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Biomedical subjects

S Farrell

Publications and source records attributed to S Farrell.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between maternal periodontitis, adverse pregnancy outcome and miscarriage in never smokers.

BACKGROUND: It has been postulated that associations between periodontal disease and systemic conditions may be because of the confounding effects of smoking. In addition, studies of this type rarely investigate the adverse pregnancy outcome of miscarriage. AIM: The aim of this prospective study was to investigate a relationship between periodontal disease in pregnancy and subsequent adverse pregnancy outcomes in a population of never smokers. MATERIALS AND METHODS: Pregnant women were recruited at 12 weeks gestation. Demographic, behavioural and medical data were collected. A periodontal examination was performed and data on each subjects' pregnancy outcome were collected. RESULTS: A total of 1793 women reported never previously smoking. Of these, 7.3% had a pre-term birth and 0.9% a late miscarriage. As expected in this population, we found no associations between poorer periodontal health and either pre-term birth or low birth weight (LBW). In contrast, the subjects who experienced a late miscarriage had a higher mean probing depth at mesial sites compared with the subjects that gave birth at term (2.69 mm versus 2.41 mm, p=0.006). CONCLUSIONS: There was an association between some measures of periodontal disease and late miscarriage; however, there was no association between periodontitis and pre-term birth or LBW in this population.

Abortion, Spontaneous↗
PubMed2003

Women's perceptions about treatment decision making for ovarian cancer.

OBJECTIVES: To identify in women with advanced epithelial ovarian cancer who had just undergone surgery the extent to which they (1) perceived that they had treatment options, (2) understood the treatment related risks and benefits, and (3) preferred to participate in the treatment decision-making process. METHODS: This qualitative study included women who underwent initial surgery for stage 3 or 4 ovarian cancer and who had received less than two cycles of chemotherapy. In depth semistructured interviews were conducted with 21 patients between June 1999 and February 2001. The interviews were content analyzed according to the themes that arose in the interview. RESULTS: Five themes were identified. (1) Knowledge of treatment benefits and risks. Women understood that the treatment had both survival and quality of life benefits. Women could clearly articulate the risks of chemotherapy. (2) Readiness to make a decision. When making treatment decisions, women described being overwhelmed by the effects of concurrent drugs like analgesics, the severity of the illness, unexpected diagnosis of cancer and grief, and feeling pressured into a decision. (3) Perception of a treatment choice. Most women felt that they made their treatment decision; however, most women did not perceive that they had a treatment choice. Thus, treatment decision making is really a process of coming to terms with the disease and the recommended treatment. (4) Physician-patient relationship. All women suggest that their doctor knew the right treatment for them and they felt confident in their cancer physician. (5) Social supports. Women described supports through decision-making processes that included individuals who advocated for them, faith, and past experience with the cancer system. Hindrances to decision making included people who were negative, the cancer label, and employers. CONCLUSIONS: Women with advanced epithelial ovarian cancer did not describe the treatment decision-making process as shared; rather they described an interaction that was directed largely by the physician. These women attribute this form of decision-making to their advanced age, severity of illness, immediate ramification of treatment choices, and lack of advocacy for a different model of interaction. Thus, the onus is on the physician to ensure that there is an environment for shared decision-making in the event that the patient is interested in such an interaction.

Aged↗
PubMed2003

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Adolescent↗
PubMed2001

Recruitment of the transcriptional machinery through GAL11P: structure and interactions of the GAL4 dimerization domain.

The GAL4 dimerization domain (GAL4-dd) is a powerful transcriptional activator when tethered to DNA in a cell bearing a mutant of the GAL11 protein, named GAL11P. GAL11P (like GAL11) is a component of the RNA-polymerase II holoenzyme. Nuclear magnetic resonance (NMR) studies of GAL4-dd revealed an elongated dimer structure with C(2) symmetry containing three helices that mediate dimerization via coiled-coil contacts. The two loops between the three coiled coils form mobile bulges causing a variation of twist angles between the helix pairs. Chemical shift perturbation analysis mapped the GAL11P-binding site to the C-terminal helix alpha3 and the loop between alpha1 and alpha2. One GAL11P monomer binds to one GAL4-dd dimer rendering the dimer asymmetric and implying an extreme negative cooperativity mechanism. Alanine-scanning mutagenesis of GAL4-dd showed that the NMR-derived GAL11P-binding face is crucial for the novel transcriptional activating function of the GAL4-dd on GAL11P interaction. The binding of GAL4 to GAL11P, although an artificial interaction, represents a unique structural motif for an activating region capable of binding to a single target to effect gene expression.

