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S Narayanan

Publications and source records attributed to S Narayanan.

At least 55 records · Page 3Linked to original sources
PubMed2000

Imaging axonal damage in multiple sclerosis by means of MR spectroscopy.

Axonal damage in multiple sclerosis has become an important issue. This has been emphasized by recent in vivo proton magnetic resonance (MR) spectroscopy and in vitro pathology studies that have found axonal damage in both lesions and the surrounding normal-appearing white matter. In particular, proton MR spectroscopy, by monitoring levels of N-acetylaspartate (a putative marker of axonal integrity), has been particularly illuminating, as the extent of axonal injury associated with white matter inflammation and demyelination had not been well appreciated from classical pathology studies. Recent MR data demonstrate that cerebral axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of axonal damage and loss in the pathogenesis of the disease should be given due importance, and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards axonal protection.

Animals↗
PubMed2000

Increased uracil misincorporation in lymphocytes from folate-deficient rats.

The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determined. Feeding male Hooded Lister rats a folate-free diet for 10 weeks created a moderate folate deficiency (25-50% (approx.) decrease in plasma, red blood cell and hepatic folate concentrations (P < 0.05) and a 20% rise in plasma homocysteine (P < 0.05)). Lymphocyte DNA strand breakage was increased successively in all groups after 4 weeks and 8 weeks on the diet (50-100% (approx.) after 8 weeks). Only low folate specifically and progressively induced uracil misincorporation throughout the study (100% (approx.) after 8 weeks). Neither folate deficiency nor choline/methionine deficiency altered oxidative DNA base damage. In summary, moderate folate deficiency in vivo is associated with a decrease in DNA stability, measured as increased DNA strand breakage and misincorporated uracil.

Animals↗
PubMed2000

Does open access endoscopy close the door to an adequately informed patient?

BACKGROUND: The use of open access endoscopy is increasing. Its effect on the adequacy of patient informed consent, procedure acceptance and the impact on subsequent communication/transfer of procedure results to the patient have not been evaluated. The aim of our study was to compare the extent of preknowledge of procedures and test explanation, patient medical complexity, information transfer and overall patient satisfaction between a patient group referred for outpatient open access endoscopy versus a patient group from a gastrointestinal (GI) subspecialty clinic. METHODS: Information was obtained from all patients presenting for outpatient upper and lower endoscopy by using a 1-page questionnaire. Patients from the two groups who had an outpatient upper/lower endoscopic procedure were contacted by phone after the procedure to obtain information with a standardized questionnaire. RESULTS: The open access patients reported receiving significantly less information to help them identify the procedure (p < 0.01) and less explanation concerning the nature of the procedure than the group of patients referred from the subspecialty clinic (p < 0.005). There was no difference between the two groups in satisfaction scores for examinations performed under conscious sedation. For flexible sigmoidoscopy without sedation, however, the GI clinic patient group were more satisfied with their procedure. The majority of patients, regardless of access, were more likely to receive endoscopic results from a gastroenterologist than the referring physician. Furthermore, the patients in the GI clinic group who underwent colonoscopy felt significantly better at follow-up. CONCLUSIONS: Patients undergoing open access procedures are less likely to be properly informed about their endoscopic procedure. Our results indicate that with open access endoscopy, a defined mechanism needs to be in place for communication of endoscopic results to the patient.

Adult↗
PubMed2000

Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis.

Axonal injury occurs even in the earliest stages of multiple sclerosis. Magnetic resonance spectroscopic imaging (MRSI) measurements of brain N:-acetylaspartate (NAA), a marker of axonal integrity, show that this axonal injury can occur even in the absence of clinically evident functional impairments. To test whether cortical adaptive responses contribute to the maintenance of normal motor function in patients with multiple sclerosis, we performed MRSI and functional MRI (fMRI) examinations of nine multiple sclerosis patients who had unimpaired hand function. We found that activation of the ipsilateral sensorimotor cortex with simple hand movements was increased by a mean of fivefold relative to normal controls (n = 8) and that the extent of this increase was strongly correlated (sigma = -0.93, P = 0.001) with decreases in brain NAA. These results suggest that compensatory cortical adaptive responses may help to account for the limited relationship between conventional MRI measures of lesion burden and clinical measures of disability, and that therapies directed towards promoting cortical reorganization in response to brain injury could enhance recovery from relapses of multiple sclerosis.

