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Biomedical subjects

A Chauhan

Publications and source records attributed to A Chauhan.

At least 19 recordsLinked to original sources
PubMed2006

Day care laparoscopic cholecystectomy: a feasibility study in a public health service hospital in a developing country.

BACKGROUND: Day care laparoscopic cholecystectomy (DCLC) has been shown to be safe in centers with adequate infrastructure for day care surgery in economically advanced countries. However, the feasibility of applying this concept in public health service hospitals in less developed and developing nation needs to studied. Unique protocols need to be developed and tested, taking into account local conditions and infrastructural constraints. PATIENTS AND METHODS: Patients less than 60 years old, graded I and II on the American Society of Anesthesiologists (ASA) physical status score, living within one hour traveling time and willing to make their own arrangements for a return to hospital in case of problems, were selected for DCLC. RESULTS: 291 cases (78%) out of 373 laparoscopic cholecystectomies done in one calendar year were found suitable for DCLC. The most common cause for omitting from DCLC was that the patient lived out of the defined area (57%). Four of 291 (1.3%) cases were cancelled due to medical condition; 270/287 (96.1%) were discharged the same evening as surgery; 6 patients were converted to open surgery; and 11 did not meet the necessary discharge criteria. Eight of 270 (2.9%) required readmission out of which 3 (1.1%) required intervention. Overall, incidence of complication rate was 3.4%. Analysis of data showed that results were comparable to previously published studies, hence extrapolating that inclusion and discharge criteria used in the study are valid. However, there are certain social constraints which hinder truly universal application of DCLC. CONCLUSIONS: DCLC is a safe and technically feasible concept, even in public health service centers without dedicated ambulatory surgery units. It has potential for much economical and social benefit in these countries.

Adult↗
PubMed2006

Syntrophic-archaeal associations in a nutrient-impacted freshwater marsh.

AIMS: Evaluation of the composition, distribution and activities of syntrophic bacteria and methanogens in soils from eutrophic and low nutrient regions of a freshwater marsh, and to compare these results with those obtained from a similar study in the Florida Everglades. METHODS AND RESULTS: Culture dependent and independent approaches were employed to study consortia of syntrophs and methanogens in a freshwater marsh. Methanogenesis from butyrate oxidation was fourfold higher in microcosms containing soil from eutrophic regions of the marsh than from low nutrient regions. Propionate was oxidized in eutrophic microcosms at lower rates than butyrate and with lower yields of methane. Sequence analysis of 16S rRNA gene clone libraries from DNA extracted from microcosms and soils revealed differences such that the dominant restriction fragment length polymorphism (RFLP) phylotypes (representing 82-88% of clone libraries) from eutrophic soils clustered with fatty acid oxidizing Syntrophomonas spp. The four dominant RFLP phylotypes (representing 11-24%) from microcosms containing soils from low nutrient regions were sequenced, and clustered with micro-organisms having the potential for fermentative and syntrophic metabolism. Archaeal 16S rRNA sequence analysis showed that methanogens from eutrophic regions were from diverse families, including Methanomicrobiaceae, Methanosarcinaceae, and Methanocorpusculaceae, but clone libraries from low nutrient soils revealed only members of Methanosarcinaceae. CONCLUSIONS: These findings indicate that syntroph-methanogen consortia differed with nutrient levels in a freshwater marsh. SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of few studies addressing the distribution of fatty acid consuming-hydrogen producing bacteria (syntrophs) and their methanogenic partners in wetland soils, and the effects of eutrophication on the ecology these groups.

Acetates↗
PubMed2005

Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha. METHODS: TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept. RESULTS: TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. CONCLUSIONS: These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.

Adult↗
PubMed2005

Multivariate prediction of major adverse cardiac events after 9914 percutaneous coronary interventions in the north west of England.

