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Biomedical subjects

M Owen

Publications and source records attributed to M Owen.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor.

UNLABELLED: We previously found that the extent of an epidural motor block produced by 0.125% ropivacaine was clinically indistinguishable from 0.125% bupivacaine in laboring patients. By adding fentanyl to the 0. 125% ropivacaine and bupivacaine solutions in an attempt to reduce hourly local anesthetic requirements, we hypothesized that differences in motor block produced by the two drugs may become apparent. Fifty laboring women were randomized to receive either 0. 125% ropivacaine with fentanyl 2 microg/mL or an equivalent concentration of bupivacaine/fentanyl using patient-controlled epidural analgesia (PCEA) with settings of: 6-mL/hr basal rate, 5-mL bolus, 10-min lockout, 30-mL/h dose limit. Analgesia, local anesthetic use, motor block, patient satisfaction, and side effects were assessed until the time of delivery. No differences in verbal pain scores, local anesthetic use, patient satisfaction, or side effects between groups were observed; however, patients administered ropivacaine/fentanyl developed significantly less motor block than patients administered bupivacaine/fentanyl. Ropivacaine 0.125% with fentanyl 2 microg/mL produces similar labor analgesia with significantly less motor block than an equivalent concentration of bupivacaine/fentanyl. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the PCEA technique remains to be determined. IMPLICATIONS: By using a patient-controlled epidural analgesia technique, ropivacaine 0.125% with fentanyl 2 microg/mL produces similar analgesia with significantly less motor block than a similar concentration of bupivacaine with fentanyl during labor. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the patient-controlled epidural analgesia technique remains to be determined.

Adult↗
PubMed2000

Radial carpal bone fractures in 15 dogs.

Between 1977 and 1992, 15 adult dogs were presented to the Universities of Bristol, Glasgow, Liverpool and London with fractures of the radial carpal bone which had occurred without a known episode of violent trauma. Eleven of the dogs were boxers and the other breeds affected were a Pharaoh hound, rottweiler, springer spaniel and a greyhound. The condition was bilateral in three cases. Eleven dogs were treated surgically by cast immobilisation (four cases), fragment removal (one case), lag screw fixation (three cases), pan-carpal arthrodesis (one case) and lag screw reduction followed by pan-carpal arthrodesis (two cases). The remaining four dogs were treated conservatively with rest and tactical use of non-steroidal anti-inflammatory drugs. Follow-up periods ranged from two months to 11 years. Varying degrees of lameness, which tended to be exacerbated by exercise, persisted in all cases. The radial carpal bone appears to have at least three separate centres of ossification which eventually fuse; their planes of fusion correspond approximately to the two main fracture lines. These areas of fusion could be weak points within the radial carpal bone.

Animals↗
PubMed1999

Synthetic [5,5] trans-fused indane lactones as inhibitors of thrombin.

Synthesis of trans-fused lactones containing the indane nucleus has resulted in a series of potent acylating inhibitors of thrombin. As an example compound 11e has an apparent second order rate constant of 11 x 10(6) M(-1)sec(-1) for the inhibition of thrombin. The anticoagulant activity of these compounds is discussed.

Anticoagulants↗
PubMed1999

Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.

Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig spanning the DD candidate region on chromosome 12q23-24.1. After screening several genes that mapped to this region, we identified mutations in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were identified, including frameshift deletions, in-frame deletions or insertions, splice-site mutations and non-conservative missense mutations in functional domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell adhesion and differentiation of the epidermis.

Calcium-Transporting ATPases↗
PubMed1999

Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice.

Osteoblasts and odontoblasts, cells that are responsible for the formation of bone and dentin matrices respectively, share several molecular characteristics. Recently, Cbfa1 was shown to be a critical transcriptional regulator of osteoblast differentiation. Mutations in this gene cause cleidocranial dysplasia (CCD), an autosomal dominant disorder in humans and mice characterized by defective bone formation. CCD also results in dental defects that include supernumerary teeth and delayed eruption of permanent dentition. The dental abnormalities in CCD suggest an important role for this molecule in the formation of dentition. Here we describe results of studies aimed at understanding the functions of Cbfa1 in tooth formation. RT-PCR and in situ hybridization analyses show that Cbfa1 has a unique expression pattern in dental mesenchyme from the bud to early bell stages during active epithelial morphogenesis. Unlike that observed in osteoblast differentiation, Cbfa1 is downregulated in fully differentiated odontoblasts and is surprisingly expressed in ectodermally derived ameloblasts during the maturation phase of enamel formation. The role of Cbfa1 in tooth morphogenesis is further illustrated by the misshapen and severely hypoplastic tooth organs in Cbfa1-/- mice. These tooth organs lacked overt odontoblast and ameloblast differentiation and normal dentin and enamel matrices. Epithelial-mesenchymal recombinants demonstrate that dental epithelium regulates mesenchymal Cbfa1 expression during the bud and cap stages and that these effects are mimicked by the FGFs but not by the BMPs as shown by our bead implantation assays. We propose that Cbfa1 regulates the expression of molecules in mesenchyme that act reciprocally on dental epithelium to control its growth and differentiation. Taken together, our data indicate a non-redundant role for Cbfa1 in tooth development that may be distinct from that in bone formation. In odontogenesis, Cbfa1 is not involved in the early signaling networks regulating tooth initiation and early morphogenesis but regulates key epithelial-mesenchymal interactions that control advancing morphogenesis and histodifferentiation of the epithelial enamel organ.

