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Biomedical subjects

R Ward

Publications and source records attributed to R Ward.

At least 19 recordsLinked to original sources
PubMed2001

mtDna and the islands of the North Atlantic: estimating the proportions of Norse and Gaelic ancestry.

A total of 1,664 new mtDNA control-region sequences were analyzed in order to estimate Gaelic and Scandinavian matrilineal ancestry in the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye and to investigate other aspects of their genetic history. A relative excess of private lineages in the Icelanders is indicative of isolation, whereas the scarcity of private lineages in Scottish island populations may be explained by recent gene flow and population decline. Differences in the frequencies of lineage clusters are observed between the Scandinavian and the Gaelic source mtDNA pools, and, on a continent-wide basis, such differences between populations seem to be associated with geography. A multidimensional scaling analysis of genetic distances, based on mtDNA lineage-cluster frequencies, groups the North Atlantic islanders with the Gaelic and the Scandinavian populations, whereas populations from the central, southern, and Baltic regions of Europe are arranged in clusters in broad agreement with their geographic locations. This pattern is highly significant, according to a Mantel correlation between genetic and geographic distances (r=.716). Admixture analyses indicate that the ancestral contributions of mtDNA lineages from Scandinavia to the populations of Iceland, Orkney, the Western Isles, and the Isle of Skye are 37.5%, 35.5%, 11.5%, and 12.5%, respectively.

Atlantic Islands↗
PubMed2000

Isolation of antibodies which neutralise the activity of early pregnancy factor.

Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. It functions as an autocrine growth factor for tumour cells and as an autocrine or paracrine growth factor for regenerating normal cells. Anti-EPF antibodies have demonstrable anti-tumour activity and, as a result, hybridomas which produce such antibodies are unstable. In this study, the phage display antibody techniques have been investigated as a means of producing recombinant anti-EPF antibodies. Mice were immunised with synthetic peptides which correspond to the N or C terminal regions of EPF, and their splenic tissue was used to make combinatorial antibody libraries. The Fab repertoire was displayed on the surface of phage and panned over recombinant EPF. Reactive Fabs were identified by ELISA and their binding was characterised by BIAcore analysis and functional studies. Three libraries with a size of greater than 5x10(7)cfu were constructed and a total of 26 unique Fabs with specific reactivity against EPF were identified. Three Fabs were purified and of these one demonstrated strong EPF neutralising activity, one had intermediate activity and the other was not neutralising. Phage display has provided the means of circumventing the problems of anti-EPF hybridoma development and has resulted in the production of antibodies with potential applications in the diagnosis of pregnancy and the diagnosis and therapy of cancer.

Amino Acid Sequence↗
PubMed2000

Pretectal connections in turtles with special reference to the visual thalamic centers: a hodological and gamma-aminobutyric acid-immunohistochemical study.

Projections of the pretectal region to forebrain and midbrain structures were examined in two species of turtles (Testudo horsfieldi and Emys orbicularis) by axonal tracing and immunocytochemical methods. Two ascending gamma-aminobutyric acid (GABA)ergic pathways to thalamic visual centers were revealed: a weak projection from the retinorecipient nucleus lentiformis mesencephali to the ipsilateral nucleus geniculatus lateralis pars dorsalis and a considerably stronger projection from the nonretinorecipient nucleus pretectalis ventralis to the nucleus rotundus. The latter is primarily ipsilateral, with a weak contralateral component. The interstitial nucleus of the tectothalamic tract is also involved in reciprocal projections of the pretectum and nucleus rotundus. In addition, the pretectal nuclei project reciprocally to the optic tectum and possibly to the telencephalic isocortical homologues. Comparison of these findings with previous work on other species reveals striking similarities between the pretectorotundal pathway in turtles and birds and in the pretectogeniculate pathway in turtles, birds, and mammals.

Animals↗
PubMed2000

Estimating Scandinavian and Gaelic ancestry in the male settlers of Iceland.

