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Biomedical subjects

S Srinivasan

Publications and source records attributed to S Srinivasan.

At least 37 records · Page 2Linked to original sources

Uric acid: an abettor or protector in calcium oxalate urolithiasis? Biochemical study in stone formers.

BACKGROUND: Free radical induced renal damage leads to crystal retention and formation of large stones. However, the scenario behind uric acid (UA) stone formation is still a mystery, as uric acid, a risk factor of stone formation, seems to be a potent antioxidant that can protect cells from damage by reactive oxygen species. This study was intended to evaluate the role of uric acid in stone formers by assessing the oxidative stress status of the stone patients. METHODS: Determination of urinary stone forming risk factors and oxidative stress factors like plasma lipid peroxidation, protein carbonyls of stone formers and histopathological changes and uric acid deposition in stone patients kidney biopsy were studied. RESULTS: Increased concentrations of urinary uric acid and oxalate in both uric acid as well as calcium oxalate stone formers were observed, whereas calcium is increased in calcium stone formers and not in the uric acid stone patients. Inhibitors such as citrate and glycosaminoglycans (GAGs) were found to be significantly decreased in all the stone patients. Histopathological studies confirmed the deposition of crystals in the damaged tubules and De Galantha staining authenticates that the damage is caused due to uric acid crystals. Increased oxidative stress is dictated by the concentrations of lipid peroxidation and protein carbonyls in stone formers. Moreover, increased activities of urinary marker enzymes substantiate the tubular damage. CONCLUSION: We speculated that uric acid acts as a calculi forming salt rather than an antioxidant and it has no role in preventing oxidative stress pertaining to urolithiasis.

Adult↗

Spectral and redox studies on mixed ligand complexes of cobalt(III) phenanthroline/bipyridyl and benzoylhydrazones, their DNA binding and antimicrobial activity.

Cobalt(III) complexes of the type [Co(N-N)2L](ClO4)2.H2O [where L=anionic form of para-substituted benzaldehyde-benzoylhydrazone (BHBX-); X=H, Me, OMe, OH, Cl or NO2; N-N=2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen)] have been synthesized and characterized through UV-Vis, IR, NMR and electrochemical studies. The IR spectral frequencies support the mode of coordination of BHBX to the metal through the imino nitrogen and enolic oxygen atoms. The electronic absorption spectra exhibit metal to ligand charge transfer (MLCT) transition around 450 nm together with intraligand (IL) bands that are comparable to that of [Co(phen/bpy)3]3+. In acetonitrile solution these complexes show two well defined redox couples corresponding to Co(III/II) and Co(II/I) processes. Binding of these complexes with herring sperm DNA have been investigated by spectroscopic and voltammetric methods. The lower binding constant values of these complexes with respect to the [Co(phen/bpy)3]3+ are ascribed to the polar interaction of the substituted benzoylhydrazone moiety with the sugar-phosphate backbone of the DNA. The UV spectrum shows reasonable hypochromism with slight (2-4 nm) red shift, while the cyclic voltammogram shows decrease in current intensity along with a very small shift in the formal potential of the Co(III/II) redox couple. These experimental results indicate that phen mixed ligand complexes bind to DNA through an intercalative mode more effectively than their bpy counterparts. These complexes are also found to have good antimicrobial activity.

2,2'-Dipyridyl↗

Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child.

BACKGROUND: Basidiobolomycosis is a rare chronic subcutaneous infection caused by Basidiobolus ranarum, which is usually treated with potassium iodide. Extensive deforming lesions in children can occur owing to lack of early diagnosis and/or inappropriate treatment. CASE REPORT: An 8-year-old girl child presented to us with extensive deforming plaque-like lesions over the left thigh and leg with multiple ulcerations of 1 year's duration. Histopathology was suggestive of subcutaneous zygomycosis with Splendore Hoeppli phenomenon. Microscopic examination of the tissue showed branching, sparsely septate fungal hyphae on a 10%KOH mount, and culture yielded Basidiobolus ranarum. The patient was initially treated with potassium iodide for 6 weeks to which only a poor response was observed. Itraconazole therapy resulted in rapid regression of the lesions and complete resolution after 15 weeks of therapy. She continues to be disease-free at 1 year of follow up. CONCLUSIONS: This case report highlights that in an older child even longstanding extensive basidiobolomycosis can be safely treated with itraconazole. Surgery is not usually necessary in these patients.