Animals↗
PubMed1999

How physician communication influences recognition of depression in primary care.

BACKGROUND: The relationship between physician communication patterns and the successful recognition of depression is poorly understood. METHODS: We used unannounced visits by actors playing standardized patients to evaluate verbal communication between primary care physicians and a patient presenting with a minor depression scenario. Participants (n = 77) were assigned to receive 2 visits from a man or woman portraying a 26-year-old patient with chronic headaches who meets the criteria for minor depression. The standardized patients carried hidden audiotape recorders and high-fidelity microphones to document the encounters. The audiotapes were coded at 2-second intervals. These data were linked to information gathered from standardized patient checklists, medical records, and debriefing telephone calls with participants. RESULTS: We obtained complete data on 59 (77%) of the physician-patient encounters; of those, 43 (73%) of the physicians recognized depression. Physicians who recognized depression asked twice as many questions about feelings and affect compared with those who did not (for feelings: 1.9% of total physician activity vs. 0.9%, P = .017; for affect: composite score of 2.7% of total physician activity vs 1.3%, P = .003). We found no differences in the proportion or timing of broad to narrow questioning between those who did and did not recognize depression. Physicians who successfully recognized depression later in the interview showed an increase in questions about feelings in the quartile just before recognition occurred. CONCLUSIONS: Physicians who recognized depression differed significantly in the percentage of questions about feeling and affect, and an increase in questions about feelings may precede a diagnosis of depression, though more research is needed to establish this as an important finding.

Adult↗
PubMed1999

Recognizing and managing depression in primary care: a standardized patient study.

BACKGROUND: Guidelines for recognition and management of depression in primary care provide a framework for detailed exploration of physician practice patterns. METHODS: Our objective was to explore physician diagnosis and management approaches to depressive disorders according to type (major vs. minor) and presenting complaint (difficulty sleeping and concentrating vs. headache). The participants were community primary care internists and family physicians in northern New England, Washington, and Alabama (N = 149) who were randomly assigned to receive a visit from an unannounced actor portraying a standardized patient in 1 of 2 depression scenarios: (A) insomnia and poor concentration meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for major depressive disorder; or (B) tension headaches meeting the criteria for minor depression. RESULTS: All physicians who were assigned to the standardized patients presenting with scenario A recognized depression, and 49% (38 of 78) of those assigned to scenario B patients diagnosed depression. Of those recognizing depression, 72% and 42% queried patients about anhedonia and mood, respectively. For both scenarios, if fewer than 2 DSM-III-R criteria were explored, depression was not diagnosed. Management for scenario A was compatible with Agency for Health Care Policy and Research guidelines, including the prescription of an antidepressant (94%), scheduling of a follow-up visit within 2 weeks (61%), and exploration of suicidal ideation (69.4%). For scenario B, management included over-the-counter analgesics for the headache (84%), exercise (63%), prescription for an antidepressant (53%), recommendation for ongoing counseling (100%), and follow-up within 2 weeks (42%). CONCLUSIONS: Major depression is recognized in primary care at a very high rate. Guidelines for recognizing and managing depression are often followed in primary care. Patients' presentations of depression influence its recognition and management.

Adult↗
PubMed1998

Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model.

Adjuvant-induced arthritis (AIA) is one of many animal models of rheumatoid arthritis, a disease characterized by a T-lymphocyte and macrophage cellular infiltrate. We have characterized the development of this disease model with respect to chemokine expression. Increased levels of two chemokines, RANTES, a T-lymphocyte and monocyte chemo-attractant, and KC a chemoattractant for neutrophils, were found in whole blood and in the joint. Surprisingly, levels of MIP-1alpha, another T-lymphocyte and monocyte chemoattractant, were unchanged throughout the course of the disease in whole blood and only slightly elevated in the joint. RANTES expression plays an important role in the disease since a polyclonal antibody to RANTES greatly ameliorated symptoms in animals induced for AIA and was found to be as efficacious as treatment with indomethacin, a non-steroidal anti inflammatory. Polyclonal antibodies to either MIP-1alpha or KC were ineffective. This is the first report to show the importance of RANTES in the development of AIA.

