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Biomedical subjects

A Maurice

Publications and source records attributed to A Maurice.

At least 19 recordsLinked to original sources

Screening younger women with a family history of breast cancer--does early detection improve outcome?

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.

Adult↗

Surgical decisions made by 158 women with hereditary breast cancer aged <50 years.

AIM: To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer. METHODS: We have assessed the surgical choices of 70 women diagnosed with breast cancer <50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation. RESULTS: Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery. CONCLUSIONS: We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.

Adult↗

[Activated protein C treatment: experience about 23 patients in the operative period].

OBJECTIVE: To evaluate the use of activated C protein (ACP) in a Surgical Intensive Care Unit. STUDY DESIGN: A prospective observational study. PATIENTS AND METHODS: All patients receiving ACP during 20 months in the operative period. RESULTS: Twenty-three patients were treated by ACP. The origin of sepsis was peritonitis (n = 14), infected pancreatitis (n = 3), mediastinitis (n = 2), one urologic sepsis, one facial cellulitis, one catheter related infection, and one postoperative pneumonia. In two cases, the peritonitis was associated with a pleuretic infection, and in two other cases with parietal cellulites. Mean age was 69+/-13 years. Severities evaluated by SAPS II, LODS were 59+/-13 and 7+/-3, respectively. Mean number organ dysfunction was 3.3+/-1.0. Septic shock was present in 91% with concomitant use of catecholamines for a mean period of 87+/-64 hours. Bacteraemia was present in 43% of the patients. A treatment with hydrocortisone was associated in 52% of the patients. The ICU and hospital lengths of stay were 15+/-16 days, and 34+/-38 days, respectively. Mortality at day 28 was 35%. Two significant bleeding were observed, one requiring red blood cell transfusion and the other one a surgical control of the bleeding associated with red blood cell transfusion. CONCLUSION: With global management of severe sepsis, including the use of activated C Protein, this prospective observational study showed a 30% reduction of the predicted mortality by SAPS II scoring without significant increase of bleeding episodes in a surgical context.

Aged↗

[Testing nasogastric tube placement: evaluation of three different methods in intensive care unit].

OBJECTIVE: Evaluation of three methods (aspiration of gastric fluid, pH measurement of gastric fluid, and insufflation of air) in order to determine the right position of the nasogastric (NG) tube. STUDY DESIGN: Prospective, observational study in an intensive care unit. PATIENTS AND METHODS: All patients requiring a NG tube were included. Since the NG tube was inserted three tests were successively performed: aspiration of gastric fluid, pH measurement of the gastric fluid, and auscultation over the epigastrium of air injected through the NG tube. The feasibility and the results obtained for each test were noted and compared to chest X-ray, considered as the reference. Chest X-ray classified the complications as major or minor. RESULTS: A total of 419 NG tube (202 decompressive NG tube and 217 gastric feeding tube) were analysed in 280 patients. Malpositions of the NG tube were observed in 10% (majors, n=11 and minors, n=31). Aspiration of gastric fluid and pH measurement were not sensible (77% and 49%, respectively) and not specific (38% and 74%, respectively). Insufflation of air was sensible (96%) but not specific (17%). The combination of the three methods did not improve the sensibility and specificity. Two complications were only detected by chest X-ray (one insertion in the intrapleural space, and one pneumothorax). CONCLUSION: None of the test evaluated, alone or associated, was sufficient to avoid chest X-ray. Moreover the occurrence of two potential and serious complications only detected by chest X-ray increase this assertion.

Auscultation↗

[Pregnancy after adjustable gastric band for morbid obesity: specific features of follow-up].

OBJECTIVE: To give pregnant women treated with an adjustable gastric band specific information on pregnancy and fetal outcome. MATERIAL AND METHOD: Case report and discussion of the main complications and specific features follow-up during pregnancy. RESULTS: In our patient the gastric band was adjusted to prevent first trimester vomiting. Diet was not modified. Weight gain during pregnancy was limited to four kilograms (kg). A hypotrophic girl was delivered by cesarean section. CONCLUSION: The main difficulties concern first trimester vomiting and dietary advice. Information regarding the effects of gastric band on pregnancies is limited and requires further investigations. A national file on outcome of pregnancy in women with gastric bands would be useful to establish appropriate recommendations.

Adult↗

Interactions of platelets with Synthocytes, a novel platelet substitute.