Administration, Oral↗

Inhalational anthrax with acute respiratory distress syndrome.

A 10-year-old boy presented with facial swelling, thick exudates in the nasal cavities with membranes covering the nasopharynx, shock and respiratory distress. X-ray of the paranasal sinuses showed opacification of both maxillary sinuses. Nasal diphtheria was suspected but culture of the membranes grew Bacillus anthracis. Chest X-ray showed mediastinal widening and extensive pulmonary infiltrates compatible with respiratory anthrax.

Anthrax↗

Inhaled foreign bodies in adolescents and adults.

BACKGROUND: Accidental foreign body inhalation is not uncommon. The incidence is high in children, especially the very young ones. We evaluated the management of inhaled foreign bodies in an adult respiratory medical unit, highlighting circumstances leading to inhalation, associated complications and difficulties encountered at bronchoscopic retrieval. METHODS: We reviewed all cases of inhaled foreign bodies presenting over a period of 12 years (1991-2003). RESULTS: 5 of 8 cases were teenagers whereas 3 were aged over 55 years. The older patients had co-morbidities and had aspirated food particles. In 2 cases, a bronchoscopy was performed primarily to exclude lung cancer, and the discovery of a foreign body was a surprise. Pulmonary complications related to foreign body inhalation were common among this group. All 5 teenage patients presented after inhalation of small objects. 4 patients from the teenage group had general anaesthesia; in 2 of them a laryngeal mask airway was employed, whilst 2 had endotracheal intubation. Only one patient was given a rigid bronchoscopy following failure of the fiberoptic instrument. Difficulties at retrieval of foreign body were frequently encountered. CONCLUSIONS: In the adolescent and adult patients, most inhaled foreign bodies are retrievable by flexible bronchoscopy. However, facilities for rigid bronchoscopy should be available as a back-up. Pulmonary complications are common after foreign body inhalation especially in the older patients. Difficulties at bronchoscopic removal may occur due to late presentation or to the site and/or position of the foreign body within the tracheobronchial tree.

Adolescent↗

Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells.

AIMS/HYPOTHESIS: Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to the reduced production of nitric oxide. The aim of this study was to investigate the regulation of endothelial nitric oxide synthase (eNOS) activity by acute and chronic elevated glucose. METHODS: Human aortic endothelial cells were cultured in 5.5 mmol/l (NG) or 25 mmol/l glucose (HG) for 4 h, 1 day, 3 days or 7 days. Mouse aortic endothelial cells were freshly isolated from C57BL/6J control and diabetic db/db mice. The expression and activity of eNOS were measured using quantitative PCR and nitrite measurements respectively. The binding of activator protein-1 (AP-1) to DNA in nuclear extracts was determined using electrophoretic mobility-shift assays. RESULTS: Acute exposure (4 h) of human aortic endothelial cells to 25 mmol/l glucose moderately increased eNOS activity and eNOS mRNA and protein expression. In contrast, chronic exposure to elevated glucose (25 mmol/l for 7 days) reduced total nitrite levels (46% reduction), levels of eNOS mRNA (46% reduction) and eNOS protein (65% reduction). In addition, AP-1 DNA binding activity was increased in chronic HG-cultured human aortic endothelial cells, and this effect was reduced by the specific inhibition of reactive oxygen species production through the mitochondrial electron transport chain. Mutation of AP-1 sites in the human eNOS promoter reversed the effects of HG. Compared with C57BL/6J control mice, eNOS mRNA levels in diabetic db/db mouse aortic endothelial cells were reduced by 60%. This decrease was reversed by the overexpression of manganese superoxide dismutase using an adenoviral construct. CONCLUSIONS/INTERPRETATION: In diabetes, the expression and activity of eNOS is regulated through glucose-mediated mitochondrial production of reactive oxygen species and activation of the oxidative stress transcription factor AP-1.

