, endoscopic examination of the fundoplication was performed. RESULTS: The "laparoscopic" GEJ was identified within 1 cm of the "endoscopic" GEJ in 36 of 40 (90%) patients. In four patients, this difference was greater and the GEJ always higher than determined by laparoscopy. These patients had greater acid exposure and esophageal injury. On two occasions, the fundoplication was reconstructed on the basis of endoscopic findings. CONCLUSIONS: With laparoscopy, the surgeon can accurately determine the GEJ location in most patients. In approximately 10%, the GEJ is actually higher than the surgeon believes, and the fundoplication may be created lower than intended. Intraoperative endoscopy helps to identify the GEJ location and evaluate the wrap once completed.

Adult↗
PubMed2002

Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients.

BACKGROUND/OBJECTIVES: A previous fMRI study demonstrated increased brain activation during working memory tasks in patients with HIV with mild dementia. The current study aims to determine whether patients who are HIV-1 positive and have normal cognitive function also show increased brain activation on fMRI. METHODS: Blood oxygenation level-dependent (BOLD) fMRI was performed in 10 patients with HIV (CD <500) and 10 age-, sex-, education-, and handedness-matched seronegative subjects. Each subject performed a battery of neuropsychological tests and fMRI with three tasks (0-back, 1-back, and 2-back) that required different levels of attention for working memory. RESULTS: Compared with control subjects, patients with HIV showed greater magnitude of brain activation (BOLD signal intensity changes, p <or= 0.001) in the lateral prefrontal cortex, with normal performance during fMRI and on a battery of neuropsychological tests. The patients with HIV also showed increased activated brain volume in the lateral prefrontal cortex (p = 0.007) but not in other activated regions, including the posterior parietal cortex, supplementary motor area, thalamus, caudate, and occipital cortex. The increase in activated brain volume was independent of task difficulty. CONCLUSION: Increased brain activation in subjects who are positive for HIV precedes clinical signs or deficits on cognitive tests. Early injury to the neural substrate may necessitate increased usage of brain reserve to maintain normal cognitive function. BOLD fMRI appears to be more sensitive than clinical and neuropsychological evaluations for detecting early HIV-associated brain injury.

AIDS Dementia Complex↗
PubMed2002

The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.

AIM: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses. METHODS: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales. RESULTS: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron. CONCLUSIONS: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.

Adult↗