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Biomedical subjects

P Burtin

Publications and source records attributed to P Burtin.

At least 73 records · Page 4Linked to original sources

Changes in hemodynamic and metabolic parameters following induced brain death in the pig.

Changes in hemodynamic and metabolic parameters (systemic oxygen delivery, [DO2], oxygen consumption [VO2], arterial lactate content) in brain-dead and control pigs in the absence of any inotropic or fluid support were studied. Brain death was induced by the inflation of a Foley catheter balloon placed into the subdural space of the animals. Serial atrial natriuretic peptide (ANP) determinations were performed to evaluate concomitant changes occurring in the endocrine function of the heart. Experiments were completed by a volume expansion protocol to provide a dynamic evaluation of these parameters. A significant increase in heart rate (from 113 +/- 5 to 176 +/- 11 beats/min), pulmonary capillary wedge pressure (from 7 +/- 1 to 12 +/- 3 mmHg), dP/dt (from 2040 +/- 340 to 4200 +/- 660 mmHg/sec-1), cardiac output (from 2.4 +/- 0.2 to 3.3 +/- 0.4 L/min), mean arterial pressure (from 66 +/- 8 to 93 +/- 14 mmHg), and systemic oxygen delivery (from 360 +/- 30 to 530 +/- 90 ml/min-1), was observed following brain death induction. These parameters returned below basal values within 60 min. On the contrary, serum lactate and VO2 remained unchanged. Following volume expansion, brain-dead pigs exhibited impaired hemodynamic response, with a significant decrease in dP/dt, MAP, and DO2. These changes were accompanied by a significant decrease in VO2 and a significant increase in lactate plasma levels. At the same time, a similar increase in ANP release was observed in both groups in response to volume expansion, suggesting that despite impaired myocardial contractility, endocrine function of the heart was preserved following brain death. We conclude that brain death leads to early impaired left ventricular contractility, which could be responsible for the changes observed in aerobic to anaerobic metabolism in response to rapid volume infusion. These results suggest that the use of fluid infusion to reduce the need in inotropic support in conventional therapeutic modalities should be used with care in the management of a brain-dead potential organ donor.

Animals↗

Purification of the plasmin receptor from human carcinoma cells and comparison to alpha-enolase.

We have characterized a receptor for plasmin (Pli-R) from a human tumor cell line, MCF7MF. The Pli-R was purified from a MCF7 0.1% Triton X-100 solubilisate by affinity chromatography. A protein of 55-60 kDa was obtained, which bound plasminogen and plasmin specifically. Chemical cross-linking of M(r) 90 kDa [125I]-Pli to the surface of MCF7 cells with DSP results in the formation of a labelled complex of M(r) 145 kDa, suggesting a M(r) of 55-60 kDa for the receptor. Comparing Pli-R with alpha-enolase (a candidate for plasminogen receptor in U937 cells) we have found a high homology between both proteins, but not an identity.

Amino Acid Sequence↗

Prognosis of stroke patients undergoing mechanical ventilation.

OBJECTIVE: to determine the outcome of stroke patients undergoing mechanical ventilation. DESIGN: retrospective chart review and follow-up telephone interview. SETTING: medical ICU in a multidisciplinary university hospital. PATIENTS AND PARTICIPANTS: 199 stroke patients from 1984-1989 where the final diagnosis was stroke. INTERVENTIONS: all patients were admitted for the need of mechanical ventilation. MEASUREMENTS AND RESULTS: demographic information, previous relevant diseases, stroke type, general clinical and neurological data, biochemical variables, severity of illness were recorded for the first 24 h following ICU admission. A 1-year follow-up was performed, including mortality and functional status of survivors. Of 170 eventually analyzable patients, 123 (72.4%) died during their ICU stay and 156 (91.8%) during the first year. Three variables were independently associated with one-year mortality: Glasgow score < 10 (p < 0.03), bradycardia (p < 0.001), absence of brainstem reflexes (p < 0.0004). CONCLUSION: overall prognosis of stroke needing mechanical ventilation is poor, strongly linked to symptoms of neurological impairment.