Animals↗

Randomized double-blind clinical trial comparing topical and sub-Tenon's anaesthesia in routine cataract surgery.

BACKGROUND: Several local anaesthetic techniques are available for cataract surgery. Recently, topical anaesthesia has gained in popularity. A randomized trial was designed to compare patient discomfort and intraoperative complications following routine cataract surgery under topical or sub-Tenon's anaesthesia. METHODS: A randomized double-blinded placebo-controlled clinical trial of 210 patients assigned to either a sub-Tenon's group (sub-Tenon's anaesthesia with placebo topical balanced salt solution, n=140) or a topical anaesthesia group (topical anaesthesia with placebo sub-Tenon's injection of balanced salt solution, n=70) was carried out. All patients underwent phacoemulsification with intraocular lens implantation. Patients in the sub-Tenon's group received a single injection (3 ml) of a combination of lidocaine 2% (2 ml) and bupivacaine 0.75% (1 ml), and four doses of topical placebo (balanced salt solution). Patients in the topical anaesthesia group received four doses of topical proxymethocaine 0.5% and a placebo sub-Tenon's injection (3 ml) of balanced salt solution. No intracameral injection of local anaesthetic was given. A 10-point visual analogue pain scale was used preoperatively and for postoperative pain assessment immediately after the operation and 30 min postoperatively. The intraoperative complications in the two groups were recorded. RESULTS: The mean pain score immediately after surgery was 2.42 (sd 2.2) in the sub-Tenon's group and 3.44 (2.3) in the topical anaesthesia group (P=0.0043). The mean pain score 30 min after surgery was 1.24 (1.7) in the sub-Tenon's group and 2.25 (2.2) in the topical anaesthesia group (P=0.0009). CONCLUSIONS: Patients undergoing cataract surgery under topical anaesthesia experience more postoperative discomfort than patients receiving sub-Tenon's anaesthesia. Surgery-related complications were similar in both groups.

Adult↗

Japanese encephalitis in India: an overview.

Japanese encephalitis (JE)-epidemics have been reported in many parts of the country. The incidence has been reported to be high among pediatric group with high mortality. The incidence of JE in recent times is showing an increasing trend. It appears that JE may become one of the major public health problems in India, considering the quantum of the vulnerable pediatric population, the proportion of JEV infections among the encephalitic children and wide scattering of JE-prone areas. JE burden can be estimated satisfactorily to some extend by strengthening diagnostic facilities for JE confirmation in hospitals and by maintenance of contact with the nearby referral hospitals to collect the particulars on JE cases. Vaccination proves to be the best to protect the individual against any disease. In the case of JE, it is essential to immunize the pigs (amplifying host) also to interrupt the transmission of the disease.

Animal Husbandry↗

Cranial computed tomography in partial motor seizures.

OBJECTIVE: To identify the pattern of intracranial structural lesions in developmentally normal children with partial motor seizures by computed tomography and to monitor the behavior of single ring enhancing lesion (SREL) after a period of time with or without treatment. METHODS: Consecutive developmentally normal children between one year and twelve years with partial motor seizures in a tertiary care referral Hospital. After clinical examination and appropriate investigation for tuberculosis and cysticercosis, CT scan was performed. In addition to anticonvulsants, children received antituberculous or anticysticercal therapy if indicated. Repeat CT was performed on children with SREL after 6 months. RESULTS: Computed tomography was abnormal in 102 (68%) children. Majority of the children (75) had SREL. The lesions were located in decreasing order of frequency in the parietal lobe (65), frontal lobe (7), occipital lobe (1), temporal lobe (1) and cerebellum (1). Repeat CT scan was performed on 50 of the 75 children with SREL. Among these, in 41 children who were only on antiepileptic therapy, the SREL had decreased in size in thirty-two whereas in the rest (9), there was no change in the size. CONCLUSION: Awareness of the existence of disappearing SREL lesions is essential to avoid unnecessary treatment with antituberculous or anticysticercal therapy and provides ample justification in treating with anticonvulsant drugs only.