Aspartic Acid↗
PubMed2000

Acoustic modeling of American English /r/.

Recent advances in physiological data collection methods have made it possible to test the accuracy of predictions against speaker-specific vocal tracts and acoustic patterns. Vocal tract dimensions for /r/ derived via magnetic-resonance imaging (MRI) for two speakers of American English [Alwan, Narayanan, and Haker, J. Acoust. Soc. Am. 101, 1078-1089 (1997)] were used to construct models of the acoustics of /r/. Because previous models have not sufficiently accounted for the very low F3 characteristic of /r/, the aim was to match formant frequencies predicted by the models to the full range of formant frequency values produced by the speakers in recordings of real words containing /r/. In one set of experiments, area functions derived from MRI data were used to argue that the Perturbation Theory of tube acoustics cannot adequately account for /r/, primarily because predicted locations did not match speakers' actual constriction locations. Different models of the acoustics of /r/ were tested using the Maeda computer simulation program [Maeda, Speech Commun. 1, 199-299 (1982)]; the supralingual vocal-tract dimensions reported in Alwan et al. were found to be adequate at predicting only the highest of attested F3 values. By using (1) a recently developed adaptation of the Maeda model that incorporates the sublingual space as a side branch from the front cavity, and by including (2) the sublingual space as an increment to the dimensions of the front cavity, the mid-to-low values of the speakers' F3 range were matched. Finally, a simple tube model with dimensions derived from MRI data was developed to account for cavity affiliations. This confirmed F3 as a front cavity resonance, and variations in F1, F2, and F4 as arising from mid- and back-cavity geometries. Possible trading relations for F3 lowering based on different acoustic mechanisms for extending the front cavity are also proposed.

Humans↗
PubMed2000

Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images.

PURPOSE: To determine the evolution of magnetization transfer (MT) in white matter regions before and after plaque development in patients with multiple sclerosis (MS). MATERIALS AND METHODS: In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional magnetic resonance (MR) imaging, MT MR imaging, and clinical assessment. Cross-sectional data in 12 healthy subjects were also collected. Semiautomated lesion classification with use of T2-weighted MR images was used to measure the time course of the MT ratio (calculated with MR data acquired without and with MT saturation) in every voxel and to help analyze the relationship with the status of lesions depicted on T2-weighted images. RESULTS: There was a significant (P <.001) temporal decline in lesion MT ratio after lesion appearance on T2-weighted images. A significant (P <. 001) progressive decline in MT ratio was also present in voxels that later became lesions, prior to initial detection on T2-weighted images. Even 1(1/2) years prior to lesion appearance, the MT ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both white matter in healthy subjects (41.3%) and other normal-appearing white matter in patients with MS (38.1%). CONCLUSION: The MT ratio reveals progressive focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T2-weighted MR images.

Adult↗
PubMed2000

Upper esophageal sphincter function during gastroesophageal reflux events revisited.

