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Biomedical subjects

S Lane

Publications and source records attributed to S Lane.

At least 19 recordsLinked to original sources
PubMed2005

A comparison of intrathecal fentanyl and diamorphine as adjuncts in spinal anaesthesia for Caesarean section.

This randomised controlled trial examines the effects of fentanyl and diamorphine, alone and in combination, as adjuncts to spinal anaesthesia for Caesarean section. Ninety-nine women undergoing elective Caesarean section with spinal anaesthesia using 0.5% hyperbaric bupivacaine were randomly allocated to receive fentanyl 15 microg (F), diamorphine 0.25 mg (D), or fentanyl 15 microg plus diamorphine 0.25 mg (FD), intrathecally. All women received morphine via a patient controlled analgesia system after surgery. There was no significant difference between the groups in time to achieve a block, discomfort, ephedrine use, nausea and vomiting, pruritus and sedation during surgery. Significant differences were observed in morphine consumption 4, 8, 12 and 24 h after surgery between both F and D groups, and F and FD groups, and also at 2 h between F and FD groups. There was a significant difference in pruritus at 4 h between the F and FD group. Our results suggest that diamorphine alone provides optimum benefits during and after surgery, when used in combination with hyperbaric bupivacaine for Caesarean section.

Adjuvants, Anesthesia↗
PubMed2005

A prospective, randomised controlled trial comparing the efficacy of pre-oxygenation in the 20 degrees head-up vs supine position.

We investigated whether positioning patients undergoing general anaesthesia for cholecystectomy in a 20 degrees head-up position, as opposed to supine, improved the efficacy of 3 min of standard pre-oxygenation via a circle breathing system. Following pre-oxygenation, patients received a standard induction of anaesthesia and the apnoea time (from administration of rocuronium to the arterial oxygen saturation to fall to 95%) was recorded. Mean (95% CI) apnoea time was 386 (343-429) s in the 20 degrees head-up position (n = 17) vs 283 (243-322) s in the supine position (n = 18; p = 0.002). Pre-oxygenation is significantly more efficacious and by inference more efficient in the 20 degrees head-up position than in the supine position.

Adult↗
PubMed2005

Handheld computers and paper diaries for documenting the use of factor concentrates used in haemophilia home therapy: a qualitative study.

A recently published randomized controlled trial (RCT) showed that adherence to infusion diary record keeping was improved by the use of handheld computers. In this study, attitudes to record keeping were explored and patient preferences regarding the method of recording determined for the patients who participated in the trial. Qualitative study consisting of individual semi-structured interviews with 20 severely affected patients with haemophilia who participated in an RCT. Individuals were purposefully sampled based on their recent method of record keeping and whether child or adult. Analysis employed a constant comparative method to identify key themes from the data. Most individuals (19 of 20, 95%) considered record keeping to be important. They readily identified reasons to keep records: to benefit themselves, their families, clinical staff, product distributors and manufacturers. Keeping records helps them: feel a part of the health care team; have confidence they would be notified of product recalls; review their past history; improve their ability to advocate for themselves and improve communication among all parties. Record keeping, particularly when using paper diaries, can be burdensome and a challenge to maintain consistently. All 10 individuals (100%) who had used both paper diaries and handheld computers preferred the latter. Most patients understand that record keeping can be of benefit to them. Clinics can use this knowledge to inspire other patients by developing educational programmes that de-emphasize authority. In addition, given the evidence of both patients' preference for handheld computers, and the effectiveness of this approach documented in an RCT, switching to handheld computers is likely to improve record keeping.

Adolescent↗
PubMed2004

Testing for HER2 in breast cancer.

