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Biomedical subjects

M Edwards

Publications and source records attributed to M Edwards.

At least 37 records · Page 2Linked to original sources
PubMed2001

Orphan receptor promiscuity in the induction of cytochromes p450 by xenobiotics.

The mechanisms by which different classes of chemicals induce the same cytochrome P450 (CYP) or the same chemical differentially induces more than one CYP are not well understood. We show that in primary hepatocytes and in vivo in liver (transfected by particle-mediated delivery) two orphan nuclear receptors, constitutive androstane receptor and pregnane X receptor (PXR1), transactivate a CYP gene via the same response element in a xenobiotic-specific manner. The constitutive androstane receptor mediates the barbiturate activation of expression of CYP2B1 and CYP3A1. PXR1 activates both genes in response to synthetic steroids. To exert their effect the receptors bind to the same direct repeat site (DR4) within the phenobarbital response element of the CYP2B1 promoter and to the same DR3 site in the pregnane X response element of CYP3A1. The receptors are therefore promiscuous with respect to DNA binding but not ligand binding. Differences in enhancer half-site spacing may influence the efficiency of interactions between the receptor and the transcription machinery and hence form the basis for the differential induction of CYP2B1 and CYP3A1 in response to barbiturates and synthetic steroids.

Animals↗
PubMed2001

Preoperative intraaortic balloon pumps in high-risk patients undergoing open heart surgery.

BACKGROUND: The use of the preoperative intraaortic balloon pump (IABP) in patients with severe left ventricular dysfunction or unstable angina with critical coronary anatomy is becoming more frequent as surgical casemix changes. The aim of this study was to determine the impact of preoperative IABP use on survival in high-risk patients having open heart surgery. METHODS: Prospectively collected data for 645 consecutive patients were reviewed. Patients receiving an IABP were identified and grouped as follows: group A (preoperative IABP for high-risk nonemergent cases), group B (preoperative IABP for emergent cases), and group C (intra/postoperative IABP). Risk-adjusted hospital mortality rates in these three groups was compared using the modified Parsonnet score for preoperative risk stratification. RESULTS: IABPs were used in 101 cases (16%). The predicted versus actual hospital mortality rate was 20% versus 5.7% in group A, 32.1% versus 47.6% in group B, and 12.6% versus 22.2% in group C (group A vs group B, p = 0.0014; group A vs group C, p = 0.012). IABP-related morbidity occurred in 3% of cases (all in group C). CONCLUSIONS: Risk-adjusted mortality was significantly lower in high-risk cases with preoperative IABPs compared with emergent cases and intraoperative/postoperative IABPs. We encourage the use of preoperative IABPs in selected high-risk patients.

Aged↗
PubMed2001

The structure of symptom report in asthma: a reevaluation.

OBJECTIVES: We studied the structure of symptom report in a sample of British asthma patients using the Asthma Symptom Checklist (ASC). METHODS: The ASC was administered to 193 patients, together with a questionnaire on demographics and asthma-related information and the Perceived Control of Asthma Questionnaire. RESULTS: Principal Component Analysis yielded evidence for a six-dimensional structure of the ASC, with positively correlated subscales for panic-fear, irritation, obstruction-dyspnea, obstruction-congestion, fatigue, and hyperventilation symptoms. Individual subscales showed good to excellent item characteristics and internal consistencies in individual subscales. Panic-fear and obstruction-congestion were related to self-reported duration of oral corticosteroid intake. Other ASC subscales were positively related to aspects of health care utilization, limitations in daily activity, and lower perceived control of asthma mainly in women. The dyspnea subscale of the ASC showed only little relationship with either of these variables. CONCLUSION: The ASC can reliably assess the multidimensional structure of asthma symptom report. Its subscales are associated with important aspects of asthma management behavior.

Administration, Oral↗
PubMed2001

Envelope size-tuning for transient disparity vergence.

Our prior studies have demonstrated that the transient-vergence system responds preferably to dichoptic stimulus pairs that contain the highest combined energy, regardless of dichoptic differences in spatial frequency, contrast, orientation, or luminance polarity (Edwards, M., Pope, D. R., & Schor, C. M. (1998), Vision Research 38, 705; Pope, D. R., Edwards, M., & Schor, C. M. (1999) Vision Research 39, 575). This broadband tuning for spatial frequency, orientation and contrast is indicative of a second order (non-linear) extraction system. The current study examined the potential size-tuning of binocular channels to the contrast envelope that is extracted by a non-linear process. Stimuli were size-scaled Gabor patches with parallel and orthogonal carrier orientations that subtended a large (3.8 degrees ) disparity. Results indicate that the transient-vergence system exhibits broad band-pass tuning to overall size of dichoptic targets, independent of interocular differences in carrier orientation, spatial frequency or contrast. Equal sizes elicited a higher proportion of vergence responses than unequal sizes, however responses to unequal size still occurred over a 2-octave range, illustrating broad band-pass tuning. Size tuning was found to be broader for small than large envelope sizes. The broad tuning for envelope size is likely to result from the overlapping extracted low-pass frequency spectra of the contrast envelopes. However, the transient-vergence system also responds to monocular, hemi-retinal stimuli over a larger (3-octave) range. Thus some of the observed "binocular tuning" may be due to these monocular responses.