We present findings based on a study of Y-chromosome diallelic and microsatellite variation in 181 Icelanders, 233 Scandinavians, and 283 Gaels from Ireland and Scotland. All but one of the Icelandic Y chromosomes belong to haplogroup 1 (41.4%), haplogroup 2 (34.2%), or haplogroup 3 (23.8%). We present phylogenetic networks of Icelandic Y-chromosome variation, using haplotypes constructed from seven diallelic markers and eight microsatellite markers, and we propose two new clades. We also report, for the first time, the phylogenetic context of the microsatellite marker DYS385 in Europe. A comparison of haplotypes based on six diallelic loci and five microsatellite loci indicates that some Icelandic haplogroup-1 chromosomes are likely to have a Gaelic origin, whereas for most Icelandic haplogroup-2 and -3 chromosomes, a Scandinavian origin is probable. The data suggest that 20%-25% of Icelandic founding males had Gaelic ancestry, with the remainder having Norse ancestry. The closer relationship with the Scandinavian Y-chromosome pool is supported by the results of analyses of genetic distances and lineage sharing. These findings contrast with results based on mtDNA data, which indicate closer matrilineal links with populations of the British Isles. This supports the model, put forward by some historians, that the majority of females in the Icelandic founding population had Gaelic ancestry, whereas the majority of males had Scandinavian ancestry.

Alleles↗
PubMed2000

Symmetry, repetition, and figural goodness: an investigation of the weight of evidence theory.

Considerable evidence has accumulated on the superiority of symmetry over repetition in the study of figural goodness. The Weight of Evidence theory of figural goodness (WoE) provides a mathematically rigorous, elegant, and testable account of how factors like symmetry and repetition affect figural goodness. In this study we investigate implications of the WoE approach. More specifically, we examine (1) embedded patterns versus simple elements, (2) the number of elements in a pattern, and (3) long-range dependencies within a pattern. Data from two experiments illustrate cases in which figures made of simple repetitions have higher figural goodness than some kinds of symmetrical patterns; thus, the generality of the symmetry over repetition phenomenon is questioned. We discuss our results with respect to WoE and suggest ways to further develop the theory.

Cognition↗
PubMed2000

Tongue reduction in Beckwith-Weidemann syndrome.

OBJECTIVE: To review our experience with patients with macroglossia as a component of Beckwith-Weidemann Syndrome (BWS). DESIGN: Chart review of six patients treated with BWS. SETTING: Tertiary care teaching hospital. PATIENTS: Six patients diagnosed with BWS and macroglossia. INTERVENTIONS: Four patients underwent at least one surgical procedure to address their macroglossia. The surgical options and potential complications are discussed. RESULTS: Three patients who have undergone tongue reduction have a functioning tongue with normal mobility. Two patients have required tracheotomy as apart of their management and still have significant tongue enlargement. CONCLUSIONS: Macroglossia as a part of BWS may present a difficult management problem. Various methods of tongue reductions have been reported with mixed results.

Beckwith-Wiedemann Syndrome↗
PubMed2000

In vitro and in vivo spin echo diffusion imaging characteristics of synovial fluid: potential non-invasive differentiation of inflammatory and degenerative arthritis.

OBJECTIVE: This study was undertaken to analyse the diffusion characteristics of synovial fluid in degenerative and inflammatory arthropathies. DESIGN AND PATIENTS: Ten in vitro specimens of synovial fluid from patients with both degenerative and inflammatory arthropathy were studied at body temperature with a navigator-corrected spin echo diffusion sequence (B values 0-512 s/mm2), on a Philips 1.5-T Gyroscan. Subsequently synovial fluid from knee joint effusions of 25 patients (10 patients with osteoarthritis, 10 patients with effusions following trauma and 5 patients with effusions secondary to inflammatory arthritis) was evaluated with the same navigator-corrected spin echo diffusion sequence. RESULTS: Both in vitro and in vivo study demonstrated decreased diffusion in patients with effusions secondary to degenerative joint disease (less than 2.40 x 10(-5) cm2/s) relative to patients with effusions accompanying knee trauma (greater than 2.75 x 10(-5) cm2/s) and inflammatory arthritis (in vitro and in vivo greater than 3.00 x 10(-5) cm2/s). CONCLUSION: Synovial fluid in degenerative arthritis shows less diffusion or free water movement than synovial fluid in inflammatory arthritis. Diffusion characteristics of synovial fluid may be used to predict the nature of the underlying form of arthritis in patients presenting with knee joint effusions.

