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Biomedical subjects

N Dean

Publications and source records attributed to N Dean.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic colposuspension and tension-free vaginal tape: a systematic review.

BACKGROUND: Advances in surgical techniques have led to the availability of a number of minimal-access procedures to treat urodynamic stress incontinence (USI). These procedures have been individually compared with the 'gold standard' open Burch colposuspension; however, it now seems appropriate to compare like with like and compare these minimal-access techniques with each other. OBJECTIVES: To determine the effectiveness of laparoscopic colposuspension with tension-free vaginal tape (TVT) for the treatment of USI. SEARCH STRATEGY: Randomised trials in woman with USI, which compared laparoscopic colposuspension with TVT in the arms of the trial, were identified from the Cochrane Incontinence Review Group's Specialised Register of Controlled Trials. SELECTION CRITERIA: The trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers using the Incontinence Group's assessment criteria. DATA COLLECTION AND ANALYSIS: The data were extracted independently, and when appropriate, meta-analysis was undertaken to calculate pooled estimates and their confidence intervals (CI). The main outcomes measured were: subjective cure, objective cure, quality of life (QoL) measurements, surgical outcomes and health economic measures. MAIN RESULTS: Seven trials compare laparoscopic colposuspension (n= 264) with TVT (n= 290). There was no statistically significant difference in the reported subjective cure rate between laparoscopic colposuspension and TVT within 18 months (relative risk [RR] 1.12, 95% CI 0.98-1.29). However, within the same time period, the overall objective cure rate was statistically significantly higher for TVT (RR 1.16, 95% CI 1.07-1.25). There were no significant differences between the two procedures with regards to perioperative complication, de novo detrusor overactivity, voiding dysfunction, procedural costs and QoL scores. However, TVT procedure is quicker to perform and has a shorter hospital stay. CONCLUSIONS The evidence so far appears to be in favour of the TVT as the minimal-access technique of choice for USI in comparison with laparosopic colposuspension; however, long-tem data are needed. Further well-designed trials with standardized outcomes are required to draw accurate conclusions from this comparison.

Colposcopy↗
PubMed2005

Reliability of carotid doppler performed in a dedicated stroke prevention clinic.

INTRODUCTION: Doppler ultrasound (DUS) is used as a screening tool to assess internal carotid artery (ICA) disease. Recent reports suggest that the DUS may be inaccurate in over 28% of patients. We sought to evaluate the accuracy of DUS, when performed in a dedicated stroke prevention clinic (SPC). METHODS: We retrospectively reviewed the charts of patients who had a DUS performed in our SPC, followed by conventional cerebral angiography. Three groups of patients were defined. Group 1 had DUS measured ICA stenosis of >50%; Group II had a DUS measured ICA stenosis of <50%; Group III had complete ICA occlusion on DUS. RESULTS: Sixty-seven patients (69 arteries) were included in the study. There were 45 patients in Group I and based on the findings of cerebral angiography, carotid endarterectomy was considered inappropriate in only one patient--a misclassification rate of 2.2% (95% CI: 0 - 6.5%). Group II consisted of 19 patients and on cerebral angiography, none of these patients had a stenosis of >50%--a misclassification rate of 0%. Group III consisted of five patients in whom DUS showed complete ICA occlusion. The angiogram confirmed the occlusion in all five patients--a misclassification rate of 0%. Overall, misclassification rate was 1.45% (95% CI: 0 - 4.3%). CONCLUSIONS: Doppler ultrasound when performed in a stroke prevention clinic (SPC), has a high accuracy in measuring ICA stenosis of >50%. Doppler ultrasound is reliable in detecting complete ICA occlusion and finally DUS is a reliable screening tool to rule out clinically significant ICA stenosis.

Aged↗
PubMed2005

Intravenous rt-PA for acute stroke: comparing its effectiveness in younger and older patients.