Algorithms↗

Oxidative stress in urogenital tuberculosis patients: a predisposing factor for renal stone formation--amelioration by vitamin E supplementation.

BACKGROUND: Previous studies have shown that urogenital tuberculosis (GuTb) patients treated or untreated with regular anti-Tb regimen excrete comparatively high levels of urinary stone forming constituents than normal subjects. Enhanced oxidative stress is also considered as a prime factor that accelerates urolithiasis. The present study was aimed to determine antioxidant status and lipid peroxidation of these individuals in order to assess their risk for kidney stone formation. METHODS: GuTb patients and age-matched normal subjects were divided into four groups: I: normal subjects (n=60), II: GuTb patients a day before treatment (n=72), III: GuTb patients after treatment with isoniazid (300 mg), rifampicin (450 mg) and pyrazinamide (1.5 g) per day for 60 days (n=42), and IV: GuTb patients supplemented with vitamin E (200 mg/day) along with regular chemotherapy for 60 days (n=30). Blood was collected and tested for various markers of oxidative stress. RESULTS: Increased levels of lipid peroxidation, protein carbonyls (PCO), advanced oxidative protein products (AOPP) and reduced antioxidant defenses by impairment in enzyme activities like superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and decreased plasma concentrations of non enzymatic antioxidants like vitamins C and E were observed in the treated and untreated GuTb patients. CONCLUSIONS: These biochemical disparities may lead to membrane disintegrity, which is favorable for retention of mirolithis. Advocation of vitamin E enhanced the antioxidant status of the plasma, thereby preventing membrane injury, consequently reducing the risk of stone formation in urogenital tuberculosis patients, who were treated with their routine anti-tuberculosis drug regimen.

Antioxidants↗

Japanese encephalitis virus (JEV) is an important cause of encephalitis among children in Cuddalore district, Tamil Nadu, India.

BACKGROUND: Japanese encephalitis (JE) is endemic in Cuddalore district, Tamil Nadu (TN), Southern India. The reports of JE cases from the local hospitals did not reflect the actual disease burden. It is likely that these cases were attending the nearby referral hospitals, for want of better treatment facilities. OBJECTIVES: Between July 2002 and February 2003, a pilot study was undertaken to examine whether JE was a component of paediatric acute encephalitis syndrome (AES) reported to two major referral hospitals adjacent to Cuddalore, and to map the distribution of the JE cases. STUDY DESIGN: A total of 58 hospitalized children [0-15 years] with AES were investigated. Other than the routine laboratory investigations, either CSF or sera or both [depending on the availability] collected from these children were analyzed at Center for Research in Medical Entomology, Madurai (TN) for JEV-antigen, antibody detection, virus isolation and virus genome detection by indirect immunofluorescence, MAC enzyme linked immunosorbent assay (ELISA), insect bioassay and by reverse transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: JE was established in 17 (29%) of 58 AES cases; half of the AES cases [31/58, 53%] and 59% [10/17] of JE cases were confined to JE-endemic areas in Cuddalore district. The JE confirmation scored by different assays varied according to the clinical phase of the illness. The attack rate was high among the children aged 3-8 years. The monthly distribution of acute encephalitic syndrome cases followed the distribution of JE cases [coinciding with the rainy season in this region] suggesting encephalitis of JE origin. CONCLUSION: In JE-endemic areas, the actual JE burden can be estimated by the collection of JE case reports from the local hospitals and from the referral hospitals. Building of diagnostic facilities in hospitals for JE is necessary to achieve this goal.

