PubMed Health⌕ Search

Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 37 records · Page 2Linked to original sources
PubMed2005

Isoflurane exerts antinociceptive and hypnotic properties at all ages in Fischer rats.

BACKGROUND: Some anaesthetic agents exhibit an age-dependent analgesic effect, for example nitrous oxide, which is ineffective in newborn rats. We investigated whether a similar time dependency existed for the responses to the volatile anaesthetic isoflurane. METHODS: The analgesic and hypnotic properties of isoflurane at various ages was assessed using four cohorts of Fischer rats aged approximately 7, 16, and 28 days and adults (11-12 weeks old). Intraplantar administration of formalin mimicked inflammatory pain, and its effects were assessed using immunohistochemical (c-Fos staining) and behavioural paradigms. The hypnotic properties of isoflurane were assessed using loss of righting reflex. RESULTS: Formalin administration produced a typical nociceptive response observed both behaviourally and immunohistochemically in all age groups; these nociceptive responses were significantly attenuated by isoflurane 0.5% at each age (P<0.05). Interestingly 7-day-old animals showed a significantly more potent hypnotic response than older animals (P<0.01): with adult rats being most resistant to isoflurane induced hypnosis (P<0.05). CONCLUSION: In contrast to nitrous oxide, isoflurane is an effective antinociceptive agent in neonatal rats. If the data can be extrapolated to clinical scenarios these results suggest that isoflurane may be analgesic in newborns as well as adult humans. In addition, isoflurane is a potent hypnotic, especially in the very young, which is in contrast to the neonate's relative resistance to anaesthesia as assessed by minimum alveolar concentration.

Aging↗
PubMed2005

The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans.

We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease (P < 0.05) in R-R interval (962 +/- 76 ms at baseline compared to 846 +/- 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R-R interval with PS was significantly less (P < 0.05, n = 3) following administration of glycopyrrolate (-8.1 +/- 4.5 ms) compared to PS alone (-54 +/- 11 ms), and also with PS during handgrip (+10 +/- 10 ms) compared with PS alone (-74 +/- 15 ms) (P < 0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R-R interval in response to PS (-107 +/- 17 ms compared to PS alone -96 +/- 13 ms, n = 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R-R interval (-39 +/- 5.5 ms) compared to PS alone (-86 +/- 17 ms) (P < 0.05, n = 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.

Adult↗
PubMed2005

Troglitazone causes acute mitochondrial membrane depolarisation and an AMPK-mediated increase in glucose phosphorylation in muscle cells.

AIMS/HYPOTHESIS: Troglitazone was the first thiazolidinedione (TZD) approved for clinical use, exerting hypoglycaemic effects related to its action as a ligand of the peroxisome proliferator-activated receptor gamma receptor in adipocytes. However, emerging evidence suggests that mitochondrial function may be affected by troglitazone, and that skeletal muscle cells acutely respond to troglitazone by enhancing glucose uptake. The aim of the present study was to determine the cellular mechanisms by which troglitazone acutely stimulates glucose utilisation in skeletal muscle cells. METHODS: L6 cells overexpressing GLUT4myc were incubated with troglitazone. Glucose uptake, transport and phosphorylation as well as AMP-activated protein kinase (AMPK) signalling and insulin signalling were examined. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye JC-1. AMPK signalling was interfered with using AMPK alpha1/alpha2 siRNA. RESULTS: Troglitazone acutely (in 10 min) reduced the mitochondrial membrane potential in L6GLUT4myc myotubes and robustly stimulated AMPK activity. Following 30 min of incubation with troglitazone or insulin, 2-deoxyglucose uptake was stimulated 1.5- and 2.1-fold respectively, and in cells treated with troglitazone, a 1.8-fold increase in the 2-deoxyglucose-6-phosphate:2-deoxyglucose ratio was observed. Moreover, contrary to insulin, troglitazone did not significantly stimulate 3-O-methylglucose uptake. Unlike insulin, troglitazone did not increase surface GLUT4myc content and did not increase IRS1-associated phosphatidylinositol 3-kinase activity or Akt phosphorylation on T308 and S473. Interestingly, interfering with troglitazone-induced activation of AMPK by decreasing the expression of the enzyme using siRNA inhibited the stimulation of 2-deoxyglucose uptake by the TZD. CONCLUSIONS/INTERPRETATION: We propose that troglitazone acutely increases glucose flux in muscle via an AMPK-mediated increase in glucose phosphorylation.

