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Biomedical subjects

C Doré

Publications and source records attributed to C Doré.

At least 19 recordsLinked to original sources
PubMed2003

High EPDS scores in women from ethnic minorities living in London.

BACKGROUND: The aim of this study was to determine whether women from ethnic minorities and/or birth in a non-English speaking country were at increased risk for postnatal depression. METHOD: The Edinburgh Postnatal Depression Scale (EPDS) was used to screen a sample of 830 primiparous women 4 weeks after delivery. Ethnicity data was available on 743, and from these, 530 responses were received (71.3%). RESULTS: Two independent variables were found to be significantly associated with high EPDS scores. These were being non White (especially Asian; adjusted Odds Ratio 2.7, 95% CI 1.3-5.8) and being born in a non-English speaking country (Odds Ratio 1.9; 95% CI 1.0-3.5). LIMITATIONS: The study was conducted using self rating questionnaires. There was only a 71% response overall, and a 50% response rate among the ethnic minority group. CONCLUSIONS: Women from ethnic minorities or from a non-English speaking background should be regarded at high risk group for postnatal depression.

Adolescent↗
PubMed2003

G-CSF and GM-CSF for treating or preventing neonatal infections.

BACKGROUND: The colony stimulating factors (CSFs), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF), are naturally occurring cytokines that stimulate the production and antibacterial function of neutrophils and monocytes. Two strategies have been adopted for exploring whether CSFs can provide clinical benefit for preterm infants. The first has investigated their use as a treatment to improve outcome in established systemic infection, especially when complicated by a low neutrophil count. The alternative strategy has been to use CSFs prophylactically, to prevent sepsis prospectively through stimulation of neutrophil production and bactericidal function. OBJECTIVES: To determine the efficacy and safety of the haemopoietic colony stimulating factors (G-CSF or GM-CSF) in newborn infants, when used for:a) treatment of suspected or proven systemic infection to reduce mortality, orb) prophylaxis, to prevent systemic infection in infants at high risk of nosocomial infection. To determine, in subgroup analysis, the influence of pre-existing or high risk of neutropenia on the outcome of therapy. SEARCH STRATEGY: PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) were searched in April 2003 using the keywords: G-CSF, GM-CSF, infant newborn, with and without the limit Clinical Trial. In addition, reference lists of identified RCTs, meta-analyses and personal files were searched. SELECTION CRITERIA: The criteria used to select studies for inclusion were: DESIGN: RCT. SUBJECTS: Newborn infants in intensive care. INTERVENTIONS: G-CSF or GM-CSF given as treatment in conjunction with antibiotics for suspected or microbiologically proven systemic infection. G-CSF or GM-CSF given as prophylaxis with the aim of reducing the incidence of systemic infection. OUTCOMES: Treatment studies reporting all cause mortality. Prophylaxis studies reporting subsequent incidence of sepsis and / or mortality. DATA COLLECTION AND ANALYSIS: Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) using the fixed effect model are reported. Number needed to treat (NNT) was calculated for the outcomes that showed a statistically significant reduction in RR. MAIN RESULTS: Seven treatment studies of 257 infants with suspected systemic bacterial infection and three prophylaxis studies comprising 359 neonates are analysed. Treatment studies: There is no evidence that the addition of G-CSF or GM-CSF to antibiotic therapy in preterm infants with suspected systemic infection reduces immediate all cause mortality. No significant survival advantage was seen at 14 days from the start of therapy [typical RR 0.71 (95% CI 0.38,1.33); typical RD -0.05 (95% CI -0.14, 0.04)]. However all seven of the treatment studies were small, the largest recruiting only 60 infants. The subgroup analysis of 97 infants from three treatment studies who, in addition to systemic infection, had clinically significant neutropenia (< 1.7 x 10(9)/l) at trial entry, does show a significant reduction in mortality by day 14 [RR 0.34 (95% CI 0.12, 0.92); RD -0.18 (95% CI -0.33, -0.03); NNT 6 (95% CI 3-33)]. Prophylaxis studies have not demonstrated a significant reduction in mortality in neonates receiving GM-CSF [RR 0.59 (95% CI 0.24,1.44); RD -0.03 (95% CI -0.08,0.02)]. The identification of sepsis as the primary outcome of prophylaxis studies has been hampered by inadequately stringent definitions of systemic infection. However, data from one study suggest that prophylactic GM-CSF may provide protection against infection when given to preterm infants who are neutropenic or at high risk of developing postnatal neutropenia. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to support the introduction of either G-CSF or GM-CSF into neonatal practice, either as treatment of established systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates. No toxicity of CSF use was reported in any systemic infection to reduce resulting mortality, or as prophylaxis to prevent systemic infection in high risk neonates. No toxicity of CSF use was reported in any study included in this review. The limited data suggesting that CSF treatment may reduce mortality when systemic infection is accompanied by severe neutropenia should be investigated further in adequately powered trials which recruit sufficient infants infected with organisms associated with a significant mortality risk.

