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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 37 records · Page 2Linked to original sources

Intracoronary stenting using slotted tubular stents with intravascular ultrasound and anticoagulation.

Intravascular ultrasound guidance has been suggested as a prerequisite before managing patients receiving slotted tubular stents without anticoagulation. The purpose of this prospective observational study was to determine if patients receiving this stent can be similarly managed following angiographic guided stent deployment without intravascular ultrasound assistance. A total of 137 patients receiving slotted tubular stents were selected to receive a protocol of aspirin 325 mg and ticlopidine 250 mg for 30 days following the satisfaction of certain angiographic criteria. These criteria were: adequate coverage of intimal dissections, absence of residual filling defects, and normal (TIMI III) flow in the stented vessel at the end of the procedure. The stenting procedure was planned in 68% of patients and unplanned in 32% of patients. During the 30 day clinical follow period there were no stent thrombosis events, no Q-wave myocardial infarctions, and no deaths. Non-Q-wave myocardial infarction occurred in 3 patients (2.2%), hemorrhage requiring blood transfusion in 3 patients (2.2%), and 1 patient (0.7%) developed a pseudo-aneurysm of the cannulated femoral artery. These data indicate that patients receiving slotted tubular stents with optimal angiographic results can be safely managed with the combination of aspirin and ticlopidine without anticoagulation or the need for intravascular ultrasound guidance.

Adult

Magnetic resonance imaging of trabecular bone structure in the distal radius: relationship with X-ray tomographic microscopy and biomechanics.

The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 microns isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156 x 156 x 300 microns). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (approximately 3 times), trabecular width (approximately 3 times), fractal dimension (approximately 1.4 times) and first Betti number/ volume (approximately 10 times), and an underestimation of trabecular spacing (approximately 1.6 times) in the MR images compared with the 18-microns XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.

Absorptiometry, Photon

Cryptococcosis associated with HIV negative Indian patients and HIV positive Indian blood donors.

Cryptococcosis, particularly cryptococcal meningitis (CM), has become an increasing problem globally in the AIDS era. In the present investigation we have made an effort for the first time to study Indian cases (100) both HIV-positive (23 cases, male, mostly Indian professional blood donors, PBDs') confirmed by an ELISA test and Western Blot but asymptomatic for CM and HIV-negative (77:49 male and 28 female) asymptomatic or symptomatic. These subjects were patients from the Lucknow hospitals admitted during the period between February, 1991 to February, 1994, for suspected cryptococcosis or CM. Of those cases, 10% were positive for cryptococcosis or CM. Meningoencephalitis was the dominant clinical manifestation in four (HIV-negative) cases of CM. CT scanning of the head of those cases revealed a noncommunicating hydrocephalus due to aqueductal stenosis (in 2 cases) and a communicating hydrocephalus with granuloma (by MRI) in another case. The latex agglutination test (LAT) of the sera was positive for Cryptococcus antigen in 6 (26%) of the (HIV-positive) patients and 4 (5%), of the HIV-negative cases. In the cases of CM, there was a lower antigen titre in CSF than in the pronase-treated sera. The LAT was found to be useful in diagnosis of cryptococcosis, especially in asymptomatic cases. The CSF of CM-positive cases revealed low levels of glucose, reduced cell count and high proteins. Among the HIV-negative cases, the onset of meningitis in 4 cases was preceded by the presence of encapsulated budding yeast cells in CSF India ink smear, or cryptococci in a direct urine smear in one case. The CSF culture of 3 cases was positive for mucoid Cryptococcus neoformans, showing brown colour effect (BCE) on Staib agar (syn. Guizotia abyssinica creatinine agar, bird seed agar). The isolated yeast strains were identified as C. neoformans var. neoformans by physiological tests. The pathogenicity test of strains revealed virulence to BALB/c mice evidenced by a high mortality of mice and significantly (p < 0.05) high CN burden (> 4-5 mean log(10) cfu), in the brain followed by other visceral organs (lung, liver, spleen, kidney and heart). The in-vitro susceptibility (MIC mu gmL(-1)) of strains.

AIDS-Related Opportunistic Infections

Decreased levels of circulating IFN-alpha and increased sCD23 in patients with acute infectious mononucleosis.

