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Biomedical subjects

S Majumdar

Publications and source records attributed to S Majumdar.

At least 73 records · Page 4Linked to original sources

In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius.

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with microFE modeling in vivo in the study of osteoporosis.

Aged↗

High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment.

OBJECTIVE: To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis. DESIGN: Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene. BACKGROUND: Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large trial populations. METHODS: A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis. RESULTS: Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups. CONCLUSIONS: The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials. RELEVANCE: A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial.

Bone Density↗

T2 relaxation time histograms in multiple sclerosis.

An accurate measurement of the transverse relaxation time T(2), and the histogram of T(2) in the brain parenchyma can be accomplished in vivo using a multi-echo magnetic resonance imaging sequence. An estimate of the error in the T(2) measurement is derived using copper sulfate doped water phantoms. Correction factors are calculated and applied to the signal intensity of each voxel prior to the in vivo T(2) evaluation. These corrected T(2) are in good agreement with the theoretical values calculated from copper sulfate concentrations. This technique is then applied to calculate T(2) histograms of the brain. The population studied was composed of normal volunteers and multiple sclerosis patients. The corrected T(2) histogram method discriminates the normal control population from the MS population, and also discriminates between relapsing-remitting patients and primary progressive or secondary progressive patients. Moreover using this approach we are able to detect in MS patients a global shift of the T(2) of the white mater toward higher values. The results of this study showed that the method is easy to implement and may be used to characterize MS pathology.

Brain↗

Ultrasound mediated alkaline hydrolysis of methyl benzoate--reinvestigation with crucial parameters.

In the present work hydrolysis of methyl benzoate was carried out using aqueous sodium hydroxide solution at room temperature in the presence of ultrasound since otherwise the same reaction takes place at relatively high temperature. Also, the above hydrolysis reaction was investigated at a relatively larger scale with the variation in parameters influencing the emulsification process and hence the reaction rates. It has been observed that the position of ultrasound source on the liquid-liquid interface is a crucial parameter affecting the two-phase emulsification rates. The poor bulk mixing occurring in the presence of ultrasound alone with an increase in the volume of the reaction mixture and its consequent effect on the reaction kinetics has been conclusively established. These studies have shown that the use of ultrasound with mechanical stirring can result in substantial reduction in the overall power consumption, especially for reaction systems like hydrolysis that do not require very high temperatures and pressures generated by cavitation.

Journal Article↗

Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI). METHODS: A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols. RESULTS: There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.

Adult↗

Facial pain following sinonasal surgery or facial trauma.

The case notes of 22 patients who reported facial pain after sinonasal surgery or trauma out of a cohort of 973 patients seen in a rhinology clinic were reviewed retrospectively. This group included 10 patients who had undergone endoscopic sinus surgery and four who had suffered facial fractures. None of the patients reported any facial pain before surgery or trauma. In only one case was there any evidence, clinically, endoscopically, or radiologically, of any paranasal sinus disease and when this resolved with nasal medical treatment the pain remained. The treatment of these patients' facial pain centred on the use of neurological medical treatment. One third of the patients responded to low-dose amitriptyline, a further third showed some response to other pharmacological agents including carbamazepine, and the remaining third showed no response. These cases illustrate the characteristics and management of facial pain after sinonasal surgery and highlight the importance of medical neurological treatment in the absence of any objective evidence of sinus disease.

Acetates↗

Clinical relevance of intracellular cytokines IL-6 and IL-12 in acute pancreatitis, and correlation with APACHE III score.

Pro-inflammatory cytokines are involved in the pathogenesis of acute pancreatitis (AP). Here, we measure and correlate clinically the percentages of peripheral blood mononuclear cells (PBMC) that contain interleukin (IL)-6 and IL-12 and compare these with acute physiology and chronic health evaluation (APACHE III) scores in 30 patients with AP. Severity of AP is determined according to the Atlanta criteria. Patients with severe AP (n = 15) had significantly higher IL-6 values compared to those with mild AP (n = 15). IL-12 levels correlated well with aetiological factors (alcohol and biliary pathology) in patients with AP. Correlation was seen between IL-6 value and APACHE score in severe AP. A score of 30 points was used as the cut off between mild (<30) and severe (>30) cases, with a sensitivity of 80% and specificity of 100%. Cut off percentages for IL-6- and IL-12-positive PBMCs were >25% (positive predictive value [PPV]: 100%) and >9% (PPV: 70%), respectively. Based on these results, it would seem logical to use both APACHE III score and IL-6 percentage to assess severity in patients with AP.

APACHE↗

Solitary plasmacytoma and extramedullary plasmacytoma of the paranasal sinuses and soft palate.

Solitary plasmacytoma of the paranasal sinuses are uncommon neoplasms of B lymphocyte origin. They comprise one per cent of all head and neck tumours of the upper respiratory tract. They can be solitary plasmacytomas of the bone (SPB), an extramedullary plasmacytoma or a local manifestation of multiple myeloma. Conversion to multiple myeloma happens more frequently in SPB. Radiotherapy is the common modality of treatment with, or without, adjuvant chemotherapy. Extramedullary plasmacytoma carries a better prognosis than a solitary plasmacytoma of the bone. We report four cases of solitary plasmacytoma of the bone and an extramedullary plasmacytoma of the paranasal sinuses and soft palate.