HER2 is a paradigm of a molecular target whose appropriate assessment is pivotal in the targeting of novel therapies for breast cancer, notably including Herceptin/Trastuzumab. Determining the correct levels requires immunohistochemical and molecular biological skills that are reproducible and measurable, coupled with a knowledge of the appropriate morphological and pathobiological context. Attaining these goals is not easy and laboratories testing for HER2 should maintain a high level of throughput of tests and engage in a recognized external quality assurance scheme. Fluorescence in-situ hybridization testing remains a particular challenge and there is a range of testing strategies. This testing forms the model for the identification of other novel molecular targets. In the future rapid throughput techniques such as real-time quantitative polymerase chain reaction (rqPCR), tissue microarrays or both should bring significant economies of cost and scale.

Breast Neoplasms↗
PubMed2003

Review article: NSAIDs, gastroprotection and cyclo-oxygenase-II-selective inhibitors.

In patients at high risk of NSAID-associated serious upper gastrointestinal complications, gastroprotection with misoprostol or a proton pump inhibitor should be considered. Only misoprostol, 800 micro g/day, has been shown to reduce serious upper gastrointestinal complications in a large clinical outcome trial. The benefit of Helicobacter pylori eradication in reducing NSAID-associated gastrointestinal toxicity is controversial, and routine testing for and eradication of H. pylori in NSAID users are not currently advised. The gastrointestinal safety of rofecoxib and celecoxib has been assessed in large clinical outcome trials which, on first analysis, show benefits over non-selective NSAIDs in the incidence of serious upper gastrointestinal complications. However, longer term gastrointestinal data from the celecoxib study (CLASS) and cardiovascular adverse event data from the rofecoxib study (VIGOR) have questioned the risk-benefit profile of these new drugs and, until they are better understood, it seems sensible not to use them routinely in large numbers of individuals. The gastrointestinal safety of meloxicam and etodolac has not been adequately assessed in such trials. Therefore, evidence for their use instead of non-selective NSAIDs, or instead of celecoxib or rofecoxib, is not robust.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Role of magnetic resonance imaging in the diagnosis and single-stage surgical resection of invasive lobular carcinoma of the breast.

BACKGROUND: Conventional imaging with mammography and ultrasonography has a low sensitivity for diagnosis and a tendency to underestimate the extent of invasive lobular carcinoma (ILC) of the breast. The aim was to determine whether magnetic resonance imaging (MRI) had any advantages for the characterization of ILC. METHODS: Twenty patients with histologically proven ILC underwent preoperative imaging with MRI. MRI was performed to aid detection of malignancy in six patients with a clinically suspicious presentation but normal or indeterminate imaging on mammography and ultrasonography. In 14 patients MRI was performed to determine tumour extent. RESULTS: MRI accurately identified malignancy in five of six patients with normal or indeterminate conventional imaging. In seven of 14 patients in whom MRI was performed to determine tumour extent, it provided significant additional information. These included four patients in whom conventional imaging grossly underestimated tumour size, two patients in whom MRI identified an unsuspected contralateral breast tumour and one patient in whom MRI predicted tumour invasion of the pectoral muscle. The correlation between tumour size on histological examination was better with MRI (r = 0.967) than with mammography (r = 0.663) and ultrasonography (r = 0.673). CONCLUSION: MRI can provide considerable additional information in the detection and characterization of ILC.

Adult↗
PubMed2001

DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida albicans.

Candida albicans, normally a human commensal, can cause fatal systemic infections under certain circumstances. Its unique ability to switch from yeast to hyphal growth in response to various environmental signals is inherent to its pathogenicity. Filamentation is regulated by multiple pathways including a Cph1-mediated mitogen-activated protein kinase pathway, an Efg1-mediated cAMP/PKA pathway, and a Cph2 pathway. To gain a general picture of how these various signaling pathways regulate differential gene expression during filamentation, we have constructed a partial C. albicans DNA array of 7,000 genes and used it to study the gene expression profiles using various mutants and growth conditions. By combining this novel technology with a new liquid medium in which cph1/cph1 is defective in filamentation, previously identified differentially expressed genes (ECE1, HWP1, HYR1, RBT1, SAPs5-6, and RBT4) are found to be regulated by all three pathways. In addition, two novel genes, DDR48 and YPL184, have been found to be differentially regulated during hyphal development and by all three pathways. This suggests that distinct filamentation signaling pathways converge to regulate a common set of differentially expressed genes. As one of the mechanisms for the observed convergence, we find that the transcription of a key regulator, TEC1, is regulated by Efg1 and Cph2. Importantly, most of the genes regulated by multiple filamentation pathways encode known virulence factors. Perhaps, C. albicans utilizes converging pathways to regulate its vital virulence factors to ensure its survival and pathogenicity in various host environments.

