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T Patel

Publications and source records attributed to T Patel.

At least 37 records · Page 2Linked to original sources
PubMed2000

A cost-benefit analysis of the effect of shipboard telemedicine in a selected oceanic region.

Data from a selected oceanic region, the UK search and rescue region, were used to establish the average annual of ship diversions and emergency service call-outs arising from urgent medical problems of passengers or crew. During the period 1997-8 there were 228 medical evacuations. An attempt was made to estimate the extent to which some or all of the diversions and call-outs could have been averted if telemedical facilities had been available on-board the ships. The analysis showed that telemedicine would be an expensive alternative to existing evacuation methods, but did not allow for the fact that helicopter and lifeboat evacuations cannot be carried out in bad weather or at distances over 200 nautical miles (370 km) from land. Taking into consideration the cost of ship diversions in such circumstances produces completely different results. Telemedicine could clearly provide substantial cost-savings for the shipping industry, and a separate analysis focused on the shipowner alone would make an overwhelming economic argument for investment in a telemedicine service simply on the strength of diversion avoidance.

Cost-Benefit Analysis↗
PubMed1999

Stabilizing potential of anterior cervical plates in multilevel corpectomies.

STUDY DESIGN: An in vitro investigation of three-dimensional kinematics of cervical spine models of one- and three-level corpectomy with anterior plate fixation. OBJECTIVES: To evaluate the capability of an anterior plate to stabilize the reconstructed cervical spine under simulated physiologic motions, and to study the effects of fatigue loading. SUMMARY OF BACKGROUND DATA: Clinical studies have found high failure rates of multilevel anterior cervical plate fusions, indicating suboptimal stabilization. However, no biomechanical studies have been done to investigate the stabilizing capabilities of long-plate instrumentations in corpectomy models. METHODS: Seven fresh human cadaveric cervical spine specimens (C2-T1) were used. Flexibility tests consisted of flexion, extension, and bilateral torsion, and lateral bending, each with a pure moment of 0.25, 0.5, 0.75, and 1.0 Nm. Stabilizing potential indices [(MotionIntact-MotionInstrumented)/MotionIntact] for ranges of motion and neutral zones obtained from the flexibility tests, were measured when the specimen was intact and after one-level (C5) and three-level (C4, C5, and C6) corpectomies and anterior plate stabilizations). The stabilizing potential indices were re-measured after a 1000-cycle fatigue loading (1 Nm flexion and extension moments at C5 vertebra at 0.14 Hz). RESULTS: The differences in stabilizing potential indices of range of motion and neutral zone between one-level and three-level plates were not significant before fatigue. However, after fatigue, the stabilizing potential indices significantly decreased (P < 0.05) for the three-level model, but not for the one-level plate model. CONCLUSIONS: The capability of an anterior cervical plate to stabilize the spine after three-level corpectomy was significantly reduced with fatigue loading.

Adolescent↗
PubMed1999

Percutaneous mitral valve dilatation with the Multi-Track System.

We developed the Multi-Track System for percutaneous mitral valvotomy and described the preliminary results in 1995. Here we report the first 100 consecutive cases after the original publication. Two separate balloon catheters are positioned on a single guidewire. The first catheter, with only a distal guidewire lumen, is introduced into the vein and then advanced into the mitral orifice. Subsequently, a rapid exchange balloon catheter running on the same guidewire is inserted and lined up with the first catheter so the two are positioned side by side. Both balloons are then inflated simultaneously. Age of the patients was 31 +/- 12.8 years and weight 50 +/- 14 kg. Valve area increased 0.75 +/- 0.22 cm(2) to 2.00 +/- 0.32 cm(2)and mean left atrial pressure dropped from 27 +/- 8 to 11 +/- 5 mm Hg. One patient had significant mitral insufficiency after dilatation, which did not require surgery. The Multi-Track System is a valid alternative to the existing procedures for the treatment of mitral stenosis and uses simpler and less costly catheters. Cathet. Cardiovasc. Intervent. 48:178-183, 1999.

Adolescent↗
PubMed1999

Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase.

The biliary epithelium is exposed to mediators of inflammation such as bacterial endotoxin or lipopolysaccharide (LPS) in a variety of inflammatory conditions. These conditions are also characterized by cholangiocyte proliferation and a predisposition to malignancy. Furthermore, LPS can enhance the expression of interleukin-6 (IL-6), a known biliary mitogen. However, the effects of LPS on cholangiocyte proliferation or IL-6 secretion are unknown. Thus, our aims were to determine if LPS stimulates cholangiocyte proliferation by IL-6-dependent signaling pathways. H69 cells derived from normal human intrahepatic cholangiocytes proliferated in response to LPS. Cholangiocytes responded to LPS (and other inflammatory cytokines such as tumor necrosis factor alpha [TNF-alpha] and IL-1beta) by increased secretion of IL-6, which had a mitogenic effect on H69 cells. Preincubation with anti-IL-6 neutralizing antibodies inhibited LPS-induced proliferation. Furthermore, cholangiocytes possessed the IL-6 receptor complex subunits and intact signaling mechanisms leading to activation of signal transducers and activators of transcription (STAT) factors. Although both p38 and p44/p42 mitogen-activated protein kinases (MAPKs) were constitutively present and active in cholangiocytes, IL-6 increased p44/p42, but not p38 MAPK activity. PD098059 inhibited activation of p44/p42 MAPK in cholangiocytes and completely blocked DNA synthesis in response to IL-6 or LPS. These studies identify a critical role for the p44/p42 MAPK in cholangiocyte proliferation and demonstrate that the proliferative response of cholangiocytes to inflammatory mediators such as LPS involves IL-6-mediated activation of the p44/p42 MAPK pathway.