Diagnosis, Differential↗
PubMed2000

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.

Administration, Inhalation↗
PubMed2000

Burkitt's lymphoma associated with Helicobacter pylori.

The association between Helicobacter pylori infection and low grade mucosa-associated lymphoid tissue lymphoma is now widely accepted. In this report, we describe the concurrent development of Burkitt's lymphoma in the stomach of a 53-year-old male with perforated duodenal ulcer and positive H. pylori serology. The temporal relationship between these two events raises the possibility of a causal link between H. pylori infection and this lymphoproliferative disease. In describing this rare case of gastric Burkitt's lymphoma, we consider the evidence that supports this possibility.

Biopsy↗
PubMed2000

mtDNA and the origin of the Icelanders: deciphering signals of recent population history.

Previous attempts to investigate the origin of the Icelanders have provided estimates of ancestry ranging from a 98% British Isles contribution to an 86% Scandinavian contribution. We generated mitochondrial sequence data for 401 Icelandic individuals and compared these data with >2,500 other European sequences from published sources, to determine the probable origins of women who contributed to Iceland's settlement. Although the mean number of base-pair differences is high in the Icelandic sequences and they are widely distributed in the overall European mtDNA phylogeny, we find a smaller number of distinct mitochondrial lineages, compared with most other European populations. The frequencies of a number of mtDNA lineages in the Icelanders deviate noticeably from those in neighboring populations, suggesting that founder effects and genetic drift may have had a considerable influence on the Icelandic gene pool. This is in accordance with available demographic evidence about Icelandic population history. A comparison with published mtDNA lineages from European populations indicates that, whereas most founding females probably originated from Scandinavia and the British Isles, lesser contributions from other populations may also have taken place. We present a highly resolved phylogenetic network for the Icelandic data, identifying a number of previously unreported mtDNA lineage clusters and providing a detailed depiction of the evolutionary relationships between European mtDNA clusters. Our findings indicate that European populations contain a large number of closely related mitochondrial lineages, many of which have not yet been sampled in the current comparative data set. Consequently, substantial increases in sample sizes that use mtDNA data will be needed to obtain valid estimates of the diverse ancestral mixtures that ultimately gave rise to contemporary populations.

DNA, Mitochondrial↗
PubMed2000

Heritability of angiotensin-converting enzyme and angiotensinogen: A comparison of US blacks and Nigerians.

Angiotensinogen (AGT) and angiotensin I-converting enzyme (ACE) are heritable traits, but whether the environmental context influences heritability has not been examined. Known genetic factors explain only a portion of variation in AGT and ACE, and levels of both proteins are influenced by the environment. The African diaspora provides an opportunity to compare these traits in genetically related populations in contrasting environments. As part of a study of the genetics of hypertension, we examined families that included 1449 Nigerians and 1147 African Americans. Body mass index (weight [kg]/height [m](2)) was 21 kg/m(2) in Nigeria and 29 kg/m(2) in the United States, which is consistent with a large environmental contrast. AGT was considerably higher among African Americans (1919 versus 1396, P<0.01), whereas ACE was higher in Nigerians (630 versus 517, P<0.01). A household effect was observed among the Nigerian families (spouse correlations 0.30 for AGT, 0.18 for ACE), and correlations among first-degree relatives were large (0.42 to 0. 51 and 0.36 to 0.38 for AGT and ACE, respectively). Among African Americans, the familial aggregations of AGT and ACE were very limited, and the familial correlation for AGT was not different from zero. Heritability was 77% for AGT and 67% for ACE in Nigeria and 18% for AGT and ACE in the United States. The familial patterns of body mass index and blood pressure were similar among both family sets. In conclusion, less familial aggregation was observed for AGT and ACE in the United States than in Nigeria, most likely reflecting a greater random individual environmental effect on these traits. Variation in heritability of traits could influence the power of epidemiological studies to identify genetic effects.