OBJECTIVE: To develop a multivariate prediction model for major adverse cardiac events (MACE) after percutaneous coronary interventions (PCIs) by using the North West Quality Improvement Programme in Cardiac Interventions (NWQIP) PCI Registry. SETTING: All NHS centres undertaking adult PCIs in north west England. METHODS: Retrospective analysis of prospectively collected data on 9914 consecutive patients undergoing adult PCI between 1 August 2001 and 31 December 2003. A multivariate logistic regression analysis was undertaken, with the forward stepwise technique, to identify independent risk factors for MACE. The area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness of fit statistic were calculated to assess the performance and calibration of the model, respectively. The statistical model was internally validated by using the technique of bootstrap resampling. MAIN OUTCOME MEASURES: MACE, which were in-hospital mortality, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accidents. RESULTS: Independent variables identified with an increased risk of developing MACE were advanced age, female sex, cerebrovascular disease, cardiogenic shock, priority, and treatment of the left main stem or graft lesions during PCI. The ROC curve for the predicted probability of MACE was 0.76, indicating a good discrimination power. The prediction equation was well calibrated, predicting well at all levels of risk. Bootstrapping showed that estimates were stable. CONCLUSIONS: A contemporaneous multivariate prediction model for MACE after PCI was developed. The NWQIP tool allows calculation of the risk of MACE permitting meaningful risk adjusted comparisons of performance between hospitals and operators.

Adult↗
PubMed2005

Regulation of high molecular weight bovine brain neutral protease by phospholipids in vitro.

The activity of the heat stable, glycosylated high molecular weight bovine brain neutral protease (HMW protease) is differentially regulated by phospholipids. While phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA) had only marginal stimulatory effect (40-75%) on the activity of HMW protease, lysophoshatidylcholine (lysoPC) and lysophosphatidic acid (lysoPA) activated the enzyme by more than two-fold. Both lysoPC and lysoPA exhibited concentration-dependent saturation kinetics for the activation of HMW protease. Surprisingly, phosphoinositides (phosphatidylinositol, PI; phosphatidylinositol 4-phosphate, PIP; and phosphatidylinositol 4,5-bisphosphate, PIP2) modulated the activity of protease differently: activation of the enzyme was higher with PIP (90%) as compared to PI (21%), whereas PIP2 inhibited the enzyme (16%). The inhibition of the protease by PIP2 was concentration-dependent. During receptor-coupled cell activation, phospholipase A2 (PLA2) converts PC and PA to lysoPC and lysoPA, respectively; PI is converted to PIP2 by successive enzymatic phosphorylation by PI 4-kinase and PIP 5-kinase; and phospholipase C (PLC) degrades PIP2 to diacylglycerol and inositol 1,4,5-trisphosphate. Therefore, the data suggest that HMW protease may be coupled to cell signal transduction where PLA2, PI 4-kinase, PIP 5-kinase and PLC are involved.

Animals↗
PubMed2005

The effect of water hydraulic permeability on the settling of a soft contact lens on the eye.

PURPOSE: Silicone-elastomer soft contact lenses (SCLs) adhere to the cornea during wear, whereas silicone-hydrogel soft contact lenses exhibit adequate on-eye movement. One explanation for the observed immunity to binding of silicone-hydrogel lenses is that some interstitial water is expelled during blinking, therefore maintaining a more stable post-lens tear film (PoLTF). We examine quantitatively whether or not water can be squeezed by hydrodynamic flow through a silicone-hydrogel membrane driven by the applied lid force during a blink. METHODS: A rigid, porous-disk model of a contact lens was devised to calculate the relative settling rates of a permeable versus a completely impermeable SCL. The settling rate depended strongly on the value of the hydraulic permeability for pressure-driven water flow through the lens. Because the hydraulic permeability of water through silicone-hydrogel materials is not well-known, we measured this value. At steady state, water was forced through flat membranes of representative lens materials under known pressure drops. The resulting volumetric flows were measured by following the transient rise height of water in a vertical, precision-bore glass capillary. Darcy's law permitted calculation of the hydrodynamic permeability. RESULTS: The settling-rate model indicated that tear can be squeezed through a SCL only when the Darcy-law hydrodynamic permeability is greater than about 10 microm2 (i.e., greater than 10 Darcy). Our measurements for silicone and HEMA hydrogel membranes reveal hydrodynamic permeabilities of the order 10(-8) microm2, almost 9 orders of magnitude smaller than that necessary to initiate hydrodynamic flow through a SCL. CONCLUSIONS: We conclude that the squeeze-through mechanism cannot quantitatively account for the observed on-eye movement of silicone-hydrogel lenses. Also, we find that the lid-applied pressure cannot squeeze enough water out of a SCL during a blink to stabilize the PoLTF. Neither a squeeze-through nor a squeeze-out mechanism can maintain a stable PoLTF and prevent adherence.

