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Biomedical subjects

V Rajagopal

Publications and source records attributed to V Rajagopal.

At least 19 recordsLinked to original sources

A biomechanical model of mammographic compressions.

A number of biomechanical models have been proposed to improve nonrigid registration techniques for multimodal breast image alignment. A deformable breast model may also be useful for overcoming difficulties in interpreting 2D X-ray projections (mammograms) of 3D volumes (breast tissues). If a deformable model could accurately predict the shape changes that breasts undergo during mammography, then the model could serve to localize suspicious masses (visible in mammograms) in the unloaded state, or in any other deformed state required for further investigations (such as biopsy or other medical imaging modalities). In this paper, we present a validation study that was conducted in order to develop a biomechanical model based on the well-established theory of continuum mechanics (finite elasticity theory with contact mechanics) and demonstrate its use for this application. Experimental studies using gel phantoms were conducted to test the accuracy in predicting mammographic-like deformations. The material properties of the gel phantom were estimated using a nonlinear optimization process, which minimized the errors between the experimental and the model-predicted surface data by adjusting the parameter associated with the neo-Hookean constitutive relation. Two compressions (the equivalent of cranio-caudal and medio-lateral mammograms) were performed on the phantom, and the corresponding deformations were recorded using a MRI scanner. Finite element simulations were performed to mimic the experiments using the estimated material properties with appropriate boundary conditions. The simulation results matched the experimental recordings of the deformed phantom, with a sub-millimeter root-mean-square error for each compression state. Having now validated our finite element model of breast compression, the next stage is to apply the model to clinical images.

Biomechanical Phenomena↗

Geographical information system (GIS) in investigation of an outbreak.

An outbreak of fever in a village in southern India was reported on 1st September, 2001. The first reported case presented with epistaxis and a platelet count of 27000h(1)/mm3. Clinical, laboratory and entomological evidence supported a diagnosis of dengue fever. One third of the village was affected and 3.7 % of the population presented with haemorrhagic symptoms; none were fatal. Five acute cases tested for dengue specific IgM showed that two were positive. The larvae of Aedes aegypti were discovered from domestic water collections in the village. Spatial analysis done with the help of Geographical Information Systems software (GIS) demonstrated a centrifugal spread of cases from the most affected street until it involved the entire village. Spatial analysis revealed that cases occurred in clusters and that these could not have occurred by chance. This was our first experience in producing a geo-referenced map of a village area and in spatial analysis. GIS is a novel and simple tool for outbreak investigations and the spatial analyst adds additional information to the data collected. Control of adult mosquitoes and larvae prevented the outbreak from spreading to an adjacent village.

Adolescent↗

Latex agglutination test in the diagnosis of pyogenic meningitis.

Samples of cerebrospinal fluid (n=204) from pediatric patients with clinically suspected pyogenic meningitis were examined by direct microscopy, bacterial culture and Latex Agglutination Test (LAT). Latex Agglutination Test was done for detection of antigen of Streptococcus pneumoniae and Haemophilus influenzae type b. Among 38 LAT positive cases, culture and/or gram stain was positive in only 20 cases and 18 cases were detected exclusively by LAT. Besides, LAT was useful in detecting the pre-treated cases as 11 out of 55 samples from pre-treated cases were positive by LAT in comparison to culture and/or Gram stain which detected only 4 of 55 cases. LAT is simple, rapid and more reliable test.

Adolescent↗

An outbreak of human anthrax in Mysore (India).

Anthrax is a zoonotic disease caused by Bacillus anthracis. Intestinal anthrax though a rare entity mostly ends with fatal outcome. Very few cases of intestinal anthrax are reported. Present outbreak of intestinal anthrax is unique in itself that four cases succumbed to the illness within a span of 48-72 hours in a small hamlet of Mysore district of Karnataka, after consuming diseased deer meat. Confirmation of the diagnosis was carried out at NICD, Delhi by bacteriological culture isolation, biochemical tests, animal pathogenicity and polymerase chain reaction (PCR). This outbreak clearly indicates surveillance of anthrax in animals in endemic areas is an essential part in the control of the disease with intersectoral coordination between the departments of health, animal husbandary, agriculture and forest.