Animals↗
PubMed1998

Dopamine markers and general cognitive ability.

Because general cognitive ability (g) is among the most heritable behavioural traits, it is a reasonable target for a search for quantitative trait loci (QTLs). We used a selected-extremes design to test candidate genes for allelic association with g. Polymorphisms in four genes in the dopamine system (DRD2, DRD3, DRD4, DAT1) were genotyped for 51 high g children with IQ scores > 130 and for 51 average g control children. No significant allelic or genotypic differences were found between the high g and average g groups for these markers of the dopamine system, even though the selected-extremes design provides power to detect QTL associations that involve a relative risk of about 1.5.

Adolescent↗
PubMed1998

Linkage analysis between bipolar affective disorder and markers on chromosome X.

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

Bipolar Disorder↗
PubMed1998

Variations in approaching the diagnosis of depression: a guided focus group study.

BACKGROUND: Primary care physicians are often held to the same standard of performance as mental health specialists, yet they face special challenges in recognizing and treating depression. The purpose of this study was to explore the range of approaches to diagnose depression. METHODS: A purposeful sample of 21 primary care physicians in three US cities participated. A semistructured series of questions and clinical cases stimulated discussions about recognizing and managing major and minor depression. The focus groups were videotaped, and data were analyzed by two independent reviewers using the classic method of content analysis. RESULTS: Primary care providers have three major ways of approaching the diagnosis of depression: a biomedical exclusionary approach, where investigation of all physical complaints occurs first; a mental health approach, where psychosocial aspects of a presentation are pursued first; and a synergistic approach, where physical and mental health complaints are addressed simultaneously. Physicians move freely across all approaches depending on patient cues. CONCLUSIONS: Physicians' approaches to depression vary depending on patient characteristics and cues. Through a better understanding of current practices, future researchers can identify the optimal clinical approaches to match the characteristics and cues of specific patients. This study informed the development of a larger objective study of primary care physician performance.

Adult↗
PubMed1997

Heparin-dependent modification of the reactive center arginine of antithrombin and consequent increase in heparin binding affinity.

Antithrombin, the principal plasma inhibitor of coagulation proteinases, circulates in a form with low inhibitory activity due to partial insertion of its reactive site loop into the A-beta-sheet of the molecule. Recent crystallographic structures reveal the structural changes that occur when antithrombin is activated by the heparin pentasaccharide, with the exception of the final changes, which take place at the reactive center itself. Here we show that the side chain of the P1 Arg of alpha-antithrombin is only accessible to modification by the enzyme peptidylarginine deiminase on addition of the heparin pentasaccharide, thereby inactivating the inhibitor, whereas the natural P1 His variant, antithrombin Glasgow, is unaffected, indicating that only the P1 Arg becomes accessible. Furthermore, the deimination of P1 Arg converts antithrombin to a form with 4-fold higher affinity for the heparin pentasaccharide, similar to the affinity found for the P1 His variant, due to a lowered dissociation rate constant for the antithrombin-pentasaccharide complex. The results support the proposal that antithrombin circulates in a constrained conformation, which when released, in this study by perturbation of the bonding of P1 Arg to the body of the molecule, allows the reactive site loop to take up the active inhibitory conformation with exposure of the P1 Arg.

Antithrombin III↗
PubMed1997

Bronchoalveolar lavage: comparison of nucleopore filters and direct smear preparations.

To determine whether cytopreparation affects the diagnostic yield of bronchoalveolar lavage specimens, we compared 50 lavage samples by using two methods. One nucleopore filter preparation and four direct slides were prepared on each sample submitted. All slides were stained by the Papanicolaou method. Assessment of cellularity, cellular preservation, and an independent diagnosis were rendered on each sample for both preparatory methods. Statistical analysis showed no difference in cellularity between the two methods (P = .06). The degree of nuclear and cytoplasmic preservation was higher using the direct method, although this did not appear to affect diagnosis in this study. One major discrepancy in diagnosis was observed between the two methods. By prospectively comparing nucleopore filter and direct preparation of bronchoalveolar lavages, we found that there was minimal affect on either cellularity or diagnosis. We conclude that either method delivers reliable cytologic results.

Bronchoalveolar Lavage↗
PubMed1997

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

Adolescent↗
PubMed1997

Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families.

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamines, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphisms), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

Amino Acid Substitution↗