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Biomedical subjects

N Sukumar

Publications and source records attributed to N Sukumar.

At least 19 recordsLinked to original sources
PubMed2006

A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.

Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.

Acute Disease↗
PubMed2006

Initial experience of laparoscopic incisional hernia repair.

Laparoscopic repair of ventral and incisional hernia has become increasingly popular as compared to open repair. The procedure has the advantages of minimal access surgery, reduction of post operative pain and the recurrence rate. A prospective study of laparoscopic incisional hernia repair was performed in our center from August 2002 to April 2004. Eighteen cases (n: 18) were performed during the study period. Fifteen cases (n: 15) had open hernia repair previously. Sixteen patients (n: 16) had successful repair of the hernia with the laparoscopic approach and two cases were converted to open repair. The mean hernia defect size was 156cm2. There was no intraoperative or immediate postoperative complication. The mean operating time was 100 +/- 34 minutes (75 - 180 minutes). The postoperative pain was graded as mild to moderate according to visual analogue score. The mean day of discharge after surgery was two days (1 - 3 days). During follow up, three patients (16.7%) developed seroma at the hernia sac which was resolved with conservative management after three weeks. One (5.6%) patient developed recurrence six months after surgery. In conclusion, laparoscopic repair of incisional hernia particularly recurrent hernia has been shown to be safe and effective in our centre. However, careful patient selection and acquiring the necessary advanced laparoscopic surgical skills coupled with the proper use of equipment are mandatory before embarking on this procedure.

Adult↗
PubMed2005

Role of amino acid properties to determine backbone tau(N-Calpha-C') stretching angle in peptides and proteins.

The analysis of the basic geometry of amino acid residues of protein structures has demonstrated the invariability of all the bond lengths and bond angles except for tau, the backbone N-Calpha-C' angle. This angle can be widened or contracted significantly from the tetrahedral geometry to accommodate various other strains in the structure. In order to accurately determine the cause for this deviation, a survey is made for the tau angles using the peptide structures and the ultrahigh resolution protein structures. The average deviation of N-Calpha-C' angles from tetrahedral geometry for each amino acid in all the categories were calculated and then correlated with forty-eight physiochemical, energetic and conformational properties of amino acids. Linear and multiple regression analysis were carried out between the amino acid deviation and the 48 properties. This study confirms the deviation of tau angles in both the peptide and protein structures but similar forces do not influence them. The peptide structures are influenced by physical properties whereas as expected the conformational properties influence the protein structures. And it is not any single property that dominates the deviation but the combination of different factors contributes to the tau angle deviation.

Algorithms↗
PubMed2005

A preliminary time-of-flight neutron diffraction study on amicyanin from Paracoccus denitrificans.

Crystals of the blue copper protein amicyanin suitable for neutron diffraction were grown by the sitting-drop method, followed by repeated macroseeding using solutions prepared with D(2)O. Although the crystal sizes were the same, crystals grown using solutions made up in H(2)O in the initial stages of macroseeding and solutions with D(2)O in later stages did not diffract neutrons well. However, when the protein was initially exchanged with buffered D(2)O and then crystallized and also macroseeded using solutions made up in D(2)O throughout, the crystals diffracted neutrons to high resolution. One of those crystals was used to collect a data set to a resolution of 1.9 A.

Crystallography↗
PubMed2005

Case report of a difficult venous access: retroperitoneal approach of inserting an improved non-heparinised port for long-term use.

This is a case report of a patient with difficult venous access following thrombosis of major superficial and deep veins of the limbs as documented by ultrasound doppler and venography. The insertion of a few central ports were infected and the vein thrombosed. Venography revealed that central venous access was no longer feasible. The previous laparotomies had resulted in dense intra-peritoneal adhesions, and rendered further laparotomy virtually impossible. The patient had occasional adhesion colics, vomiting and hypoglycemic episodes. A rarely performed retro-peritoneal approach of inserting an improved non-heparinised port proved to be effective for long-term management of this patient. The surgical approach and the selected port are discussed.

Adult↗
PubMed2005

Metastatic cervical carcinoma in the caecum.

A patient who presented with acute intestinal obstruction had a right hemicolectomy for a caecal tumour. The histopathology report confirmed metastatic carcinoma in the caecum from the cervical carcinoma. Caecum is a very rare site of metastasis from cervical carcinoma. From our literature review, there have been no such cases reported.

Aged↗
PubMed2005

Review of risk factors associated with the anastomosis leakage in anterior resection in Hospital Universiti Kebangsaan Malaysia.