Epstein-Barr virus (EBV) is the etiological agent for acute infectious mononucleosis (AIM). It is also associated with certain malignant disorders in individuals with immunodeficiencies such as B cell lymphoproliferative disorder (BLPD). Our previous study with BLPD patients had demonstrated significantly higher serum IL-4 and IgE levels and significantly decreased IFN-alpha levels. These observations were consistent with the model of regulation of B cell growth by T cell-derived cytokines, in which IL-4 promotes B cell growth and switch to IgE synthesis whereas IFN-alpha and IFN-gamma inhibit these IL-4 mediated effects. Since AIM is also EBV associated, this study was designed to examine IL-4, IFN-alpha, IFN-gamma, IgE, and soluble CD23 (sCD23) serum levels in AIM patients. In this study we report for the first time that in contrast to BLPD patients, AIM patients did not exhibit increased levels of IL-4 and IgE; however AIM patients to exhibit decreased IFN-alpha levels and, additionally, also exhibit significantly higher sCD23 levels. This could result in B cell activation and have implications for the survival of the virus in B cells.

Acute Disease

Decreased production of IL-2 and IFN-gamma by stimulated splenocytes from mice bearing plasma cell tumors is associated with alteration of DNA-binding factors.

We have previously demonstrated that polyclonally stimulated splenocytes as well as enriched T cells from mice bearing plasma cell tumors (PCT) show decreased production of the Th1-associated cytokines, IL-2 and IFN-gamma. This observed loss of IL-2 and IFN-gamma production could be attributed to possible alterations in various factors required for T cell activation and cytokine production. We find that B7 co-stimulatory molecules and IL-2R are up-regulated normally on splenocytes from PCT mice. Concanavalin A (Con A) stimulation of splenocytes from PCT mice in the presence of immobilized anti-CD28 antibody does not enhance proliferation. Exogenous rIL-2 addition to cultures of splenocytes from PCT mice also does not enhance proliferative responses or cytokine production. Furthermore, we do not observe inhibition of normal splenocyte proliferation and IL-2 production in the presence of splenocytes from PCT mice, suggesting that the appearance of suppressor cells cannot account for the decreased responses by splenocytes from PCT mice. Also, IL-2 mRNA levels are decreased in stimulated splenocytes from PCT mice, suggesting that there may be an alteration of transcription factors required for activation of IL-2. Therefore, we have evaluated the DNA-binding activity of transcription factors involved in activation of IL-2 and IFN-gamma gene transcription. We find that binding activities of AP-1, Oct-1 and Oct-2 transcription factors in stimulated splenocytes from PCT mice are similar to normal splenocytes. However, the binding activities of NF-kappa B complexes and factors that bind to the proximal conserved element in the IFN-gamma promoter are dramatically altered in splenocytes from PCT mice. These results suggest that PCT induce changes in certain transcription factors that are important for anti-tumor responses, including T cell proliferative responses and Th1-associated cytokine production.

Animals

In vitro and in vivo recovery of IFN-gamma, but not IL-2, production by IL-12 in mice with plasma cell tumors.

We have previously found that T cells from mice bearing plasma cell tumors (PCT mice) demonstrate decreased proliferation as well as decreased production of the Th 1-associated cytokines IL-2 and IFN-gamma in response to polyclonal stimulation. In the present study, we have examined soluble factors as possible elements required to rescue this decreased proliferation and cytokine production by splenocytes from PCT mice. We find that the addition of supernatants from stimulated normal splenocytes has no effect on proliferation of IL-2 production by splenocytes from PCT mice. In contrast, these supernatants completely restore IFN-gamma production by splenocytes from PCT mice. We have found that IL-12 is responsible for the observed increase in IFN-gamma production because: (i) addition of anti-IL-12 antibody blocks this recovery of IFN-gamma production by these supernatants, (ii) the addition of recombinant IL-12 to cultures of splenocytes from PCT mice results in increased IFN-gamma production and (iii) in vivo treatment of PCT mice in IL-12 also results in increased IFN-gamma production by the subsequently activated splenocytes, but has little effect on proliferation or IL-2 production. These results demonstrate that both in vitro and in vivo, IL-12 selectively restores the decreased production of IFN-gamma by splenocytes from PCT mice.

Animals

Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid.