Adult↗
PubMed2000

Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma.

Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but in contrast to asthma there is no variable airflow obstruction or airway hyperresponsiveness. Our hypothesis was that the differences in airway pathophysiology maybe due to less active airway inflammation in eosinophilic bronchitis, with reduced release of important effector mediators. We measured the concentration of various proinflammatory mediators in induced sputum cell-free supernatant in eight patients with eosinophilic bronchitis, 17 patients with asthma matched for sputum eosinophil count, and 10 normal subjects. Cysteinyl-leukotrienes (cys-LT) were measured by enzyme immunoassay, eosinophilic cationic protein (ECP) by fluoroimmunoassay, prostanoids (PGE(2), PGD(2), TXB(2), and PGF(2alpha)) by gas chromatography-negative ion chemical ionization-mass spectroscopy, and histamine by radioenzymic assay. The geometric mean sputum eosinophil count was similar in asthma (13.4%) and eosinophilic bronchitis (12.5%). Sputum cys-LT and ECP were a mean (95% CI) 1.6-fold (1.1, 2.5) and 6.4-fold (1.4, 28) higher in eosinophilic bronchitis and 1.9-fold (1.3, 2.9) and 7.7-fold (1.2, 46) higher in asthma compared with that in control subjects (geometric mean, 5.9 and 95 ng/ml, respectively). In eosinophilic bronchitis the mean concentration of sputum PGD(2) (0.79 ng/ml) and histamine (168 ng/ml) were significantly higher than in asthma (mean absolute difference in PGD(2) concentration, 0.47 ng/ml [95% CI, 0.19 to 0. 74] and mean-fold difference in histamine concentration, 6.7 [95% CI 1.7 to 26]) and normal subjects (0.64 ng/ml [0.36 to 0.90] and 11-fold [3.3 to 36]), respectively. In conclusion, eosinophilic bronchitis is associated with active airway inflammation with increased release of vasoactive and bronchoconstrictor mediators.

Adult↗
PubMed2000

Analysis of diffusion changes in posttraumatic bone marrow using navigator-corrected diffusion gradients.

OBJECTIVE: This study was undertaken to analyze diffusion characteristics of normal and posttraumatic bone marrow. MATERIALS AND METHODS: Fifty consecutive patients with knee pain underwent both conventional and diffusion-weighted MR imaging (b values, 0-980 sec/mm2). Diffusion maps derived from source data were analyzed on a workstation using region-of-interest techniques. Apparent diffusion values recorded in normal marrow were compared with values recorded in abnormal posttraumatic bone marrow (square centimeters per second). RESULTS: Normal bone marrow identified in 35 patients showed minimal diffusion, with a mean value of 0.15x10(-5) cm2/sec. Bone marrow in 15 patients sustaining direct traumatic injury (21 bone bruises) showed markedly increased diffusion, with a mean value of 0.8x10(-5) cm2/sec (range, 0.4-1.3 cm2/sec). CONCLUSION: Marrow injury after trauma with trabecular damage allows increased movement or diffusion of interstitial water relative to normal marrow. The magnitude of diffusion change appears to reflect the severity of marrow injury.

Adult↗
PubMed1999

Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program: OPALS study phase II. Ontario Prehospital Advanced Life Support.