Bile Ducts↗
PubMed1999

Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line.

Biliary tract malignancies represent challenges because of the lack of effective therapy and poor prognosis, in part because of the paucity of information regarding the mechanisms regulating their growth. We have recently identified a critical role for the p44/p42 mitogen-activated protein kinase (MAPK) pathway in interleukin 6 (IL-6)-stimulated growth of human cholangiocytes. Although IL-6 is a potential mitogen for cholangiocarcinoma, the role of this cytokine and its intracellular signaling pathways in cholangiocarcinoma growth is unknown. Thus, our aims were to determine the role of IL-6-mediated signaling mechanisms, and in particular the MAPK pathways, in the growth regulation of human cholangiocarcinoma. KMCH-1 cells (malignant cholangiocyte cells) secreted IL-6 constitutively, and increased IL-6 secretion in response to inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and IL-1beta. Stimulation with IL-6 resulted in proliferation of malignant cholangiocytes. These cells also possessed the IL-6 receptor complex subunits as directly assessed by immunoblot analysis. Furthermore, proliferation was completely inhibited by preincubation with anti-IL-6 neutralizing antibodies, indicating that the proliferative response to IL-6 involved receptor-mediated signaling. Both p38 and p44/p42 MAPKs were constitutively present and active in malignant cholangiocytes, and increased activity of both was observed within 15 minutes of stimulation with IL-6. Selective inhibition of either the p44/p42 MAPK pathway, by PD098059, or of the p38 MAPK pathway, by SB203580, blocked proliferation in response to IL-6. Thus, IL-6 can contribute to the autocrine and/or paracrine growth stimulation of malignant cholangiocytes via activation of either p38 or p44/p42 MAPK signaling pathways.

Bile Duct Neoplasms↗
PubMed1999

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour.

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT.

Amino Acid Sequence↗
PubMed1999

Surgery in the patient with liver disease.

Patients with liver disease often undergo surgery. With the increasing prevalence of liver disease and improved survival due to newer medications and treatments, a growing number of patients with liver disease will require preoperative assessment. Because of the multiple physiological roles of the liver, hepatic dysfunction places these patients at an increased risk of perioperative morbidity and mortality. The precise risks associated with specific liver diseases are poorly understood but are greater with increased impairment of hepatic function. Identifying preexisting problems that could be optimally and appropriately managed before surgery (e.g., coagulation status, intravascular volume, renal function, electrolytes, cardiovascular status, and nutrition) may reduce these risks and decrease mortality in patients with liver disease undergoing surgery.

Anesthesia, General↗
PubMed1998

Serotonin transporters are located on the axons beyond the synaptic junctions: anatomical and functional evidence.

The serotonin (5-HT) transporter (5-HTT) is known to play a role in depression and many 5-HT related diseases, and is the target site for drugs of abuse, such as cocaine, MDMA, and methamphetamine. The major role of the 5-HTT has long been considered to be to inactivate serotonin transmission through the elimination of serotonin at release sites. However, immunocytochemistry using an antibody against the N-terminal of the 5-HTT at the light microscopic (LM) level indicates that the 5-HTT is associated not only with 5-HT varicosities but also with axons. Electron microscopy (EM) reveals that the majority of the 5-HTTs exist on the axolemma outside the synaptic junctions. In studying whether axonal 5-HTTs are involved in the uptake of 5-HT, we found with autoradiography that [3H]citalopram bound to all major 5-HT fibers, not only in the terminal regions, but also in 5-HT axonal bundles such as the cingulum bundle and medial forebrain bundle. Furthermore, voltammetry recordings indicated that serotonin axonal bundles were actively engaged in high affinity serotonin uptake. The evidence indicates that 5-HTTs on 5-HT axons away from the synapse are likely to be functional in a manner similar to the terminal 5-HTT for serotonin uptake. It also suggests that the role of the 5-HTT may not only be for the termination of synaptic transmission, but also for the regulation of 5-HT through extrasynaptic (volume) transmission. Our findings may also impact the understanding of the sites of action of selective serotonin reuptake inhibitors and drug entry into serotonin neurons via the numerous axonal sites.

Animals↗
PubMed1998

Human T cell IgD receptors react with O-glycans on both human IgD and IgA1.