Adult↗
PubMed2001

Envelope size tuning for stereo-depth perception of small and large disparities.

Stereopsis is the sense of depth derived from binocular disparities that are formed between targets that are matched between the two retinal images. Binocular matches for sustained stereopsis are based on similarity of orientation, spatial frequency and contrast of the two retinal images whereas matches for transient stereopsis depend on these parameters to a very limited extent. In this investigation we have tested the possibility that transient stereopsis forms matches between objects of similar overall size. The tuning of sustained and transient stereopsis to contrast-envelope size was investigated by presenting narrow-band Gabor targets of unequal size to the two eyes. Bandwidth for envelope-size tuning was estimated from the range of dichoptic size-differences over which stereo performance remained above chance level. An equal bandwidth of 2 octaves was found for the sustained and transient stereo systems when stimulated with parallel orientation Gabors that subtended a small disparity. Sustained-stereo performance with orthogonal carriers was reduced with large envelope sizes. Bandwidth of the transient stereo system increased to 3 octaves when tested with a larger disparity stimulus and it was independent of carrier orientation. Reducing the contrast of the larger-size Gabor improved transient-stereo performance from near chance (48-58%) to 85-95%. Thus the bandwidth for envelope-size tuning is much broader than indicated with equal physical contrast stimuli. The observed tuning to envelope size, while broad, is tighter than that observed for carrier spatial-frequency [Vis. Res. 38 (1998) 3057], carrier orientation [Vis. Res. 39 (1999) 2717] and contrast polarity [Vis. Res. 39 (1999) 4010] of the stimulus. Thus it would appear that envelope size and, to a greater extent, temporal synchrony of the dichoptic stimuli [Perception 24 (1995) 33] are the primary means for selecting matched binocular inputs for transient stereopsis.

Contrast Sensitivity↗
PubMed2001

Spatial interactions minimize relative disparity between adjacent surfaces.

Computational models of stereopsis employ a number of algorithms that constrain stereo matches to produce the smallest absolute disparity and to minimize the relative disparity between nearby features. In some natural scenes, such as large slanted textured surfaces, these two constraints lead to different matching solutions. The current study utilized a stimulus in which there was a large discrepancy in both the magnitude and direction of matches that solved for minimum absolute and minimum relative disparity. This discrepancy revealed a dominance for the minimum relative disparity over the minimum absolute disparity matching solution that increased with spatial proximity, spatial frequency and width of adjacent features. The likelihood of a minimum-relative-disparity matching solution also increased when the difference between the amplitudes of the alternative relative disparities was large. When alternative relative disparity matching solutions had similar amplitudes but opposite signs (crossed vs. uncrossed), an idiosyncratic depth bias served as a tie-breaker. The present results show that absolute disparity matches are constrained to minimize relative disparity between adjacent features.

Depth Perception↗
PubMed2001

Role of temperature, chlorine, and organic matter in copper corrosion by-product release in soft water.

Soft, low alkalinity drinking waters tend to cause relatively high copper corrosion by-product release in plumbing systems. Long-term tests (6-8 months) in a synthetic, microbially stable soft tap water confirmed that lower pHs and higher temperatures increased copper release to water. Soluble copper release increased at lower temperature and lower pH. Low levels of free chlorine (0.7 mg/L) slightly increased copper release at pH 9.5, in marked contrast to the dramatic reductions in copper release that have been observed in soft waters in which Type III pitting corrosion is occurring. Gum xanthan and sodium alginate produced a microbially unstable water that reduced the pH and DO during stagnation in pipes--these indirect effects far outweighed their possible role in chelation or other modes of direct attack on copper surfaces.

Chlorine↗
PubMed2001

Pregnancy outcomes after laparoscopic myomectomy with ultrasonic energy and laparoscopic suturing of the endometrial cavity.