Brain Ischemia↗

Population pharmacokinetics of midazolam in neonates.

OBJECTIVE: To describe the pharmacokinetics of midazolam, a water-soluble benzodiazepine with a short half-life, in critically ill neonates. HYPOTHESIS: Midazolam clearance is reduced in neonates compared with clearance in children, and the doses currently in use, which are derived from pediatric studies, are excessive. PATIENTS AND METHODS: This population study was conducted in 187 neonates requiring intravenous sedation for artificial ventilation. The 531 midazolam concentration measurements obtained were analyzed by use of NONMEM and a two-compartment model with four parameters: clearance (CL), central volume (Vc), peripheral volume (Vp), and intercompartmental clearance (Q). The influence of birth weight (range, 700 to 5200 gm), gestational age (range, 26 to 42 weeks), postnatal age (range, 0 to 10 days), and comedications were investigated. RESULTS: CL and Vc (mean +/- SE) were found to be directly proportional to birth weight (CL = 0.070 +/- 0.013 L/kg/hr; VC = 0.591 +/- 0.065 L/kg). The CL was 1.6 times higher in neonates with a gestational age of more than 39 weeks. It was 0.7 times lower in neonates receiving inotropic support. The postnatal age had no apparent effect on midazolam kinetics. The Vp and Q (mean +/- SE; 0.42 +/- 0.11 L and 0.29 +/- 0.08 L/hr, respectively) were not influenced by any of the covariates studied. There was a large interindividual variability for the pharmacokinetic parameters. CONCLUSION: The mean midazolam doses required for critically ill neonates are lower than those required for older infants.

Critical Illness↗

Saliva versus blood sampling for therapeutic drug monitoring in children: patient and parental preferences and an economic analysis.

The objective of this study was to conduct an assessment of patient and parental preferences and an economic analysis of hospital costs in sampling blood and saliva for therapeutic drug monitoring (TDM). Costs and preferences were evaluated in the course of a study, which compared anticonvulsant concentrations in blood routinely drawn for therapeutic monitoring and in saliva in infants and children attending a pediatric neurology clinic. Parents of 84.8% of children, and half of the children, indicated a preference for saliva sampling over venous blood drawing. Children who had been on medications that required therapeutic monitoring for < 2 years were more likely to prefer saliva sampling as compared to those who were under treatment for > or = 2 years. Computation, based upon a basic assumption that a registered nurse obtained blood and a medical technician or a registered nurse assistant sampled saliva, indicated that for every 1,000 cases of changing from blood to saliva sampling, total cost savings would amount to $1,930 for cooperative children and $1,660 for infants and uncooperative children. This saving is equivalent to approximately 100 h of a registered nurse's initial salary. The important contributions to the differential cost were derived from the requirements for more highly trained individuals to take the blood sample and from the doubling time required for the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Risk of infectious diseases in children attending different types of day-care setting. Epicrèche Research Group.

This population-based prospective cohort study compared the risk of recurrent infections in children attending family day care (< or = 3 children per family), small (10-20 children) day-care centers (DCCs), and large (> or = 40 children) DCCs. The parents of a total of 1,242 children participated in the study (97% of the families initially contacted). An infectious episode was defined as the acute occurrence of a new symptom lasting for at least 48 h and resulting in specific treatment. Two episodes were counted as such only if they were separated by a symptom-free week. Surveillance was under the responsibility of a nursing director and was similar for all three types of DCCs. During the 8.5-month follow-up period, 3,639 infectious episodes were recorded. Compared to those in family day-care, children attending small DCCs presented a higher risk for > or = 6 total infectious episodes [odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.6-3.7]; > or = 5 upper respiratory tract infections (OR = 2.2; 95% CI = 1.4-3.4); > or = 2 episodes of otitis media (OR = 2.6; 95% CI = 1.0-2.6); > or = 2 episodes of conjunctivitis (OR = 4.1; 95% CI = 2.1-8.2); and > or = 2 episodes of croup (OR = 4.1; 95% CI = 1.6-10.9). The risk for children attending large DCCs was intermediate between those in family day care and those in small DCCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Care↗

The plasminogen-activation system in ovarian tumors.