Basic Helix-Loop-Helix Proteins↗
PubMed2001

Novel alkylpolyamine analogues that possess both antitrypanosomal and antimicrosporidial activity.

A novel series of alkyl- or aralkyl-substituted polyamine analogues was synthesized containing a 3-7-3 polyamine backbone. These analogues were evaluated in vitro, and in one case in vivo, for activity as antitrypanosomal agents, and for activity against opportunistic infection caused by Microsporidia. Compound 21 inhibits trypanosomal growth with an IC(50) as low as 31nM, while compound 24 shows promising activity in vitro against trypanosomes, and against Microsporidia in vitro and in vivo.

Animals↗
PubMed2001

Phase ii comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer.

PURPOSE: Topotecan, administered intravenously, is active in small-cell lung cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan was investigated. PATIENTS AND METHODS: Patients with SCLC that had relapsed 90 days or more after cessation of initial chemotherapy were randomized to receive either oral topotecan (Hycamtin) 2.3 mg/m(2)/d x 5 (52 patients) or IV topotecan 1.5 mg/m(2)/d x 5 (54 patients), every 21 days. RESULTS: Response rates in this phase II randomized study were 23% (12/52) in the oral topotecan arm and 15% (8/54) in the IV topotecan arm. All radiological responses were confirmed by an independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV). Good symptom control, defined as sustained improvement or no deterioration, was evident in both treatment groups. Topotecan was generally well tolerated, with myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3% of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was statistically significant (P =.001). Fever/infection more than or equal to grade 2 associated with grade 4 neutropenia, together with sepsis, occurred in only 5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and nausea (oral: 26.9% of patients; IV: 40.7% of patients). CONCLUSION: This study found oral topotecan to be similar in efficacy to IV topotecan in the treatment of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less grade 4 neutropenia and greater convenience of administration.

Administration, Oral↗
PubMed2001

Trypanocidal activity of dicationic compounds related to pentamidine.

Eight dicationic compounds related to pentamidine were studied for trypanocidal activity in seven trypanosome isolates. In vitro studies revealed that diamidines are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a diimidazoline) inhibited the growth of KETRI 243 with IC50 values of 2.3 and 900 nM, respectively. Introduction of polar groups into the linker decreased the effectiveness of the compounds against drug-resistant trypanosomes. In compounds with a 2-butene linker between the cationic groups, trans-isomers were more potent than cis-isomers. The cis- and trans-buteneamidines cured infection caused by Trypanosoma brucei brucei (EATRO Lab 110) and protected mice against infection by Trypanosoma brucei rhodesiense isolates, some of which are resistant to diamidines and melarsoprol.

Animals↗
PubMed2001

Use of a genetic marker to examine genetic interaction among subpopulations of pink salmon (Oncorhynchus gorbuscha).

