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Biomedical subjects

A Fortin

Publications and source records attributed to A Fortin.

At least 19 recordsLinked to original sources

[Reflection on one case of acute peritonitis due to adjustable gastric banding during pregnancy].

Improving the information delivered to pregnant women with adjustable gastric banding is desirable. Indeed, we report a case of peritonitis on gastric banding due to Klebsiella pneumoniae complicated with fetal death. Then, we discuss the specific risks of infection on the gastric band during pregnancy. Although, according to the literature, prophylactic fluid removal from the band in early pregnancy is not recommended, data about complications in pregnancy due to gastric banding are limited.

Acute Disease↗

[Neurological outcome of children from twin pregnancies].

The neurological outcome is an important issue regarding twin pregnancies. In fact, twin pregnancy is clearly associated with an important neurological morbidity, roughly 4 times higher than singleton pregnancy. It is possible to distinguish some high-risk situations, making it possible to calculate more accurately the individual risk. The different aetiologies are analysed: hypotrophy, prematurity, malformations, prenatal occurrence of anoxic and ischemic lesions, and particularly the link with monochorionicity. The neurological outcome is mainly depending on hypotrophy and prematurity. However, the rate of long-term neurological complications is not different between twins and singletons after adjustment for term and birth weight. An increased risk of malformation is associated with twin pregnancies, essentially a high rate of abnormal neural tube closing (RR=2). Monochorionic pregnancies have a specific morbidity, not related to these aetiologies, with characteristic anoxic and ischemic lesions. Cerebral palsy is observed in 10-20% of the monochorionic pregnancies, vs 3.7% of the bichorionic ones. These complications are linked to the constant vascular anastomoses, between the circulations of the two monochorionic twins. When the twin-to-twin transfusion syndrome is severe, a poor neurological outcome is observed in 4 to 18% of the surviving children. However, this rate depends on studies, treatments, and methods of neurological evaluation. The laser destruction of anastomoses could decrease this morbidity. The stillbirth rate, either associated or not with twin to twin transfusion syndrome, is increased by monochorionicity. The death of one of the twins is associated with a 20% higher risk of neurological sequelae for the surviving co-twin.

Congenital Abnormalities↗

[Endorectal sonography in gynecology: usefulness and diagnostic accuracy].

OBJECTIVE: The aim of this study was to assess feasibility and diagnostic accuracy of endorectal sonography (ERS) in comparison with transabdominal sonography (TAS) in women with a contraindication to endovaginal sonography (EVS). PATIENTS AND METHODS: ERS was proposed to 32 patients in the immediate continuation of TAS. It was performed either with a specific probe or with a vaginal probe. The protocol included a complete evaluation of pelvic structures observed with both sonographic techniques. RESULTS: After counselling and assent, 29 of the 32 patients (90%) accepted ERS. The examination was regarded as complete in 28 cases. ERS confirmed the absence of pelvic anomaly in the 12 cases of normal TAS. ERS modified diagnosis in 5 of the 8 cases of anechoic ovarian cysts seen in TAS. In 4 cases, PCOs not seen in TAS were identified. Two partially sub-mucous myomas not recognized by TAS were diagnosed by ERS. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TAS and ERS were 38,4 and 87,5%, 41,6 and 100%, 50 and 100%, 40 and 85,7% respectively. DISCUSSION AND CONCLUSION: These findings suggest ERS is an effective diagnostic tool in pelvic exploration when EVS cannot be performed. It should be widely proposed after information and assent.

Adolescent↗

Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model.