Alanine↗
PubMed2001

Mathematical model of a hybrid dispersed network-membrane-based controlled release system.

A mathematical model with an exact solution is presented for the controlled release of a drug from a hybrid dispersed network-membrane based system. Both hollow fiber and flat membrane device geometries are considered. The reservoir is loaded with a drug dispersed in a liquid phase. This reservoir is bounded by a microporous membrane, the pores of which are filled with liquid immiscible with the reservoir phase liquid. The drug dissolves from the solid network into the reservoir liquid and migrates through the reservoir toward the microporous membrane. At the interface between the reservoir and the pore, the solute partitions between the reservoir and the pore liquid phases, before diffusing outward through the membrane pore. Experimental results are in close agreement with the release profiles predicted by the mathematical model. Parametric studies reveal the interaction between system parameters and the controlled release behavior. The presence of a dispersed drug phase in the reservoir results in the release of drug for an extended time. The release rate of the drug may be controlled by its rate of diffusion through the membrane pores or by its rate of dissolution into the reservoir liquid.

Chemistry, Pharmaceutical↗
PubMed2001

An openness scale for the California Psychological Inventory.

We developed a 36-item scale to measure Openness, using items on the California Psychological Inventory (CPI; Gough, 1957, 1987, 1996), Form 434. Items were initially chosen on the basis of content validity. Five samples (N = 2,375) were used to establish reliability, validity, and norms; 4 samples consisted of university undergraduate students, and 1 comprised applicants for nonmanagement call centerjobs. Internal consistency estimates obtained in each sample averaged approximately .75, and test-retest stability, assessed in 1 sample, was estimated at .84. Cross-correlations with related scales, for example, the NEO Personality Inventory-Revised Openness scale (Costa & McCrae, 1992) and other CPI-based scales, provided evidence of construct validity. Statistically significant predictive validities were obtained in 2 call centerjob-incumbent samples, with range-corrected true validities of .20 to .36 for a number of job performance criteria. Construct and predictive validity were found to be higher than for other scales consisting of CPI items designed to measure Openness or a related construct. Finally, norms were prepared for university undergraduate students (n = 1,847) and nonmanagement service-sector job applicants (n = 528).

Adult↗
PubMed2000

Drug release characteristics of unimolecular polymeric micelles.

Biodegradable, unimolecular polymeric micelles possess several features that are attractive for drug delivery applications: Thermodynamic stability, ability to encapsulate and solubilize a hydrophobic guest molecule, biodegradability, as well as size and surface characteristics that prevent rapid clearance by the RES. Here we investigate the potential of these unimolecular polymeric micelles to release a drug for an extended time. Lidocaine was used as a model drug for in vitro studies using a horizontal diffusion cell and cellulose membrane that prevented polymer transport from the source to the receiver compartment. The transport of free lidocaine from source to receiver under sink conditions was zero-order and complete within 8 h. The transport of lidocaine initially encapsulated in polymer was zero-order for the first 14 h, and 96% of the lidocaine was detected within 24 h.

Diffusion↗
PubMed2000

A redintegration account of the effects of speech rate, lexicality, and word frequency in immediate serial recall.

Short-term serial recall performance is strongly affected by the nature of the items to be remembered. For example, memory span declines with decreasing speech rate (i.e., increasing pronunciation duration) of the items and, for a given speech rate, memory for non-words is poorer than for words. Similarly, words of high natural language frequency are recalled better than low-frequency words. Existing descriptive models have identified redintegration as underlying many of those effects. Redintegration refers to the process by which partially retrieved memorial information is converted into an overt response. This article presents a process model of redintegration based on a non-linear dynamic network, which is shown to handle the effects of speech rate, lexicality, and word frequency on memory span. Unlike previous descriptive efforts, the redintegration model also predicts the shape of the underlying serial position curves.

Humans↗
PubMed2000

A negative SimpliRED D-dimer assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients.