AMP-Activated Protein Kinases↗
PubMed2005

Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery.

BACKGROUND: Cystoid macular oedema (CMO) is the accumulation of fluid in the central retina (the macula) due to leakage from dilated capillaries. It is the most common cause of poor visual outcome following cataract surgery. The exact cause is unclear. Acute CMO, defined as oedema of less than four months duration, often resolve spontaneously. CMO that persists for four months or more is termed chronic CMO. Different types of non-steroidal anti-inflammatory agents (NSAIDs) are used in the treatment of CMO which may be delivered topically or systemically. OBJECTIVES: To examine the effectiveness of NSAIDs in the treatment of CMO following cataract surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 2 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to May 2004), LILACS (April 2004) and the reference lists of identified trials. We searched conference abstracts (sessions related to cataract) in ARVO 1975 to 2003. We contacted experts in the field and NSAIDs manufacturers for details on published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating the effects of NSAIDs in the treatment of CMO following cataract surgery. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data. Since considerable heterogeneity was observed between studies we did not conduct meta-analyses. MAIN RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three examined the effect of NSAIDs in acute CMO. Of the studies examining chronic CMO, one study enrolled 120 participants, but the remainder had 34 or fewer participants. Four different NSAIDs were used and administered in different ways. Indomethacin was used orally and was found to be ineffective for chronic CMO in one trial. Topical fenoprofen was also found to be ineffective for chronic CMO in another small trial. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials. Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of an NSAID to placebo, prednisolone or another NSAID. The study design differed between the studies in other important aspects thus they could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: This review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO. However, the effects of NSAIDs in acute CMO remains unclear and needs further investigation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Effect of carbonate substitution on the ultrastructural characteristics of hydroxyapatite implants.

Carbonate ion substitution has been shown to be beneficial for increasing the amount of in vivo osseointegration to hydroxyapatite (HA). Nevertheless, mechanisms by which carbonate ions increase in vivo bioactivity are not fully understood. Sintered granules of HA and carbonate-substituted hydroxyapatite (CHA) were implanted for 6 and 12 weeks in an ovine model. Samples containing the bone-implant interface were prepared for transmission electron microscopy (TEM) and TEM was used to compare the in vivo reactivity of sintered granules of HA and CHA. The current findings demonstrated that CHA (1.2 and 2.05 wt.%) is more soluble than pure HA in vivo. More dissolution was observed from the CHA, at the bone-implant interface and within the implant, when compared to pure HA. A less crystalline phase was formed between the 2.05 wt.% CHA and bone at 12 weeks in vivo. Bone surrounding both the pure HA and 1.2 wt.% CHA was relatively disorganised at 12 weeks. In comparison, bone surrounding the 2.05 wt.% CHA was considerably more organised and in many regions collagen fibrils were present. Despite increased quality of bone surrounding 2.05 wt.% CHA, compared to 1.2 wt.% CHA, the amount of dissolution from both materials was similar.

Animals↗
PubMed2005

In vivo assessment of hydroxyapatite and silicate-substituted hydroxyapatite granules using an ovine defect model.

Phase pure hydroxyapatite (HA) and two silicate-substituted hydroxyapatites (0.8 and 1.5 wt% Si, or 2.6 and 4.9 wt% SiO4) were prepared by aqueous precipitation methods. The filter-cakes of HA and silicate-substituted hydroxyapatite (SiHA) compositions were processed into granules 1.0-2.0 mm in diameter and sintered at 1200 degrees C for 2 h. The sintered granules underwent full structural characterisation, prior to assessment in an ovine defect model by implantation for a period of 6 and 12 weeks. The results indicate that HA and SiHA implants were well accepted by the host tissue, with no evidence of inflammation. New bone formation was observed directly on the surfaces and in the spaces between the granular implants. Quantitative histomorphometry as determined by the percentage of bone ingrowth and bone coverage for both SiHA implant compositions was significantly greater than that for phase pure HA. These findings indicate that the in vivo bioactivity of hydroxyapatite was significantly improved by the incorporation of silicate ions into the HA structure, making SiHA ceramics attractive alternatives to conventional HA materials for use as bone graft substitute ceramics.