This is a retrospective study evaluating the risk factors for clinical anastomotic leakage after anterior resection in 64 patients with rectal cancer operated from November 2001 till August 2003. The percentage of anastomosis leakage was higher in those patients with diabetic, low albumin level, neoadjuvant radiotherapy, higher staging, and poorly differentiated tumour. However, these differences were statistically not significant. There was a significant difference (p=0.03) of anastomosis leakage in those patients with very distal tumour of < 4cm from anal verge (42%), when compare to those patients with proximal tumor of > 15cm from anal verge (4.3%). The mortality associated with this complication was 30%. Hence, a surgeon may consider a covering stoma or be more vigilant in operating patients with multiple risk factors.

Adenocarcinoma↗
PubMed2004

Three-dimensional quantitative structure-activity relationship analyses of piperidine-based CCR5 receptor antagonists.

The CCR5 chemokine receptor has recently been found to play a crucial role in the viral entry stage of HIV infection and has therefore become an attractive potential target for anti-HIV therapeutics. On the other hand, the lack of CCR5 crystal structure data has impeded the development of structure-based CCR5 antagonist design. In this paper, we compare two three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) methods: Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) on a series of piperidine-based CCR5 antagonists as an alternative approach to investigate the interaction between CCR5 antagonists and their receptor. Superimposition of antagonist structures was performed using two alignment rules: atomic/centroid rms fit and rigid body field fit techniques. The 3D QSAR models were derived from a training set of 72 compounds, and were found to have predictive capability for a set of 19 holdout test compounds. The resulting contour maps produced by the best CoMFA and CoMSIA models were used to identify the structural features relevant to biological activity in this series of compounds. Further analyses of these interaction-field contour maps also showed a high level of internal consistency.

Animals↗
PubMed2004

Bogota bag in the treatment of abdominal wound dehiscence.

A patient who underwent emergency laparotomy for rectal prolapse developed repeated abdominal wound dehiscence and subsequently an enteric fistula. The management of abdominal wound dehiscence is discussed, specifically with regards to the Bogota bag. Use of Bogota bag has been reported worldwide but this may be the first report here.

Abdomen↗
PubMed2004

Heterotopic pancreas in the stomach.

A patient diagnosed with gastrointestinal stromal tumour of the stomach underwent gastrectomy. Post-operatively, histopathology was reported as heterotopic pancreas of the stomach. Heterotopic pancreas is very rare and though most of them appear asymptomatic, surgical resection is advisable.

Choristoma↗
PubMed2003

Prediction of the effect of mobile-phase salt type on protein retention and selectivity in anion exchange systems.

This study examines the effect of different salt types on protein retention and selectivity in anion exchange systems. Particularly, linear retention data for various proteins were obtained on two structurally different anion exchange stationary-phase materials in the presence of three salts with different counterions. The data indicated that the effects are, for the most part, nonspecific, although various specific effects could also be observed. Quantitative structure retention relationship (QSRR) models based on support vector machine feature selection and regression models were developed using the experimental chromatographic data in conjunction with various molecular descriptors computed from protein crystal structure geometries. Star plots for each descriptor used in the final model were generated to aid in interpretation. The resulting QSRR models were predictive, with cross-validated r2 values of 0.9445, 0.9676, and 0.8897 for Source 15Q and 0.9561, 0.9876, and 0.9760 for Q Sepharose resins in the presence of three different salts. The predictive power of these models was validated using a set of test proteins that were not used in the generation of these models. Interpretation of the models revealed that particular trends for proteins and salts could be captured using QSRR techniques.

Algorithms↗
PubMed2003

Transferable atom equivalent multicentered multipole expansion method.

The transferability of atomic and functional group properties is an implicit concept in chemistry. The work presented here describes the use of Transferable Atom Equivalents (TAE) to represent molecular electrostatic potential fields through the use of integrated atomic multipole moments that are associated with each TAE atom type used in the reconstruction. TAE molecular surface distributions of electrostatic potentials are compared with analytical ab initio and empirical (Gasteiger) partial charge reference models for several conformations of test peptides. Surface electrostatic potential distributions computed using TAE multipole representations were found to converge at the octopole level, with incremental improvement observed when hexadecapoles were included. Molecular electrostatic potential fields that were produced using the TAE method were observed to be responsive to conformational changes and to compare well with ab initio reference distributions. Generation of TAE atom types and their associated multipoles does not involve fitting to sample electrostatic potential fields, but rather utilizes integrated AIM atomic electron density distributions within representative chemical environments. The RECON program was used for TAE reconstruction. RECON is capable of processing 5,000 drug-sized molecules or 25 proteins per minute per 1.7 GHz P4 Linux processor.

Alanine↗
PubMed2002

High-throughput screening and quantitative structure-efficacy relationship models of potential displacer molecules for ion-exchange systems.