Female↗

Spontaneous CSF rhinorrhoea from separate defects of the anterior and middle cranial fossa.

Multiple congenital dehiscence of the skull base is rare and can give rise to spontaneous CSF rhinorrhoea. A search of the world literature revealed only five reports of CSF leak with more than one concomitant skull base defect. When treating a patient with spontaneous CSF rhinorrhoea the possibility of its originating from the middle ear and eustachian tube should be considered. An intrathecal injection of fluorescein is useful in establishing the site of a CSF leak especially when a computed tomography scan (CT) or magnetic resonance image (MRI) has not localized the site. We discuss a case of a 72-year-old lady presenting with CSF rhinorrhoea, who had an anterior skull base defect localized with the help of intrathecal fluorescein and repaired surgically. Subsequent to this she had a further episode of CSF rhinorrhoea that originated from a middle-ear meningocele that was then repaired.

Aged↗

Surfactant protein-A in lung lavage fluid obtained from patients with idiopathic pulmonary fibrosis.

BACKGROUND: Alterations in surface-active material may contribute to the pathogenesis of idiopathic pulmonary fibrosis both by increasing the elastic recoil due to surface forces and by promoting alveolar collapse. This study intends to evaluate the surfactant protein-A levels in bronchoalveolar lavage in patients of idiopathic pulmonary fibrosis. MATERIAL AND METHODS: Ten patients of idiopathic pulmonary fibrosis (IPF) of either sex were taken up for estimation of surfactant protein-A (SP-A) levels in bronchoalveolar lavage. The final diagnosis of IPF was based on histopathology and high resolution CT. Ten controls were taken out of which five patients were histopathologically proven cases of sarcoidosis and five patients with normal chest X-ray and CT scan. History, physical examination and routine investigations were done to rule out any concomitant illness. RESULTS: Age range of patients varied from 37-65 years (mean +/- SD of 50.65 +/- 9.05) and controls 30-62 years (42.50 +/- 9.95). Fiberoptic bronchoscopy and bronchoalveolar lavage was carried out and fluid aspirated was studied for surfactant protein-A. The level of surfactant protein-A recovered was lower in patients with idiopathic pulmonary fibrosis in comparison to control group p < 0.01 (1.86 +/- 1.26 and 5.76 +/- 2.0 microg/ml respectively). The levels of surfactant protein-A also revealed that the level decreased with derangement of pulmonary function. CONCLUSIONS: The study thus showed that the level of surfactant protein A is reduced in patients with idiopathic pulmonary fibrosis. It is likely that they have a significant role in pathogenesis of idiopathic pulmonary fibrosis and its progression. Surfactant-A may have important therapeutic implications. Further studies are required for a definite answer.

Adult↗

Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells.

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV(1)% of predicted of 43-77% and FEV(1)/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA(+) cells. The highest number of IL-4 mRNA(+) cells were in the submucosal glands of the CB group with normal lung function (216/mm(2)), significantly higher than the values in either the AS (63/mm(2)) or the CB+COPD (87/mm(2)) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA(+) cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8(+) and IL-4 or IL-5 mRNA(+) cells. Of 1328 IL-4(+) and 1404 CD8(+) cells counted none was double labeled. Of 727 IL-5(+) and 1569 CD8(+) cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-alpha(+) cells were also CD8(+) and 15% of CD8(+) cells were TNF-alpha positive. Thus, cells other than the CD8(+) phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.

Aged↗

Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro.

STUDY DESIGN: Twelve lumbar intervertebral disc specimens were imaged with magnetic resonance imaging to estimate relaxation constants, T1 and T2, and tissue water diffusion, before and after applying compression. OBJECTIVES: The objectives of the study were to measure T1, T2, and water diffusion for differences with loading state, region of the disc (anulus fibrosus or nucleus pulposus), and grade of degeneration. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging can be used qualitatively to estimate water content and degeneration of the intervertebral disc. Beyond structural information of images, the relaxation times T1 and T2 may contain information on the changes occurring with degeneration. A modified spin-echo sequence can be used to estimate tissue water diffusion in cartilage and disc specimens with the ability to measure anisotropy. METHODS: Specimens were imaged in a 1.5-Tesla clinical scanner. T1, T2, and water diffusion were estimated from midsagittal images. Magnetic resonance imaging parameters were calculated before and after axial loading. The measured T1, T2, and D (diffusion coefficient) were compared before and after compression, and for the diffusion data, also by direction to consider anisotropy. RESULTS: For the T1 data, a significant difference was found by region, nucleus > anulus, and loading state, loaded > unloaded. For the T2 values, there was a significant difference by region, nucleus > anulus, and Thompson grade. For diffusion, significant differences were found by region, nucleus > anulus, Thompson grade, direction of diffusion, and state of compression, loaded > unloaded. CONCLUSIONS: This study demonstrated that magnetic resonance imaging can be used to measure significant changes in T1, T2, or diffusion in intervertebral disc specimens by region, loading condition, or Thompson grade.