Animals↗
PubMed2005

Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Animals↗
PubMed2005

Is stroke unit care portable? A systematic review of the clinical trials.

BACKGROUND: It is not known if mobile stroke teams can achieve the good results seen in trials of geographically discrete stroke wards (stroke units). OBJECTIVE: To establish the effectiveness of mobile stroke teams. DESIGN: Systematic review of controlled clinical trials that compared peripatetic systems of organised stroke care (stroke team care) with alternative hospital services. METHODS: Systematic review and meta-analysis (using Cochrane Collaboration methodology and involving the primary trialists). Clinical outcomes included death, dependency, the need for institutional care and measures of the process of care such as the delivery of key investigations and treatments. RESULTS: Six clinical trials (1,085 patients) were identified; five (781 patients) compared some form of stroke team care with conventional care in general medical wards and one (304 patients) compared team care with a comprehensive stroke unit. Compared with care in general wards, stroke team care improved some aspects of the process of care, but clinical outcomes were similar. Compared with a comprehensive stroke unit, stroke team patients were significantly less likely to survive (P <0.001), return home (P < 0.001) or regain independence (P < 0.0001). Most aspects of the process of care were also poorer than in the stroke unit. CONCLUSIONS: Care from a mobile stroke team had no major impact on death, dependency or the need for institutional care.

Controlled Clinical Trials as Topic↗
PubMed2005

Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitis C.

BACKGROUND AND AIMS: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer. MATERIALS AND METHODS: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively. All were HCV RNA positive on polymerase chain reaction testing. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, untreated patients were divided into mild hepatitis (F < or =2/6, NI < or =3/18), moderate/severe hepatitis (3 < or =F <6 or NI > or =4), and cirrhosis (F=6/6) groups. In addition, 20 age matched healthy volunteers were studied. After an overnight fast, a bolus of contrast agent (Levovist) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis. HVTTs were calculated as the time from injection to a sustained rise in Doppler signal >10% above baseline. The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times (CDT) calculated as the difference between carotid and hepatic vein arrival times. The earliest HVTT in each patient was used for analysis. RESULTS: Mean (SEM) HVTT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis groups showed a monotonic decrease of 38.1 (2.8), 38.8 (2.4), 26.0 (2.4), and 15.8 (0.8) seconds, respectively. Mean (SEM) CDT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis patients again showed progressive shortening of 30.3 (2.6), 25.9 (2.6), 14.8 (2.1), and 5.6 (1.2) seconds, respectively. There were significant differences between the groups for HVTT (ANOVA, p<0.001) and CDT (ANOVA, p<0.001). There was 100% sensitivity and 80% specificity for diagnosing cirrhosis and 95% sensitivity and 86% specificity for differentiating mild hepatitis from more severe liver disease. CONCLUSION: We have shown, for the first time, that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis. There were significant differences between these two groups and the moderate/severe hepatitis group. CDT offers no additional benefit or greater differentiation than HVTT and can be omitted, thus simplifying this technique. HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy.

Adult↗
PubMed2005

Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study.

BACKGROUND: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). PATIENTS AND METHODS: We used 1H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. RESULTS: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0-39.0)) than in normal volunteers (GM 2.7 (IQR 0.7-9.3); p=0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) >25 kg/m2 (n=23): GM 7.7 (IQR 4.0-28.6) v BMI <25 kg/m2 (n=11): GM 1.3 (IQR 0.3-3.6; p=0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p=0.001), total subcutaneous AT (p=0.007), and central obesity (subcutaneous abdominal AT (p=0.001) and intra-abdominal AT (p=0.001)), after allowing for sex and age. No correlation between IHCL content and IMCL was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r=0.57, p=0.006). CONCLUSIONS: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies.

Abdomen↗
PubMed2005

ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Adenosine Triphosphatases↗
PubMed2004

Interactions between colloidal particles in polymer solutions: A density functional theory study.