STUDY OBJECTIVE: To evaluate pregnancy outcomes in women with laparoscopic removal of myomas that resulted in entry into the endometrial cavity and required laparoscopic repair of the endometrial cavity. DESIGN: Retrospective chart review (Canadian Task Force classification II-2). SETTING; Private obstetrics-gynecology practice and departments of obstetrics and gynecology at two university-affiliated hospitals. PATIENTS: Seven women with symptomatic uterine leiomyomata treated by laparoscopic myomectomy, who achieved pregnancy. INTERVENTION: Laparoscopic dissection of myomas with the ultrasonic scalpel and laparoscopic suturing of the uterus with the Endo Stitch device in three layers. MEASUREMENTS AND MAIN RESULTS: Indications for laparoscopic myomectomies were excessive bleeding and significant growth of uterine myomas. The size of myomas in all patients ranged from 12 to 2 cm. Average operating time was 232.8 minutes and average blood loss was 117.8 ml. The largest number of myomas removed from a single patient was nine. All procedures were performed on an outpatient basis and no complications occurred. All women easily achieved pregnancy and four were delivered at or near term by cesarean section. One delivered vaginally at 28 weeks secondary to uncontrolled premature labor, without uterine dehiscence. Two had elective terminations at 8 weeks. CONCLUSION: Laparoscopic suturing of the endometrial cavity in three layers does not prevent future pregnancies, and pregnancies can progress to term and in some cases be delivered vaginally without dehiscence. (J Am Assoc Gynecol Laparosc 8(1):129-136, 2001)

Adult↗
PubMed2001

Laparoscopic myomectomy after failure of uterine artery embolization.

A patient experienced continuing pain and growth of a broad-based pedunculated myoma 6 months after uterine artery embolization (UAE). A 7-cm myoma was found growing directly from the serosa of the fallopian tube and was removed laparoscopically. To our knowledge, this is the first report of laparoscopic myomectomy performed after failure of UAE. This case identifies one of the predictable limitations of UAE of which gynecologists must be cognizant when recommending the procedure.

Embolization, Therapeutic↗
PubMed2001

Programmed cell death in human acute cutaneous wounds.

Resolution of the inflammatory response in acute cutaneous wounds is critical to healing and delays in this process may lead to impaired wound maturation and closure. Apoptotic cells were identified by histological examination of tissue sections and by in situ TdT-mediated dUTP end-labelling of DNA fragments. Apoptotic cells were detected in the dermal inflammatory infiltrate at the wound margins and in the granulation tissue of 7-day healing wounds. In 42-day healing wounds a large proportion of the apoptotic cells were localised to the mature granulation tissue and to the dermal inflammatory infiltrate under the newly closed epidermis. Apoptotic cells were not detected in the epidermis of 7-day and 42-day healing wounds. The percentage of apoptotic cells to the total number of cells in the dermal inflammatory infiltrate of 7-day wounds was 30.5% (26-35%) and 60.7% (range 56-67%) in 42-day healing wounds. The existence of an overall relationship between the numbers of apoptotic cells in the 7-day and 42-day healing wounds was determined using the Spearman's rank correlation coefficient. Taking all the samples into consideration, apoptosis in 7-day wounds was not found to be related (r=0.123, p=0.050) to apoptosis in the 42-day healing wounds. This study demonstrates that programmed cell death or apoptosis is responsible for the elimination of the dermal inflammatory infiltrate from healing human cutaneous acute wounds.

Acute Disease↗
PubMed2001

Combined strabismus and phacoemulsification cataract surgery: a useful option in selected patients.

PURPOSE: To evaluate the role of combined strabismus and phacoemulsification cataract extraction in patients with symptomatic cataract and strabismus. METHODS: Four procedures of combined strabismus and cataract surgery are described in 3 elderly patients with strabismus of differing aetiologies. Two patients underwent one procedure; the other patient underwent two combined procedures, one to each eye. RESULTS: The visual acuity improved in all 3 patients. Post-operative alignment of the visual axis was achieved which allowed resolution of symptomatic diplopia in patient 1, functional binocular single vision in patient 2 and a noticeably reduced compensatory head posture in patient 3. CONCLUSIONS: Combined strabismus and cataract surgery is a safe procedure that can optimise visual alignment and improve visual acuity with a minimum number of operations.

Aged↗
PubMed2001

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3).

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine, commonly diagnosed as either ulcerative colitis (UC) or Crohn's disease (CD). Epidemiological studies have consistently shown that both genetic and environmental factors influence the pathogenesis of IBD. A number of genome scans have been conducted in cohorts of IBD families with affected sibling pairs (ASPs) to identify chromosomal regions that harbour IBD susceptibility genes. Several putative linked loci have been identified, including two loci on chromosomes 16 and 12, IBD1 and IBD2, which have subsequently been replicated by independent region-specific studies. We have conducted both a replication study on another linkage region, chromosome 6p (IBD3), and extension studies on two other regions, chromosomes 3p and 7q. Microsatellite markers across each region were genotyped in 284 IBD ASPs from 234 families. A nonparametric peak multipoint LOD score of 3.0 was observed near D6S291, replicating the previous linkage to chromosome 6p (IBD3). Nominal evidence of linkage was observed at both the 3p and 7q regions.