Upper esophageal sphincter (UES) function during gastroesophageal reflux events is not completely elucidated because previous studies addressing this issue yielded conflicting results. We reexamined the UES pressure response to intraluminal esophageal pressure and pH changes induced by reflux events. We studied 14 healthy, asymptomatic volunteers (age 49 +/- 6 yr) and 7 gastroesophageal reflux disease patients (age 48 +/- 5 yr). UES pressure, intraesophageal pressure, and pH were monitored at the distal, middle, and proximal esophagus concurrently in the supine position 1 h before and 2 h after a 1,000-calorie meal. A total of 321 reflux events were identified by the development of abrupt reflux-induced intraesophageal pressure increase (IPI); 285 events occurred in patients and 36 in control subjects. In control subjects 33 of 36 and in patients 252 of 285 IPI events were associated with a pH drop. Among patients and control subjects, 99% and 100%, respectively, of all IPI events irrespective of pH drop were associated with abrupt increase in UES pressure (34 +/- 2 and 27 +/- 6 mmHg, respectively). The average percentage of maximum UES pressure increase over prereflux values ranged between 66% and 96% (control subjects) and 34% and 122% (patients). IPIs induced by both acidic and nonacidic reflux events evoke strong UES contractile responses.

Acids↗
PubMed2000

Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells.

Epidemiological studies have indicated that folic acid protects against a variety of cancers, particularly cancer of the colorectum. Folate is essential for efficient DNA synthesis and repair. Moreover, folate can affect cellular S-adenosylmethionine levels, which regulate DNA methylation and control gene expression. We have investigated the mechanisms through which folate affects DNA stability in immortalized normal human colonocytes (HCEC). DNA strand breakage, uracil misincorporation, and DNA repair, in response to oxidative and alkylation damage, were determined in folate-sufficient and folate-deficient colonocytes by single cell gel electrophoresis. In addition, methyl incorporation into genomic DNA was measured using the bacterial enzyme Sss1 methylase. Cultured human colonocyte DNA contained endogenous strand breaks and uracil. Folate deficiency significantly increased strand breakage and uracil misincorporation in these cells. This negative effect on DNA stability was concentration dependent at levels usually found in human plasma (1-10 ng/ml). DNA methylation was decreased in HCEC grown in the absence of folate. Conversely, hypomethylation was not concentration dependent. Folate deficiency impaired the ability of HCEC to repair oxidative and alkylation damage. These results demonstrate that folic acid modulates DNA repair, DNA strand breakage, and uracil misincorporation in immortalized human colonocytes and that folate deficiency substantially decreases DNA stability in these cells.

Aged↗
PubMed2000

The preanalytic phase. An important component of laboratory medicine.

The preanalytic phase is an important component of total laboratory quality. A wide range of variables that affect the result for a patient from whom a specimen of blood or body fluid has been collected, including the procedure for collection, handling, and processing before analysis, constitute the preanalytic phase. Physiologic variables, such as lifestyle, age, and sex, and conditions such as pregnancy and menstruation, are some of the preanalytic phase factors. Endogenous variables such as drugs or circulating antibodies might interact with a specific method to yield spurious analytic results. The preanalytic phase variables affect a wide range of laboratory disciplines.

Adolescent↗
PubMed2000

Proton MR spectroscopy to assess axonal damage in multiple sclerosis and other white matter disorders.

Proton MR spectroscopy allows in vivo measurement of N-acetylaspartate in white matter, providing a biochemical index of axonal integrity. Several recent studies of patients with multiple sclerosis and other white matter disorders have shown both transient and sustained decreases in N-acetylaspartate in white matter lesions and in brain regions appearing normal on conventional MRI. These data have emphasised that a substantial amount of axonal damage or loss (presumably secondary to myelin pathology) is consistently present in most of these disorders. Recent post-mortem studies support these results. In contrast to changes seen with conventional MR imaging, decreases in N-acetylaspartate have shown a close correlation with changes in neurological status. This suggests that axonal damage may be more relevant than demyelination for determining chronic functional impairments in primary white matter diseases. Thus, serial measurement of brain N-acetylaspartate with proton MR spectroscopy can provide a reliable and clinically-relevant monitor of disease evolution. As pathological changes responsible for long-term morbidity are logically important targets for therapeutic agents, early treatment directed at axonal protection should be useful in these disorders.

Axons↗
PubMed2000

Utility of polymerase chain reaction using two probes for rapid diagnosis of tubercular pleuritis in comparison to conventional methods.