We present a density functional theory study of colloidal interactions in a concentrated polymer solution. The colloids are modeled as hard spheres and polymers are modeled as freely jointed tangent hard sphere chains. Our theoretical results for the polymer-mediated mean force between two dilute colloids are compared with recent simulation data for this model. Theory is shown to be in good agreement with simulation. We compute the colloid-colloid potential of mean force and the second virial coefficient, and analyze the behavior of these quantities as a function of the polymer solution density, the polymer chain length, and the colloid/polymer bead size ratio.

Journal Article↗
PubMed2004

Effect of long-term progestin treatment on endometrial vasculature in normal cycling mice.

The aim of this study was to develop a mouse model to investigate the effects of long-term progestin-only exposure on endometrial vascular structure. Normal cycling mice received Silastic implants containing either medroxyprogesterone acetate (MPA) or levonorgestrel (LNG) and were dissected after 1, 3 or 6 weeks. Endometrial vascular density increased significantly within 1 week of MPA (482 +/- 40.2 vessels/mm2) or LNG (440 +/- 26.5 vessels/mm2) treatment compared with normal cycling mice (293 +/- 10.5 vessels/mm2). MPA increased stromal cell density within 1 week of treatment (13813 +/- 1450 cells/mm2) compared with normal cycling mice (8256 +/- 928 cells/mm2). However, although LNG significantly increased stromal cell density overall, the increase did not reach significance within the individual weeks examined. There was no significant change in the ratio of vascular to stromal cell density among treated and normal cycling mice. Epithelial cell height significantly decreased within 1 week of LNG (17.6 +/- 1.3 microm) treatment compared with normal cycling mice (23.5 +/- 1.3 microm); epithelial cell height also decreased within 1 week of MPA treatment (16.6 +/- 2.1 microm), although this did not reach statistical significance. VEGF immunostaining increased significantly in luminal epithelium after MPA or LNG treatment, and in glandular epithelium after LNG treatment. These observations are similar to those reported in human endometrium, suggesting that this mouse model may facilitate further investigations into breakthrough bleeding due to long-term progestin use.

Animals↗
PubMed2004

The changing face of femoral artery false aneurysms.

OBJECTIVES: To review the aetiology and method of treatment of all femoral artery false aneurysms from a single centre during the last 9 years. DESIGN: Retrospective case-note study. METHODS: All patients with a diagnosis of false aneurysm were identified from the hospital data-base between January 1995 and September 2003. A manual search of the case-notes was performed, and data collected on the location, cause and method of repair of the false aneurysm. For all patients with a diagnosis of femoral artery false aneurysm, the patients' medical and drug history and admission time attributable to the false aneurysm were recorded. RESULTS: One hundred and seven patients were identified. Seventy-nine had false aneurysms of the femoral artery. The majority (40.5%) were caused by coronary angiography, the second commonest cause being breakdown of previous graft anastomosis (29.1%). Over time, the method of treatment became increasingly radiological (most commonly ultrasound-guided thrombin injection), resulting in a significantly reduced hospital admission time (P=0.018). CONCLUSIONS: The incidence of femoral artery false aneurysms appears to be increasing. This is largely a result of an increase in the number of cardiac interventional and diagnostic procedures performed. The introduction of ultrasound-guided thrombin-injection has reduced the inpatient stay of patients with femoral false aneurysms.

Aged↗
PubMed2004

Prevalence and epidemiological variation of anomalous muscles at guyon's canal.

Ultrasound was performed in 116 wrists of asymptomatic volunteers to determine the prevalence and morphology of anomalous muscles in Guyon's canal in the normal population. The size of the muscle was correlated with sex, hand-dominance and occupation. Anomalous muscles were identified in 47% of volunteers and 35% of wrists (male prevalence (50%); female prevalence (21%)). All were variants of abductor digiti minimi. Bilateral muscles were present in 50% of index cases in both sexes. Mean muscle thickness was 1.7 mm overall with no inter-sex variation. Muscle thickness did not vary with hand dominance or manual employment. The prevalence of anomalous muscles is higher than previously reported and may be sex-linked. The size of the muscle may be an important factor in determining whether an anomalous muscle is significant in cases of ulnar nerve compression at Guyon's canal.

Female↗