OBJECTIVE: To study the short and long term differences in outcome between patients > or =80 years of age and those < or =79 years of age who received intravenous recombinant tissue plasminogen activator (iv rt-PA) for acute stroke within the first 3 hours of symptom onset. METHODS: We studied consecutive patients treated with iv rt-PA for acute stroke, with prospective follow up of up to 3 years. Outcome measures included National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index (BI), modified Rankin score (MRS), and stroke mortality. Patients were split into two groups: younger (< or =79 years) and older (> or =80 years). RESULTS: There were 65 patients in the younger cohort and 31 patients in the older. Older patients were more likely to present with more severe baseline stroke (p = 0.04; odds ratio (OR) 3.04; 95% confidence interval (CI) 1.03 to 8.98). Stroke mortality at 90 days was 10.8% in the younger and 32.3% in the older cohort (p = 0.01). At 90 days' follow up, patients in the older cohort with more severe stroke (NIHSS score > or =11) were nearly 10 times more likely to have poor outcome compared with their younger counterparts presenting with severe stroke (p = 0.001; OR = 10.36; 95% CI 2.16 to 49.20). Baseline stroke severity and age were the only independent and equal predictors for stroke outcome. No threshold was found for age or baseline stroke severity predicting outcome. CONCLUSION: Older patients presenting with more severe baseline stroke are much less likely to benefit from iv rt-PA as compared with their younger counterparts.

Acute Disease↗
PubMed2002

Inhibition of spinal protein kinase Calpha expression by an antisense oligonucleotide attenuates morphine infusion-induced tolerance.

Protein kinase C isoforms including the alpha isozyme have been implicated in morphine tolerance. In the present study, we examined the effect of intrathecal delivery of an antisense oligonucleotide targeting rat protein kinase Calpha mRNA on the expression of spinal protein kinase Calpha isozyme and spinal morphine tolerance. Continuous intrathecal infusion of rats with morphine produced an increase in paw withdrawal threshold to thermal stimulation on day 1, which disappeared by day 5. On day 6, a bolus intrathecal injection of morphine (a probe dose) produced significantly less analgesia in morphine-infused rats than in saline-infused rats, suggesting tolerance. Intrathecal treatment with the protein kinase Calpha antisense concurrent with spinal morphine infusion not only maintained the analgesic effect of morphine during the 5-day infusion, it also significantly increased responsiveness to the probe morphine dose on day 6. In comparison, the missense used in the same treatment paradigm had no effect. The inhibitory effect of protein kinase Calpha antisense on spinal morphine tolerance was dose-dependent, and reversible. Intrathecal treatment with the antisense, but not the missense, in rats decreased expression of spinal protein kinase Calpha mRNA and protein, as revealed by real-time quantitative reverse transcription-polymerase chain reaction and western blots. Expression of the gamma isozyme was not affected by the oligonucleotides. The antisense also attenuated protein kinase C-mediated phosphorylation in spinal cord. These results demonstrate that selective reduction in the expression of the spinal protein kinase Calpha isozyme followed by a decrease of local protein kinase C-mediated phosphorylation will reverse spinal morphine infusion-induced tolerance. This finding is consistent with the view that tolerance produced by morphine infusion is dependent upon an increase in phosphorylation by protein kinase C, and also it emphasizes that the protein kinase Calpha isozyme and its activation in spinal cord may specifically participate in the phenomenon of opiate tolerance.

Animals↗
PubMed2001

The yeast ALG11 gene specifies addition of the terminal alpha 1,2-Man to the Man5GlcNAc2-PP-dolichol N-glycosylation intermediate formed on the cytosolic side of the endoplasmic reticulum.

The initial steps in N-linked glycosylation involve the synthesis of a lipid-linked core oligosaccharide followed by the transfer of the core glycan to nascent polypeptides in the endoplasmic reticulum (ER). Here, we describe alg11, a new yeast glycosylation mutant that is defective in the last step of the synthesis of the Man(5)GlcNAc(2)-PP-dolichol core oligosaccharide on the cytosolic face of the ER. A deletion of the ALG11 gene leads to poor growth and temperature-sensitive lethality. In an alg11 lesion, both Man(3)GlcNAc(2)-PP-dolichol and Man(4)GlcNAc(2)-PP-dolichol are translocated into the ER lumen as substrates for the Man-P-dolichol-dependent sugar transferases in this compartment. This leads to a unique family of oligosaccharide structures lacking one or both of the lower arm alpha1,2-linked Man residues. The former are elongated to mannan, whereas the latter are poor substrates for outerchain initiation by Ochlp (Nakayama, K.-I., Nakanishi-Shindo, Y., Tanaka, A., Haga-Toda, Y., and Jigami, Y. (1997) FEBS Lett. 412, 547-550) and accumulate largely as truncated biosynthetic end products. The ALG11 gene is predicted to encode a 63.1-kDa membrane protein that by indirect immunofluorescence resides in the ER. The Alg11 protein is highly conserved, with homologs in fission yeast, worms, flies, and plants. In addition to these Alg11-related proteins, Alg11p is also similar to Alg2p, a protein that regulates the addition of the third mannose to the core oligosaccharide. All of these Alg11-related proteins share a 23-amino acid sequence that is found in over 60 proteins from bacteria to man whose function is in sugar metabolism, implicating this sequence as a potential sugar nucleotide binding motif.

