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Biomedical subjects

Alpesh Patel

Publications and source records attributed to Alpesh Patel.

16 recordsLinked to original sources
PubMed2006

Elastin biosynthesis: The missing link in tissue-engineered blood vessels.

Nearly 20 years have passed since Weinberg and Bell attempted to make the first tissue-engineered blood vessels. Following this early attempt, vascular tissue engineering has emerged as one of the most promising approaches to fabricate orderly and mechanically competent vascular substitutes. In elastic and muscular arteries, elastin is a critical structural and regulatory matrix protein and plays an important and dominant role by conferring elasticity to the vessel wall. Elastin also regulates vascular smooth muscle cells activity and phenotype. Despite the great promise that tissue-engineered blood vessels have to offer, little research in the last two decades has addressed the importance of elastin incorporation into these vessels. Although cardiovascular tissue engineering has been reviewed in the past, very little attention has been given to elastin. Thus, this review focuses on the recent advances made towards elastogenesis and the challenges we face in the quest for appropriate functional vascular substitutes.

Arteries↗
PubMed2006

Modelling of a metal-containing hepcidin.

Hepcidin was originally identified as a liver-expressed antimicrobial peptide but further studies have shown that it also has a key role in iron homeostasis. The NMR structure of the synthetic peptides reveal a distorted beta-sheet containing 4 disulphide bridges, with an unusual vicinal disulphide bridge which has been suggested to be functionally significant. In this study, we report the presence of co-purified iron with the urine-purified 20 and 25 residue hepcidins. Since the published structure does not allow metal binding, the interaction of hepcidin with metals was investigated for other possible structural conformations by threading its primary sequence onto existing 3D folds. Several alignments were obtained and the best scores were used to build a 3D model of hepcidin containing one atom of iron. The new 3D structure, that contains only reduced Cys residues, is completely different from the solved structure of the synthetic peptide. Although the model presented here shows only one metal bound to the peptide, the binding of several metal atoms cannot be excluded from such a short flexible peptide. The co-purification of iron with both peptides, together with our 3D model, suggest a conformational polymorphism for hepcidin, reminiscent of the iron regulatory proteins IRPs.

Amino Acid Sequence↗
PubMed2006

Synthesis, swelling behavior, and biocompatibility of novel physically cross-linked polyurethane-block-poly(glycerol methacrylate) hydrogels.

Physically cross-linked novel block copolymer hydrogels with tunable hydrophilic properties for biomedical applications were synthesized by controlled radical polymerization of polyurethane macroiniferter and (2,2-dimethyl-1,3-dioxolane) methyl methacrylate. The block copolymers were converted to hydrogels by the selective hydrolysis of poly[(2,2-dimethyl-1,3-dioxolane) methyl methacrylate] block to poly(glycerol methacrylate). The block copolymerization has been monitored by monomer conversion and molecular weight increase as a function of time. It was observed that the polymerization proceeded with a characteristic "living" behavior where both monomer conversion and molecular weight increased linearly, with increasing reaction time. The resulting hydrogels were investigated for their equilibrium water content (EWC), dynamic water contact angles, swelling kinetics, thermodynamic interaction parameters, plasma protein adsorption, and platelet adhesion. Similar to our previous mechanically responsive hydrogels (Mequanint, K.; Sheardown, H. J. Biomater. Sci. Polym. Ed. 2005, 10, 1303-1318), the present results indicated that block copolymer hydrogels have excellent hydrophilicity and swelling behavior with improved modulus of elasticity. The equilibrium swelling was affected by the hydrolysis time, block length of poly(glycerol methacrylate), temperature, and the presence of soluble salts. Fibrinogen adsorption and platelet adhesion were significantly lower for the hydrogels than for the control polyurethane, whereas albumin adsorption increased for the hydrogels in proportion to the contents of poly(glycerol methacrylate). These hydrogels have potential in a number of biomedical applications such as drug delivery and scaffolds for tissue engineering.

Adsorption↗
PubMed2006

Nerve root blocks in the treatment of lumbar radicular pain. A minimum five-year follow-up.

BACKGROUND: In a previous prospective, randomized, controlled, double-blinded study on the effect of nerve root blocks on the need for operative treatment of lumbar radicular pain, we found that injections of corticosteroids were more effective than bupivacaine for up to thirteen to twenty-eight months. We performed a minimum five-year followup of those patients who had avoided surgery. METHODS: All of the patients were considered to be operative candidates by the treating surgeon, and all had initially requested operative intervention. They had then been randomized to be treated with a selective nerve-root block with either bupivacaine or bupivacaine and betamethasone. Both the treating physician and the patient were blinded to the type of medication. Of fifty-five randomized patients, twenty-nine avoided an operation in the original study. Twenty-one of those twenty-nine patients were reevaluated with a follow-up questionnaire at a minimum of five years after the initial block. RESULTS: Seventeen of the twenty-one patients still had not had operative intervention. There was no difference between the group treated with bupivacaine alone and the group treated with bupivacaine and betamethasone with regard to the avoidance of surgery for five years. At the five-year follow-up evaluation, all of the patients who had avoided operative treatment had significant decreases in neurological symptoms and back pain compared with the baseline values. CONCLUSIONS: The majority of patients with lumbar radicular pain who avoid an operation for at least one year after receiving a nerve root injection with bupivacaine alone or in combination with betamethasone will continue to avoid operative intervention for a minimum of five years.