Acute Disease↗

A quantitative comparison of modulus images obtained using nanoindentation with strain elastograms.

Tissue stiffness is generally known to be associated with pathologic changes. Ultrasound (US) elastography, on the other hand, is capable of imaging tissue strain, which may or may not be well-correlated with tissue stiffness. Hence, a quantitative comparison between the elastographic tissue strain images and the corresponding tissue modulus images needed to be performed to evaluate the usefulness of elastography in imaging tissue stiffnesss properties. Simulations were performed to demonstrate and quantify the similarities between modulus images and strain elastograms. This was followed by comparing nanoindenter-based modulus images with strain elastograms of thin slices of tissue-mimicking phantoms. Finally, some beef slices, canine prostates, ovine kidneys and breast cancers grown in mice were used to demonstrate the qualitative correspondence between modulus images and strain elastograms. The simulations and the experiments indicated that it is feasible to perform quantitative comparisons between strain images (using elastography) and modulus images on certain tissue structures and geometries. A good quantitative correspondence (correlation values of greater than 0.8) between structures in the modulus and strain images could be obtained at scales equal to or larger than 20 Qlambda (where Q is the quality factor defined as the ratio of the center frequency over the band width and lambda is the wavelength of the US system) modulus contrasts larger than 5, applied strains between 0.5% and 3% and window lengths for computing strain elastograms between 3 Qlambda and 5 Qlambda. The gelatin-phantom experiments showed lower values of correlation (values around 0.5) than with theory and simulations. The decrease in correlation was attributed to the presence of measurement noise in both strain elastography and modulus imaging, an increase of dimensionality of the problem (from 2-D to 3-D), local anisotropy, heterogeneity and nonstationarity. Experiments on real tissue slices showed further decrease in the correlation to around 0.3, possibly due to additional confounding factors such as time-dependent mechanical properties and geometrical distortions in the tissue during imaging. The work presented in this paper demonstrates that there is an intrinsic relationship between strain elastograms and the actual distribution of soft tissue elastic moduli, and bodes well for continued work in the area of elastography.

Algorithms↗

An experimental characterization of elastographic spatial resolution: analysis of the trade-offs between spatial resolution and contrast-to-noise ratio.

An experimental study of the spatial resolution in elastography was conducted. Models that involved two cylindrical inclusions arranged as a wedge were used to characterize the axial and lateral resolution of the axial strain elastograms. A study of the dependence of the spatial resolution on several factors such as the algorithmic parameters, the applied strain and the modulus contrast was performed. The axial resolution was found to show a linear dependence with respect to the algorithmic parameters, namely the window length and the window shift used for strain estimation. The lateral resolution showed a weak dependence on the algorithmic parameters. A weak dependence of the spatial resolution on factors such as the modulus contrast and the applied strain was found. The trade-offs between the spatial resolution and the elastographic contrast-to-noise ratio (CNR(e)) were then analyzed. A nonlinear trade-off between the CNR(e) and the axial and lateral resolution was shown for conventional strain estimation techniques, with the CNR(e) improving at a more than linear rate with respect to a linear degradation in the resolution. This study provided an experimental framework for characterizing the spatial resolution in elastography and facilitating a comparison of the CNR(e) with spatial resolution.

Elasticity↗

Theoretical derivation of SNR, CNR and spatial resolution for a local adaptive strain estimator for elastography.

Conventional techniques in elastography estimate the axial strain as the gradient of the displacement (time-delay) estimates obtained using cross-correlation of pre- and temporally stretched postcompression radiofrequency (RF) A-line segments. The use of a constant stretch factor for stretching the postcompression A-line is not adequate in the presence of heterogeneous targets that are commonly encountered. This led to the development of several adaptive strain estimation techniques in elastography. Yet, a theoretical framework for the image quality of adaptive strain estimation has not been established. In this work, we develop theoretical expressions for the image quality [measured in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution] of elastograms obtained using an adaptive strain estimator developed by Alam et al. (1998). We show a linear trade-off between the SNR and axial resolution of the strain elastogram with respect to the window length used for strain estimation. The CNR shows a quadratic tradeoff with the axial resolution with respect to the window length. The SNR, CNR and axial resolution are shown to improve with the ultrasonic bandwidth.