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. We measured the total amounts [picograms (pg)] and concentrations.(pg/microliter) of interleukin-1 alpha (IL-1 alpha), interleukin-8 (IL-8) and interferon-alpha (IFN-alpha) in 20 s gingival crevicular fluid (GCF) samples obtained from 2 diseased and 2 healthy sites in 20 subjects with periodontitis, and from 2 healthy sites in 20 subjects without disease. Both the mean amount and concentration of IL-1 alpha were significantly higher (p < 0.001) in diseased sites compared to healthy sites in subjects with disease. The results for IL-8 and IFN-alpha differed depending on the method of reporting. Whereas the amount of IL-8 was significantly higher (p < 0.01) in diseased sites, the mean concentration of IL-8 was lower compared to healthy sites. The mean amount of IFN-alpha was similar in health and disease; however, the concentration of IFN-alpha was significantly lower in diseased sites (p < 0.001) corresponding to the significant increase in crevicular fluid volume (p < 0.001). There were no significant differences in the amount or concentrations of the 3 cytokines between healthy sites from subjects with disease and healthy sites from healthy controls. The total amounts of both IFN-alpha and IL-8 were correlated between healthy and diseased sites in subjects. These data suggest that, while the disease status of a site is the major determinant of the levels of these cytokines locally, subjects with high levels of IL-8 and IFN-alpha in healthy sites also tend to have high levels of these cytokines in diseased sites. Finally, both the concentrations and total amounts of IL-8 and IFN-alpha were significantly correlated in diseased sites, suggesting that levels of these two cytokines rise or fall in tandem. The combination of decreased IL-8 and decreased IFN-alpha concentrations at diseased sites may reflect the reduced anti-bacterial host defense activity at that site.

Adult

Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density.

PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.

Albumins

Osteoporosis: association of recent fractures with quantitative US findings.

PURPOSE: To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. MATERIALS AND METHODS: The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. RESULTS: The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. CONCLUSION: Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.

Aged

cGMP-dependent protein kinase inhibitors block light-induced phase advances of circadian rhythms in vivo.

Synchronization of circadian rhythms is thought to be accomplished primarily through daily phase delays and advances of the endogenous circadian clock that, in mammals, is located in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, numerous second messenger pathways may participate in photic signal transduction. In these studies, the involvement of cyclic nucleotide-dependent kinases was examined in vivo using inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP)- and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent kinase (PKA and PKG, respectively). In constant dark, selective and nonselective inhibitors of PKG injected near the SCN of hamsters had no effect on phase delays produced by light pulses given in the early subjective night (early in the animals' active period) but significantly attenuated phase advances induced late in the subjective night. PKA inhibition had no effect at either time point. In addition, cGMP agonists had no effect on rhythmicity in the absence of light. The results suggest that PKG activity is necessary, but not sufficient, for normal photic responsiveness and that PKA activity is not required. The phase dependence of the effect of PKG inhibition supports the notion that photic entrainment is influenced by biochemical pathways that differentially regulate sensitivity in a phase-dependent manner.

Alkaloids

Detection of local and systemic cytokines in adult periodontitis.

Periodontitis is a chronic inflammatory disease of the soft and hard supporting tissues of the teeth and is a major cause of tooth loss in adults. The local host response to periodontopathic bacteria results in the release of inflammatory mediators and cytokines. Since cytokines are indicative of effector functions, we compared the pattern of cytokine production in periodontal patients and healthy controls. Specifically, we investigated the simultaneous presence of cytokines produced by T helper (Th)1, Th 2, and inflammatory cells which could be involved in periodontitis. We also compared the expression of these cytokine mRNAs in healthy and diseased tissues. No significant differences were detected at the protein or mRNA levels of the cytokines in the systemic circulation of patients and controls. The surface markers CD16 and CD56 were expressed on significantly fewer peripheral mononuclear cells of patients when compared to controls. gamma delta + T cells were found in half of the diseased tissues, but in none of the healthy tissues of either patients or controls. Finally, significant differences were observed between healthy and inflamed gingival tissues in the cytokine mRNA profile. Expression of IL-6 and IFN-alpha mRNA was significantly higher in diseased tissues compared to healthy tissues in patients.

Adult

Quantitative CT assessment of the lumbar spine and radius in patients with osteoporosis.