Adult↗

Surgical management of cirsoid aneurysms.

BACKGROUND: Cirsoid aneurysms (arteriovenous fistulas) of the scalp are rare lesions. They are infrequently encountered in neurosurgical practice. These lesions are difficult to manage because of their complex vascular anatomy, high shunt flow and cosmetic disfigurement. We report our experience in the surgical management of these lesions. METHODS: We treated 11 patients with cirsoid aneurysms surgically. All except one patient were males who were in the second and third decades of life. History of trauma was present in 6 patients. In one patient, the lesion had been present since birth. Occipital and frontal regions were the sites commonly involved. Superficial temporal, occipital and posterior auricular arteries were the most frequent feeding arteries. The size ranged from 3 cms to 12 cms. Following investigations were done: CT, MRI, MRA, angiography and Doppler studies. FINDINGS: Excision of the lesion was done in 8 patients and en bloc resection of the lesion with the scalp with reconstruction was done in the remaining three. One among the three patients who underwent en bloc resection had undergone prior surgery. None of the patients underwent preoperative endovascular treatment. One patient had undergone intralesional injection of sclerosing agents twice. Superficial scalp necrosis occurred in two patients but was treated successfully. All the patients except one had good cosmetic results and there was no recurrence during an average follow up of 18 months. INTERPRETATION: Surgical excision with good cosmetic results is feasible in patients with cirsoid aneurysms.

Adolescent↗

A study of dermatophytes and their in-vitro antifungal sensitivity.

Of the 150 clinically suspected cases of Dermatophytosis studied, majority of the cases were from age group 11-20 and 21-30 (51.4%), Tinea corporis (48.7%) and Tinea capitis (18%) were the commonest clinical types. The isolation rate was 24% (36) of which 19 (52.7%) were Trichophyton rubrum, 11 (30.55%) were Trichophyton mentagrophytes and 4 (11.1%) were Trichophyton violaceum. One isolate each of Microsporum gypseum & Epidermophyton floccosum were obtained. Griseofulvin proved to be the best drug with a sensitivity of 94.4% followed by Miconazole (75% sensitive). Tolnaftate showed a sensitivity of 47.22%. For Clotrimazole only 30.55% of the isolates were sensitive.

Adolescent↗

Rapid diagnosis of cholera by coagglutination test.

In this study the coagglutination test for the rapid diagnosis of cholera is evaluated in comparison with the conventional culture method. A total of 553 stool specimens were processed from cases of acute gastro-enteritis. The sensitivity and specificity of coagglutination test was 92.77% and 95.65% respectively. The coagglutination test is found to be simple, reliable and rapid method for the diagnosis of cholera.

Agglutination Tests↗

Recombinant toxins that bind to the urokinase receptor are cytotoxic without requiring binding to the alpha(2)-macroglobulin receptor.

The alpha(2-)macroglobulin receptor (alpha(2)MR) has been reported to mediate the internalization of the urokinase plasminogen activator receptor (uPAR) via ligand binding to both receptors. To target malignant uPAR-expressing cells and to determine whether uPAR can internalize without ligand binding to alpha(2)MR, we engineered two recombinant toxins, ATF-PE38 and ATF-PE38KDEL. Each consists of the amino-terminal fragment (ATF) of human urokinase and a truncated form of Pseudomonas exotoxin (PE) devoid of domain Ia, which binds alpha(2)MR. ATF-PE38 and ATF-PE38KDEL were cytotoxic toward malignant uPAR-bearing cells, with IC(50) values as low as 0.02 ng/ml (0.3 pM). Cytotoxicity could be blocked using either recombinant urokinase or free ATF, indicating that the cytotoxicity of the recombinant toxins was specific. Radiolabeled ATF-PE38 had high affinity for uPAR (K(d) = 0.4-8 nM) on a variety of different malignant cell types and internalized at a rate similar to that of ATF. The cytotoxicity was not diminished by receptor-associated protein, which binds and shields the alpha(2)MR from other proteins, or by incubation with phorbol myristate acetate, which is known to decrease the number of alpha(2)MRs in U937 cells or by antibodies to alpha(2)MR. Therefore, these recombinant toxins appear to internalize via uPAR without association with the alpha(2)MR.