We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase-type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-I (PAI-I) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-I concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA x PAI-I/t-PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer.

Carcinoma↗

Biochemical characterization of a rat oncofetal colonic antigen defined by a monoclonal antibody raised against gastric surface epithelium.

The 660 epitope was defined by a monoclonal antibody raised against rat gastric surface epithelium scrapings. This epitope, a marker of goblet cell differentiation, shows oncofetal behaviour in the colonic mucosa. We found that it co-purified with gastric mucin glycoproteins. We isolated rat gastric mucus glycoproteins using standard techniques: gastric scrapings in PBS were submitted to isopycnic density gradient centrifugation in CsCl in the presence of proteinase inhibitors. Fractions of relative density 1.4-1.45 with a high neutral sugar/protein ratio were chromatographed on an Ultrogel A4 column. According to the usual criteria, the high-molecular mass glycoproteins recovered in the excluded volume were purified mucins; when stained with periodic acid/Schiff reagent, they showed little migration on 4-15% gradient gel acrylamide electrophoresis. Serine+threonine+proline residues accounted for 35% of the total amino acids; the carbohydrate composition consisted of galactose, fucose, N-acetylgalactosamine and N-acetylglucosamine. These mucus glycoproteins carried the 660 epitope. After disulphide bond reduction, the remaining high-molecular-mass subunits were retained by the Ultrogel A4 column; amino acid and saccharide compositions were generally similar to those of the unreduced fraction. Trypsin digestion of the 660 epitope glycoprotein carrier did not modify its chromatographic and electrophoretic patterns, nor its chemical composition. The 660 epitope was still present after these treatments. However, trypsin digestion of subunits gave rise to smaller components that were retained by an Ultrogel A4 column. The saccharide composition of these fragments was unchanged, but the proportion of serine+threonine+proline residues rose to 46% of the total. These digested subunits had lost nearly all reactivity with monoclonal antibody 660. Our results fit well with the macromolecular model of Carlstedt, Lindgren and Sheehan [(1983) Biochem. J. 213, 427-435]: mucin glycoproteins are homopolymers of subunits assembled end-to-end via disulphide bonds into very large linear macromolecules. After disulphide bond reduction, proteolytic attack sites are uncovered and trypsin digestion results in glycopeptides bearing the typical oligosaccharidic units and with enhanced amounts of serine, threonine and proline, the characteristic amino acids of this hyperglycosylated region of the peptide core. These digested subunits have lost virtually all 660 epitope reactivity. We thus show that the 660 epitope, a determinant of a mucin molecule, is probably associated with the peptide core of the glycoprotein.

Amino Acids↗

Visualization of the plasmin receptor on sections of human mammary carcinoma cells.

In previous studies we observed the presence of an antigen reacting with anti-plasminogen serum on tumor cells found in sections of human colorectal and mammary carcinomas, using immunofluorescence. This antigen could be plasminogen, or plasmin or both. These results led us to surmise that carcinoma cells, and not normal epithelial cells, had a receptor for plasmin and plasminogen. We demonstrated the existence of such a receptor on cells of established tumor cell lines of colonic and mammary origin. We observed that binding of plasmin(ogen) to its receptor was inhibited by lysin and its analogs. We undertook to characterize the plasmin receptor on sections of human mammary carcinomas (18 series of sections, originating from 15 infiltrating ductal carcinomas). In our immunofluorescence studies, we observed that the fluorescence induced by anti-plasminogen serum was suppressed by pre-treatment of the sections with tranexamic acid, a lysin analog. Furthermore, when parallel sections were incubated with tranexamic acid, then with solutions of plasminogen, tumor cells were made fluorescent again. Another important finding was the strong increase of labelling observed when sections were incubated with plasminogen or plasmin before reaction with anti-plasminogen serum. This labelling disappeared when tranexamic was added to plasminogen. As a whole, these results confirm the existence of plasmin receptors on tumor cells in mammary carcinoma sections. They also show that these receptors are not saturated in vivo and may bind, in vitro, additional amounts of ligand.