Blinking↗
PubMed2005

Percutaneous coronary intervention: recommendations for good practice and training.

Cardiologists undertaking percutaneous coronary intervention (PCI) are excited by the combination of patient and physician satisfaction and technological advance occurring on the background of the necessary manual dexterity. Progress and applicability of percutaneous techniques since their inception in 1977 have been remarkable; a sound evidence base coupled with the enthusiasm and ingenuity of the medical device industry has resulted in a sea change in the treatment of coronary heart disease (CHD), which continues to evolve at breakneck speed. This is the third set of guidelines produced by the British Cardiovascular Intervention Society and the British Cardiac Society. Following the last set of guidelines published in 2000, we have seen PCI activity in the UK increase from 33,652 to 62,780 (87% in four years) such that the PCI to coronary artery bypass grafting ratio has increased to 2.5:1. The impact of drug eluting stents has been profound, and the Department of Health is investigating the feasibility of primary PCI for acute myocardial infarction. Nevertheless, the changes in the structure of National Health Service funding are likely to focus our attention on cost effective treatments and will require physician engagement and sensitive handling if we are to continue the rapid and appropriate growth in our chosen field. It is important with this burgeoning development now occurring on a broad front (in both regional centres and district general hospitals) that we maintain our vigilance on audit and outcome measures so that standards are maintained for both operators and institutions alike. This set of guidelines includes new sections on training, informed consent, and a core evidence base, which we hope you will find useful and informative.

Angioplasty, Balloon, Coronary↗
PubMed2005

Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation.

Antithrombotic agents have verified efficacy in reducing the thromboembolic risk associated with atrial fibrillation. This article focuses on the emergence of a new oral direct thrombin inhibitor, ximelagatran, into the arena of atrial fibrillation thromboprophylaxis. This review does not cover atrial fibrillation in the context of valvular heart disease. The efficacy of aspirin and warfarin will be discussed briefly.

Administration, Oral↗
PubMed2003

Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants.

OBJECTIVE: To determine the role of oxidative stress in mediating HIV dementia and to identify novel therapeutic compounds that may block this oxidative stress. METHODS: Brain tissue from patients with HIV encephalitis and macaques with simian immune deficiency virus encephalitis was immunostained for lipid peroxidation. Oxidized proteins in CSF of patients with various stages of HIV dementia were quantitated and we determined whether CSF from these patients could alter mitochondrial function. Several novel compounds with antioxidant effects were screened to determine their relative efficacy in protecting against CSF-induced neurotoxicity. RESULTS: Evidence for oxidative stress was present both in brain and in CSF. The presence of oxidized proteins in the CSF and CSF-induced progressive decrease in mitochondrial activity correlated with the severity of cognitive impairment, but only the group of patients with moderate to severe dementia reached statistical significance. L-deprenyl, didox, imidate, diosgenin, and ebselen blocked the CSF-induced toxicity. No effect of trimidox, ruthenium red, or Quercetin was seen. CONCLUSIONS: Increased oxidative stress is present in brain and CSF of HIV-infected patients. There is also an accumulation of toxic substances in the CSF that are capable of inducing oxidative stress. The authors have identified several novel compounds that are capable of blocking the CSF-induced toxicity, the therapeutic potential of which is worthy of further exploration.

