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Biomedical subjects

L Muller

Publications and source records attributed to L Muller.

At least 19 recordsLinked to original sources
PubMed2006

[General practitioners' and intensivists' relationships: intensivists' point of view from eight French southern regional areas].

OBJECTIVES: Assessment of relationship between general practitioners and intensivists. STUDY DESIGN: Intensivists were questioned by phone from June 14th to September 28th 2004. METHODS: 245 out of 264 intensivists from 8 French Southern regional areas were questioned concerning their relationship with critically ill patients' general practitioner. RESULTS: Patients were mainly admitted into Intensive care Unit (ICU) from the Emergency Department (55%). An information letter from the general practitioner was reported for 20% of admitted patients but 50% of these letters was assumed as not informative. The informations concerning the patient's medical history, therapies, and disease leading to admission and the patient's status were assessed with 6.5, 7.0, 6.0 and 2.0, respectively (maximal note=10). The intensivists contacted the general practitioner for 30% of admitted patients. During the stay in ICU, 33% general practitioners were reported to request informations by phone or visit in ICU. When the stay in ICU was>10 days, the general practitioner was nearly never regularly informed about patient's status. When the patient was discharged from the ICU, 80% of intensivists used an exhaustive typed report to inform the general practitioner. The overall relationship between the general practitioner and the intensivist was assessed as 5.5/10. Insufficient information in the general practitioner's letter at admission, the lack of request for information during the stay in ICU, the lack of contact with the general practitioner by the intensivist and an intensivist's age between 46 and 55 were associated with a relationship assessment<4/10).

Adult↗
PubMed2004

[Short term effects of hypertonic saline during severe sepsis and septic shock].

OBJECTIVE: Assessment of haemodynamic effects of 250 ml hypertonic saline 7.5% (HS) perfusion in critically ill patients with severe sepsis or septic shock. STUDY DESIGN: Observational study. PATIENTS: Twelve mechanically ventilated patients with severe sepsis or septic shock requiring a pulmonary artery catheter and volume loading. INTERVENTION: Two hundred and fifty millilitres HS were given over 15 min. Were measured: heart rate (HR), mean arterial pressure (MAP) and pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), cardiac index (CI), indexed systemic vascular resistance (ISVR), indexed pulmonary vascular resistance (IPVR), plasma sodium, chloride, protein and haemoglobin concentrations and arterial blood lactate. Studied parameters were assessed at baseline (T(0)) and 5 (T(0)) and 105 min (T(120)) after the end of HS infusion. RESULTS: MAP, HR and RAP were not altered. HS increased PAPM (25 +/- 5-30 +/- 6 mmHg), PCWP (13 +/- 3-18 +/- 4 mmHg) and CI (3.5 +/- 1.2-4.6 +/- 1.1 l/min per m(2)) at T(20) (P < 0.05). ISVR and IPVR were decreased at T(20). Protein and haemoglobin were decreased at T(20). Sodium and chloride were increased at T(20) (from 136 +/- 4 to 147 +/- 4 and from 110 +/- 6 to 123 +/- 6 mmol/l, respectively, P < 0.01) and T(120). CONCLUSION: In patients with severe sepsis or septic shock, 250 ml HS transiently (<120 min) increases CI and PCWP and induces an increase in sodium and chloride concentrations.

Adult↗
PubMed2004

Profile analysis of organic micropollutants in the environment of a coal burning area, NW Greece.

The concentrations and profiles of dibenzo-p-dioxins, dibenzofurans, polychlorinated biphenyls and polynuclear aromatic compounds in various environmental matrices are presented in this study. The examined environmental matrices are total suspended particles, fly ash and soil collected in NW Greece, an area characterized by intensive coal burning for electrical power generation. Moreover, the occurrence of organic micropollutants in soot after an accidental fire was examined and the possible impact on the outdoor environment was evaluated. Results were statistically treated to obtain information on representative PCDD/F profiles in each matrix and to compare these profiles with the compositional patterns of possible sources from literature. Coal combustion, fly ash and vehicle exhausts appeared to be the most possible sources in local atmosphere.

Benzofurans↗
PubMed2003

Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

OBJECTIVE: Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. DESIGN: Prospective cohort study. SETTING: Intensive Care Unit of a University-Hospital. PATIENTS: Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). INTERVENTION: Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. MEASUREMENTS AND MAIN RESULTS: The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). CONCLUSION: In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

Aged↗
PubMed2002

Risk factors of failure and immediate complication of subclavian vein catheterization in critically ill patients.