Breast Neoplasms↗

Comparative localization of receptors for plasmin and for urokinase on MCF 7 cells.

The receptor for plasmin and the receptor for urokinase-type plasminogen activator were characterized on MCF 7 cells either independently or simultaneously, using fluorescence microscopy and confocal microscopy. The plasmin receptor was visualized, as previously described by Correc et al. (Int. J. Cancer 50, 767, 1992) using biotinylated plasminogen and fluoresceinated streptavidin. The urokinase receptor was revealed by both polyclonal and monoclonal antibodies reacting specifically with this receptor and by binding of urokinase aminoterminal fragment. On unfixed cells, these methods gave the same heterogeneous patterns of surface staining, consisting of contours and grains, localized mainly at the upper nonadherent face of the tumor cells by confocal microscopy. Only a part of the cells was stained. When both receptors were characterized together, their presence was found on the same cells and they gave almost superimposable patterns in many cases, as shown by confocal microscopy. In contrast, when MCF 7 cells were fixed or permeabilized before staining, quite different patterns were observed: almost all the cells were labeled. The staining was mainly cytoplasmic and localized preferentially in the center and close to the upper face of the cells. Similar results were found with antiserum against urokinase receptor and monoclonal antivinculin antibody. It is likely that the receptor for urokinase and the receptor for plasmin have similar localizations on MCF 7 cells, thus resulting in a functional cooperation.

Breast Neoplasms↗

Malignant lymphoma in the donor heart after heart transplantation.

A case of post-transplant lymphoproliferative disease (PTLD) with donor heart involvement is reported. The 49-year-old patient presented with heart failure initially ascribed to acute graft rejection. The treatment with high doses of immunosuppressive agents was unsuccessful and the outcome rapidly fatal. This case suggests that cardiac failure occurring after high doses of immunosuppressive therapy could be a sign of early PTLD in heart transplant recipients.

Biopsy↗

[Laser therapy of villous rectocolonic tumors. Evaluation of results by multivariate analysis].

One hundred and twenty-four patients (mean age: 70 years) with a villous tumour of the rectum (n = 98) or the colon (n = 26) were treated by laser therapy from 1985 to 1991. Initial complete eradication was obtained in 93.5% of cases with a median time of 16 months. Using multivariate analysis, the tumor size (> 4 cm) only was predictive of eradication (P < 0.001). At 6 and 12 months, the actuarial eradication rates were 91 and 98% for small tumours versus 45 and 74% for larger tumours respectively. The actuarial recurrence rates were 10.5, 23, and 37% at 6, 12 and 24 months, and no longer increased after 3 years. No predictive factor of recurrence was isolated by multivariate analysis. Seven complications (5.6%) and 4 malignant transformations (3.4%) occurred. This study confirms the efficiency and low morbidity of laser therapy, especially in patients with small tumors, less than 4 cm in size.

Adenoma, Villous↗

[Prognostic factors of hepatocellular carcinoma. Multifactorial analysis of 84 cases].

To identify prognostic factors taking in account recent advances in diagnosis and treatment, 24 clinical, biological, and morphological factors were evaluated by means of uni- and multivariate analysis in 84 patients with hepatocellular carcinoma diagnosed between 1984 and 1991. Okuda's grading (P < 0.01), creatininemia (P < 0.01), and treatment (P < 0.05) were independent prognostic factors. Des-gamma-carboxyprothrombin reached a significant level (P < 0.05) in a subgroup of 32 recent patients but its prognostic value needs to be confirmed. Further prospective randomized trials comparing surgical and non-surgical treatment should take these factors into account.

Adult↗