A platelet substitute, Synthocytes, is being developed for the prevention and treatment of thrombocytopenia. Synthocytes are composed of fibrinogen adsorbed on heat stabilised albumin microcapsules of defined size. The purpose of this study was to perform experiments in vitro to investigate the capacity of Synthocytes to interact with platelets, one of the means through which Synthocytes may contribute to haemostatic plug formation in vivo. Synthocytes were found to interact with platelets as shown by platelet aggregation assays and measurements of [(14)C]5HT release from platelets in whole blood and platelet-rich plasma. Platelet-Synthocytes co-aggregate formation was demonstrated directly using flow cytometry and the presence of activated platelets in these co-aggregates was demonstrated using an antibody to P-selectin. Synthocytes enhanced platelet responsiveness to conventional aggregating agents such as ADP. Indeed, antagonists of the action of ADP on platelets inhibited the direct effects of Synthocytes on platelets in whole blood, as did a GPIIb/IIIa antagonist. Enhancement of annexin V binding was also observed, indicative of increased pro-coagulant activity. Experiments performed with control microcapsules (lacking fibrinogen) confirmed the importance of fibrinogen in the interactions that occurred. The results suggest that fibrinogen on the surface of Synthocytes can interact with GPIIb/IIIa on platelets to induce platelet activation, secretory activity and aggregation, and that ADP contributes to this process. This initial interaction renders platelets more susceptible to the stimulatory effects of other platelet-activating agents. It is considered likely that in the clinical setting of thrombocytopenia any interaction between Synthocytes and residual platelets that are present may contribute to primary haemostasis.

Adenosine Diphosphate↗

Can mentoring or skill training reduce recidivism? Observational study with propensity analysis.

We compared juvenile offenders' recidivism following nonrandom assignment to juvenile diversion (JD, n = 137), JD plus skill training (ST, n = 55), or JD plus mentoring (MEN, n = 45). Intake characteristics that distinguished intervention groups were used to calculate assignment propensity scores. After propensity score blocking balanced intake characteristics, ST proved more cost effective than MEN, achieving a 14% relative reduction in recidivism at a savings of $33,600 per hundred youths. In ST, 37% were rearrested 2 years or more after intake, compared to 51% in MEN and 46% in JD. In two of five propensity subclasses, time to first rearrest was longer in ST (M = 767 days) than in MEN (M = 638 days) or JD (M = 619 days). These results argue for an experimental comparison of ST and MEN and for observational studies with propensity analysis when randomization to juvenile justice interventions is infeasible.

Adolescent↗

Factors influencing metabolic rate in naked mole-rats (Heterocephalus glaber).

Naked mole-rats (Heterocephalus glaber) are fossorial, eusocial mammals that live in colonies averaging about 70 individuals. Metabolic regulation is of particular interest in this species because it is one of only two naturally occurring small mammals that are hairless. Further, relative to other small mammals, naked mole-rats exhibit low body temperature (Tb) and weak capacity to maintain Tb above the ambient temperature (Ta). The present study examined effects of Ta, norepinephrine (NE), and chronic food restriction on O2 consumption (as a measure of metabolism) in naked mole-rats. Studies were performed in both awake and anesthetized animals. Metabolic rate decreased with increasing T. over the range of 23-34 degrees C in awake mole-rats, whereas in anesthetized animals rates of O2 consumption were very low over this entire range of Ta and tended to increase with increasing Ta. Injections of NE led to rapid increases in metabolic rate at all Tas in anesthetized subjects and also at Ta = 34 degrees C in awake mole-rats. However, at Tas of 29 and 23 degrees C, awake subjects given NE showed little stimulation of O2 consumption beyond the already elevated baseline rates observed at these Tas. During chronic restriction of food to 60-70% of their normal daily consumption mole-rats exhibited decreased rates of metabolism; metabolic rate was not altered following several hours of acute food deprivation. Food consumption remained somewhat decreased after a period of chronic food restriction, even when animals were returned to ad lib conditions. However, body weights returned to prerestriction values, despite the continued reduction in ad lib food intake. These observations suggest that mole-rats may be capable of long-lasting metabolic adaptations as a means to cope with restricted food supply. These findings are discussed in relation to adaptation of this fossorial species to a habitat where food has a patchy distribution. Naked mole-rats, with their several unusual thermoregulatory and behavioral features, provide an intriguing model for studies of mammalian metabolic regulation.

Adaptation, Physiological↗

Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression.