Follow-Up Studies↗
PubMed2004

Long adult deformity fusions to L5 and the sacrum. A matched cohort analysis.

STUDY DESIGN: A matched cohort analysis of long adult deformity fusions according to distal fusion level (L5 vs. S1). OBJECTIVE.: To compare the results of long adult deformity fusions to either L5 or the sacrum in the presence of a "healthy" 5-1 disc using a matched cohort analysis. SUMMARY OF BACKGROUND DATA: For adult spinal deformity, the decision often arises whether to terminate a long fusion at L5 or the sacrum. The decision is especially challenging in the presence of a "healthy" (Grade 0 to 1 degeneration) 5-1 disc. MATERIALS AND METHODS: A total of 95 adult deformity patients that underwent fusion from the thoracic spine to either L5 or the sacrum were sorted according to five preoperative criteria: 5-1 disc status, patient age, smoking status, number of levels fused, and sagittal balance. Two cohorts (L5, 27 patients; sacrum, 12 patients) were precisely matched according to the five criteria. Patients were evaluated at 2-year minimum follow-up according to radiographic data, complications, and SRS-24 outcomes. RESULTS: Correction of sagittal imbalance was superior for sacrum patients (C7 plumb line: L5, 0.9 cm; sacrum, 3.2 cm; P = 0.03). At latest follow-up (L5, 5.2 years; sacrum, 3.7 years), 67% of L5 patients had radiographic evidence of advanced 5-1 disc degeneration and the L5 cohort tended to have inferior sagittal balance (C7 plumb line: L5, +4.0 cm; sacrum, +1.2 cm; P = 0.06). The sacrum cohort, however, required more surgical procedures (L5, 1.7; sacrum, 2.8; P = 0.03) and experienced a greater frequency of major complications (L5, 22%; sacrum, 75%; P = 0.02), including nonunion (L5, 4%; sacrum, 42%; P = 0.006) and medical morbidity (L5, 0%; sacrum, 33%; P = 0.001). SRS-24 scores reflected a similar patient assessment of outcome and function for the two cohorts (L5, 89; sacrum, 87). DISCUSSION AND CONCLUSION: At 3 to 5 years' mean follow-up, long adult fusions to the sacrum required more procedures and had a higher frequency of complications than similar fusions to L5. For fusions to L5, subsequent subjacent disc degeneration is common and may be associated with a forward shift in sagittal balance. The ultimate influence of these factors on long-term outcomes remains to be seen.

Adult↗
PubMed2004

Effect of chain length on transfection properties of spermine-based gemini surfactants.

The synthesis and associated structure-activity relationships for gene transfection of a series of spermine-derived cationic gemini surfactants incorporating diamino acid headgroups and either identical (symmetrical) or different (unsymmetrical) lipophilic tailgroups is described. Transfection activity is found to depend critically upon the structural elements present.

Cell Line↗
PubMed2004

Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling.

Antimicrobial peptides bovine lactoferricin (LfcinB) and human lactoferricin (LfcinH) are produced from the respective lactoferrin, but are more active than their precursors. Despite sequence homology, the bovine peptide and its derivatives are more active than their human homologs. Such differences between not only the peptides and their precursor but also between the bovine and the human peptides could relate to structural differences. Upon sequence alignment of both peptides with their parental proteins, the structural differences observed between the bovine lactoferrin (BLf) and LfcinB were also found between the human lactoferrin (HLf) and the LfcinH. The helical structures in HLf are replaced by beta-strands separated by a strong turn in LfcinH suggesting an antiparallel beta-sheet structure similar to LfcinB. MIC assays with HLP-2 and BLP-2, 11-residue peptides derived from the active core of both Lfcins, against Escherichia coli, showed that the bovine derivative, BLP-2, is more active than its human homolog HLP-2. Both 3D models for HLP-2 and BLP-2 showed that the beta-strand is centred between the aromatic residues giving both side chains the same orientations. The displacement towards the N-terminus observed for the beta-strand in HLP-2, compared with its central location in BLP-2, could be less favourable to membrane interaction and therefore responsible for the decrease in activity. Such a model suggests for LfcinH a mechanism similar to the one observed for LfcinB, where the absence of long-range interaction, present in lactoferrin, destabilises the first alpha helix, as observed in solution and, upon interaction with the membrane, could result in the formation of a beta-strand, as observed in the presence of LPS. The location of the beta-strand in relation to the positive charges, seems to define the efficiency of the activity of the peptide and may explain the difference in activity obtained between HLP-2 and BLP-2.