Chromosome Mapping↗
PubMed2001

Aedes aegypti transducing densovirus pathogenesis and expression in Aedes aegypti and Anopheles gambiae larvae.

Aedes aegypti densovirus (AeDNV) is a small DNA virus that has been developed into an expression and transducing vector for mosquitoes [Afanasiev et al. (1994) Exp Parasitol 79: 322-339; Afanasiev et al. (1999) Virology 257: 62-72; Carlson et al. (2000) Insect Transgenesis: Methods and Applications (Handler, A.M. & James, A.A., eds), pp. 139-159. CRC Press, Boca Raton]. Virions carrying a recombinant genome expressing the GFP gene were used to characterize the pathogenesis of the virus in 255 individual Aedes aegypti larvae. The anal papillae of the larvae were the primary site of infection confirming previous observations (Afanasiev etal., 1999; Allen-Muira et al. (1999) Virology 257: 54-61). GFP expression was observed in most cases to spread from the anal papillae to cells of the fat body, and subsequently to many other tissues including muscle fibers and nerves. Infected anal papillae were also observed to shrink, or melanize and subsequently fall off in a virus dependent manner. Three to four day-old larvae were less susceptible to viral infection and, if infected, were more likely to survive into adulthood, with 14% of them still expressing GFP as adults. Higher salt concentrations of 0.10-0.15 M inhibited viral infection. Anopheles gambiae larvae also showed infection of the anal papillae (17%) but subsequent viral dissemination did not occur. The persistence of the reporter gene expression into adulthood of Aedes aegypti indicates that transduction of mosquito larvae with recombinant AeDNV may be a means of introducing a gene of interest into a mosquito population for transient expression.

Aedes↗
PubMed2001

Imaging posterior polymorphous corneal dystrophy by in vivo confocal microscopy.

To identify features of posterior polymorphous dystrophy (PPMD) by in vivo confocal microscopy, the corneas of a female patient with PPMD were exam ned using slit-lamp biomicroscopy and slit-scanning in vivo confocal microscopy. Characteristic endothelial vesicular and band lesions were seen clinically and easily identified using in vivo confocal microscopy. However endothelial pleomorphism, an increased density and reflectance of posterior stromal keratocytes, and prominence of corneal nerves were also delineated. In vivo confocal microscopy enhances clinicopathological diagnosis and follow up of corneal dystrophies with subtle clinical presentations, such as PPMD.

Corneal Dystrophies, Hereditary↗
PubMed2001

The genetics of keratoconus.

Keratoconus is a relatively common, bilateral, non-inflammatory corneal ectasia. The aetiology of this condition is probably multifactorial, or it represents the final common pathway for a variety of different pathological processes. Although a familial history is present only in a minority of cases, one of the major aetiological factors is certainly genetic. This is evidenced by: the condition's familial inheritance; its discordance between monozygotic and dizygotic twins; and its association with other known genetic disorders such as Down's and Marfan's syndromes. In the keratoconic cornea, a possible genetic predisposition to increased sensitivity to apoptotic mediators by keratocytes has also been hypothesized. Differences in prevalence between ethnic groups have been identified. Recent advances in computerized topographic diagnostic techniques for keratoconus, including forme fruste keratoconus, enables higher accuracy in delineating abnormal from normal, and helps define study populations for genetic linkage studies. However, genetic heterogeneity and the phenotypic diversity of keratoconus means that genetic analysis continues to be a complex process. None the less, it is foreseeable that over the next decade, improved diagnostic techniques, in combination with molecular genetics, may reveal conclusive data on the precise nature of the genetic inheritance of keratoconus in specific populations. This review considers the evidence that suggests keratoconus is primarily an inherited condition, and examines research strategies aimed at unveiling the genetic predisposition, and the enigma of environmental influences on its phenotypic expression.

Cornea↗
PubMed2001

Outcomes of decreased length of hospital stay among geriatric patients with dementia.

This study examined the outcomes associated with shortening hospital stays for geriatric inpatients with dementia at a Veterans Administration medical center. Thirty-three patients who were admitted after January 1997, when the hospital decided to reduce patients' lengths of stay, were matched with 33 patients who were admitted before January 1997. Despite significant differences in lengths of stay, no differences were found between the groups on measures of agitation or overall functioning. Despite significantly shorter stays since January 1997, the results of our study indicate that the cognitive and emotional status of patients discharged since that time are equivalent to those of patients discharged after longer hospital stays.

Aged↗