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Biomedical subjects

N Simon

Publications and source records attributed to N Simon.

At least 55 records · Page 3Linked to original sources

Melatonin high-affinity binding to alpha-1-acid glycoprotein in human serum.

The binding of 3H-melatonin to human serum proteins was investigated by equilibrium dialysis at 37 degrees C and pH 7.4. The binding to serum was moderate (53%) for physiological melatonin concentrations below 1 nmol/L. alpha 1-Acid glycoprotein and albumin bound melatonin with high 27 +/- 3 and low 1.5 +/- 0.1 (mmol/l)-1 affinity, respectively. Melatonin binding to other serum proteins, gamma-globulins and lipoproteins was not significant. The serum binding was characterized by a saturable and a nonsaturable component. The saturable component resulted from the high-affinity binding to alpha 1-acid glycoprotein and the nonsaturable component resulted from the low-affinity binding to albumin. The number of binding sites was 0.36/molecule of alpha 1-acid glycoprotein, when either pure alpha 1-acid glycoprotein or serum were studied, indicating that only a fraction of alpha 1-acid glycoprotein bound melatonin. The observed binding parameters did not enable simulation of the observed serum binding, and melatonin binding to an alpha 1-acid glycoprotein-albumin mixture was higher than that expected from the binding to each isolated protein. The high-affinity melatonin binding to alpha 1-acid glycoprotein might result from a potentiation of the binding interaction by albumin and the amount of melatonin bound in plasma might vary according to the alpha 1-acid glycoprotein concentration.

Blood Proteins↗

Potential interest of anti-ischemic agents for limiting cyclosporin A nephrotoxicity.

Chronic administration of cyclosporin A induces nephrotoxicity in humans. This is related to a cyclosporin A-induced constriction of afferent glomerular arterioles and mesangial cells, which leads to a decrease in filtration pressure and creatinine clearance. Afterwards, cellular lesions are observed involving mainly tubular atrophy and interstitial fibrosis, both of which are nonspecific. The initial mechanism of its toxicity is not clearly explained. The current pharmacological approach is symptomatic in order to counteract or minimize the consequences of a prime cause, which still remains to be defined. However, cyclosporin A has a deletereous effect on mitochondrial functions and mainly on ATP synthesis, which occurs when Ca2+ accumulates in matrix mitochondria. The effects of trimetazidine, an antischemic drug used in the treatment of angina pectoris, have been assessed. This drug is effective in experimental models of hypoxia induced by cyclosporin A: it restores ATP synthesis previously decreased by Ca2+ and cyclosporin A, and releases a part of Ca2+ excess accumulated by mitochondria at concentrations reached in humans at usual dosage regimens. At higher concentrations, it reverses the mitochondrial permeability transition previously generated (opened) by Ca2+ and a pro-oxidant such as terbutylperoxide (t-BH). It was also observed that trimetazidine does not modify the immunosuppressive effects of cyclosporin A in various models. These data suggest that nephrotoxicity of cyclosporin A is not irrevocably linked to its immunosuppressive effect but that it may be possible to counteract at least partly its nephrotoxic effects without altering its effectiveness in preventing graft rejection.

Adenosine Triphosphate↗

[Evaluation of pediatric advise asked by telephone in emergency units].

BACKGROUND: Telephone calls for advice are common in pediatric emergency departments. This study was conducted to determine the nature of these calls and the answers provided. METHODS: From 24 April through 24 July 1994, all telephone calls requesting pediatric advice in the emergency department of the Poissy Hospital were independently analysed by two pediatricians from forms prospectively filled in for each call by the resident or the attending people who answered the call. RESULTS: Of the 239 registered calls, 186 could be analysed. They represented, in number, 15.25% of the children seen at the same emergency department during the study period. Weekend and holiday calls accounted for 35.5% of calls. 7.8% of calls were received from 0.01 am to 8.00 am, 28.7% from 8.01 am to 4.00 pm, and 63.5% from 4.01 pm to 12.00 pm. Thirty-seven percent concerned children under one year of age. The caller was one of the parents in 93% of cases. The four most frequent complaints were fever (26.5%), requests for information (17.2%), rash (12.3%), and vomiting (10.2%). The review of calls by two pediatricians determined that 67% of children did not need to be seen by a physician within six hours; 28% needed to be seen within 6 hours, and 5% needed to be seen within one hour. The advice given was followed in 88% of cases; 96% of callers were satisfied with their calls management. CONCLUSIONS: Telephone advice constitutes an important part of the activity in the pediatric emergency department. Instructional programs in telephone management are necessary for physicians. These programs should include communication skills and familiarization with protocols concerning the most frequent complaints, especially those regarding children under one year of age.