Anti-Bacterial Agents↗
PubMed2001

Effects of different concentrations of sevoflurane and desflurane on subcortical somatosensory evoked responses in anaesthetized, non-stimulated patients.

Twenty-four patients were recruited and given either sevoflurane or desflurane as their sole anaesthetic. Each patient was given sequentially increasing or decreasing doses at 0.5 MAC intervals, and the median nerve somatosensory evoked response recorded after an equilibration at each concentration. The N20-P25 and P25-N35 amplitudes decreased with increasing agent concentration. However, for both agents the P15-N20 amplitude response was quadratic in shape. The peak inflection points were at 3.2% for sevoflurane and 4.9% for desflurane. There were no differences between the ascending and descending groups. This increase in activity in the midbrain at 'surgical' end-tidal anaesthetic concentrations suggests more complex neuroelectrical responses to anaesthesia than simple global suppression.

Adult↗
PubMed2000

Bioactive interleukin-8 is expressed in wounds and enhances wound healing.

BACKGROUND: Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing. MATERIALS AND METHODS: Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model. RESULTS: IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8. CONCLUSIONS: These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.

Animals↗
PubMed2000

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.

Amino Acid Sequence↗
PubMed2000

Experimental study of faecal continence and colostomy irrigation.

BACKGROUND: Colostomy irrigation is a useful method of achieving faecal continence in selected conditions, but remains largely underutilized because it is time consuming. This study investigated the effect of modifying irrigation technique (route, infusion regimen and pharmacological manipulation) on colonic emptying time in a porcine model. METHODS: An end-colostomy and caecostomy were fashioned in six pigs. Twenty markers were introduced into the caecum immediately before colonic irrigation. Irrigation route (antegrade or retrograde), infusion regimen (tap water, polyethylene glycol (PEG), 1.5 per cent glycine) and pharmacological agent (glyceryl trinitrate (GTN) 0.25 mg/kg, diltiazem 3.9 mg/kg, bisacodyl 0.25 mg/kg) were assigned to each animal at random. Colonic transit was assessed by quantifying cumulative expelled markers (CEM) and stool every hour for 12 h. RESULTS: Mean CEM at 6 h for bisacodyl, GTN and diltiazem were 18.17, 12.17 and zero respectively; all pairwise differences in means were significant (P < 0.001). The difference at 12 h between the two routes (P = 0.001) and three fluids (tap water 6.75, glycine 14.83, PEG 16.33; P < 0. 001) was significant, but not for PEG versus glycine and bisacodyl versus GTN. Cumulative output was significantly more with the antegrade than retrograde route using PEG, but the difference in mean cumulative output for bisacodyl and GTN at 12 h was not significant. CONCLUSION: Colonic emptying is more efficient with antegrade than retrograde irrigation. PEG and glycine enhance emptying similar to bisacodyl and GTN solution. These findings show promise for improved faecal continence by colostomy irrigation and may justify construction of a Malone conduit at the time of colostomy in selected patients who wish to irrigate. Presented in part to the British Society of Gastroenterology in Glasgow, UK, March 1999, and published in abstract form as Gut 1999; 44(Suppl 1): A135

Analysis of Variance↗
PubMed2000

Enteral nutritional support and wound excision and closure do not prevent postburn hypermetabolism as measured by continuous metabolic monitoring.

