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Biomedical subjects

S Sandhu

Publications and source records attributed to S Sandhu.

At least 19 recordsLinked to original sources
PubMed2006

Postkeratoplasty emergency visits--a review of 100 consecutive visits.

PURPOSE: Preoperative counselling for penetrating keratoplasty should include awareness of symptoms and signs of possible complications as early presentation can enhance long-term success. In our corneal transplantation service, all patients are routinely instructed to arrange a same day emergency visit through a dedicated telephone line if they experience any symptoms in eyes that have undergone keratoplasty. This study was designed to evaluate the reason for presentation, management outcome of each visit and the efficiency of the system in management of postkeratoplasty complications. METHODS: A review of 100 consecutive emergency visits by postpenetrating keratoplasty (PKP) patients in a tertiary eye care centre was included. RESULTS: Sixty-two patients with varied preoperative diagnoses presented during the review period. Sixteen visits were within the first month after surgery and 40 visits within the first year. Ten patients (16%) sought consultation more than twice during the study period with one patient presenting five times. Pain and grittiness were the main presenting symptoms (68%). Loose corneal suture (25%) necessitating removal was the most common diagnosis. Sixteen visits resulted in hospital admission for treatment. The graft survived in all patients and the visual acuity was preserved in 95% of our patients. CONCLUSION: Most corneal surgeons educate their patients to seek prompt treatment for symptoms such as redness, sensitivity to light, loss of vision, pain, or any other symptoms in eyes that have undergone keratoplasty. Early intervention of sight threatening complications increases the chance of graft survival and best-obtained vision. This review shows a simple open access system facilitates early presentation and successful management of postgraft complications.

Adolescent↗
PubMed2005

Transient paralysis after administration of a single dose of cyclizine.

Two patients with underlying neuromuscular disorders developed varying degrees of paralysis after a single dose of cyclizine, one necessitating full mechanical ventilation. These cases appear to be unique in the literature and represent an increasing spectrum of adverse reactions seen with the greater use of cyclizine.

Adult↗
PubMed2005

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Biomedical Research↗
PubMed2004

Preoperative vascular assessment of the lower limb for harvest of a fibular flap: the views of vascular surgeons in the United Kingdom.

Adequate preoperative vascular assessment of the lower limb is essential before harvesting fibular free flaps to prevent ischaemic complications or failure of the flap. The best method of assessment remains controversial. Clinical examination, conventional angiography, colour flow Doppler, and magnetic resonance angiography have all been advocated. We asked 206 UK vascular surgeons for their opinions on preoperative assessment and potential issues of negligence and 85 (42%) completed the questionnaire. All respondents thought that further imaging should be done in addition to clinical examination, most of whom (n = 70) favoured colour flow Doppler (82%). In addition 75 (88%) considered that the surgeon would be judged to be negligent if clinical examination was the only preoperative assessment. In the light of these findings, we suggest that an objective assessment of the vasculature of the leg should be obtained before a fibular flap is harvested.

Fibula↗
PubMed2003

Assembly of N-methyl-D-aspartate (NMDA) receptors.

The N-methyl-D-aspartate receptor (NMDAR) requires both NR1 and NR2 subunits to form a functional ion channel. Despite the recent advances in our understanding of the contributions of these different subunits to both the function and pharmacology of the NMDAR, the precise subunit stoichiometry of the receptor and the regions of the subunits governing subunit interactions remain unclear. Since NR2 subunits are not transported to the cell surface unless they associate with NR1 subunits, cell-surface expression of NR2A can be used to monitor the association of the different subunits in cells transfected with N- and C-terminally truncated NR1 subunits. By combining measurements of cell-surface expression of NR2A with co-immunoprecipitation experiments, and by using Blue Native gel electrophoresis to determine the oligomerization status of the subunits, we have shown that regions of the N-terminus of NR1 are critical for subunit association, whereas the truncation of the C-terminus of NR1 before the last transmembrane region has no effect on the association of the subunits. Evidence from the Blue Native gels, sucrose-gradient centrifugation and size exclusion of soluble NR1 domains suggests that NR1 subunits alone can form stable dimers. Using a cell line, which can be induced to express the NMDAR following exposure to dexamethasone, we have shown that NMDARs can be expressed at the cell surface within 5 h of the recombinant gene induction, and that there appears to be a delay between the first appearance of the subunits and their stable association.