AIDS Dementia Complex↗
PubMed2002

Settling and deformation of a thin elastic shell on a thin fluid layer lying on a solid surface.

placement of a soft contact lens onto the cornea, the upper eyelid deforms and settles the lens by squeezing fluid out of the post-lens tear film or POLTF (i.e., the tear fluid layer sandwiched between the lens and the cornea). This paper studies the physical mechanisms that control the dynamic state of the contact lens during blinking, i.e., its shape and its distance from the cornea, especially a long time after insertion. We model the lens as a deformable elastic shell and the cornea as a flat nondeformable body. The tear fluid is assumed to be Newtonian, and the lens is characterized by an elastic modulus and a Poisson ratio. Lubrication equations under creeping flow are used to solve the fluid problem, while the thin-shell approximation is applied to the solid lens. The solid and fluid mechanics problems are coupled by maintaining continuity of stress and velocity at the solid/liquid interface. Lid applied pressure causes the lens to approach the cornea by squeezing tear fluid out and also leads to the deformation of the lens. Subsequently, in the interblink period, since there is no applied force, the elastic energy stored in the lens due to its deformation is released causing it to move away from the cornea by imbibing tear fluid into the POLTF. If the POLTF thickness is large, the inward motion of the lens in the blink is more than the outward motion during interblink, and this causes the lens to settle closer to the cornea. Eventually, there may be a balance of the inward motion during the blink and the outward motion during the interblink. If so, the lens subsequently exhibits periodic steady-state motion. However, it is also possible that a balance of inward and outward motion is never achieved, and the lens continues to settle endlessly. If this happens, then the thinfilm interactions between the mucin-covered corneal surface and the lens material determine whether the lens actually touches the cornea and possibly adheres. Our elastohydrodynamic analysis serves as a useful tool to elucidate the effects of various lens parameters on the final settled state of the lens. In particular, we are concerned about eventual adherence and/or mechanical abrasion to the cornea, which is very important to the ocular health of soft contact lens wearers.

Journal Article↗
PubMed2001

Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours.

Previously we analysed overlapping homozygous deletions in lung and breast tumours/tumour lines and defined a small region of 120 kb (part of LCTSGR1) at 3p21.3 that contained putative lung and breast cancer tumour suppressor gene(s) (TSG). Eight genes including RASSF1 were isolated from the minimal region. However, extensive mutation analysis in lung tumours and tumour lines revealed only rare inactivating mutations. Recently, de novo methylation at a CpG island associated with isoform A of RASSF1 (RASSF1A) was reported in lung tumours and tumour lines. To investigate RASSF1A as a candidate TSG for various cancers, we investigated: (a) RASSF1A methylation status in a large series of primary tumour and tumour lines; (b) chromosome 3p allele loss in lung tumours and (c) RASSF1 mutation analysis in breast tumours. RASSF1A promoter region CpG island methylation was detected in 72% of SCLC, 34% of NSCLC, 9% of breast, 10% of ovarian and 0% of primary cervical tumours and in 72% SCLC, 36% NSCLC, 80% of breast and 40% of ovarian tumour lines. In view of the lower frequency of RASSF1 methylation in primary breast cancers we proceeded to RASSF1 mutation analysis in 40 breast cancers. No mutations were detected, but six single nucleotide polymorphisms were identified. Twenty of 26 SCLC tumours with 3p21.3 allelic loss had RASSF1A methylation, while only six out of 22 NSCLC with 3p21.3 allele loss had RASSF1A methylation (P=0.0012), one out of five ovarian and none out of six cervical tumours with 3p21.3 loss had RASSF1A methylation. These results suggest that (a) RASSF1A inactivation by two hits (methylation and loss) is a critical step in SCLC tumourigenesis and (b) RASSF1A inactivation is of lesser importance in NSCLC, breast, ovarian and cervical cancers in which other genes within LCTSGR1 are likely to be implicated.