BACKGROUND: Estimation of nutritional needs in burn patients is difficult. In 24 severely burned patients, we measured CO2 production and O2 consumption continuously during their period of mechanical ventilation. METHODS: Patients with extensive burns were placed on a continuous metabolic monitor (CMM) (Puritan Bennett Co., Kingwood, TX), and metabolic expenditure was recorded each 24 hours. High protein enteral feedings were started within several hours of admission, and administration rates were adjusted to meet daily caloric demands as determined by the CMM. Full-thickness wounds were excised as early as patient condition permitted, and wounds were closed with autograft, allograft, or TransCyte (Advanced Tissue Sciences Inc., La Jolla, CA). Daily 24-hour caloric needs as measured by CMM were compared with baseline caloric needs predicted by the Harris-Benedict equation and also compared with actual daily caloric intake. Patients were removed from study when they were off continuous mechanical ventilation. RESULTS: A total of 24 patients were studied, with a mean age of 46 years and a 44% total body burn size (partial- and full-thickness). All full-thickness burns were completely excised by a mean of 6.5 days postburn. Mean daily energy expenditures remained elevated through the duration of the study period (42 days), with a mean elevation of 184.9% of baseline as predicted by Harris-Benedict equation. Patients received enteral feedings, which met 99.4% of actual caloric needs as predicted by CMM during the study period. CONCLUSION: Continuous metabolic monitoring demonstrates that early wound excision and wound closure, coupled with aggressive enteral nutritional support with high protein formulas, do not prevent the marked hypermetabolism that accompanies thermal injury.

Burns↗
PubMed1999

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is a neurodegenerative disease frequent in northeastern Québec. In a previous study, we localized the disease gene to chromosome region 13q11 by identifying excess sharing of a marker allele in patients followed by linkage analysis and haplotyping. To create a detailed physical map of this region, we screened CEPH mega-YACs with 41 chromosome 13 sequence-tagged-sites (STSs) known to map to 13q11-q12. The YAC contig, composed of 27 clones, extends on the genetic map from D13S175 to D13S221, an estimated distance of at least 19.3 cM. A high-resolution BAC and PAC map that includes the ARSACS critical region flanked by D13S1275 and D13S292 was constructed. These YAC and BAC/PAC maps allowed the accurate placement of 29 genes and ESTs previously mapped to the proximal region of chromosome 13q. We confirmed the position of two candidate genes within the critical region and mapped the other 27 genes and ESTs to nearby intervals. Six BAC/PAC clones form a contig between D13S232 and D13S787 for sequencing within the ARSACS critical region.

Bacteriophage P1↗
PubMed1999

Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study.

Heparin plus aspirin significantly improves the live birth rate of women with primary antiphospholipid syndrome. Osteopenia is a major concern of long-term heparin therapy. We studied prospectively the bone mineral density (BMD) changes during pregnancy and the puerperium in 123 women with primary antiphospholipid syndrome treated with low-dose aspirin and subcutaneous low-dose heparin (46 women took unfractionated heparin and 77 took low-molecular-weight heparin). Lumbar spine, neck of femur and forearm BMD were measured, using dual energy X-ray absorptiometry, at 12 weeks gestation, immediately postpartum and 12 weeks postpartum. The mean heparin duration was 27 weeks (range 22-29). During pregnancy, BMD decreased by 3.7% (P < 0.001) at the lumbar spine and by 0.9% (P < 0.05) at the neck of femur with no significant change at the forearm. Lactation was associated with a significant decrease in the lumbar spine and neck of femur BMD. There was no significant difference in BMD changes between the two heparin preparations. No woman suffered a symptomatic fracture. Long-term heparin treatment during pregnancy is associated with a small but significant decrease in BMD at the lumbar spine and neck of femur. This decrease is similar to that previously reported to occur in untreated pregnancies.