OBJECTIVE: To identify the risk factors of failure and immediate complication of subclavian vein catheterization (SVC). DESIGN: Prospective observational study. SETTING: Surgical critical care unit of a tertiary university hospital. PATIENTS: Critically ill patients requiring a first SVC. INTERVENTION: Subclavian vein catheterization was attempted in 707 patients without histories of surgery or radiotherapy in the subclavian area. Failed catheterizations, arterial punctures, pneumothoraces and misplacements of the catheter tip were recorded. Risk factors of failure and immediate complication were isolated among patients' characteristics, procedure parameters (side and number of venipunctures) and the operator's experience using a univariate +/- multivariate analysis. MEASUREMENTS AND MAIN RESULTS: Five hundred sixty-two SVCs (79.5%) were achieved without adverse events. Among the remaining 145 catheterizations, 67 (9.5%) failures, 55 (7.8%) arterial punctures, 22 (3.1%) pneumothoraces and 30 (4.2%) misplacements of the catheter tip occurred. More than one venipuncture was the only risk factor of failed catheterization [2 venipunctures, odds ratio =7.4 (2.1-26); >2 venipunctures, odds ratio =49.1 (16.8-144.1)]. More than one venipuncture and age 77 years or more were predictive of the occurrence of immediate complications [2 venipunctures, odds ratio =3.6 (1.8-7.0); >2 venipunctures, odds ratio =14 (7.7-25.3); age >or=77, odds ratio =1.8 (1.0-3.1)]. The operator's training was not predictive of failed catheterization or immediate complication. CONCLUSION: For SVC, more than one venipuncture is predictive of failed catheterization and immediate complication. Age 77 years or more was predictive of immediate complications.

Adolescent↗
PubMed2002

A computed tomography assessment of femoral and acetabular bone changes after total hip arthroplasty.

Using computed tomography-assisted (CT) osteodensitometry, we studied the bone changes that occurred in 12 patients at 2 weeks and again at 1 year after total hip arthroplasty with insertion of a press-fit acetabular cup and an uncemented femoral tapered stem. There was a greater decrease in full bone density (BD) lateral to the femoral stem when compared to the medial side, at the proximal end of the femur this difference was significant (-22.1% versus -16.2%) ( P<0.001). At the tip of the stem cortical BD had decreased between 2.3% and 1.9% only. Proximal to the cup, the cortical BD increased by about 3.4% ( P< or =0.05), while the full BD decreased markedly by 8% ( P< or =0.001). These changes represent a response to a decrease in regional bone stress induced by the presence of the press-fit implant, and this might be considered as retro-acetabular stress shielding. No focal bone resorption was found.

Acetabulum↗
PubMed2002

Pharmacodynamics and atracurium and laudanosine concentrations during a fixed continuous infusion of atracurium in mechanically ventilated patients with acute respiratory distress syndrome.

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg x kg(-1)) followed by a 72-hour continuous infusion (1 mg x kg(-1) x h(-1)). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1 > or = 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always < or = 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value = 45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 microg x ml(-1) and from 3 to 20 microg x ml(-1) respectively. In four patients with renal impairment, the highest laudanosine concentration was > 10 microg x ml(-1). No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.

Aged↗
PubMed2001

Selective in vivo and in vitro effects of a small molecule inhibitor of cyclin-dependent kinase 4.

BACKGROUND: Cyclin-dependent kinase 4 (Cdk4) represents a prime target for the treatment of cancer because most human cancers are characterized by overexpression of its activating partner cyclin D1, loss of the natural Cdk4-specific inhibitor p16, or mutation(s) in Cdk4's catalytic subunit. All of these can cause deregulated cell growth, resulting in tumor formation. We sought to identify a small molecule that could inhibit the kinase activity of Cdk4 in vitro and to then ascertain the effects of that inhibitor on cell growth and tumor volume in vivo. METHODS: A triaminopyrimidine derivative, CINK4 (a chemical inhibitor of Cdk4), was identified by screening for compounds that could inhibit Cdk4 enzyme activity in vitro. Kinase assays were performed on diverse human Cdks and on other kinases that were expressed in and purified from insect cells to determine the specificity of CINK4. Cell cycle effects of CINK4 on tumor and normal cells were studied by flow cytometry, and changes in phosphorylation of the retinoblastoma protein (pRb), a substrate of Cdk4, were determined by western blotting. The effect of the inhibitor on tumor growth in vivo was studied by use of tumors established through xenografts of HCT116 colon carcinoma cells in mice. Statistical tests were two-sided. RESULTS: CINK4 specifically inhibited Cdk4/cyclin D1 in vitro. It caused growth arrest in tumor cells and in normal cells and prevented pRb phosphorylation. CINK4 treatment resulted in statistically significantly (P: =.031) smaller mean tumor volumes in a mouse xenograft model. CONCLUSIONS: Like p16, the natural inhibitor of Cdk4, CINK4 inhibits Cdk4 activity in vitro and slows tumor growth in vivo. The specificity of CINK4 for Cdk4 raises the possibility that this small molecule or one with a similar structure could have therapeutic value.