CONTEXT: Survival rates for out-of-hospital cardiac arrest are low; published survival rates in Ontario are only 2.5%. This study represents phase II of the Ontario Prehospital Advanced Life Support (OPALS) study, which is designed to systematically evaluate the effectiveness and efficiency of various prehospital interventions for patients with cardiac arrest, trauma, and critical illnesses. OBJECTIVE: To assess the impact on out-of-hospital cardiac arrest survival of the implementation of a rapid defibrillation program in a large multicenter emergency medical services (EMS) system with existing basic life support and defibrillation (BLS-D) level of care. DESIGN: Controlled clinical trial comparing survival for 36 months before (phase I) and 12 months after (phase II) system optimization. SETTING: Nineteen urban and suburban Ontario communities (populations ranging from 16 000 to 750 000 [total, 2.7 million]). PATIENTS: All patients who had out-of-hospital cardiac arrest in the study communities for whom resuscitation was attempted by emergency responders. INTERVENTIONS: Study communities optimized their EMS systems to achieve the target response interval from when a call was received until a vehicle stopped with a defibrillator of 8 minutes or less for 90% of cardiac arrest cases. Working both locally and provincially, communities implemented multiple measures, including defibrillation by firefighters, base paging, tiered response agreements with fire departments, continuous quality improvement for response intervals, and province-wide revision and implementation of standard dispatch policies. All response times were obtained from a central dispatch system. MAIN OUTCOME MEASURE: Survival to hospital discharge. RESULTS: The 4690 cardiac arrest patients studied in phase I and the 1641 in phase II were similar for all clinical and demographic characteristics, including age, sex, witnessed status, rhythm, and receipt of bystander cardiopulmonary resuscitation. The proportion of cases meeting the 8-minute response criterion improved (76.7% vs 92.5%; P<.001) as did most median response intervals. Overall survival to hospital discharge for all rhythm groups combined improved from 3.9% to 5.2 % (P = .03). The 33% relative increase in survival represents an additional 21 lives saved each year in the study communities (approximately 1 life per 120000 residents). The charges were estimated to be US $46900 per life saved for establishing the rapid defibrillation program and US $2400 per life saved annually for maintaining the program. CONCLUSION: An inexpensive, multifaceted system optimization approach to rapid defibrillation can lead to significant improvements in survival after cardiac arrest in a large BLS-D EMS system.

Aged↗
PubMed1999

Retinal projections in two crocodilian species, Caiman crocodilus and Crocodylus niloticus.

The retinal projections of Caiman crocodilus and Crocodylus niloticus were investigated by means of the orthograde axonal transport of either rhodamine beta-isothiocyanate or tritiated proline. In these two species, each tracer revealed contralateral retinal projections to three hypothalamic regions (subventricular gray matter, nucleus suprachiasmaticus, and area optica hypothalami lateralis), five thalamic regions (nuclei ovalis, dorsolateralis anterior, ventrolateralis and ventrobasalis, and lateral geniculate complex, of which six subcomponents can be distinguished), six pretectal regions (nuclei posterodorsalis, lentiformis mesencephali, griseus tectalis, geniculatus pretectalis, area optica commissurae posterior and area optica pretectalis lateroventralis), six outermost layers of the optic tectum, and the nucleus opticus tegmenti. Weak ipsilateral retinal projections have been observed in two hypothalamic nuclei and in the nucleus opticus tegmenti. Comparative analysis with other data show that the contralateral retinal projections of crocodiles are considerably more reptilian than avian. Moreover, crocodiles share with birds an extremely poor contingent of ipsilateral retinal projections.

Alligators and Crocodiles↗
PubMed1999

The Ontario Prehospital Advanced Life Support (OPALS) study Part II: Rationale and methodology for trauma and respiratory distress patients. OPALS Study Group.

The Ontario Prehospital Advanced Life Support (OPALS) Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period (1994-2002). The current article, Part II, describes in detail the rationale and methodology for major trauma and respiratory distress patients and for an economic evaluation of Advanced Life Support (ALS) programs in the OPALS Study. The OPALS Study, using a rigorous controlled methodology and a large sample size, should clearly indicate the benefit in trauma and respiratory distress patient survival and morbidity that results from the widespread introduction of prehospital ALS programs to communities of many different sizes. [Stiell IG, Wells GA, Spaite DW, Nichol G, O'Brien B, Munkley DP, Field BJ, Lyver MB, Luinstra LG, Dagnone E, Campeau T, Ward R, Anderson S, for the OPALS Study Group: The Ontario Prehospital Advanced Life Support (OPALS) Study Part II: Rationale and methodology for trauma and respiratory distress patients.

Emergency Medical Services↗