A technique is presented for the high-throughput screening of ion-exchange displacers. Potential displacers were employed to displace proteins in parallel batch ion-exchange experiments. The percentage of protein displaced from a particular stationary phase was then used as a parameter to rank the displacers. By employing this technique, a large number of molecules possessing a range of affinities and properties could be rapidly evaluated. This data was then used together with traditional and electron density-based transferable atom equivalent (TAE) molecular descriptors computed for the displacer molecules to produce quantitative structure-efficacy relationship (QSER) models using a genetic algorithm/partial least squares (GA/PLS) regression approach. The QSER models were generated using a portion of the protein-displacement data, with the remainder serving as a test set. Descriptor selection and model building was accomplished using a genetic algorithm/partial least squares approach. The resulting models were found to have high-correlation coefficients and could be used to accurately predict the behavior of molecules not included in the training set. In addition, the models were employed to examine a virtual library of displacers based on modifications of neomycin to provide further insight into displacer design. The results presented here indicate that it may be possible to design displacers that can dramatically improve the effective selectivity of ion-exchange chromatographic materials.

Algorithms↗
PubMed2002

Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase.

The crystal structure of the catalytic core of murine terminal deoxynucleotidyltransferase (TdT) at 2.35 A resolution reveals a typical DNA polymerase beta-like fold locked in a closed form. In addition, the structures of two different binary complexes, one with an oligonucleotide primer and the other with an incoming ddATP-Co(2+) complex, show that the substrates and the two divalent ions in the catalytic site are positioned in TdT in a manner similar to that described for the human DNA polymerase beta ternary complex, suggesting a common two metal ions mechanism of nucleotidyl transfer in these two proteins. The inability of TdT to accommodate a template strand can be explained by steric hindrance at the catalytic site caused by a long lariat-like loop, which is absent in DNA polymerase beta. However, displacement of this discriminating loop would be sufficient to unmask a number of evolutionarily conserved residues, which could then interact with a template DNA strand. The present structure can be used to model the recently discovered human polymerase mu, with which it shares 43% sequence identity.

Amino Acid Sequence↗
PubMed2001

Prediction of protein retention in ion-exchange systems using molecular descriptors obtained from crystal structure.

In this paper, a novel approach is described for the a priori prediction of protein retention in ion exchange systems. Quantitative structure retention relationship (QSRR) models based on a genetic algorithm/partial least squares approach were developed using experimental chromatographic data in concert with molecular descriptors computed using protein crystal structures. The resulting QSRR models were well-correlated, with cross-validated r2 values of 0.938 and 0.907, and the predictive power of these models was demonstrated using proteins not included in the derivation of the models. Importantly, these models were able to predict selectivity reversals observed with two different stationary phase materials. To our knowledge, this is the first published example of predictive QSRR models of protein retention based on crystal structure data.

Chromatography, Ion Exchange↗
PubMed2001

Structure of an active soluble mutant of the membrane-associated (S)-mandelate dehydrogenase.

The structure of an active mutant of (S)-mandelate dehydrogenase (MDH-GOX2) from Pseudomonas putida has been determined at 2.15 A resolution. The membrane-associated flavoenzyme (S)-mandelate dehydrogenase (MDH) catalyzes the oxidation of (S)-mandelate to give a flavin hydroquinone intermediate which is subsequently reoxidized by an organic oxidant residing in the membrane. The enzyme was rendered soluble by replacing its 39-residue membrane-binding peptide segment with a corresponding 20-residue segment from its soluble homologue, glycolate oxidase (GOX). Because of their amphipathic nature and peculiar solubilization properties, membrane proteins are notoriously difficult to crystallize, yet represent a large fraction of the proteins encoded by genomes currently being deciphered. Here we present the first report of such a structure in which an internal membrane-binding segment has been replaced, leading to successful crystallization of the fully active enzyme in the absence of detergents. This approach may have general application to other membrane-bound proteins. The overall fold of the molecule is that of a TIM barrel, and it forms a tight tetramer within the crystal lattice that has circular 4-fold symmetry. The structure of MDH-GOX2 reveals how this molecule can interact with a membrane, although it is limited by the absence of a membrane-binding segment. MDH-GOX2 and GOX adopt similar conformations, yet they retain features characteristic of membrane and globular proteins, respectively. MDH-GOX2 has a distinctly electropositive surface capable of interacting with the membrane, while the opposite surface is largely electronegative. GOX shows no such pattern. MDH appears to form a new class of monotopic integral membrane protein that interacts with the membrane through coplanar electrostatic binding surfaces and hydrophobic interactions, thus combining features of both the prostaglandin synthase/squaline-hopine cyclase and the C-2 coagulation factor domain classes of membrane proteins.

Alcohol Oxidoreductases↗
PubMed2001

Appendicular metastasis from carcinoma cervix.

A young lady who was treated for early squamous cell carcinoma of cervix presented with perforated appendicitis. Appendicectomy was done and the histopathology was reported as metastatic squamous cell carcinoma. Squamous cell carcinoma of the cervix metastasizing to the appendix is extremely rare and we previously unreported.

Adult↗