Algorithms↗

The relation of obesity throughout life to carotid intima-media thickness in adulthood: the Bogalusa Heart Study.

OBJECTIVE: Although obese children are at increased risk for coronary heart disease in later life, it is not clear if this association results from the persistence of childhood obesity into adulthood. We examined the relation of adiposity at various ages to the carotid intima-media thickness (IMT) at age 35 y. DESIGN: Prior to the determination of IMT by B-mode ultrasound, subjects (203 men, 310 women) had, on average, six measurements of body mass index (BMI) and triceps skinfold thickness (TSF) between the ages of 4 and 35 y. Mixed regression models for longitudinal data were used to assess the relation of these characteristics to adult IMT. RESULTS: Overall, adult IMT was associated with levels of both BMI and TSF (P<0.001), with the magnitudes of the associations with childhood adiposity comparable to those with adult levels of BMI and TSF. Furthermore, adult obesity modified the association between childhood adiposity and IMT: high IMT levels were seen only among overweight (BMI > or =95th percentile) children who became obese (BMI > or =30 kg/m2) adults (P<0.01 for linear trend). In contrast, IMT levels were not elevated among (1) overweight children who were not obese in adulthood, or among (2) thinner children who became obese adults. CONCLUSIONS: These results emphasize the adverse, cumulative effects of childhood-onset obesity that persists into adulthood. Since many overweight children become obese adults, the prevention of childhood obesity should be emphasized.

Adipose Tissue↗

Salubrious effect of vitamin E supplementation on renal stone forming risk factors in urogenital tuberculosis patients.

The incidence of renal calculi has been evaluated to be 25% in urogenital tuberculosis patients. The stone could be caused due to the host, the pathogenic organism, or possibly by the treatment. Studies were carried out to find out the efficacy of vitamin E supplementation in reducing the risk of stone formation in renal tuberculosis patients. The study constituted four groups, Group I with 30 normal volunteers, the second group comprised of 36 renal tuberculosis patients (GuTb) a day before treatment. Third group comprised of 24 patients with regular anti tuberculosis drug regimen for sixty days. In the fourth group, 12 patients were treated with anti tuberculosis drug regimen along with supplementation of antioxidant vitamin E (200 mg/day) for sixty days. Hyperuricosuria and hypercalciuria were observed in group II and group III patients, along with increased excretion of oxalate and creatinine, accompanied by decreased excretion of inhibitors such as citrate and glycosaminoglycans (GAGs). Renal damage was evident with increased leakage of Lactate dehydrogenase (LDH), Alkaline phosphatase (ALP) and gamma-Glutamyl transferase (gamma-GT) in renal tuberculosis patients. From the results of the above study, it is obvious that increased urinary oxalate levels leads to cellular damage in GuTb patients, which is a prerequisite for crystal retention as revealed by the elevated urinary marker enzymes. Antioxidant therapy prevents membrane injury thereby reducing the risk of stone formation. Hence vitamin E supplementation has a salubrious effect in preventing stone forming tendency with routine anti tuberculosis drug regimen.

Adult↗

Hospital- and laboratory-based investigations of hospitalized children with central nervous system-related symptoms to assess Japanese encephalitis virus etiology in Cuddalore District, Tamil Nadu, India.

A collaborative investigation of hospitalized encephalitic children in south India, between July 2002 and February 2003, has indicated that Japanese encephalitis was confirmed in 27.3% of these children. In developing countries, assessment of actual Japanese encephalitis disease burden requires strengthening of diagnostic laboratory capacities at hospitals.

Adolescent↗