STUDY OBJECTIVE: To determine whether a negative SimpliRED D-dimer assay result excludes the diagnosis of deep vein thrombosis (DVT) or pulmonary embolus (PE) in emergency department patients. METHODS: This prospective, institutional review board-approved, clinical trial enrolled consecutive adult ED patients with the suspected diagnosis of venous thromboembolism (VTE) (DVT or PE). Initial ED evaluation included the SimpliRED D-dimer assay (American Diagnostica Inc, Greenwich, CT). Physicians were blinded to assay results. The diagnosis of DVT was made with positive findings on lower-extremity ultrasonography. PE was confirmed by a high-probability ventilation/perfusion (V/Q) scan, a positive pulmonary angiogram, or a positive finding on lower-extremity ultrasonography. A presumptive diagnosis of VTE was made in patients who had VTE at follow-up or unexplained death during the study period. RESULTS: One hundred ninety-eight patients were enrolled during the study period. Twenty-five patients were excluded from data analysis; 9 had no diagnostic testing and 16 were lost to follow-up. Of the 173 patients analyzed, 57 (33%) had VTE-16 of 48 evaluated for DVT and 41 of 125 for suspected PE. The SimpliRED assay had a sensitivity of 65% and a negative predictive value of 81% for detection of VTE. In patients evaluated for DVT alone, the sensitivity was 56% and the negative predictive value was 77%. For patients with suspected PE, the sensitivity and negative predictive value were 68% and 83%, respectively. CONCLUSION: In contrast to earlier reports on the SimpliRED D-dimer assay, a negative result failed to exclude the diagnosis of VTE in our ED population.

Adult↗
PubMed2000

A connectionist model of complacency and adaptive recovery under automation.

Automation is intended to reduce the demands on operators in complex environments, thereby enhancing overall system performance. Although automation usually reduces workload, it is often accompanied by a decline in monitoring performance, an effect known as complacency. The circumstances under which complacency occurs and how it can be prevented, for example by intermittently returning control to the operator, are empirically well understood. To date, that empirical knowledge has not been accompanied by strong psychological theory. This article presents a computational model of human performance under automation based on connectionist principles. The model is shown to explain several benchmark findings, among them the basic complacency effect; the effect of the variability of automation reliability on complacency; the effect of task complexity; and the effect of intermittently returning control to the operator.

Attention↗
PubMed2000

Family-focused case management: a case study of an innovative demonstration program.

Using results from a formative evaluation, the paper describes family-focused case management (FFCM). FFCM is an innovative community mental health service designed to support both consumers/survivors and their families. The formative evaluation used a multi-informant, multi-method approach to describe FFCM services and assess their quality. Focus groups with program stakeholders produced a "program-logic model" and identified minimum standards for FFCM. Service activities and outcomes defined in the program-logic model were typical of those offered to consumers/survivors in intensive case management programs, but were supplemented with support being offered to their families. Monitoring of service activities showed that the case manager had regular contact with families and offered them a mix of direct and indirect services that corresponded, in most cases, to defined program standards. Interviews with 14 family members and 8 consumers/survivors receiving FFCM services revealed high levels of satisfaction with most aspects of the program. Overall, evaluation findings suggest that intensive case management can be expanded to include providing support to families. Future directions for developing FFCM are discussed.

Case Management↗
PubMed1999

A mathematical model of an aqueous-organic partition-based controlled release system using microporous membranes.

A mathematical model with an exact solution is presented for the membrane-controlled release of small molecules such as nicotine, caffeine, and benzoic acid initially present in solution in the reservoir of the device. Both hollow fiber and flat membrane device geometries are considered. The reservoir is bounded by a microporous membrane, the pores of which are filled with a pore liquid immiscible with the reservoir phase liquid. At the interface between the reservoir and the pore, the solute partitions between the reservoir and the pore liquid phases, before diffusing outward through the membrane pore. The model results compare well with experimental data. Parametric studies reveal the interaction between system parameters and the controlled release behavior. A high partition coefficient of the solute between the reservoir and pore phases is found to effect pseudo-zero order release for an extended time. Similarly, when the ratio of time constants for transport of the solute through the reservoir and membrane regions is small, a constant release rate is achieved for an extended time.

Benzoic Acid↗
PubMed1999

Cytogenetic aspects of the Canadian early and mid-trimester amniotic fluid trial (CEMAT).

Cytogenetic results from a large multicentre randomized controlled study of 2108 amniotic fluids obtained at 11+0-12+6 weeks (EA) and 1999 fluids at 15+0-16+6 weeks (MA) were compared. There was no statistically significant difference in the rate of chromosome abnormalities (EA =1.9 per cent; MA=1.7 per cent) or level III mosaicism (EA=0.2 per cent; MA= 0.2 per cent) between the groups. Level I and Level II mosaicism occurred more frequently in MA. Maternal cell contamination was not significantly different between the groups, but maternal cells only were analysed from one bloody EA fluid. The number of repeat amniocenteses because of cytogenetic problems was 2.2 per cent in the EA group compared with only 0.3 per cent in the MA group. On average, culture of EA fluids required one day more than MA fluids. Although both culture success (97.7 per cent) and accuracy (99.8 per cent) were high for patients randomized to the EA group, routine amniocentesis prior to 13 weeks' gestation is not recommended for clinical reasons including an increased risk of fetal loss and talipes equinovarus.