Amino Acid Sequence↗
PubMed2001

Ongoing twin pregnancy after ICSI of PESA-retrieved spermatozoa into in-vitro matured oocytes: case report.

The recovery of immature oocytes from unstimulated ovaries followed by in-vitro maturation (IVM) is an attractive alternative to conventional IVF in the treatment of female infertility. Similarly, surgical recovery of spermatozoa from the epididymis by percutaneous sperm aspiration (PESA) has simplified the retrieval of the male gamete in treatment of men with obstructive azoospermia. We report the first ongoing clinical twin pregnancy resulting from intracytoplasmic sperm injection (ICSI) of spermatozoa retrieved by PESA into IVM oocytes. In the treatment of a 24-year old woman, 12 immature oocytes were retrieved. Six oocytes matured (maturation rate 50%) after 24-hour incubation and were inseminated by ICSI. Four oocytes had two pronuclei (fertilization rate 67%) and 3 good quality embryos were transferred. A viable twin pregnancy was confirmed by ultrasound scan. This report illustrates the use of a combination of less invasive assisted reproductive techniques in overcoming barriers to infertility.

Adult↗
PubMed2001

Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway.

Heterologous expression of the transient receptor potential-1 gene product (Trp1) encodes for a Ca2+ entry pathway, though it is unclear whether endogenous Trp1 contributes to a selective store-operated Ca2+ entry current. We examined the role of Trp1 in regulating both store-operated Ca2+ entry and a store-operated Ca2+ entry current, I(SOC), in A549 and endothelial cells. Twenty different 'chimeric' 2'-O-(2-methoxy)ethylphosphothioate antisense oligonucleotides were transfected separately using cationic lipids and screened for their ability to inhibit Trp1 mRNA. Two hypersensitive regions were identified, one at the 5' end of the coding region and the second in the 3' untranslated region beginning six nucleotides downstream of the stop codon. Antisense oligonucleotides stably decreased Trp1 at concentrations ranging from 10 to 300 nM, for up to 72 h. Thapsigargin increased global cytosolic Ca2+ and activated a I(SOC), which was small (-35 pA @ -80 mV), reversed near +40 mV, inhibited by 50 microM La3+, and exhibited anomalous mole fraction dependence. Inhibition of Trp1 reduced the global cytosolic Ca(2+) response to thapsigargin by 25% and similarly reduced I(SOC) by 50%. These data collectively support a role for endogenously expressed Trp1 in regulating a Ca2+-selective current activated upon Ca2+ store depletion.

Base Sequence↗
PubMed2001

Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury.

Bile acids cause liver injury during cholestasis by inducing hepatocyte apoptosis by both Fas-dependent and -independent mechanisms. However, the Fas-independent apoptosis also appears to be death receptor-mediated. Because death receptor-mediated apoptosis in hepatocytes requires proapoptotic Bcl-2 BH3 domain only protein Bid, we postulated that Fas-independent but death receptor-mediated bile acid cytotoxicity would be Bid-dependent. We used Fas-deficient lymphoproliferative (lpr) mouse hepatocytes for these studies, and inhibited Bid expression using an antisense approach. Glychochenodeoxycholate (GCDC) was used to induce apoptosis. Bid cleavage and translocation to mitochondria was observed in GCDC-treated cells as assessed by immunoblot analysis and confocal imaging of Bid-green fluorescent protein, respectively. Bid translocation to mitochondria was associated with cytochrome c release. A Bid antisense 2'-MOE modified oligonucleotide inhibited Bid expression in hepatocytes and markedly attenuated hepatocytes apoptosis by GCDC. Treatment of lpr mice with Bid antisense also ameliorated liver injury following bile duct ligation of the mice, a model of extrahepatic cholestasis. These results suggest that bile acid cytotoxicity is Bid-dependent despite the absence of Fas. Bid antisense therapy is a promising approach for the treatment of cholestatic liver injury.