We have used polymerase chain reaction (PCR) with IS6110 and a new set of primers from an insertion element like repetitive sequence, (TRC4) to detect Mycobacterium tuberculosis in pleural effusion samples from 50 patients having pleuritis. The results of PCR were compared with the results of conventional methods like smear, culture and adenosine deaminase activity. Thirty six specimens were positive and 14 were negative by PCR. Among the 36 samples, 33 were from patients with clinical evidence of tuberculosis including response to anti-tuberculosis therapy. Only six samples were positive by the gold standard which is culture, and three were positive by smear. The measurement of adenosine deaminase activity classified 19 samples as positives. The overall sensitivity and specificity of PCR was 100 and 85 per cent respectively. PCR using IS6110 and TRC4 primers is a sensitive test as compared to conventional tests for detection of M. tuberculosis from pleural fluid samples of patients with tubercular pleuritis.

Adenosine Deaminase↗
PubMed2000

Technology and laboratory instrumentation in the next decade.

We are affected by many forces as we approach the first decade of the new millennium. Rapid advances in computer technology and robotic automation, from sample identification to collection, processing, analysis, and reporting of results, are opening doors for drastic improvements that will ultimately lead to miniaturization and cost reduction. Noninvasive technology, whether in vivo or ex vivo, is waiting in the wings to make its debut. Technology that has previously had an inordinately long period of gestation, such as near-infrared sensors for noninvasive measurement of glucose and other analytes, could well become a reality. The end of the next decade may be an era of nanotechnology that will drastically change the face of today's clinical laboratory.

Automation↗
PubMed2000

Proton MR spectroscopy in multiple sclerosis.

Axonal injury in multiple sclerosis (MS) is focal and diffuse, and is directly responsible for irreversible disability. Acute inflammatory events can be associated with reversible disability that may parallel reversible axonal injury. This in part accounts for the remission following relapses early in the disease. By the time there is clinical disability, substantial axonal injury already has occurred. This provides a strong rationale for the early limitation of inflammation and its consequences.

Aspartic Acid↗
PubMed1999

Orphanin FQ and behavioral sensitization to cocaine.

The recently identified endogenous ligand for the ORL-1 (opioid receptor-like) receptor, orphanin FQ, has been shown to induce hypolocomotion and to decrease extracellular dopamine levels in the nucleus accumbens (N.Acc) after intraventricular (ICV) administration. This study investigated the effect of intraventral tegmental area (VTA) administration of orphanin FQ on the hyperlocomotor effects of peripheral cocaine administration and on the development of behavioral sensitization to cocaine. The administration of cocaine (40 mg/kg IP) once daily for 3 days to male Sprague-Dawley rats resulted in an enhanced locomotor response to a subsequent challenge of cocaine (10 mg/kg IP) 5 days later. The bilateral administration of orphanin FQ (10 microg/side or 30 microg/side) into the VTA 5-10 min prior to the administration of cocaine (40 mg/kg IP) produced a transient (15-30 min) decrease in the hyperlocomotor response to cocaine on day 1 but not on days 2 and 3 of the sensitization paradigm. Such orphanin FQ pretreatment on days 1-3 had no effect on the development of a sensitized response to cocaine (10 mg/kg IP) 5-7 days after the last orphanin FQ injection. However, repeated intra-VTA administration of orphanin FQ (30 microg/side) alone for 3 days resulted in a sensitized response to a single dose of cocaine (10 mg/kg IP) given 5-7 days later. These results indicate that orphanin FQ decreases the activity of mesolimbic dopamine neurons via an action in the VTA, an effect that is both transient and demonstrates rapid tolerance, and consequently, is insufficient to prevent the development of cocaine sensitization. The ability of the peptide to induce cocaine sensitization when administered alone despite its acute inhibitory effects is unique and requires further study to elucidate the mechanisms responsible.