Amino Acid Sequence↗
PubMed2004

Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity.

Synthetic peptides derived from human and bovine lactoferricin, as well as tritrpticin sequences, were assayed for antimicrobial activity against wild-type Escherichia coli and LPS mutant strains. Antimicrobial activity was only obtained with peptides derived from the bovine lactoferricin sequence and peptides corresponding to chimeras of human and bovine sequences. None of the peptides corresponding to different regions of native human lactoferricin showed any antimicrobial activity. The results underline the importance of the content of tryptophan and arginine residues, and the relative location of these residues for antimicrobial activity. Results obtained for the same assays performed with LPS mutants suggest that lipid A is not the main binding site for lactoferricin which interacts first with the negative charges present in the inner core. Computer modelling of the most active peptides led to a model in which positively charged residues of the cationic peptide interact with negative charges carried by the LPS to disorganise the structure of the outer membrane and facilitate the approach of tryptophan residues to the lipid A in order to promote hydrophobic interactions.

Amino Acid Sequence↗
PubMed2004

Detection of occult liver metastases during EUS for staging of malignancies.

BACKGROUND: EUS is commonly used in the staging of GI, thoracic, and other malignancies. Studies suggest EUS can detect occult liver metastases, but the frequency with which this occurs is unknown. METHODS: Records were reviewed for all patients seen during a 3-year period who underwent EUS of the upper-GI tract for staging of known or suspected malignancy. Patients were included if there was histopathologic evidence of malignancy, they had undergone noninvasive liver imaging within 6 weeks of EUS, and liver surveillance was specifically mentioned in the report of the EUS procedure. RESULTS: A total of 222 patients were included. Liver lesions were seen in 27 patients, 17 of whom had an abnormal noninvasive liver imaging test. EUS-guided FNA of the liver was performed in 21 patients and was diagnostic of malignancy in 15 (6.8%), 5 of whom (2.3%) had normal noninvasive imaging. In 6 patients, the EUS-guided FNA result was benign. EUS missed liver lesions in 4 patients known to have abnormalities by other imaging modalities. CONCLUSIONS: EUS can detect occult liver metastases in patients in whom noninvasive hepatic imaging studies are normal, although the frequency at which such lesions are detected is low. Liver surveillance during EUS is worthwhile for patients in whom there is another indication for the procedure; but, at present, EUS should not replace traditional imaging modalities.

Adolescent↗
PubMed2004

An outbreak of ammonia poisoning from chicken tenders served in a school lunch.

Although foodborne outbreaks of illness are relatively common, they are rarely caused by chemical agents. An outbreak of gastrointestinal illness occurred among students at two schools shortly after lunch was served. A cohort study, an environmental investigation, and microbiological and toxicological laboratory testing of food samples were performed. A case was defined as a student or teacher who ate food prepared in the kitchen at school A on 25 November 2002 (and served at schools A and B) and who later developed headache or symptoms of gastrointestinal tract irritation, with onset within 180 min of eating lunch. Among 312 persons interviewed, 157 persons became ill (attack rate = 49%; attack rate 41% for school A, 11% for school B). Onset of illness occurred within 60 min for 81% of cases; 91% of students reported that their chicken tenders smelled unusual. Eating chicken tenders that smelled unusual was associated with being a case (relative risk 9.2, 95% confidence interval 1.4 to 62.6, P < 0.05). Ammonia was detected in uncooked chicken tenders at levels as high as 2,468 ppm. The chicken had been contaminated during a warehouse leak of ammonia refrigerant. This outbreak of ammonia poisoning is only the second reported in food, and the first in a solid food. Heated chicken tenders contaminated with ammonia can cause acute illness within a short period of time.

Adolescent↗
PubMed2003

Thoracolumbar deformity arthrodesis to L5 in adults: the fate of the L5-S1 disc.