In 1979 and 1981, a genetic marker was bred into one of the five identifiable subpopulations of pink salmon [Oncorhynchus gorbuscha (Walbaum)] in the Auke Lake drainage in Southeast Alaska. As a result of the marking effort, the frequencies of two malate dehydrogenase (MDH-B1, 2*) alleles were changed in the marked subpopulation, but not in other subpopulations that spawn at different times or places. Between 1983 and 1989, the marker allele frequencies were monitored in many of these subpopulations and in early- and late-run pink salmon spawning in nearby Waydelich Creek, located approximately 1 km away. Changes in allele frequencies at MDH-B1, 2*, used to obtain direct estimates of average migration rates (m) from the marked to the unmarked subpopulations, revealed little or no introgression into early subpopulations or into nearby Waydelich Creek. Moreover, spatially distinct late-run Auke Creek subpopulations were not immediately overrun by the more abundant marked subpopulation. These observations suggest that genetic isolation exists between temporally distinct spawning runs and that small temporal and spatial (or ecological) differences contribute to population structure. These observations should be considered in taking actions that affect conservation and harvest management or extensive culture of salmonids.

Alleles↗
PubMed2001

The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1.

Candida albicans undergoes a morphogenetic switch from budding yeast to hyphal growth form in response to a variety of stimuli and growth conditions. Multiple signaling pathways, including a Cph1-mediated mitogen-activated protein kinase pathway and an Efg1-mediated cyclic AMP/protein kinase A pathway, regulate the transition. Here we report the identification of a basic helix-loop-helix transcription factor of the Myc subfamily (Cph2) by its ability to promote pseudohyphal growth in Saccharomyces cerevisiae. Like sterol response element binding protein 1, Cph2 has a Tyr instead of a conserved Arg in the basic DNA binding region. Cph2 regulates hyphal development in C. albicans, as cph2/cph2 mutant strains show medium-specific impairment in hyphal development and in the induction of hypha-specific genes. However, many hypha-specific genes do not have potential Cph2 binding sites in their upstream regions. Interestingly, upstream sequences of all known hypha-specific genes are found to contain potential binding sites for Tec1, a regulator of hyphal development. Northern analysis shows that TEC1 transcription is highest in the medium in which cph2/cph2 displays a defect in hyphal development, and Cph2 is necessary for this transcriptional induction of TEC1. In vitro gel mobility shift experiments show that Cph2 directly binds to the two sterol regulatory element 1-like elements upstream of TEC1. Furthermore, the ectopic expression of TEC1 suppresses the defect of cph2/cph2 in hyphal development. Therefore, the function of Cph2 in hyphal transcription is mediated, in part, through Tec1. We further show that this function of Cph2 is independent of the Cph1- and Efg1-mediated pathways.

Amino Acid Sequence↗
PubMed2001

Persistence of gap junction communication during myocardial ischemia.

During myocardial ischemia, severe ATP depletion induces rigor contracture followed by intracellular Ca2+ concentration ([Ca2+]i) rise and progressive impairment of gap junction (GJ)-mediated electrical coupling. Our objective was to investigate whether chemical coupling through GJ allows propagation of rigor in cardiomyocytes and whether it persists after rigor development. In end-to-end connected adult rat cardiomyocytes submitted to simulated ischemia the interval between rigor onset was 3.7 +/- 0.7 s, and subsequent [Ca2+]i rise was virtually identical in both cells, whereas in nonconnected cell pairs the interval was 71 +/- 12 s and the rate of [Ca2+]i rise was highly variable. The GJ blocker 18alpha-glycyrrhetinic acid increased the interval between rigor onset and the differences in [Ca(2+)]i between connected cells. Transfer of Lucifer yellow demonstrated GJ permeability 10 min after rigor onset in connected cell pairs, and 30 min after rigor onset in isolated rat hearts submitted to nonflow ischemia but was abolished after 2 h of ischemia. GJ-mediated communication allows propagation of rigor in ischemic myocytes and persists after rigor development despite acidosis and increased [Ca2+]i.

Animals↗
PubMed2000

Quality of care and temperament determine changes in cortisol concentrations over the day for young children in childcare.