A methodology to dissect the genetic architecture of quantitative variation of numerous gene products simultaneously is proposed. For each individual of a segregating progeny, proteins extracted from a given organ are separated using two-dimensional electrophoresis, and their amounts are estimated with a computer-assisted system for spot quantification. Provided a complete genetic map is available, statistical procedures allow determination of the number, effects and chromosomal locations of factors controlling the amounts of individual proteins. This approach was applied to anonymous proteins of etiolated coleoptiles of maize, in an F2 progeny between two distant lines. The genetic map included both restriction fragment length polymorphism and protein markers. Minimum estimates of one to five unlinked regulatory factors were found for 42 of the 72 proteins analyzed, with a large diversity of effects. Dominance and epistasis interactions were involved in the control of 38% and 14% of the 72 proteins, respectively. Such a methodology might help understanding the architecture of regulatory networks and the possible adaptive or phenotypic significance of the polymorphism of the genes involved.

Chromosome Mapping↗

Mapping factors controlling genetic expression.

A methodology relying on two-dimensional (2D) electrophoresis and genetic mapping is proposed to dissect the genetic architecture of the quantitative control of gene products. Seventy-two anonymous polypeptide spots resolved using silver-stained high-resolution 2D gels of maize coleoptile extracts were automatically quantified for every individual of an F2 progeny between distant lines. A complete genetic linkage map, including 70 RFLP and 39 protein markers, allowed us to map Mendelian factors underlying quantitative variation for 42 polypeptides. One to 5 unlinked chromosomal regions were found to affect single polypeptides, 27% of which resulted in more than a doubling of the polypeptide spot intensity. Dominance was observed for half of the factors, with high amount dominant over low amount in most cases, which is consistent with the observation that the relative abundance of proteins in F1 hybrids is in average deviated to the high parental values. Epistatic interactions were shown to be involved in the control of 14% of the proteins. These features contrast sharply with the observations from 20 agromorphological traits measured in the same progeny, where limited substitution and dominance effects, and no epistatic interaction, were found.

Alleles↗

Phosphatidylethanolamine: ceramide-ethanolaminephosphotransferase activity in synaptic plasma membrane vesicles. Influence of some cations and phospholipid environment on transferase activity. Further proof of its location.

1. Synaptic plasma membrane vesicles (SPMV) from rat brain synthesized ceramide-phosphoethanolamine (SpE), an analogue of sphingomyelin (SpC) from phosphatidylethanolamine (PE) and ceramide. 2. This reaction was catalyzed by PE: ceramide-phosphotransferase. 3. The presence of PC did not modify the SpE synthesis and PI and PS at twice PE concentration seemed to be activators; only PG was an inhibitor at all concentrations. 4. Some cations (Mg2+, Mn2+) were without effect, while Ca2+ increased transferase activity, so was interesting to study. 5. Transferase was compared with sialidase (external enzyme). 6. Kinetics other than those already performed by us were undertaken in order to confirm its location.

Animals↗

Evidence for the biosynthesis of ceramide-phosphoethanolamine in brain synaptic plasma membrane vesicles and in sciatic nerve microsomes from normal and Trembler mice.

Synaptic plasma membrane vesicles (SPMV) from brains of normal and Trembler mice synthesized ceramide-phosphoethanolamine, and analogue of sphingomyelin from phosphatidylethanolamine (PE) and ceramide. The rate of this synthesis (6 nmol/mg of protein/h) and the (Na+)-K+)ATPase activity (about 70 mumol Pi per mg of protein/h) were very similar in normal and Trembler. The synthesis increased as a linear function of protein when endogenous PE was taken into account, but the addition of exogenous ceramide was without effect. Likewise, PE was the donor of phosphoethanolamine for the synthesis of the ceramide-phosphoethanolamine in normal and Trembler mouse sciatic nerves and this synthesis was 3.5 times greater in the mutant than in controls.

Animals↗

Sidedness of ceramide-phosphoethanolamine synthesis on rat liver plasma membrane.