Animals↗
PubMed2000

Identification of a conserved motif in the yeast golgi GDP-mannose transporter required for binding to nucleotide sugar.

Glycoproteins and lipids in the Golgi complex are modified by the addition of sugars. In the yeast Saccharomyces cerevisiae, these terminal Golgi carbohydrate modifications primarily involve mannose additions that utilize GDP-mannose as the substrate. The transport of GDP-mannose from its site of synthesis in the cytosol into the lumen of the Golgi is mediated by the VRG4 gene product, a nucleotide sugar transporter that is a member of a large family of related membrane proteins. Loss of VRG4 function leads to lethality, but several viable vrg4 mutants were isolated whose GDP-mannose transport activity was reduced but not obliterated. Mutations in these alleles mapped to a region of the Vrg4 protein that is highly conserved among other GDP-mannose transporters but not other types of nucleotide sugar transporters. Here, we present evidence that suggest an involvement of this region of the protein in binding GDP-mannose. Most of the mutations that were introduced within this conserved domain, spanning amino acids 280-291 of Vrg4p, lead to lethality, and none interfere with Vrg4 protein stability, localization, or dimer formation. The null phenotype of these mutant vrg4 alleles can be complemented by their overexpression. Vesicles prepared from vrg4 mutant strains were reduced in luminal GDP-mannose transport activity, but this effect could be suppressed by increasing the concentration of GDP-mannose in vitro. Thus, either an increased substrate concentration, in vitro, or an increased Vrg4 protein concentration, in vivo, can suppress these vrg4 mutant phenotypes. Vrg4 proteins with alterations in this region were reduced in binding to guanosine 5'-[gamma-(32)P]triphosphate gamma-azidoanilide, a photoaffinity substrate analogue whose binding to Vrg4-HAp was specifically inhibited by GDP-mannose. Taken together, these data are consistent with the model that amino acids in this region of the yeast GDP-mannose transporter mediate the recognition of or binding to nucleotide sugar prior to its transport into the Golgi.

Alleles↗
PubMed2000

Distinct protein domains of the yeast Golgi GDP-mannose transporter mediate oligomer assembly and export from the endoplasmic reticulum.

The substrates for glycan synthesis in the lumen of the Golgi are nucleotide sugars that must be transported from the cytosol by specific membrane-bound transporters. The principal nucleotide sugar used for glycosylation in the Golgi of the yeast Saccharomyces cerevisiae is GDP-mannose, whose lumenal transport is mediated by the VRG4 gene product. As the sole provider of lumenal mannose, the Vrg4 protein functions as a key regulator of glycosylation in the yeast Golgi. We have undertaken a functional analysis of Vrg4p as a model for understanding nucleotide sugar transport in the Golgi. Here, we analyzed epitope-tagged alleles of VRG4. Gel filtration chromatography and co-immunoprecipitation experiments demonstrate that the Vrg4 protein forms homodimers with specificity and high affinity. Deletion analyses identified two regions essential for Vrg4p function. Mutant Vrg4 proteins lacking the predicted C-terminal membrane-spanning domain fail to assemble into oligomers (Abe, M., Hashimoto, H., and Yoda, K. (1999) FEBS Lett. 458, 309-312) and are unstable, while proteins lacking the N-terminal cytosolic tail are stable and multimerize efficiently, but are mislocalized to the endoplasmic reticulum (ER). Fusion of the N terminus of Vrg4p to related ER membrane proteins promote their transport to the Golgi, suggesting that sequences in the N terminus supply information for ER export. The dominant negative phenotype resulting from overexpression of truncated Vrg4-DeltaN proteins provides strong genetic evidence for homodimer formation in vivo. These studies are consistent with a model in which Vrg4p oligomerizes in the ER and is subsequently transported to the Golgi via a mechanism that involves positive sorting rather than passive default.

Carrier Proteins↗
PubMed2000

The outcome of IVF-embryo transfer treatment in patients who develop three follicles or less.