The current study investigated whether patterns of cortisol production in preschool-aged children in group care were influenced by characteristics such as group size, adult:child ratio, separation from family/parents, and quality of attention and stimulation from the childcare provider. Data were obtained from preschoolers attending home-based childcare. Cortisol levels were sampled at home and at childcare. Parents and teachers assessed the child's temperament (CBQ, TBQ). At childcare, the children were observed using the Observational Ratings of the Caregiving Environment (ORCE). Childcare characteristics were independent of family or child characteristics. In home-based childcare, children's cortisol patterns over the day correlated significantly with the amount of attention and stimulation provided by the childcare provider. Using a median split on the quality index measure of focused attention/stimulation, children in settings that were above the median exhibited no change in cortisol from home to childcare, while those in settings below the median exhibited a reversal of the typical pattern of cortisol production from morning to afternoon. At home these children exhibited the expected decrease in cortisol from morning to afternoon. Patterns of cortisol production at childcare were also correlated with child temperament with larger increases from morning to afternoon for more emotionally negative children and those with less self-control. Finally, cortisol production in home-based childcare was compared to data from children in center-based childcare and children not enrolled in full-day childcare.

Attention↗
PubMed1999

The High-Resolution FTIR Far-Infrared Spectrum of Formamide.

The far-infrared spectrum of formamide (HCONH2) has been recorded at high resolution and over 9000 vibration-rotation lines assigned. Molecular parameters from the rovibrational analyses of the unperturbed 12(1)0 out-of-plane vibration band have been obtained for the ground state and the excited state. An analysis of the complicated resonance system between the 9(1)0, 11(1)0, and 12(2)0 bands has also been carried out. The mid-infrared spectrum of formamide has been recorded at low resolution and assignments for the fundamental, combination, and overtone bands in this region are given. The Large Amplitude Motion (LAM) of the out-of-plane mode has been reanalyzed using the new parameter set. Copyright 1999 Academic Press.

Journal Article↗
PubMed1998

Ipsapirone neuroendocrine challenge: relationship to aggression as measured in the human laboratory.

Thirty-one human subjects were administered a neuroendocrine challenge with the 5-HT1a agonist ipsapirone after completing six sessions of a laboratory measure of aggression, the Point Subtraction Aggression Paradigm (PSAP), in order to determine if a laboratory measure of aggression was related to serotonin function. Subjects who showed more aggressive responding on the PSAP (n = 11) had a significantly blunted temperature response to ipsapirone compared to those with less aggressive responding (n = 20). There was no difference between the two groups on the cortisol response to ipsapirone. This study supports a relationship between serotonin function and aggression as measured in the human laboratory, similar to the well-documented association between self-reported aggression and serotonin.

Adult↗
PubMed1998

The importance of the 4'-hydroxyl hydrogen for the anti-trypanosomal and antiviral properties of (+)-5'-noraristeromycin and two 7-deaza analogues.

(+)-5'-Noraristeromycin (1) has shown significant antiviral activity while its 7-deaza analogue 2 is an antitrypanosomal candidate. To determine the relevance of the 4'-hydroxyl hydrogen in these activities, a derivative of 1 (that is, 3) where the C-4' hydroxyl hydrogen has been replaced by a methyl group has been prepared beginning with palladium (0) mediated coupling of the sodium salt of N6-benzoyladenine (9) and (1S,4R)-4-methoxy-2-cyclopenten-1-yl acetate (5). The synthesis of compound 5 is described from (1S,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-hydroxycyclopent-2-ene (6) in three steps. Analogous preparations of the 7-deaza and 8-aza-7-deaza derivatives of 3 related to 2 (that is, 4 and 12) are also reported. The new derivatives (3, 4, and 12) failed to show improved antiviral activity. Compound 12 was the only derivative with some anti-trypanosomal activity, giving 40% inhibition of growth at 100 microM against bloodstream forms of a Typanosoma brucei brucei isolate in a standard in vitro screen. This study indicated that the C-4'-hydroxyl hydrogen plays a role in the medicinal properties of 1 and 2.

Adenosine↗