Adolescent↗

Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation.

Methotrexate (MTX), a folate antagonist, is a commonly used anti-inflammatory, antiproliferative, and immunosuppressive drug whose mode of action is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that MTX must mediate its effects through suppression of NF-kappaB activation. We investigated the effects of MTX on NF-kappaB activation induced by TNF in Jurkat cells. The treatment of these cells with MTX suppressed TNF-induced NF-kappaB activation with optimum effects occurring at 10 microM MTX for 60 min. These effects were not restricted to Jurkat cells because other cell types were also inhibited. Besides TNF, MTX also suppressed the NF-kappaB activation induced by various other inflammatory stimuli. The suppression of TNF-induced NF-kappaB activation by MTX correlated with inhibition of IkappaBalpha degradation, suppression of IkappaBalpha phosphorylation, abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Because ecto 5' nucleotidase inhibitor (alpha,beta-methylene adenosine-5'-diphosphate) blocked the effect of MTX, adenosine mimicked the effect of MTX, and adenosine A2b receptor antagonist (3,7-dimethyl-1-propargylxanthine) reversed the inhibitory effect of MTX, we suggest that MTX suppresses NF-kappaB activation by releasing adenosine. A partial reversal of MTX-induced NF-kappaB suppression by thymidine and folinic acid indicates the role of the thymidylate synthase pathway also. Overall, our results clearly demonstrate that MTX suppresses NF-kappaB activation through the release of adenosine, which may contribute to the role of MTX in anti-inflammatory, immunomodulatory, and antiproliferative effects.

5'-Nucleotidase↗

Expression of activation, adhesion molecules and intracellular cytokines in acute pancreatitis.

Adhesion and activation molecules as well as cytokines play an important role in an immune scenario. In acute pancreatitis, we have studied some of these in order to evaluate dysregulation. For this we took peripheral blood mononuclear cells and pancreatitis tissue cells. We analysed activation markers like CD69, CD25 and HLA-DR and found a marked elevation of CD69 as well as CD25 in both peripheral blood cells and tissue mononuclear cells when compared to controls. In PBMC-CD69: P<0.01 and CD25: P<0.01; in tissue-CD69: P<0.001 and CD25: P<0.001. The HLA-DR levels, however, were reduced in the disease state (in acute pancreatitis patient blood (P<0.01) and tissue cells (P<0.001)). The adhesion molecules showed unanimous rise in the blood and the tissue samples. In blood samples, CD11a: P<0.05 and CD11b: P<0.05 and tissue samples CD11a: P<0.01 and CD11b: P<0.01and CD54 in peripheral blood (P<0.05) and tissue (P<0.01) of AP was high as compared to controls. By simultaneous flowcytometric analysis, we determined the co-expression of a surface marker (CD4/CD8/CD14) and intracellular cytokine (TNF-alpha and IFN-gamma) in individual cells. The IFN-gamma producing CD8+T cells were elevated in pancreatic tissue (P<0.01). TNF-alpha producing cell numbers were significantly higher in tissue cells than in blood and also in CD8+ T cells (P<0.001). We conclude that monocyte function is affected in AP as shown by reduced HLA-DR numbers and lowered TNF-alpha producing cells. Moreover, the CD8+T cells appear to play an important role in cytokine synthesis at the effector site.

Acute Disease↗

Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants.

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV(1) % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.

Adult↗

Characterization of a galactose specific adhesin of enteroaggregative Escherichia coli.

A fimbrial adhesin was identified from an enteroaggregative Escherichia coli strain. The adhesin was purified to 740-fold by sequential chromatography on an affinity matrix and gel filtration column in the FPLC system. The homogeneity of the purified protein was established by analytical isoelectrofocussing (pI 7.25). The native adhesin appeared as a high-molecular-weight aggregative protein as revealed by gel filtration chromatography on Superose 12HR10/30 column. However, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis the molecular weight of the adhesin was found to be 18 kDa and this was further confirmed by gel filtration chromatography on Superose 6HR 10/30 column presence of 6 M guanidine hydrochloride. The N-terminal 15-amino-acid sequence of the adhesin did not show homology with any of the previously reported fimbrial adhesins. The purified adhesin showed adhesion to human erythrocytes in the presence of Ca(2+) (5 mM). The optimum temperature and pH for the hemadhesion activity was found to be 25 degrees C and 6.5, respectively. The inhibition study clearly suggested that the binding site of the adhesin could recognize galactose as the specific sugar. The fluorescence of 4-methylumbelliferyl-alpha-D-galactopyranoside was quenched on binding to the adhesin and maximum reversal of fluorescence quenching was observed by competitive substitution titration with raffinose. The adhesin was found to contain one binding site per monomer for its specific sugar residue. The association constant and the free energy of binding were obtained as 3.98 x 10(5) M(-1) and -31.97 kJ/mol, respectively. The adherence of the bacteria to HEp-2 monolayer was inhibited in presence of galactose and this was further supported by a significant reduction in the bacterial adherence to the HEp-2 cells, pretreated with beta-D-galactosidase.

Adhesins, Escherichia coli↗