The recombinant congenic mouse strains AcB55 and AcB61 are extremely resistant to malaria (Plasmodium chabaudi AS) despite the presence of susceptibility alleles at the known Char1/Char2 resistance loci. Resistance in AcB55 and AcB61 is controlled by a locus on chromosome 3 (Char4) shown to be allelic with or tightly linked to a loss-of-function mutation in pyruvate kinase (Pklr). AcB55 and AcB61 show important splenomegaly prior to infection caused by the expansion of the red pulp, and display histological signs of extramedullary erythropoiesis in the liver. Examination of splenic cell populations by flow cytometry demonstrates elevated numbers of TER119-positive erythroid precursor cells (>30% of total spleen cells), while RNA expression studies show elevated expression of erythrocyte-specific transcripts such as globin, transferrin receptor, and Nramp2/Slc11a2 in the spleen of both strains. Hematological profiling in both strains is consistent with the presence of anemia as evidenced by low total erythrocyte counts, decreased hemoglobin, as well as abnormally high numbers of circulating reticulocytes (15-20%). These results strongly suggest that the mutant Pklr allele (Pklr(269A)) of AcB55/61 strains causes hemolytic anemia compensated by constitutive erythropoiesis, which in turn protects the mice against P. chabaudi infection. The possible molecular basis of the Pklr protective effect is discussed and is under current investigation in these two strains.

Anemia, Hemolytic↗

Stereoscopic processing in the human brain as a function of binocular luminance rivalry.

We investigated the neural substrates of a recent model of human stereodepth perception by obtaining measurements of regional cerebral blood flow (rCBF) using PET. Subjects experienced the perceptual properties of stereopsis by viewing rival-luminance stereograms displaying an identical random-dot pattern in their central portion while the backgrounds exhibited correspondent dots contrasting in black/white luminance. The stereoscopic vision induced by retinal luminance rivalry coincided with a significant elevation of rCBF in the dorsal visual pathway. Area V5 (MT) was activated bilaterally by the experimental condition while the remaining active loci were restricted to the right hemisphere. The neural sites that responded to this novel stereoscopic stimulus are similar to those activated by traditional stereograms containing horizontal disparities.

Adult↗

Growth performance, carcass and pork quality of finisher pigs fed oat-based diets containing different levels of beta-glucans.

A study was undertaken to investigate the growth performance and carcass and meat quality of pigs (BW = 52 to 108 kg) fed oat-based (Avena sativa L.) diets containing four levels of mixed-linkage (1 --> 3), (1 --> 4)-beta-D-glucans. One hundred sixty pigs-80 barrows and 80 gilts (average starting BW = 52.7 kg)--were allocated to one of five diets: a wheat-barley-based control diet and four experimental diets. The groats of Marion, a covered oat, and OT789, a hulless oat, were used to formulate four isonitrogenous and isocaloric diets to achieve 4.1,3.3, 2.1, or 1.6% total /beta-glucans (as fed). Growth performance (daily gain and gain to feed ratio) was not affected (P > 0.05) by the different levels of beta-glucans. Carcass yield, although lower (P < or = 0.05) for pigs fed the control diet, was similar (P > 0.05) for pigs fed any of the experimental diets. Cutout yields were also alike (P > 0.05) across the five diets. Beta-glucan content had no effect (P > 0.05) on the longissimus muscle area, or, by and large, on the proportions of commercial cuts; the only exceptions were a commercial picnic from pigs fed the 2.1% diet lower (P < 0.05) relative to all other diets and a lower (P < 0.5) commercial loin from pigs fed diets 4.1 or 3.3% relative to the control diet. Furthermore, the relative proportions oftotal lean, total bone, and total dissectable fat in the four lean cuts (picnic, butt, loin, and ham) were not different (P > 0.05) among the five diets. For pigs fed 4.1% beta-glucans, the proportion of lean in each of the four major cuts was lower (P < 0.05). No differences (P > 0.05) associated with the level of beta-glucans were detected for either the initial or ultimate pH mean values, the subjective assessment of color or structure of the longissimus muscle, or the instrumentally measured color (L value). Similarly, drip loss was not influenced (P > 0.05) by the level of beta-glucans in the diets. Soluble protein did differ (P < 0.05) among the high- to low-beta-glucans diets. No differences (P > 0.05) associated with diets were found for fat hardness and shear values of grilled pork chops. Chemical fat of the longissimus muscle from pigs fed 4.1, 3.3, or 2.1% beta-glucans was lower (P < 0.05) compared to pigs fed the control or 1.6% beta-glucans diets. In summary, no evidence of detrimental effect of beta-glucans in oat-based diets, particularly at levels below 4%, was detected, lending support for the inclusion of oat into finisher diets.