Animals↗
PubMed2001

Identification of molecular determinants that are important in the assembly of N-methyl-D-aspartate receptors.

To determine which domains of the N-methyl-d-aspartate (NMDA) receptor are important for the assembly of functional receptors, a number of N- and C-terminal truncations of the NR1a subunit have been produced. Truncations containing a complete ligand binding domain bound glycine antagonist and gave binding constants similar to those of the native subunit, suggesting they were folding to form antagonist binding sites. Since NR2A is not transported to the cell surface unless it is associated with NR1 (McIlhinney, R. A. J., Le Bourdellès, B., Tricuad, N., Molnar, E., Streit, P., and Whiting, P. J. (1998) Neuropharmacology 37, 1355-1367), surface expression of NR2A can be used to monitor the association of the subunits. There was progressive loss of NR2A cell surface expression as the N terminus of NR1a was shortened, with complete loss when truncated beyond residue 380. Removal of the C terminus and/or the last transmembrane domain did not affect NR2A surface expression. Similar results were obtained in co-immunoprecipitation experiments. The oligomerization status of the co-expressed NR1a constructs and NR2A subunits was investigated using a non-denaturing gel electrophoresis system (blue native-polyacrylamide gel electrophoresis) and sucrose density gradient centrifugation. The blue native-polyacrylamide gel electrophoresis system also showed that the NR1a subunits could form a homodimer, which was confirmed using soluble constructs of the NR1a subunit. Together these results suggest the residues N-terminal of residue 380 are important for the association of NR2A with NR1a and that the complete N-terminal domain of the NR1a subunit is required for oligomerization with NR2A.

Animals↗
PubMed2001

Outcomes following physical restraint reduction programs in two acute care hospitals.

BACKGROUND: Physical restraint rates can be reduced safely in long term care settings, but the strategies used to prevent wandering, falls, and patient aggression have not been tested for their effectiveness in preventing therapy disruption. A restraint reduction program (RRP) consisting of four core components (administrative, educational, consultative, and feedback) was implemented in 1998-1999 in 14 units at two acute care hospitals in geographically distant cities. METHODS: The RRP was targeted at units with prevalence rates of > or = 4% for non-intensive care units (non-ICUs) and > or = 25% for ICUs, as well as two additional units. The RRP was implemented by an interdisciplinary team consisting of geriatricians and nurse specialists. RESULTS: Of the 16,605 admissions to the RRP units, 2,772 cases received RRP consultations. Only six units (four of seven general units and two of six ICUs) demonstrated a relative reduction of > or = 20% in the physical restraint use rate. No increase in secondary outcomes of patient falls and therapy disruptions (patient-initiated discontinuation or dislodgment of therapeutic devices) occurred, injury rates were low, and no deaths occurred as a direct result of either a fall or therapy disruption event. DISCUSSION: Given the minimal success in the ICU settings, further studies are needed to determine effective nonrestraint strategies for critical care patients. ICU clinicians need to be persuaded of the favorable risk-to-benefit ratio of alternatives to physical restraint before they will change their practice patterns. SUMMARY: Efforts to identify more effective interventions that match patient needs and to identify non-clinician factors that affect physical restraint use are needed.

Academic Medical Centers↗
PubMed2001

Contractile actions of proteinase-activated receptor-derived polypeptides in guinea-pig gastric and lung parenchymal strips: evidence for distinct receptor systems.