Previous studies on murine T cell IgD-R have shown that these receptors recognize N-glycans of murine IgD, and not of other Ig isotypes. We have now studied the specificity of IgD-R on human T cells. Human IgD digested with proteinase K to fragments of < 5 kDa inhibit the ability of T cells to form rosettes with IgD-coated ox erythrocytes. The same amount of digested IgG does not. We tested all the human Ig isotypes: IgG1, -2, -3, -4, IgA2, IgE and IgM fail to inhibit significantly at 20 microg/assay. However, IgA1 is as effective as IgD itself, showing approximately 60 % and 80 % inhibition at 5 microg and 10 microg/assay. Human IgA1 and IgD both contain Gal-1 --> 3-GalNac-rich O-linked glycans, and on this basis are both bound to ricin and jacalin. The O-linked glycans may therefore also represent the common moiety binding to IgD-R. Disaccharides Gal-1 --> 3-GalNac, and Gal-1 --> 4-Glc at 10 microg/assay blocked IgD rosetting while Gal-1 --> 6-Glc did not. We conclude that the human IgD-R is a lectin, differing from the murine IgD-R in that it has both IgA1 and IgD as ligands.

Animals↗
PubMed1998

Dysregulation of apoptosis as a mechanism of liver disease: an overview.

Apoptosis is a morphologically distinct form of cell death which occurs in a wide variety of liver diseases. In this overview chapter, we review: (1) the current definitions of apoptosis; (2) the biochemical pathways effecting apoptosis; and (3) the intracellular pathways regulating apoptosis. We also describe how apoptosis is identified in the liver and review the ligand/receptor interactions which trigger hepatobiliary apoptosis. Finally, we speculate on potential therapeutic applications for modulating apoptosis in human liver diseases. This information is meant to provide a foundation for the following chapters each focused on a specific role of apoptosis in liver diseases.

Apoptosis↗
PubMed1998

Role of oligosaccharides in the pharmacokinetics of tissue-derived and genetically engineered cholinesterases.

To understand the role of glycosylation in the circulation of cholinesterases, we compared the mean residence time of five tissue-derived and two recombinant cholinesterases (injected intravenously in mice) with their oligosaccharide profiles. Monosaccharide composition analysis revealed differences in the total carbohydrate, galactose, and sialic acid contents. The molar ratio of sialic acid to galactose residues on tetrameric human serum butyrylcholinesterase, recombinant human butyrylcholinesterase, and recombinant mouse acetylcholinesterase was found to be approximately 1.0. For Torpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was approximately 0.5. However, the circulatory stability of cholinesterases could not be correlated with the sialic acid-to-galactose ratio. Fractionation of the total pool of oligosaccharides obtained after neuraminidase digestion revealed one major oligosaccharide for human serum butyrylcholinesterase and three or four major oligosaccharides in other cholinesterases. The glycans of tetrameric forms of plasma cholinesterases (human serum butyrylcholinesterase, fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase) clearly demonstrated a reduced heterogeneity and higher maturity compared with glycans of monomeric fetal bovine serum acetylcholinesterase, dimeric tissue-derived T. californica acetylcholinesterase, and recombinant cholinesterases. T. californica acetylcholinesterase, recombinant cholinesterases, and monomeric fetal bovine serum acetylcholinesterase showed a distinctive shorter mean residence time (44-304 min) compared with tetrameric forms of plasma cholinesterases (1902-3206 min). Differences in the pharmacokinetic parameters of cholinesterases seem to be due to the combined effect of the molecular weight and charge- and size-based heterogeneity in glycans.

Acetylcholinesterase↗
PubMed1997

Inhibition of bile-salt-induced hepatocyte apoptosis by the antioxidant lazaroid U83836E.

Intracellular retention of toxic bile salts contributes to hepatocellular injury during cholestasis. We have recently demonstrated that toxic bile salts directly induce apoptosis in hepatocytes. As oxidative stress has been implicated in many models of apoptosis, our aim was to determine if oxidative injury is a critical event during bile-salt-induced hepatocyte apoptosis. Cultured rat hepatocytes incubated with 50 microM glycochenodeoxycholate (GCDC) exhibited the characteristic morphological features of apoptosis such as nuclear fragmentation and cellular fragmentation into organelle-containing membrane-bound apoptotic bodies. After a 3-hr incubation, apoptosis was observed in 60 +/- 8% of cells compared to <1% in controls. GCDC-induced apoptosis was associated with lipid peroxidation as demonstrated by an increase in 8-isoprostane release. The antioxidant lazaroid U83836E inhibited 8-isoprostane generation during GCDC-induced hepatocye apoptosis. In addition, U83836E also reduced GCDC-mediated apoptosis by 70% as assessed using both stringent morpholgic (nuclear fragmentation) and biochemical (determination of DNA strand breaks) criteria. In summary, during treatment of hepatocytes with GCDC, (1) apoptosis is associated with lipid peroxidation, and (2) the antioxidant lazaroid U83836E inhibits both lipid peroxidation and apoptosis. In conclusion, these data suggest that oxidative stress contributes to bile-salt-induced apoptosis. We speculate that antioxidants may be useful in ameliorating liver injury during chronic cholestasis.

Animals↗