Animal Feed↗

Susceptibility to malaria as a complex trait: big pressure from a tiny creature.

Malaria, which is a major infectious disease worldwide, is caused by the Plasmodium parasite, one of the longest-known parasites infecting humans. The malaria situation is complicated by the emergence of drug resistance and the lack of an effective vaccine. Genetic factors play a key role in disease susceptibility, progression and outcome. Interestingly, an increasing large number of polymorphisms associated with resistance and susceptibility in humans have been found in proteins from erythrocytes, the site of Plasmodium replication. Some of these deleterious alleles have been selected by direct genetic pressure from the parasite in endemic areas of malaria. A number of additional gene effects have been mapped both in humans and in mice using population studies and experimental models of malaria, respectively. These recent studies have started to reveal additional aspects of the complex host-parasite interactions.

Animals↗

[Fetal macrosomia: management, obstetrical and neonatal results. Multicenter case-control study in 15 maternity hospitals in Paris and the Ile de France area].

OBJECTIVE: To study the perinatal management of fetal macrosomia (FM) and the obstetrical and neonatal results related to FM in the Ile de France area. MATERIALS AND METHODS: Case-control study from the fifteenth of July to the fifteenth of September 1999 in fifteen maternity in Paris and the Ile de France area. All singletons, without malformation, weighing more than 4,000 grams, born after 37 weeks of pregnancy during the study were included. The control group had the same inclusion and exclusion criteria (except the birth-weight) and was defined by the next delivery of same parity. RESULTS: 384 FM and 384 controls have been included. Usual risk factors of macrosomia have been found. The screening of gestational diabetes was realised in 56.8% and FM was suspected before delivery in 59.3% in the FM group. In cases of FM, the midwife was alone at the time of delivery in 53.4% of spontaneous vaginal delivery. FM was associated with a longer labour and a more frequent use of oxytocin. There was six times more severe perineal tears (1.7 vs 0.3%; p = 0.05) for women with FM whereas the rate of haemorrhage at delivery was the same in both groups. Cesarean section' rate before and during labor was higher in the FM group whereas instrumental extraction was not different. In this study, FM was not associated with an excess of fetal morbidity (injury, Apgar score, pH cord) even if we found ten times more shoulder dystocia. CONCLUSION: Complications related to FM were mainly maternal in this study. Some recommendations accounting fetal macrosomia were not widely adopted as screening of gestational diabetes or necessity to have a whole obstetric team at the time of delivery.

Adult↗

Complex genetic control of susceptibility to malaria in mice.

Malaria is a major infectious disease worldwide, with over 1 million deaths in African children every year. The molecular pathways of pathogenesis of the Plasmodium parasite and the host mechanisms of defense against this infection remain poorly understood. Epidemiological studies, together with linkage analyses in endemic areas have clearly pointed at a genetic component of innate susceptibility and severity of disease. In humans, this genetic trait is complex, and has been studied in a mouse experimental model over the past few years. Inbred strains of mice show different degrees of susceptibility to infection with Plasmodium chabaudi, and the genetic component of these inter-strain differences has been studied in standard informative backcross and F2 populations, as well as in recombinant inbred strains and more recently, in recombinant congenic strains. These studies have shown that genetic susceptibility to malaria is also complex in mice, and have led to the mapping of major susceptibility Char (Chabaudi resistance) loci, located on chromosomes 9 (Char1), 8 (Char2), 17 (Char3) and 3 (Char4).

Animals↗

Does histologic grade have a role in the management of head and neck cancers?

PURPOSE: High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. RESULTS: There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). CONCLUSION: Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Aged↗

APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death.

p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5-6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53-DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter-luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury.

Animals↗

Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice.