ADP Ribose Transferases↗

Serotypes and phage types of Vibrio cholerae in Mysore.

A total of 565 samples of acute diarrhoeal stools from children received over a period of twelve months from November 1996 to October 1997, yielded 289 (51.15%) isolates of V. cholerae. Out of these, 277 (95.85%) were V. cholerae 01 serotype Ogawa, 7 (2.42%) were V. cholerae 0139 and 5 (1.73%) were V. cholerae non-O1 non-0139. Phage typing of the isolates was carried out by NICED Calcutta. Out of 78 isolates, 69 (88.46%) belong to phage type T27. Of the remaining, 3 (3.85%), 3(3.85%), 2(2.56%) and 1(1.28%) belong to the phage types T26, T13, T8 and T4 respectively.

Bacterial Typing Techniques↗

Similarities in the biodistribution of iodine-labeled anti-Tac single-chain disulfide-stabilized Fv fragment and anti-Tac disulfide-stabilized Fv fragment.

We evaluated the biodistribution and pharmacokinetics of two different iodine-labeled Fv fragments of anti-Tac monoclonal antibody (MAb) in normal and tumor-bearing nude mice. One was a disulfide-stabilized Fv fragment (dsFv), and the other was a single-chain disulfide-stabilized Fv fragment (scdsFv). The scdsFv is a newly developed type of Fv fragment superior to the dsFv in which the VH and VL are linked by covalent bonds through a spacer arm and by an internal disulfide bond. These modifications increase the yield of scdsFv. Both reagents recognize the alpha subunit of the interleukin-2 receptor (IL-2Ralpha). The biodistribution of the Fv fragments was evaluated in normal mice co-injected with 50 mg of L-lysine and in a no-lysine control group. Biodistribution was also evaluated in nude mice bearing subcutaneous tumor xenografts derived from IL-2Ralpha-positive ATAC4 cells and receptor-negative A431 cells. These mice were co-injected with 125I-labeled anti-Tac scdsFv (6 microCi/0.7 microg) and 131I-labeled anti-Tac dsFv (2 microCi/0.7 microg) or with 131I-labeled anti-Tac scdsFv (6 microCi/0.7 microg) and 125I-labeled anti-Tac dsFv (4 microCi/0.7 microg). The biodistribution of 125I-labeled anti-Tac scdsFv and 131I-labeled anti-Tac dsFv was very similar in all organs and the tumors. The renal uptake of both reagents was blocked effectively (<93%) and similarly by lysine. The scdsFv cleared slightly faster from the circulation than did the dsFv because there were more aggregates of dsFv than of scdsFv (3% vs. 1%, respectively). The scdsFv-to-dsFv ratio ranged from 0.79 to 1.20 in all organs at all time points we examined. In conclusion, the first biodistribution study of an scdsFv molecule shows that the scdsFv had a biodistribution very similar to that of the dsFv and seems to be a good alternative to the dsFv because of its higher production yield.

Animals↗

A form of anti-Tac(Fv) which is both single-chain and disulfide stabilized: comparison with its single-chain and disulfide-stabilized homologs.