Phosphatidylethanolamine:ceramide-ethanolaminephosphotransferase catalyzes the synthesis of ceramide-ethanolamine, a sphingomyelin analogue. Its transverse localization in rat liver plasma membrane was studied by treating intact and deoxycholate- or Triton X-100-disrupted membrane vesicles with trypsin or bacterial protease. The latency of ATPase was preserved during protease treatment; its value was 80% in the membrane vesicles obtained by sucrose gradient procedure alone and 91.2% in the vesicles isolated after sucrose gradient plus two-phase partitioning. This suggested that membrane integrity was not altered and that 90% of the vesicles were right-side out. When the sucrose gradient was followed by the two-phase procedure, 62% of phosphatidylethanolamine:ceramide-ethanolamine-phosphotransferase was accessible to the protease action, but only 45% in vesicles obtained by sucrose gradient alone. Our results suggest that at least a sizable portion of the active center of the enzyme responsible of biosynthesis of ceramide-phosphoethanolamine is located on the external side of liver plasma membrane and that the other is embedded in the membrane interior and is not accessible to trypsin, even in the presence of detergent.

Adenosine Triphosphatases↗

Sidedness of ceramide-phosphoethanolamine synthesis on rat liver and brain microsomal membranes.

Phosphatidylethanolamine:ceramide-ethanolamine-phosphotransferase catalyzes the synthesis of ceramide-phosphoethanolamine, a sphingomyelin analogue. Its localization was studied in rat liver and brain microsomes. After testing the integrity and the sidedness of microsomal vesicles, trypsin treatment of intact or deoxycholate-disrupted microsomes made it possible to conclude that both the transferase and the ceramide-phosphoethanolamine are located in the cisternal leaflet of the membrane bilayer. Using trinitrobenzenesulfonic acid as a probe, no trace of newly synthesized ceramide-phosphoethanolamine was detectable on the cytoplasmic side of the microsomes.

Animals↗

Sphingomyelin and ceramide-phosphoethanolamine synthesis by microsomes and plasma membranes from rat liver and brain.

Pulse-chase experiments showed that phosphatidylethanolamine (PE) was the direct precursor for ceramide-phosphoethanolamine, a sphingomyelin analogue, in the same way as phosphatidylcholine was for sphingomyelin. Ceramide-phosphoethanolamine could be identified by incorporation of radioactivity from labeled PE, as well as by its stability in alkaline methanolysis and its ability to be methylated by S-adenosyl-methionine. Ceramide-phosphoethanolamine synthesis from labeled exogenous PE seemed to be independent of exogenous ceramide; it was proportional to the amount of incubated membrane, when taking into account the isotopic dilution of labeled precursor by endogenous PE. Sphingomyelin synthesis, which was demonstrated using natural PC as a substrate, was not possible using dipalmitoyl-PC. The formation of sphingomyelin and ceramide-phosphoethanolamine was demonstrated in microsomes and plasma membranes from rat brain and liver.

Animals↗

[Biosynthesis and metabolism of phosphonolipids and phospholipids in rat hepatocytes and Saccharomyces cerevisiae].

In rat hepatocytes, ciliatine (2 aminoéthylphosphonic acid) is incorporated into phosphonolipid (PnE) by the same pathway leading from phosphorylethanolamine to phospholipid (PE). The two resulting lipids are isolated from mitochondria and microsomes. The rates of biosynthesis are quite comparable; the processes of trimethylation and of in vitro transfer in the presence of a specific exchange protein are very similar. In yeast, on the other hand, the uptake of the two precursors is very slight, suggesting that the direct cytidylic pathway of phospholipid biosynthesis is strongly repressed. Despite small amounts of PE and PnE produced, methylation occurs with a good yield. The good incorporation of ethanolamine may be understood by a base-exchange mechanism. The natural PE biosynthesis is achieved through the decarboxylation of phosphatidylserine, and followed by methylation leading to phosphatidylcholine. The use of very small amounts of precursors does not modify the natural course of phospholipid biosynthesis.

Animals↗

Phospholipid synthesis and exchange between rat liver microsomes and mitochondria in the presence of benzo(a)pyrene.

Benzo(a)pyrene injection increased the phospholipid content in membranes of rat liver mitochondria and microsomes. There was a large relative increase of phosphatidylcholine, especially in microsomes, as compared with normal liver. The quantity of phosphatidylethanolamine seemed not be affected and the other phospholipid classes decreased. In vivo [U-14C]glycerol incorporation into phospholipids was greater after benzo(a)pyrene injection, especially into phosphatidylcholine. Liver microsomes derived from rats injected with [U-14C]glycerol or from liver slices incubated with the same precursor were incubated with unlabeled mitochondria in the presence of 105,000 g supernatant fraction; labeled microsomal phospholipids exchanged to a greater extent in the presence of benzo(a)pyrene, suggesting either a stimulation of activity of the exchange proteins, or a relative membrane disorganization facilitating the phospholipid transfer.

Animals↗