Among 828 patients undergoing IVF-embryo transfer treatment, the implantation and pregnancy rates of patients who developed < or = 3 follicles were compared prospectively with those patients who had a normal response. Patients who developed 1 to 3 follicles during ovarian stimulation elected to proceed with oocyte collection, have intrauterine insemination if appropriate, or to have their cycle cancelled. In the group of patients who developed < or = 3 follicles and who were aged <40 years, despite a significantly lower number of oocytes collected [2 versus 7; median difference (MD) = 9; confidence interval (CI) = 7-11, and lower number of embryos developed and transferred (1 versus 3; MD = 2; CI = 1-2), no difference in either implantation rate [27.8 versus 20.4%; odds ratio (OR) = 1.58; CI = 0.46-4.54] or pregnancy rate (27.8 versus 36.7%; OR = 0.7; CI = 0.2-2.0) was noted when compared with similarly aged patients who developed >3 follicles. However, in patients aged >40 years who developed < or = 3 follicles, a moderate, albeit non-significant decrease in implantation rate (3.8 versus 7.8%; OR = 1.91; CI = 0.4-57.0) and pregnancy rate (4.2 versus 18.3%; OR = 1.92; CI = 0.38-57.0) was observed when compared with patients of a similar age who developed >3 follicles. Patients aged <40 years, unlike older patients, maintain good implantation and pregnancy rates despite a poor response to ovarian stimulation. This study indicates that for this group of women, continuation of IVF treatment is a better option than cancellation.

Adult↗
PubMed1999

Asparagine-linked glycosylation in the yeast Golgi.

The Golgi complex is the site where the terminal carbohydrate modification of proteins and lipids occurs. These carbohydrates play a variety of biological roles, ranging from the stabilization of glycoprotein structure to the provision of ligands for cell-cell interactions to the regulation of cell surface properties. Progress in our understanding of the biosynthesis and regulation of glycoconjugates has been accelerating at a rapid pace. Recent advances in the field of yeast glycobiology have been particularly impressive. This review focuses on glycosylation of proteins in the Golgi of the yeast Saccharomyces cerevisiae, with emphasis on the candidate mannosyltransferases that participate in the synthesis of N-linked oligosaccharides. Current views on how these enzymes may be regulated and how glycosylation relates on other cellular processes are also discussed.

Asparagine↗
PubMed1999

Is routine synovial fluid analysis necessary? Lessons and recommendations from an audit.

This audit of 408 synovial fluid samples, analysed for cell counts and crystals, revealed that crystals were present in only 25 samples (6.1%). Of these, in only three patients was the diagnosis uncertain and therefore the analysis helpful. Cell counts and types generally reflected known underlying diagnoses of inflammatory arthritis or osteoarthritis. Routine synovial fluid analysis does not contribute to diagnosis or management in established rheumatic disorders and should be performed only when the underlying cause is uncertain or in newly presenting patients. Major savings can be made by abandoning routine synovial fluid analysis.

Diagnostic Tests, Routine↗
PubMed1998

Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent implantation and pregnancy rates.

OBJECTIVE: To assess the effect of pretreatment with an oral contraceptive (OC) on ovarian cyst formation during pituitary suppression with buserelin acetate. DESIGN: Prospective randomized trial. SETTING: Academic medical center. PATIENT(S): Eighty-three patients who were undergoing IVF-ET treatment. INTERVENTION(S): Patients in the study group were pretreated with an OC for 14 days starting on the first day of menstruation. The administration of SC buserelin acetate was initiated on the last day of OC administration. Patients in the control group began to receive buserelin acetate on day 2 of menstruation. Hormonal assays and ultrasound scans were performed on the first day of menstruation, and 7, 11, and 14 days after the commencement of buserelin acetate administration. Thereafter, these tests were performed weekly until pituitary suppression was achieved. MAIN OUTCOME MEASURE(S): Incidence of cyst formation. RESULT(S): A cyst developed in 27 patients in the control group (52.9%) and no patients in the study group (odds ratio [OR]=115; 95% confidence interval [CI]=10-617). Patients in the study group achieved pituitary suppression faster (median difference [MD]=7 days; 95% CI=4-14) and required fewer ampules of gonadotropin (MD=10; 95% CI=6-14). They recruited more follicles (MD=3; 95% CI=0-5) and had higher pregnancy rates (37.2% versus 33.3%). CONCLUSION(S): Pretreatment with an OC abolishes ovarian cyst formation, shortens the time required to achieve pituitary suppression, and decreases gonadotropin requirements without having a negative effect on pregnancy rates.

Adult↗