Absorptiometry, Photon↗
PubMed1997

Role of melanoma growth stimulatory activity (MGSA/gro) on keratinocyte function in wound healing.

Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha-chemokine family, is produced by a variety of dermal and epidermal cells and can act in a paracrine and autocrine fashion. However, little is known about the importance of MGSA in wound healing. In this study, we quantified the levels of MGSA protein in burn blister and donor site wound fluids. We studied the effects of MGSA on proliferation and migration of primary human keratinocytes and modulation of their integrin expression. Blister fluids contained 0.79 ng/ml (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were found in donor site fluids from day 1 through day 5 with mean levels ranging from 1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA production. In vitro proliferation experiments revealed a maximum stimulation (2.6-fold) with 10 ng/ ml MGSA for 7 days over unstimulated keratinocyte controls; the ED50 was 0.2 ng/ml. DNA content analysis revealed an increase in S phase with 10 ng/ml MGSA stimulation. In cultured keratinocytes, MGSA enhanced the mean fluorescence intensity for alpha 6, while no significant change was seen for beta 1, alpha 2 and alpha 5. We also studied the effect of topically applied MGSA (50 ng/cm2) on the healing of meshed split-thickness human skin grafts on athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P < 0.05) at day 7, and an increased proportion of mitotic keratinocytes was observed. Wound contraction was significantly (P < 0.05) reduced on days 7 and 14 in the MGSA-treated group. These results suggest that MGSA participates in wound healing by stimulating keratinocyte proliferation.

Animals↗
PubMed1997

Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats.

Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosome 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.

Animals↗
PubMed1997

Stereological estimation of blood vessel surface and volume densities in human normal and rhinitic nasal mucosa.

A technique is proposed for applying well-established stereological methods to study fixed nasal biopsy material to obtain an unbiased estimate of blood vessel surface and volume densities. Biopsies of the nasal mucosa from the anterior 10 mm of an inferior turbinate were obtained from 18 subjects (15 males, 3 females with a mean age of 28.5 years [range: 17-54 years]), ten of whom had perennial allergic rhinitis, and eight control subjects. The mucosal tissue volumes were estimated by water displacement. Zamboni's-fixed cryostat sections (10 microns thick), stained with haematoxylin and eosin, were examined histologically. Computerised images of randomly selected tissue sections were analysed with point-counting and intercept-counting techniques to determine large blood vessel volume and surface densities, respectively. There were no significant differences between the volumes of tissue analysed from the control and rhinitic subjects (p = 0.35). The average volume density of the vessels was similar in the control group (6.17 +/- 1.41%) and the rhinitic group (7.8 +/- 5.59%; p = 0.38), but with a greater variability in the rhinitic group. Surface density estimations were 3.14 +/- 0.74 mm-1 in the control group and 3.10 +/- 1.41 mm-1 in the rhinitic group. Therefore, on average, the volume and surface densities of the cavernous blood vessels in rhinitis were unaltered and there was no evidence of vascular remodelling.

Adolescent↗
PubMed1997

[Prescription of stimulants for hyperactive children: a pilot study of incentives and constraints on parents, teachers and physicians].