Animals↗
PubMed2001

[Pulmonary artery catheterization in the intensive care unit: at what time?].

OBJECTIVES: Recording the time at which the insertion of a pulmonary artery catheter was decided. STUDY DESIGN: Prospective and descriptive study. PATIENTS: Critically ill patients in an university hospital. METHODS: The times at which the insertion of a PAC was decided were recorded. For each pulmonary artery catheterization, immediate complications were recorded (arterial puncture, pneumothorax, ventricular arrhythmia, hard and failed pulmonary artery catheterization). RESULTS: One hundred and forty-nine patients were included (99 males, age = 63 +/- 15 year, body mass index = 25 +/- 6 kg.m-2, median Apache II score = 16). One hundred and sixty-five PAC insertions were decided (16 patients requiring two PACs). Nine arterial punctures, two pneumothoraces, 42 ventricular arrhythmias, 32 hard and eight failed pulmonary artery catheterizations occurred. Thirty-four PAC insertions were decided between 9 and 10 am whereas = 3 PAC insertions per hour were decided between 1 and 9 am. CONCLUSION: The rate of decision of PAC insertion are decreased during the second half of the night (1 to 9 AM).

APACHE↗
PubMed2001

The comparative electrophysiologic and hemodynamic effects of a large dose of ropivacaine and bupivacaine in anesthetized and ventilated piglets.

UNLABELLED: Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 +/- 22 to 49 +/- 31 mm Hg and from 87 +/- 17 to 58 +/- 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 +/- 95 to 689 +/- 482 mm Hg/s and from 1963 +/- 92 to 744 +/- 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 +/- 5 to 9 +/- 5 mm Hg and from 6 +/- 4 to 12 +/- 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 +/- 139 to 706 +/- 228 ms and from 451 +/- 87 to 666 +/- 194 ms, respectively), atria His (from 71 +/- 15 to 113 +/- 53 ms and from 64 +/- 6 to 86 +/- 10 ms, respectively), and QTc (QTc = QT x R-R(-0.5), Bazett formula; from 380 +/- 71 to 502 +/- 86 ms and from 361 +/- 33 to 440 +/- 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 +/- 20 to 211 +/- 60 ms versus from 91 +/- 8 to 145 +/- 38 ms, P < 0.05), QRS (from 58 +/- 3 to 149 +/- 34 ms versus from 60 +/- 5 to 101 +/- 17 ms, P < 0.05), and His ventricle interval (from 25 +/- 4 to 105 +/- 30 ms vs from 25 +/- 4 to 60 +/- 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent. IMPLICATIONS: A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.

Amides↗
PubMed2000

Processing and sorting of the prohormone convertase 2 propeptide.

The prohormone convertases (PCs) are synthesized as zymogens whose propeptides contain several multibasic sites. In this study, we investigated the processing of the PC2 propeptide and its function in the regulation of PC2 activity. By using purified pro-PC2 and directed mutagenesis, we found that the propeptide is first cleaved at the multibasic site separating it from the catalytic domain (primary cleavage site); the intact propeptide thus generated is then sequentially processed at two internal sites. Unlike the mechanism described for furin, our mutagenesis studies show that internal cleavage of the propeptide is not required for activation of pro-PC2. In addition, we identified a point mutation in the primary cleavage site that does not prevent the folding nor the processing of the zymogen but nevertheless results in the generation of an inactive PC2 species. These data suggest that the propeptide cleavage site is directly involved in the folding of the catalytic site. By using synthetic peptides, we found that a PC2 propeptide fragment inhibits PC2 activity, and we identified the inhibitory site as the peptide sequence containing basic residues at the extreme carboxyl terminus of the primary cleavage site. Finally, our study supplies information concerning the intracellular fate of a convertase propeptide by providing evidence that the PC2 propeptide is generated and is internally processed within the secretory granules. In agreement with this localization, an internally cleaved propeptide fragment could be released by stimulated secretion.