Adolescent↗

[Telephonic advice by an emergency department given in a simulated pediatric case].

BACKGROUND: Emergency departments (ED) are requested everyday to dispense medical telephone advice for children. To evaluate the quality of telephone management, a mock scenario simulating a febrile 4 month-old-girl with signs compatible with septicemia was used. METHODS: One hundred randomly selected French emergency departments were called on. Half of the hospitals had a pediatric department with more than 20 beds; the other half did not have a pediatric department. A research technician called and said: "My baby has got fever and I do not know what to do". Additional information was given only on request. RESULTS: Ninety-four ED gave medical advice by telephone: 65% of the cases by a physician, 24.5% by a nurse, 9.5% by a nurse technician and 1% by a secretary. In hospitals without a pediatric department, physicians took calls in 76.5% of the cases, whereas in hospitals with a pediatric department they only took calls in 53% of the cases. The mean number of questions asked per ED was 3.1. The age of the child was requested by 87.2% of the respondents. Advice was given by 36.1% of the ED without asking either the age of the patient or grade of the fever. The advice given by the respondents was: come to the ED immediately (30.9%), see a community physician immediately (51%), come to the ED tomorrow (2.1%), see a community physician tomorrow (8.5%), and manage at home (7.5%). CONCLUSIONS: This study has shown important inadequacies in pediatric telephone advice given by some ED. It suggests that the respondents do not use a protocol to handle the calls; development of such protocols to guide the histories taken and advice given for the most common telephone queries is urged.

Attitude of Health Personnel↗

Early inflammatory response correlates with the severity of injury.

OBJECTIVE: To determine if the early inflammatory response correlates with the severity of injury in a blunt trauma model in rats. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats, weighing 250 to 400 g. INTERVENTIONS: Twenty-two male Sprague-Dawley rats were divided randomly into single hindlimb fracture, bilateral hindlimb fracture, and no fracture groups. At 90 mins, all animals underwent midline laparotomy and aspiration of blood from the inferior vena cava. Venous blood gas, plasma lactate, and plasma concentrations of tumor necrosis factor (TNF), prostaglandin F(6-keto-PGF1 alpha), and interleukin (IL)-6 were sampled. Statistical analysis was done via one-way analysis of variance and Scheffé post hoc analysis. In a second part of this experiment, the effect of hemorrhage on the release of IL-6 was evaluated. Animals in this group were compared with control and bilateral hindlimb fracture animals, using the Student's t-test. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in venous pH or base deficit among the groups. Oxygen saturation was significantly decreased in the bilateral hindlimb fracture group when compared with the control group. In the hemorrhage plus bilateral fracture group, oxygen saturation was significantly decreased when compared with the bilateral fracture group. lactate concentrations in plasma were increased in both fracture groups as well as the hemorrhaged groups. Plasma TNF concentrations were increased in the injured groups but there was no significant difference between single and bilateral hindlimb fracture groups. The 6-keto-PGF1 alpha concentrations were increased in both of the fracture groups when compared with the control group and there was a significant difference between single and bilateral hindlimb fracture groups. Similarly, circulating IL-6 concentrations were significantly higher in the bilateral fracture group than in the single fracture group; both fracture groups were significantly higher than the control group. Hemorrhaged animals had even higher IL-6 concentrations. CONCLUSIONS: Plasma lactate and TNF concentrations were affected by injury, however their concentrations did not correlate with degree of injury. IL-6 concentrations were increased early postinjury and correlated with severity of injury. The 6-keto-PGF1 alpha concentrations in plasma also correlated with the severity of injury and this phenomenon may represent early endothelial activation which may be the source of IL-6 release.

6-Ketoprostaglandin F1 alpha↗

Inhibition of rat cerebral mitochondrial respiration by cyclosporins A, D, and G and restoration with trimetazidine.