The scientific consensus on the use of stimulants to treat "hyperactive" or ADHD-diagnosed children amounts to recognizing a calming effect on children's disruptive behavior and better performance of repetitive tasks, both in the short-term. Long-term effects remain unknown. Still, in Québec, prescription of stimulants to children of welfare recipients nearly tripled between 1990 and 1994, reaching a prevalence of 11.9%. Using a systemic model integrating three approaches (medicalization of deviance, political economy, and strategic analysis), we conceptualized the decision to prescribe as the result of interactions involving different actors holding unequal power and seeking to further their interests. We attempted to establish the defendability of this model by means of in-depth interviews with five parents, four primary school teachers and three physicians in prolonged contact with a hyperactive child receiving stimulant medication. Data from the interviews reveal the omnipresence of the medical model in the hyperactivity treatment system, although teachers rather than physicians appear as the engine of this medicalization. According to parents and physicians, teachers identify and "diagnose" children, propose the use of medication to parents and, in some cases, the school requires that doctors write a prescription. Doctors admit that medical evaluation of referred children is often inadequate. For their part, teachers stress the growing difficulties of their task and the lack of psychosocial supports in the schools. Our respondents' comments highlight the divergent interests of the actors involved as well as each actor's own perception that he or she wishes to act differently but lacks any real choice other than opting for medication. These limited observations should be validated in further studies. They suggest that the current system functions irrationally and that we should not expect it to act in the best interests of children.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Urinary phenylethylamine and cortisol levels in the early puerperium.

Phenylethylamine and cortisol were measured in 24-h urine samples taken from women day 2/3 postpartum, and matched controls. They also completed self-rating blues and highs scales. There was no significant difference in phenylethylamine excretion in those who scored highly with blues or highs, and either postpartum or normal controls. The number of raised values for phenylethylamine output was significantly greater in the postpartum women, who had no psychopathology, than in normal controls. Cortisol levels were significantly raised in postpartum controls compared with normal controls; women with the highs excreted significantly less cortisol than other postpartum women.

Adolescent↗
PubMed1996

Spontaneous movement after injection of propofol.

Spontaneous movement following injection of propofol at induction was studied in 303 patients. Two hundred patients were Caucasians and 103 were Asians. In a pilot study carried out prior to the main study, 26% of the Asians moved at induction as compared with 6% of the Caucasians. The patients were studied in relation to a number of variables; age, sex, weight, height, race, smoker/non smoker, vegetarian/non vegetarian, alcohol consumption, premedication, use of fentanyl at induction and dose of propofol. When race was included as the sole variable there was a marginal but not significant difference between the two groups in terms of movement (p = 0.06). However, when the other recorded variables were taken into account, race was not included as a predictor of whether or not the patient moved. The best model for predicting whether the patients moved or not combines the variables weight and dose of propofol. Patients were more likely to move if they were lighter and the dose of propofol used at induction was higher.

Adult↗
PubMed1995

Variation of aortic blood velocity with age at rest and during exercise in normal subjects.

The effect of age on aortic blood velocity signal and its derived indices of left ventricular function namely peak velocity, stroke distance (the velocity-time integral) and minute distance (stroke distance x heart rate) was studied at rest and at maximal-tolerated supine exercise using a 2-mHz continuous-wave Doppler ultrasound applied via the suprasternal notch in 66 normal healthy volunteers. The peak velocity, stroke distance and the minute distance, both at rest and at maximal exercise decreased with advancing age by 1-1.1% per annum between the ages of 20 and 70 years. Accordingly a method for age-adjustment of the peak velocity, stroke and minute distances was introduced for clinical use in assessing individual subjects. These results indicate that age is an important variable affecting aortic blood velocity and its derived variables as non-invasive measures of left ventricular function both at rest and with exercise. The relationship with age is an important consideration when assessing individual subjects.

Adolescent↗
PubMed1995

Different muscle graft denaturing methods and their use for nerve repair.

In an attempt to enhance recovery through denatured muscle grafts we have used different methods to denature muscle, either using dry heat in a microwave oven or by warming in sterile distilled water. Axonal regeneration was studied at intervals from day 5 to day 60 after insertion of the muscle grafts and compared to results found in frozen-thawed muscle grafts and in autologous nerve grafts used as controls. Axonal regeneration, Schwann cell behaviour and the degree of inflammation were quantified using immunohistochemical techniques and computerised image analysis. Autologous nerve grafts supported the highest rates and volumes of axonal regeneration until day 30 when the microwaved muscle grafts had the highest values for axonal immunostaining and at 60 days the highest level of Schwann cell immunoreactivity. We conclude that microwave heating is suitable as an alternative denaturing method for successful muscle grafts and has a potential clinical use.

Animals↗