Amino Acid Sequence↗
PubMed2000

Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product.

Small chemical molecules that interfere with biological proteins could be useful for gaining insight into the complex biochemical processes in mammalian cells. Cdk4 is a key protein whose activity is required not only for emergence of cells from quiescence but also at the G1/S transition in the cell cycle and which is misregulated in 60-70% of human cancers. We set out to identify chemical inhibitors of Cdk4 and discovered that, in vitro, fascaplysin specifically inhibited Cdk4. Molecular modelling based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. Treatment of tumour (p16(-), pRb(+)) and normal (p16(+), pRb(+)) cell lines with fascaplysin caused G1 arrest and prevented pRb phosphorylation at sites implicated as being specific for Cdk4 kinase. Fascaplysin will therefore prove to be a useful tool in studying the consequence of Cdk4 inhibition, especially in cells containing inactivated p16.

3T3 Cells↗
PubMed2000

Novel Cdk inhibitors restore TGF-beta sensitivity in cdk4 overexpressing epithelial cells.

Transforming growth factor-beta (TGF-beta) is a potent mitogen that effects a wide variety of cells by blocking cell growth. TGF-beta acts by interacting with components of cell cycle machinery to cause G1 arrest and in mink lung epithelial cells (Mv1Lu) it does so by inhibiting Cdk4 synthesis. Overexpression of Cdk4 in these cells (B7) renders them resistant to the effects of TGF-beta. Here we report that two novel Cdk inhibitors (pyridopyrimidines) that not only inhibit Cdk4 and Cdk2 in an in vitro kinase assay but also, in the absence of TGF-beta, block growth of Mv1Lu cells in G1 more efficiently than their B7 (overexpressing Cdk4) counterparts. Interestingly, these inhibitors restored sensitivity of B7 cells towards TGF-beta. This may have implications for the treatment of tumors that have lost TGF-beta responsiveness due to deregulated cellular growth in vivo. These Cdk inhibitors could therefore be used in conjunction with TGF-beta to understand the mechanism of growth arrest in normal versus tumour cells.

Animals↗
PubMed2000

Mutations in the catalytic domain of prohormone convertase 2 result in decreased binding to 7B2 and loss of inhibition with 7B2 C-terminal peptide.

Prohormone convertases 1 (PC1) and 2 (PC2) are members of a family of subtilisin-like proprotein convertases responsible for proteolytic maturation of a number of different prohormones and proneuropeptides. Although sharing more than 50% homology in their catalytic domains, PC1 and PC2 exhibit differences in substrate specificity and susceptibility to inhibitors. In addition to these differences, PC2, unlike PC1 and other members of the family, specifically binds the neuroendocrine protein 7B2. In order to identify determinants responsible for the specific properties of the PC2 catalytic domain, we compared its primary sequence with that of other PCs. This allowed us to distinguish a PC2-specific sequence at positions 242-248. We constructed two PC2 mutants in which residues 242 and 243 and residues 242-248 were replaced with the corresponding residues of PC1. Studies of in vivo cleavage of proenkephalin, in vivo production of alpha-MSH from proopiomelanocortin, and in vitro cleavage of a PC2-specific artificial substrate by mutant PC2s did not reveal profound alterations. On the other hand, both mutant pro-PC2s exhibited a considerably reduced ability to bind to 21-kDa 7B2. In addition, inhibition of mutant PC2-(242-248) by the potent natural inhibitor 7B2 CT peptide was almost completely abolished. Taken together, our results show that residues 242-248 do not play a significant role in defining the substrate specificity of PC2 but do contribute greatly to binding 7B2 and are critical for inhibition with the 7B2 CT peptide.

Amino Acid Sequence↗
PubMed2000

[Surgical abstention in closed injuries of the spleen].

Splenic conservation avoids the overwhelming postsplenectomy infection. The high percentage of patients treated by noninvasive procedures would be due to the simple clinical course of splenic trauma and precision of diagnosis, using CT scan. Only clinical evaluation could provide further information on the indications for surgical treatment, as there is no available score regarding the value of CT scan for choosing the therapeutical option. Non-operative management of splenic ruptures should be considered in selected patients in whom hemodynamics is stable and closely monitored.

Adult↗