The aim of this work was to investigate possible inhibitory effects of Ca+ and different cyclosporins (Cs) on the rat brain mitochondrial respiratory control ratio (RCR) and whether or not these effects could be antagonized by trimetazidine (TMZ). The RCR was evaluated as the state 3/state 4 ratio of oxidative phosphorylation. CsA, D, and G inhibited about 10% of RCR in a concentration-dependent manner with EC50 of 57, 19 and 7 nM, respectively, whereas CsH did not modify RCR. TMZ was able to fully antagonize this inhibitory effect in a concentration-dependent manner with EC50 of 5,200, 180, and 1 nM, respectively. The Ca2+ added to the mitochondrial preparation decreased RCR in a concentration-dependent manner with a maximal effect of 46% obtained with 100 microM Ca2+. In the presence of TMZ (100 microM), the inhibitory effect of Ca2+ was partly reversed (9%). TMZ alone showed no inhibitory or stimulant effect on RCR. These results show that restoration of RCR by TMZ is due to a Ca(2+)-dependent mechanism, promoting Ca2+ efflux from the mitochondrial matrix. However, Ca2+ efflux is only partial in case of Ca2+ overload. These data suggest that TMZ may restore ATP synthesis in circumstances where neither Ca2+ overload, nor a prooxidant have generated a RCR decrease.

Analysis of Variance↗

HCV-associated liver cancer without cirrhosis.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.

Adult↗

[Intraosseous infusion in children].

BACKGROUND: Intravenous access in critically ill patients may be very difficult to obtain. The intraosseous route is an alternate way to administer fluids and drugs. CASE REPORT: A five month old infant was brought to the emergency department in profound hypovolemia requiring immediate tracheal intubation. A peripheral venous access was established and 35 ml of colloid were rapidly infused. Unfortunately, fluid extravasated and the intravenous line had to be removed. As further attempts to gain intravenous access were unsuccessful, an intraosseous needle was inserted into the left tibia 1 cm below the tibial tuberosity, and colloid and human albumin solution were infused rapidly, followed by 1.4% sodium bicarbonate. After ninety minutes of intraosseous rehydration, 2 peripheral venous lines were inserted, and the intraosseous needle was removed. Bacteriological and viral cultures were negative. Four days after admission, the child was discharged in good condition. CONCLUSIONS: Intraosseous infusion provides safe, rapid and reliable access to the circulation for administration of fluids and drugs in the critically ill child or during cardiac arrest.

Emergencies↗

[Sedation and analgesia in children].

This article describes the most current and effective means for providing sedation and analgesia for the pediatric patient. Three basic levels for sedation can be defined: conscious sedation, deep sedation and general anesthesia. Treatment of pain is also established according to an analgesic ladder. Providing safe and effective sedation and analgesia to children requires appropriate selection of drugs and dosage, proper monitoring, knowledge of potential side effects, and adequate airway management equipment and personnel. Agents available for sedation and analgesia of children and therapeutic options according to different clinical situations are described.

Analgesia↗

Utilization of exogenous siderophores and natural catechols by Listeria monocytogenes.

Listeria monocytogenes does not produce siderophores for iron acquisition. We demonstrate that a number of microbial siderophores and natural iron-binding compounds are able to promote the growth of iron-starved L. monocytogenes. We suggest that the ability of L. monocytogenes to use a variety of exogenous siderophores and natural catechols accounts for its ubiquitous character.

Animals↗

Fluorescent in situ hybridization with rRNA-targeted oligonucleotide probes to identify small phytoplankton by flow cytometry.

Because of their tiny size (0.2 to 2 microns), oceanic picophytoplanktonic cells (either cultured strains or natural communities) are difficult to identify, and some basic questions concerning their taxonomy, physiology, and ecology are still largely unanswered. The present study was designed to test the suitability of in situ hybridization with rRNA fluorescent probes detected by flow cytometry for the identification of small photosynthetic eukaryotes. Oligonucleotide probes targeted against regions of the 18S rRNAs of Chlorophyta lineage (CHLO probe) and of non-Chlorophyta (NCHLO probe) algal species were designed. The CHLO and NCHLO probes, which differed by a single nucleotide, allowed discrimination of chlorophyte from nonchlorophyte cultured strains. The sensitivity of each probe was dependent upon the size of the cells and upon their growth stage. The mean fluorescence was 8 to 80 times higher for specifically labeled than for nonspecifically labeled cells in exponential growth phase, but it decreased sharply in stationary phase. Such taxon-specific probes should increase the applicability of flow cytometry for the rapid identification of cultured pico- and nanoplanktonic strains, especially those that lack taxonomically useful morphological features.