The genetic component of susceptibility to malaria is complex, both in humans and in the mouse model of infection. Two murine loci on chromosomes 8 (Pchr/Char2) and 9 (Char1) have previously been mapped in F(2) crosses, and play an important role in regulating blood parasitemia and survival to infection with Plasmodium chabaudi. These loci explain only part of the interstrain phenotypic variance, and their penetrance and expressivity vary in different inbred strains. Novel loci regulating response to P. chabaudi infection were investigated by using an alternative strategy based on a newly derived set of AcB/BcA recombinant congenic strains bred from malaria-susceptible A/J (A) and resistant C57BL/6J (B6). One of the AcB strains, AcB55, is shown to be highly resistant to infection despite 83% susceptible A genomic composition, including susceptibility alleles at Char1 and Pchr/Char2. Early onset of parasite clearance in AcB55 is associated with lower peak parasitemia and absence of mortality. Linkage analysis in an informative (AcB55 x A)F(2) population, using peak parasitemia as a quantitative trait, located a new B6-derived resistance locus on chromosome 3 (lod score = 6.57) that we designate Char4. A second, suggestive linkage on chromosome 10 (lod score = 2.53) shows additive effect with Char4 on peak parasitemia. Char4 maps to a small congenic B6 fragment in AcB55 that should facilitate the search for candidate genes. Our findings provide an entry point for parallel association studies in humans between the syntenic 4q21-4q25 region and susceptibility to disease in endemic areas of malaria.

Alleles↗

Recombinant congenic strains derived from A/J and C57BL/6J: a tool for genetic dissection of complex traits.

Complex genetic traits can be dissected in mice, using well-defined sets of recombinant inbred strains, congenic strains, and recombinant congenic strains (RCS). We report the creation of a series of 37 independent RCS derived from the commonly used inbred strains of laboratory mouse A/J (A) and C57BL/6J (B6). These RCS were derived by systematic inbreeding of independent pairs of animals from a (F1 x A) x A and a (F1 x B) x B double backcross (N3), to create AcB and BcA strains, respectively. Fifteen AcB strains and 22 BcA strains at between 18 and 30 generations of inbreeding have been generated, are healthy, and show stable breeding performance. These strains have been genotyped for a total of 625 informative microsatellite DNA markers covering the entire genome, with an average spacing of 2.6 cM. Haplotype analyses indicate that on average, AcB and BcA strains contain 13.25% of the donor genome, a value close to the 12.5% expected from the breeding scheme used in their creation. In the AcB set, approximately 79% of the B6 genome has been transferred in independent strains, while in the BcA set approximately 84% of the A genome is represented on the B6 background. This represents an excellent coverage of congenic segments from both parental genomes in the two sets of strains, which can now be used to map simple and complex traits in a genome-wide fashion. As an example of the power of AcB/BcA strains as a mapping tool, the 37 strains were typed for susceptibility to infection with Legionella pneumophila, a monogenic trait controlled by the Lgn1 locus on Chromosome 13. Analysis of the strain distribution pattern of L. pneumophila susceptibility allowed direct mapping of Lgn1 to a 3-cM interval. The AcB/BcA set should prove a useful tool with which to investigate the complex genetic basis of known interstrain differences between A and B6 for many important diseases.

Animals↗

Markers of neck failure in oral cavity and oropharyngeal carcinomas treated with radiotherapy.

BACKGROUND: Neck management after radiotherapy remains controversial. It is not clear which patients may benefit from postradiotherapy neck dissection. Biologic markers may be useful in this setting. METHOD: This study includes 81 patients with oral cavity and oropharyngeal carcinomas. The primary tumor had been treated with radical radiotherapy. Immunohistochemical staining to p53, ki-67, NEU, HSP-27, and GST has been performed. RESULTS: There were 50 T1-2 and 31 T3-4 patients, as well as 36 NO and 45 N1-3. A total of 25 nodal failures was observed. With expressed HSP2, 23% of patients had neck failure compared with 51% when HSP-27 was absent (p = .02). With NEU overexpression, nodal control decreased from 72% to 34% (p = .008). In a Cox model, NEU (p = .01) and HSP-27 (p = .05) were associated with neck failure. CONCLUSIONS: HSP-27 and NEU expression may play a role in predicting nodal failure. This should be confirmed in a larger, prospective study.

Biomarkers, Tumor↗

Outcome of patients treated with cobalt and 6 MV in head and neck cancers.