STUDY DESIGN: A retrospective clinical and radiographic analysis of long adult deformity fusions terminating at L5. OBJECTIVES: To define the results of thoracolumbar fusions to L5 in adult deformity patients with critical evaluation for potential subsequent L5-S1 disc degeneration and L5 implant loosening. SUMMARY OF BACKGROUND DATA: Few studies have reported the results of long adult fusions to L5 and the potential for subsequent advanced L5-S1 disc degeneration is unknown. MATERIALS AND METHODS: Thirty-four consecutive patients fused from the thoracic spine to L5 at a single institution were evaluated at a mean follow-up of 5.6 years (2.1-14.3 years). SRS-24 functional outcome questionnaire results were obtained for all patients at most recent follow-up. RESULTS: By latest follow-up, subsequent advanced L5-S1 disc degeneration (SAD) developed in 19 of 31 patients (61%) assessed as having "healthy" discs before surgery. SAD was associated with a forward shift in sagittal balance (P = 0.02) and need for revision surgery (P = 0.02). Risk factors for the development of SAD were preoperative positive sagittal balance (P = 0.01), younger age (P = 0.03), and the presence of even mild radiographic degeneration before surgery (P = 0.004). Loss of L5 implant fixation occurred in six patients (18%) and was associated with deep seating of L5 within the pelvis (P = 0.0001). Inferior SRS-24 outcome measures were associated with preoperative advanced L5-S1 disc degeneration and the development of postoperative sagittal imbalance. CONCLUSIONS: Subsequent L5-S1 DDD developed in 61% of patients after long adult fusions to L5 and was associated with a significant loss of sagittal alignment and an increased likelihood for or definite need for another operation. Loss of L5 implant fixation is not uncommon, especially in patients with a deep-seated L5 vertebra.

Adult↗
PubMed2003

Abundance ratio-dependent proteomic analysis by mass spectrometry.

The goal of quantitative proteomics is to determine the identity and relative quantity of each protein present in two or more complex protein samples. Here we describe a novel approach to quantitative proteomics. It is based on a highly accurate algorithm for the automated quantification of chromatographically fractionated, isotope-coded affinity-tagged peptides and MALDI quadrupole time-of-flight tandem mass spectrometry for their identification. The method is capable of detecting and selectively identifying those proteins within a complex mixture that show a difference in relative abundance. We demonstrate the effectiveness and the versatility of this approach in the analysis of a standard protein mixture, protein expression profiling in a human prostate cancer cell line model, and identification of the specific components of the multiprotein transcriptional machinery in S. cerevisiae.

Humans↗
PubMed2003

The management of congenital tracheal stenosis.

This paper reviews current concepts and results in the management of congenital tracheal stenosis (CTS). Diagnostic options are considered and the requirements for successful management defined. Chief amongst these is a multi-disciplinary approach with individualised patient management. Severe long-segment CTS represents the biggest challenge to clinicians and the worst problems for affected families. Near-death episodes are frequent in affected infants and some cannot be ventilated and require ECMO. Associated cardiovascular anomalies are frequent. Patients require immediate resuscitation and transfer to a specialist unit. After careful assessment, accurate diagnosis and discussion, primary resection and end-to-end repair with a slide technique should always be the first option, with concomitant repair of associated cardiac anomalies. If this is impossible because of the severity of the lesion, some form of patch tracheoplasty will be indicated. Cardiopulmonary bypass is often required. Patches include pericardium, autograft trachea, carotid artery, cartilage, and allograft trachea. Mortality ranges from 0 to 30% in the literature, which largely comprises single-centre long-term experience. Recurrence is common and can be managed by stenting and tracheal homograft implantation. Long-term quality of life of survivors is little reported but seems good. Physiological data are lacking. To improve results, we suggest a treatment algorithm to rationalise care.

Airway Obstruction↗
PubMed2003

Repair of tuberculous aneurysm of distal aortic arch.

A 65 year old female patient presented with one episode of massive haemoptysis requiring transfusion and subsequently cough with streaky haemoptysis. Computerized tomographic scan and angiogram revealed aneurysm of the distal aortic arch. She underwent elective repair of the pseudoaneurysm through median sternotomy and the bronchial communication was closed through left thoracotomy. Tubercle bacilli were identified in the contents and excised wall of aortic tissue.

Aged↗
PubMed2002

Analysis of the human hephaestin gene and protein: comparative modelling of the N-terminus ecto-domain based upon ceruloplasmin.

Hephaestin was implicated in mammalian iron homeostasis following its identification as the defective gene in murine sex-linked anaemia. It is a member of the family of copper oxidases that includes mammalian ceruloplasmin, factors V and VIII, yeast fet3 and fet5 and bacterial ascorbate oxidase. Hephaestin is different from ceruloplasmin, a soluble ferroxidase, in having a membrane-spanning region towards the C-terminus. Here we report the gene structure, spanning approximately 100 kb, of the human homologue of mouse hephaestin. The sequence was assembled from the cDNA clones and the chromosome X genomic sequence data available at the Sanger Centre. It has an open reading frame that encodes a protein of 1158 residues, 85% identical with the murine homologue. A model of the N-terminal ecto-domain has been built based on the known three-dimensional structure of human ceruloplasmin. The overall tertiary structure for the hephaestin and the putative residues involved in binding copper and iron appear to be highly conserved between these proteins, which suggests they share the same fold and a conserved function.

Base Sequence↗