Disulfide-stabilized Fvs (dsFvs) are recombinant proteins composed of a heavy-chain variable domain (VH) of an antibody connected via a disulfide bond to the light-chain variable domain (VL). In single-chain Fvs (scFvs), a peptide connector links VH and VL. The dsFv form of the anti-Tac monoclonal antibody which reacts with the alpha subunit of the IL2 receptor was recently reported to be more stable and to aggregate less during renaturation than anti-Tac(scFv). In addition, it could be produced in a better yield owing to less aggregation. However, the yields are still too low to permit the production of material for clinical trials in which the dsFv will be used to image or treat IL2 receptor (CD25)-containing tumors. To increase the efficiency by which VH and VL associate and form a disulfide bond during renaturation, we have prepared an Fv form of anti-Tac which is both single chain and disulfide stabilized (scdsFv). The recombinant protein is expressed in Escherichia coli, where it accumulates in inclusion bodies. Using inclusion body protein as the reference point, the yield of purified anti-Tac(scdsFv) was 13% compared with 2% for anti-Tac(dsFv). Anti-Tac(scdsFv) has equivalent binding affinity, immunoreactivity after radiolabeling and stability. The results show that a linker between VH and VL facilitates heterodimer formation and leads to disulfide bond formation in a higher percentage of the molecules renatured. Thus anti-Tac(scdsFv) is the preferred form of anti-Tac(Fv) to be used for clinical studies. We anticipate that scdsFvs will be the optimum recombinant form of Fv to produce from bacteria.

Antibody Specificity↗

Mobile extracorporeal shockwave lithotripsy.

During the last 18 months, extracorporeal shockwave lithotripsy (ESWL) has been provided at Epsom District Hospital using a mobile unit containing a Dornier HM4 lithotriptor. Patients with upper ureteric and renal stones were selected for treatment, which was performed without anaesthesia or sedation as a day-case procedure; 83 patients were treated, 5 of them with bilateral stones. Seventy patients required 1 treatment session, 17 required 2 and 1 patient required 3. There were no serious complications but 3 patients needed ureteroscopy to remove obstructing stones. The overall success rate was 86%. The cost to treat each NHS patient was 253 pounds. Mobile lithotripsy as a day-case procedure is a safe and cost-effective means of treating urolithiasis and can be performed in a District General Hospital.

Ambulatory Care↗

Strictures of the penile urethra.

One hundred and eighty-seven patients with urethral strictures have been treated over a period of 2 1/2 years. In nearly 50%, strictures were confined to the penile urethra, involving the meatus, the fossa navicularis or varying lengths of the urethra up to the bulb. Of these, 95.3% were inflammatory in nature. Overall, 85.5% were managed with a single surgical procedure. The single-stage technique using a skin inversion pedicled flap was done in 15 cases and was found to be useful, with less morbidity than the staged procedure.

Adolescent↗

Trimethoprim in pediatric urinary tract infection.

The efficacy of trimethoprim (TMP) as a single therapeutic agent in the treatment of urinary tract infection (UTI) in children was studied in 112 children prospectively comparing TMP against trimethoprim-sulfamethoxazole (TMP/Sulfa), sulfamethoxazole and ampicillin. Children with repeated colony counts of greater than 100,000 CFU/ml of the same organism grown in 2-3 consecutive clean catch specimens were successively assigned to each treatment group for 10 days' therapy. TMP achieved a cure rate of 100% compared to TMP/Sulfa 100% (p greater than 0.05), sulfamethoxazole 93% (p less than 0.05) and ampicillin 63% (p less than 0.01). TMP and TMP/Sulfa groups had no failures while sulfamethoxazole and ampicillin groups had 7% (p less than 0.05) and 37% (p less than 0.01), respectively. Relapses occurred in 4% of the TMP group whereas TMP/Sulfa had 7% (p greater than 0.05); sulfamethoxazole and ampicillin groups had none. TMP group had 7% recurrence compared to 6% TMP/Sulfa, 4% sulfamethoxazole and 7% ampicillin (p greater than 0.05). Gastrointestinal side effects and skin rashes were not encountered in the TMP group; depression of WBC was the lowest in this group. As a single therapeutic agent, TMP appears to be safe and efficacious for treatment of acute UTI in children.

Ampicillin↗