1. We have measured the contractile activities and relative potencies (EC(50)s) of six thrombin PAR(1) receptor-derived receptor-activating peptides (PAR-APs): AparafluroFRChaCit-y-NH(2) (Cit-NH(2)); SFLLRNP(P7); SFLLRNP-NH(2) (P7-NH(2)); SFLLR (P5); SFLLR-NH(2) (P5-NH(2)); TFLLR-NH(2) (TF-NH(2)) and a PAR(2) receptor activating peptide [SLIGRL-NH(2) (SL-NH(2))] (a) in a guinea-pig lung peripheral parenchymal strip preparation and (b) in a gastric longitudinal smooth muscle preparation. 2. The relative potencies of the PAR-APs in the lung preparation (Cit-NH(2) congruent with TF-NH(2) congruent with P5-NH(2) > P7 congruent with P5 congruent with P7-NH(2); SL-NH(2) not active) differed appreciably from their relative potencies in the gastric preparation: Cit-NH(2) congruent with TF-NH(2) congruent with P7-NH(2) congruent with P5-NH(2) > P7 congruent with SL-NH(2). 3. The contractile actions of the PAR(1)-selective peptide, TF-NH(2) in the gastric preparation were entirely dependent on extracellular calcium and were blocked by tyrosine kinase inhibitors (genistein, tyrphostin 47/AG213, PP1) and by the cyclooxygenase inhibitor, indomethacin, whereas in the lung preparation, the PAR(1)-mediated contractile response was only partially dependent on extracellular calcium and was refractory to the actions of either tyrosine kinase inhibitors or indomethacin. 4. Partial sequencing of the PAR cDNAs detected by RT - PCR both in whole lung and in the peripheral parenchymal strip bioassay tissue demonstrated the presence of both PAR(1) and PAR(2) mRNA; the expression of PAR(2) was detected by immunohistochemistry. 5. The data point to the presence of distinct receptor systems for the PAR(1)-APs in guinea-pig lung parenchymal and gastric smooth muscle and indicate that PAR(2) does not regulate contractile activity in peripheral parenchymal guinea-pig lung tissue

Amino Acid Sequence↗
PubMed2000

Effects of chemical contaminants on genetic diversity in natural populations: implications for biomonitoring and ecotoxicology.

The conservation of genetic diversity has emerged as one of the central issues in conservation biology. Although researchers in the areas of evolutionary biology, population management, and conservation biology routinely investigate genetic variability in natural populations, only a handful of studies have addressed the effects of chemical contamination on population genetics. Chemical contamination can cause population reduction by the effects of somatic and heritable mutations, as well as non-genetic modes of toxicity. Stochastic processes in small populations, increased mutation load, and the phenomenon of mutational meltdown are compounding factors that cause reduced fitness and accelerate the process of population extirpation. Although the original damage caused by chemical contaminants is at the molecular level, there are emergent effects at the level of populations, such as the loss of genetic diversity, that are not predictable based solely on knowledge of the mechanism of toxicity of the chemical contaminants. Therefore, the study of evolutionary toxicology, which encompasses the population-genetic effects of environmental contaminants, should be an important focus of ecotoxicology. This paper reviews the issues surrounding the genetic effects of pollution, summarizes the technical approaches that can be used to address these issues, and provides examples of studies that have addressed some of them.

Alleles↗
PubMed1999

Significance of a Q wave in lead I in the newborn.

We present 11 healthy newborns whose electrocardiograms had a pure Q wave in lead I and who did not have a myocardial infarction clinically. We propose that in the healthy newborn, a pure Q wave in lead I may be due to increased right ventricular mass, not myocardial infarction.

Arrhythmias, Cardiac↗
PubMed1999

Pharmacological similarities between native brain and heterologously expressed alpha4beta2 nicotinic receptors.