BACKGROUND: Since 1992, we have been using a 6-MV linear accelerator instead of a cobalt machine. The aim of the study is to evaluate the impact of this on neck control, particularly on postoperative patients in which subcutaneous tissues are at risk. METHOD: A retrospective study including all of 1,452 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All stages and subsites of the head/neck were included. Local and neck control were evaluated by the Kaplan Meier method, and comparisons were made between the cobalt and the 6-MV subgroups with a subsequent Cox analysis. For neck control analysis, the postoperative patients were divided in low and high risk (extracapsular extension [ECE], >two nodes, or T4). RESULTS: Radical radiotherapy: A better local control (LC) is observed with 6 MV than with cobalt, but neck control was similar. Postoperative radiotherapy: A better LC is observed with 6 MV. In high-risk patients, the neck control was higher for the cobalt group (79%) vs 60% for the 6-MV group (p = .09 and .03 in a Cox model). CONCLUSION: In postoperative patients at high risk for neck relapse, cobalt seems to give a better neck control. We are currently doing a prospective study in which a bolus is added for half the treatment when patients at high risk for neck relapse are treated with 6 MV.

Adult↗

'Seeing' in the blind hemifield following hemispherectomy.

Destruction of the striate cortex has traditionally been thought to lead to permanent blindness in the contralateral visual field and to the dogma that this region is indispensable for vision in primates. For over 25 years now, evidence has been accumulating that hemianopic human subjects and monkeys possess wide-ranging residual visual capacities or 'blindsight' in the blind part of their visual field. For some researchers, isolated islands of the striate cortex have been associated with patches of degraded vision and made responsible for blindisight. Artefacts such as light scatter, criterion effects, macular sparing, eccentric fixation and minute eye movements have also been linked with the residual vision. For others, the fact that certain aspects of the visual information can be processed without the geniculostriate pathway suggests mediation by the visual subsystems such as extrastriate visual cortical areas which receive visual information via subcortical pathways, that escaped the cortical damage. Subjects who have had a whole cerebral hemisphere removed or disconnected (for the treatment of uncontrollable epilepsy) and who show residual vision in their blind field offer a remarkable opportunity to help clear the controversy regarding the neural substrate of blindsight. Because it is certain that no functional striate or extrastriate cortex remains on the ablated side, these subjects have contributed significantly to identifying the critical pathways involved in blindsight.

Awareness↗

The impact of skin washing with water and soap during breast irradiation: a randomized study.

BACKGROUND: The effect of washing the irradiated skin during radiotherapy for breast cancer is uncertain. The purpose of this study was to evaluate the impact of washing the breast skin with water and soap during radiotherapy on the intensity of acute skin toxicity. MATERIALS AND METHODS: Ninety-nine patients treated for breast cancer were prospectively randomized prior to receiving radiotherapy to the breast into two groups: (1), no washing was allowed during radiotherapy (49 patients); and (2), washing was allowed with water and soap (50 patients). Acute toxicity was recorded according to the Radiation Therapy Oncology Group (RTOG) acute skin toxicity scale for each patient every week during radiotherapy and 1 month after the end of radiotherapy. Symptoms related to skin toxicity were scored by visual analogue scales at the same time intervals. Other data collected included sociodemographic data, characteristics related to the tumor and previous treatments, radiation technique, necessity for a second simulation due to loss of skin marks and treatment interruptions. RESULTS: In the non-washing group, the following maximum acute toxicity scores were observed: grade 0, 2%; grade 1, 41%; grade 2, 57%; grades 3 and 4, 0%. For the washing group, the scores were: grade 0, 0%; grade 1, 64%; grade 2, 34%; grade 3, 2%; and grade 4, 0%. Moist desquamation was seen in 33% of non-washing patients, but in only 14% of washing patients. The median scores of pain, itching and burning of the treated skin were higher in the non-washing group, although this was not statistically significant. In a multivariate analysis using logistic regression, acute skin toxicity was associated with the patient's weight, concomitant radiochemotherapy and hot spots on dosimetry, and there was a trend toward more acute skin toxicity in the non-washing group. CONCLUSION: Washing the irradiated skin during the course of radiotherapy for breast cancer is not associated with increased skin toxicity and should not be discouraged.

Acute Disease↗