Amino Acid Sequence↗
PubMed2001

Fibrillar amyloid beta-protein forms a membrane-like hydrophobic domain.

Microviscosity of the biological membranes is determined by measuring the fluorescence polarization of diphenylhexatriene (DPH). DPH, a hydrophobic probe, has negligible fluorescence in the solution. When DPH is incorporated into the membrane, it is localized in the membrane hydrophobic core and fluoresces strongly. We report here that DPH also fluoresces in the presence of fibrillar Abeta (fAbeta). However, it does not fluoresce when it is added to the soluble Abeta (sAbeta). DPH inserts into Abeta fibrils in a time-dependent manner, and upon centrifugation, it is sedimented along with fibrils. The steady state fluorescence polarization of DPH with fAbeta1-40 and fAbeta 1-42 was 0.4592 and 0.4898 respectively. These results suggest that fAbeta (but not sAbeta) forms a hydrophobic domain similar to that of membrane.

Alzheimer Disease↗
PubMed2001

Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma.

BACKGROUND: APC 366, a selective inhibitor of mast cell tryptase, has been shown to inhibit antigen-induced early asthmatic response (EAR), late asthmatic response (LAR), and bronchial hyperresponsiveness (BHR) in a sheep model of allergic asthma. OBJECTIVE: The purpose of this study was to investigate the effects of APC 366 on antigen-induced EAR, LAR, and BHR in mild atopic asthmatics not on any anti-inflammatory therapy. METHODS: Sixteen mild atopic asthmatics, each with a demonstrable antigen-induced EAR, LAR, and BHR to histamine, were recruited into this randomized, double-blinded, crossover study. APC 366 (5 mg)/placebo was administered by aerosol inhalation 3 times per day on treatment days 1 through 4. Allergen challenge was carried out on day 4. Histamine challenge was performed the following morning, 1 hour after final dosing. RESULTS: Subjects were shown to have a significantly smaller overall mean area under the curve for the LAR (P =.012) and mean maximum fall in FEV(1) for the LAR (P =.007) after pretreatment with APC 366 in comparison with placebo. No significant effects on BHR were demonstrable. Although the EAR was reduced by 18% after treatment with APC 366 in comparison with placebo, this was not statistically significant. CONCLUSION: Short-term repeated administration of APC 366 significantly reduced the magnitude of antigen-induced LAR in atopic asthmatics, which supports the role of mast cell tryptase in the pathophysiology of the LAR.

Administration, Inhalation↗
PubMed2001

Modeling the vertical motion of a soft contact lens.

PURPOSE: The motion of a soft contact lens in the up-down or vertical (inferior-superior) and in-out (anterior-posterior) directions drives mixing in the post lens tear film. Thus, it is important to obtain an accurate assessment of lens motion. The commonly used experimental technique to measure the vertical motion, video microscopy, only gauges motion during the interblink period. Since most of the eyelid force, which drives the motion, is exerted during the blink, it is reasonable to assume that the majority of the lens motion in the up-down direction takes place during the blink and is, therefore, hidden from view. Thus, experimentally measured values of vertical lens travel are currently underpredicted. METHODS: In this paper, we use a simple mechanical force balance on the lens to predict its motion in the vertical direction. The forces included in our model are due to the upper and the lower eyelids, gravity, elasticity, and viscous stresses. We input the lens physical parameters, the various tear film thicknesses, and the upper eyelid velocity. Then we integrate a macroscopic force balance to obtain the lens vertical position as a function of time. RESULTS: The proposed model predicts that the downward lens motion during a blink is about 2--3 times the downward motion during the interblink (centration). CONCLUSIONS: The up-down motion observable during the interblink period is only a small fraction of the total lens vertical travel.

Biomechanical Phenomena↗