1 We studied the pharmacological properties of native rat brain and heterologously expressed rat alpha4beta2 nicotinic receptors immunoprecipitated onto a fixed substrate with the anti-alpha4 antibody mAb 299. 2 Immunodepletion with the anti-beta2 antibody mAb 270 showed that 89% of the mAb-299-precipitated rat brain receptors contained beta2. 3 The association and dissociation rate constants for 30 pM +/-[3H]-epibatidine binding to alpha4beta2 receptors expressed in oocytes were 0.02+/-0.01 and 0.03+/-0.01 min-1 (+/-standard error, degrees of freedom=7 - 8) at 20 - 23 degrees C. 4 The Hill coefficients for +/-[3H]epibatidine binding to the native brain, alpha4beta2 receptors expressed in oocytes, and alpha4beta2 receptors expressed in CV-1 cells (using recombinant adenovirus) were 0.69 - 0.70 suggesting a heterogeneous receptor population. Fits of the +/-[3H]-epibatidine concentration-binding data to a two-site model gave KD s of 8 - 30 and 560 - 1,200 pM. The high-affinity sites comprised 73 - 74% of the native brain and oocyte alpha4beta2 receptor population, 85% of the CV-1 alpha4beta2 receptor population. 5 The expression of rat alpha4beta2 receptors in CV-1 cells using vaccinia viral infection-transfection resulted in a more homogeneous receptor population (Hill coefficient of 1. 0+/-0.2). Fits of the +/-[3H]-epibatidine binding data to a single-site model gave a KD of 40+/-3 pM. 6 DHbetaE (IC50=260-470 nM) and the novel nicotine analogue NDNI (IC50=7-10 microM) inhibited 30 pM+/-[3H]-epibatidine binding to the native brain and heterologously expressed alpha4beta2 receptors equally well. 7 The results show that alpha4beta2-containing nicotinic receptors in the rat brain and heterologously expressed rat alpha4beta2 receptors have similar affinities for +/-[3H]-epibatidine, DHbetaE, and NDNI.

Animals↗
PubMed1999

Social comparison, self-esteem and depression in people with intellectual disability.

The present study explores the relationship between social comparison processes, self-esteem and depression in people with intellectual disability. Forty-three people with mild and moderate intellectual disability completed adapted measures of self-esteem and social comparison. The social comparison scale offers subscale scores on achievement, social attractiveness and group belonging dimensions. The self-esteem scale offers subscale scores for positive and negative self-esteem. A significant positive correlation was found between positive self-esteem and social comparison on the achievement dimension. Depression was significantly negatively correlated with social comparison on the social attractiveness and group belonging dimensions, and with positive self-esteem. Regression analysis showed that depression was significantly and independently predicted only by social comparison on the social attractiveness dimension. The present authors conclude that social comparison is associated with self-esteem and depression in people with intellectual disability in the same way as it is for people without intellectual disability. Further exploration of social comparison process in people with intellectual disability may inform cognitive behavioural interventions for this group of people.

Adult↗
PubMed1999

Delineation of the structural determinants of the N-methyl-D-aspartate receptor glycine binding site.

In this study, we have further delineated the domains of the N-methyl-D-aspartate receptor NR1 subunit that contribute to the glycine co-agonist binding site. Taking an iterative approach, we have constructed truncation mutants of the NR1 subunit, transiently expressed them in HEK-293 cells, and determined the binding of the glycine site antagonist [3H]L-689,560. Amino acids 380-811 were sufficient to form a glycine binding site with affinities for [3H]L-689,560 and glycine that were not significantly different from wild-type NR1. More extensive deletions, from either the amino- or the carboxy-terminal end, resulted in loss of ligand binding. Additional constructs were made starting from amino acids 380-843 of NR1, replacing the transmembrane (TMI-TMIII) domain with intervening linker sequences while retaining the TMIV domain so as to anchor the polypeptide to the membrane. Although robust amounts of polypeptides were synthesised by transfected cells, only low levels of [3H]L-689,560 binding sites could be detected. This suggests that only a small proportion of the synthesised polypeptide folds in the appropriate manner so as to form a ligand binding site. These data indicate that although it is possible to reduce the glycine binding site to minimal so-called S1 and S2 domains, efficient folding of the polypeptide so as to form a ligand binding site may require sequences within the TMI-TMIII domain.