OBJECTIVE: We undertook this study to quantify the relationship between bone mineral assessments of the lumbar spine using quantitative CT (QCT) and of the radius using peripheral QCT (pQCT) and to test the sensitivity of both techniques in detecting changes in bone mass that are related to age and osteoporosis. SUBJECTS AND METHODS: Forty-two healthy premenopausal, 38 healthy postmenopausal, and 97 osteoporotic postmenopausal women were examined with pQCT of the distal radius and with QCT of the lumbar spine (L1-L4). The bone mineral density (BMD), bone mineral content (BMC), and a cross-sectional area of cortical bone were assessed at the distal radius. The BMD of trabecular and total bone and the BMC of total bone were assessed at the midvertebral bodies of the lumbar spine. RESULTS: In the healthy women, correlations of radial BMD with spinal trabecular and total BMD were modest (r = .39 and r = .49, respectively) but were higher for total BMC (r = .79). All correlations in osteoporotic women (r = .19 for trabecular BMD, r = .31 for total BMD, and r = .47 for total BMC) were lower than those in healthy women. For measurement of spinal bone mass in healthy women, trabecular BMD showed a higher correlation with age (r = .81) and a larger relative annual decrease (1.2%) than did total BMD (r = .75, .78%) or total BMC (r = .54, .55%). At the radius, the highest correlations with age were found for total BMC (r = .57, .53%), cortical area (r - .52, .67%), and cortical BMC (r = .48, .78%). Age-adjusted odds ratios for prevalent vertebral fractures were highest for total (4.5) and trabecular (4.4) spinal BMD. For radial measurements, odds ratios were highest for both total BMD (2.3) and cortical area (2.3). CONCLUSION: QCT of spinal trabecular bone showed the strongest capability for assessment of age-related bone loss and for discrimination of osteoporotic vertebral fractures. In comparison, pQCT of radial trabecular bone showed the weakest capability for these applications, and pQCT of radial cortical or total bone showed intermediate capability.

Aged

HIV-2 prevalence in Uttar Pradesh.

Serum samples collected since 1989 with various patterns of reactivity for human immunodeficiency virus (HIV)-1, on the basis of screening ELISA and confirmatory Western blot (WB) test, were subjected to the detection of HIV-2 infection based on screening dot immunoassay and confirmatory WB for HIV-2. Significant prevalence of HIV-2 infection was (37.03%) among sera reactive for HIV-1 by ELISA but indeterminate by Western blot, compared with sera reactive for HIV-1 by ELISA and WB (3.29%) or negative by WB (2.63%). Out of 16 HIV-2 positive sera, 5 (31.25%) showed evidence of concomitant HIV-1 infection. This study demonstrates evidence of HIV-2 infection as early as 1989, earlier than reported so far from India.

Acquired Immunodeficiency Syndrome

Psychologic stress in the workplace and spontaneous abortion.

The relation of work-related psychologic stress to spontaneous abortion was examined in a prospective study of 3,953 pregnant, employed members of a prepaid health plan in California, recruited between 1990 and 1991. Information on occupation, psychologic stress-related factors at work, social support at work, physical exertion at work, life events, pregnancy worries, and potential confounders was obtained by a telephone interview. Psychologic job stress and social support at work were assessed using an abbreviated version of the instrument developed by Karasek and colleagues (Los Angeles: University of Southern California, 1986). Results from the multivariate model indicated that, overall, stressful work was not associated with an increased risk of spontaneous abortion. However, interactions were observed between stressful work and maternal age over 32 years (p = 0.04), cigarette smoking (p = 0.02), and primigravidity (p = 0.06). Relative to the odds ratio for stressful work in young, nonsmoking, multigravid women without a history of two or more spontaneous abortions, the odds ratios for spontaneous abortion given stressful work were higher by 2.45 (95% confidence interval (CI) 1.03-5.81) for older women, 2.96 (95% CI 1.16-7.52) for smokers, and 2.27 (95% CI 0.97-5.27) for primigravid women.

Abortion, Spontaneous

Plasma cells tumors decrease CD23 mRNA expression in vivo in murine splenic B cells.

CD23, the low-affinity Fc receptor for IgE, is constitutively expressed on mature, naive B cells, but is lost following B cell activation. We and others have shown that CD23 expression on B cells decreases in mice bearing plasma cell tumors. In contrast to these findings, we find that IgE-secreting tumors do not cause a loss of CD23 expression on host splenic B cells. Decreased expression of CD23 on B cells induced by plasma cell tumors requires direct contact between tumor cells and B cells; and other host cells are not involved. The loss of surface CD23 expression is associated with a decrease in steady-state CD23 mRNA levels in B cells from plasma cell tumor-bearing mice. Interestingly, loss of CD23 mRNA is observed even in B cells from mice with IgE-secreting tumors, where we find surface CD23 protein expression to be similar to that of normal mice. The maintenance of surface CD23 expression on B cells in mice with IgE-secreting tumors is dependent solely on the presence of IgE, and is not a tumor-specific effect. Therefore, we conclude that in vivo, IgE secreted by plasma cell tumors can result in the maintenance of normal levels of surface CD23 expression by a post-transcriptional mechanism, even when the tumor induces a down-regulation of CD23 mRNA levels.

Animals