Amniocentesis↗
PubMed1999

Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome with associated visceral and skeletal abnormalities. Alterations in the glypican-3 gene (GPC3), which is located on Xq26, have been implicated in the etiology of relatively milder cases of this disorder. Not all individuals with SGBS have demonstrated disruptions of the GPC3 locus, which raises the possibility that other loci on the X chromosome could be responsible for some cases of this syndrome. We have previously described a large family with a severe form of SGBS that is characterized by multiple anomalies, hydrops fetalis, and death within the first 8 wk of life. Using 25 simple tandem-repeat polymorphism markers spanning the X chromosome, we have localized the gene for this disorder to an approximately 6-Mb region of Xp22, with a maximum LOD score of 3.31 and with LOD scores <-2.0 for all of Xq. These results demonstrate that neither the GPC3 gene nor other genes on Xq26 are responsible for all cases of SGBS and that a second SGBS locus resides on Xp22.

Abnormalities, Multiple↗
PubMed1999

Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator.

The p300 and CREB binding protein (CBP) transcriptional coactivators interact with a variety of transcription factors and regulate their activity. Among the interactions that have been described, the COOH-terminal region of p300 binds to cyclin E-cyclin-dependent kinase 2 (cyclin E-Cdk2) and TFIIB, as well as to the E1A gene products of adenovirus. Inhibition of Cdk activity by Cdk inhibitors, such as p21 or p27, potentiates NF-kappaB activity and provides a mechanism to coordinate cell cycle progression with the transcription of genes expressed during growth arrest. In this report, we analyze the specific domains of p300 required for the binding of p300 to cyclin E-Cdk2, TFIIB, and E1A and the ability of these proteins to interact with p300, alone or in combination. 12S E1A, an inhibitor of p300-dependent transcription, reduces the binding of TFIIB, but not that of cyclin E-Cdk2, to p300. In contrast, 13S E1A, a pleiotropic transcriptional activator, does not inhibit TFIIB binding to p300, although it enhances the interaction of cyclin E-Cdk2 with p300. Modification of cyclin E-Cdk2 is most likely required for association with p300 since the interaction is observed only with cyclin E-Cdk2 purified from mammalian cells. Domain swap studies show that the cyclin homology domain of TFIIB is involved in interactions with p300, although the homologous region from cyclin E does not mediate this interaction. These findings suggest that p300 or CBP function is regulated by interactions of various proteins with a common coactivator domain.

Adenovirus E1A Proteins↗
PubMed1997

Reliability of blood pressure determination with the Finapres with altered physiological states or pharmacodynamic conditions.

The blood pressure waveform is modified on distal propagation by phenomena such as dispersion, reflection and the state of the arterial compliance. The consequent effects are amplification and narrowing of the wave, with an increased systolic, reduced diastolic and essentially unaltered mean blood pressure. The Finapres measures the peripheral pressure using the volume clamp principle; it has not been validated under altered physiological conditions and during pharmacodynamic interventions. We studied simultaneous Finapres and brachial blood pressures (using a conventional oscillometric sphygmomanometer-Vitalmap) in ten normal volunteers at rest, and during dynamic exercise and a cold pressor test. The effects of pharmacodynamic intervention were examined following beta-adrenoceptor blockade with propranolol (160 mg) or beta-adrenoceptor modulation with the beta-adrenoceptor partial agonist celiprolol (400 mg). The Finapres systolic pressure was significantly higher than the brachial value during all three test states. The difference between the systolic pressures measured by the two devices was shown to increase significantly during the cold pressor test, but not during dynamic (supine bicycle) exercise. The Finapres diastolic pressure was significantly higher than the Vitalmap value during exercise and the cold pressor test. The differences between the two methods increased significantly over time. Beta-adrenergic blockade with propranolol or modulation with celiprolol had no significant interaction with the pressure differences between the Finapres and Vitalmap techniques. The results would support the view that the Finapres can provide blood pressure information which is robust under most circumstances. Although this pharmacodynamic intervention did not alter the relationship between the peripheral and central blood pressure, it is important to note that this dynamic relationship is sensitive to circulatory loading conditions and wave transmission characteristics; it is possible that the Finapres could be less reliable in clinical settings where potent vasoactive agents were being administered.

Adrenergic beta-Antagonists↗