Amino Acid Sequence↗
PubMed1999

Ultraviolet and visible light spectrophotometric approach to blood typing: objective analysis by agglutination index.

BACKGROUND: A new blood typing technology based on ultraviolet (UV) and visible light spectroscopy (UV/visible spectroscopy) has been developed. Blood groups and types are determined by quantifying reproducible changes in the UV and visible light spectra of blood in the presence of agglutinating antibodies. STUDY DESIGN AND METHODS: Samples of red cells in the presence and absence of agglutinating antibodies were examined by UV/visible spectroscopy. Blood groups and types were determined by comparing the optical density spectra obtained between 665 and 1000 nm. These comparisons generate numbers (agglutination index) ranging from 0 to 100, with smaller numbers corresponding to lack of agglutination and larger numbers corresponding to agglutination. RESULTS: The optical density of agglutinated blood is dramatically different from that of unagglutinated blood. The agglutination index derived from the relative slopes of the spectra is an objective indicator of agglutination strength. An agglutination index greater than 17 consistently and accurately established blood group- and type-specific agglutination. CONCLUSION: The method accurately predicted A, B, and O blood groups, and D type in over 275 samples. Scattering theory-based calculations of relative volumes of red cells before and after agglutination show a direct correlation with the agglutination index and provide the theoretical basis of the analysis. This quantitative technique is reproducible and has the potential for automation.

Blood Grouping and Crossmatching↗
PubMed1999

In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis.

To test for axonal damage or dysfunction in white matter tracts remote from acute demyelinating lesions, we used brain proton magnetic resonance spectroscopic imaging to measure changes in N-acetyl aspartate (NAA), an index of neuronal integrity, in the white matter of the normal-appearing hemisphere of three patients with large, solitary brain demyelinating lesions of the type seen early in multiple sclerosis. During the acute phase of their disease, all patients showed normal ratios of NAA to creatine (Cr) resonance intensity throughout the hemisphere contralateral to the lesion. However, on examination 1 month later, all of the patients showed abnormally low NAA/Cr resonance intensity ratios (reduction of NAA/Cr by 22-35%) in voxels of the contralateral hemisphere which were homologous to the demyelinating lesion. Other voxels in the normal-appearing hemisphere showed normal NAA relative resonance intensities. The decrease in NAA/Cr in voxels of the normal-appearing hemispheres resolved in all patients after 6 months, with a time course similar to that observed for NAA from voxels within the lesions. We conclude that effects of damage or dysfunction to axons traversing inflammatory lesions can be transmitted over long distances in the normal-appearing white matter. Such remote, secondary effects may be an expression of dysfunction of axons in projection pathways or of the reorganization of functional pathways seen in brains recovering from an acute injury.

Acute Disease↗
PubMed1999

Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis?

It is generally believed that most T2-weighted (T2) lesions in the central white matter of patients with multiple sclerosis begin with a variable period of T1-weighted (T1) gadolinium (Gd) enhancement and that T1 Gd-enhancing and T2 lesions represent stages of a single pathological process. Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population. The simplest prediction of this hypothesis would be that the spatial distributions of T1 Gd-enhancing and T2 lesions are identical. We generated T1 Gd-enhancing and T2 lesion probability maps from 19 patients with relapsing-remitting multiple sclerosis. There was a significantly higher probability (P = 0.001) for T2 lesions to be found in the central relative to the peripheral white matter (risk ratio 4.5), although the relative distribution of T1 Gd-enhancing lesions was not significantly different (P = 0.7) between central and peripheral white matter regions (risk ratio 0.6). Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry between new T1 Gd-enhancing and new T2 lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested. We found no spatial difference in the likelihood of development of persistent T2 lesions following T1 Gd enhancement. The relative distribution of T1 Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning. Our findings suggest that a proportion of the periventricular T2 lesion volume may arise from mechanisms other than those associated with early breakdown of the blood-brain barrier leading to T1 Gd enhancement.

Adult↗