Base Sequence↗

[Hepatitis C virus infection in hemodialysis].

The surveillance of HCV infections is now a must in the clinical management of hemodialysis patients. The natural history of HCV has shown acute hepatitis to be a constant feature although rarely symptomatic. Progression to chronicity occurs in 90% of the cases with detectable viremia in 80% of the cases. The long-term impact of the liver disease in chronic hemodialyzed patients remains to be defined. HCV is responsible for more than 90% of the non-A, non-B hepatitis case diagnosed among hemodialyzed patients. The transmission is either transfusional or nosocomial. Following recent transfusion safety regulations, the nosocomial risk became the predominant residual risk. Thus, all efforts should target HCV eradication. In the absence of specific prophylaxis, this can only be achieved by enforcement of very stringent precautions.

Chronic Disease↗

A twelve year natural history of hepatitis C virus infection in hemodialyzed patients.

A prospective non-A, non-B follow-up program, implemented in a hepatitis B surface antigen-free dialysis unit, enabled us to report on the natural history of hepatitis C virus (HCV) infection in hemodialyzed patients between 1980 and 1992. For this program, every patient was prospectively monitored every two weeks for alanine amino transferase (ALT) activity, and every month for gammaglutamyl transpeptidase (GGT) activity and systematic collection of frozen sera. Sequences of stored sera from 217 patients were repeatedly tested for anti-HCV antibodies using second generation assays. Eighty-six of the 217 patients (39.6%), including 61 of the 67 patients with non-A, non-B hepatitis (91%), had HCV infection repeatedly evidenced by positive ELISA in all, and confirmed by RIBA in 84 of 86 (97.5%). In addition, 19 out of 23 patients (82.6%) were positive for HCV RNA by the polymerase chain reaction (PCR). Of the 86 anti-HCV positive patients, 41 had previously acquired HCV infection, and 45 seroconverted during chronic dialysis. Of these, all but one patient developed hepatitis with raised ALT activity which lasted for at least six months in all. Only 29 of 45 patients (64.5%) had a history of blood transfusion. Seventy-eight of the 86 patients (91%) who were followed up for one to 11.5 years (median 5) retained anti-HCV for several years. Nineteen liver biopsies performed in 16 patients showed chronic active hepatitis in 8 (50%) and hepatocellular carcinoma without cirrhosis in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Anti-hepatitis C virus (anti-HCV) seroconversion in patients undergoing hemodialysis: comparison of second- and third-generation anti-HCV assays.

BACKGROUND: The results obtained in sequential specimens from recently infected subjects generally provide the best means of comparing the sensitivity of assays. STUDY DESIGN AND METHODS: The sensitivity of second- and third-generation assays for antibody to hepatitis C virus (HCV) was compared on sequential specimens, generally collected at monthly intervals from 45 patients undergoing hemodialysis who seroconverted for HCV between 1980 and 1990. RESULTS: Fifteen patients (33%) were positive earlier in the third-generation enzyme-linked immunosorbent assay (ELISA), with a mean difference of 17 days (range, 7-30) between the last negative and the first positive specimens. At the first rise in alanine aminotransferase, and at its peak, 63 and 91 percent of the patients, respectively, were anti-HCV positive in the third-generation ELISA. Third-generation recombinant immunoblot assay (RIBA) reacted at the same time as third-generation ELISA. Of the first specimens that were positive in second-generation ELISA, 44 percent reacted and 56 percent were indeterminate in third-generation RIBA, while 10 percent reacted, 72 percent were indeterminate, and 18 percent did not react in second-generation RIBA. From the beginning to the end of the follow-up, antibody to c33c was the most prevalent, followed in descending order by antibody to c22-3, antibody to c100-3, and antibody to NS5: 56, 54, 26, and 18 percent, respectively, at time 0, and 100, 86, 83, and 31 percent, respectively, 12 months later. CONCLUSION: Third-generation assays (both ELISA and RIBA) were more sensitive than second-generation assays in the diagnosis of HCV infection, in that positive results were obtained earlier and a higher proportion of specimens were confirmed positive in RIBA testing.

Alanine Transaminase↗