Amino Acid Sequence↗
PubMed1998

Analgesia in the accident and emergency department: do SHOs have the knowledge to provide optimal analgesia?

OBJECTIVE: To assess senior house officers' knowledge in prescribing emergency analgesia for acute presentations in the accident and emergency (A&E) department. DESIGN: Prospective telephone survey of a defined population of SHOs, using a standardised structured questionnaire, in the months of October and November, 1995; 231 SHOs from 215 A&E departments were interviewed. The questionnaire required responses to hypothetical scenarios. A six member expert panel from the local region was consulted for suggestions for appropriate responses. MAIN OUTCOME MEASURES: Comparisons between SHO responses and those of an expert panel. RESULTS: For choice of analgesic agent, 83% of SHO responses were appropriate, for route of administration 57%, and for the dose of drug 34%. The scenario with the best overall response was a sprained ankle. The paediatric case with partial burns faired worse. Responses to a myocardial infarction scenario were the most consistent. CONCLUSIONS: A&E SHOs lack knowledge and confidence when asked to prescribe emergency analgesia for acute conditions. Responses to certain scenarios were extremely varied, indicating a need for national analgesia guidelines and protocols. Recognised training in pain management should be more readily available.

Analgesia↗
PubMed1998

A cluster of tuberculosis cases in a family.

A 40 year old Indian woman who had recently returned from a visit to India with her eldest son was diagnosed with miliary tuberculosis in January 1994. Contact tracing revealed that her three sons, aged 19, 21, and 22, all had BCG scars from vaccinations administered at birth in India and Heaf tests of grades 2-3. None of them was given chemoprophylaxis, although this was considered, as suggested by the guidelines then available (1990). About 18 months later, the eldest son was notified as a case of tuberculosis. The youngest son, who shared a room with the eldest, developed a right tuberculous pleural effusion over three years after his mother became ill. The 41 year old husband of the index case and their 21 year old son remain well at the time of this report and are being followed up. These cases highlight the importance of stringent follow up, contact tracing, good liaison between general practitioners and chest clinic staff, and chemoprophylaxis for the contacts of tuberculosis cases. Guidelines about the management of contacts of sputum positive cases over 16 years old need to be clarified. A history of a recent overseas trip should raise suspicions of infection with tuberculosis.

Adult↗
PubMed1997

Effects of sex hormones on fluid and solute transport in Madin-Darby canine kidney cells.

Polycystic kidney disease progresses more rapidly in men than in women. To investigate the basis for this sexual dimorphism, we exposed Madin-Darby canine kidney (MDCK) cells grown on collagen-coated cell culture inserts to control media, or to estradiol or testosterone (1 nM-1 microM). Compared to control and estradiol-treated cells, testosterone stimulated fluid secretion in a dose-dependent manner, enhancing fluid secretion 4.8-fold at 1 nM and 19.7-fold at 1 microM (0.59 +/- 0.18 vs. 0.03 +/- 0.01 microliter/cm2/hr, P < 0.001). Chloride transport paralleled fluid secretion. Testosterone increased cellular cyclic AMP levels 3.2-fold at 1 nM and 12.3-fold at 1 microM (81.3 +/- 30.7 vs. 6.6 +/- 3.3 pmol/mg protein, P < 0.001). GDP beta S (500 microM), an inhibitor of Gs, and 2',3'-dideoxyadenosine (10 microM), an inhibitor of the catalytic subunit of adenylate cyclase, suppressed testosterone-induced fluid and solute secretion. Neither testosterone nor estradiol had any effect on microsomal Na,K-ATPase activity, cellular proliferation or cellular total protein content. Our studies show that testosterone stimulates fluid secretion and solute transport by MDCK cells by increasing cAMP generation. In vivo, testosterone may contribute to cyst expansion by enhancing fluid secretion. This observation may help explain the worse prognosis of polycystic kidney disease observed in men.

Animals↗