Biomedical subjects

F Schiele

Publications and source records attributed to F Schiele.

At least 37 records · Page 2Linked to original sources

PubMed2000

Need for revisiting the concept of reference values.

The reference values concept has been adopted by health care professionals, including clinical chemists, laboratory scientists, and clinicians and simultaneously by all the official organizations in charge of the establishment of legislation. But the estimation of reference limits, and the evaluation of biological variability need to be improved at the level of the procedures, which are currently too long and too expensive and not feasible easily for all laboratories. The procedures for obtaining reference values, if we follow the original documents, are complex, and that is the main reason that clinical chemists or diagnostic kit manufacturers have not used them systematically. There is clearly a need that scientific societies and international organizations propose practical recommendations: 1) Recommendations to describe methods linked to systematic error. * How to transfer reference limits from one laboratory to another laboratory using different methods? * Should we determine reference limits for each method? * How can we differentiate bias due to the populations from these due to the method? Clear collaborations with manufacturers involved in kits and diagnostic systems are needed. 2) Practical recommendations linked to the reference population. * How to select a homogeneous population? (Careful recommendations on the choice between healthy individuals, blood donors and individuals hospitalised for other diseases should be given.) * How to estimate ethnic differences? * How to define the exclusion and inclusion criteria according to quantity? * How to deal with the question of reference limits for unstable periods, aging or old people particularly, when the difference between aging and disease is very difficult to define? 3) Practical recommendations on the statistical methods to be used. * How to make a good choice of the interquartile interval? Should we use and present only the centiles 2.5 or 97.5, or on the contrary should we give other centiles in addition, for example 5, 10, 75, 80, 85, 90? 4) Practical recommendations linked to the use of the concept of the reference values. * How to make this concept more concrete and to have official definitions which are better understandable and not only abstract? * How to demonstrate the value of using simultaneously reference limits and decision limits, and what does each of these limits bring to results interpretation? * How to improve the presentation of the results? How to give more information on biological variability in the laboratory data, taking into account the scientific validity of their determination? Should we use new information techniques and new communication systems for reaching these objectives? The responses to all these questions could only be provided if there is a concerted effort at the international level. Practical recommendations should be given, which would be very useful for a better understanding and use of reference values by laboratory scientists and clinicians.

Clinical Chemistry Tests↗

PubMed2000

Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses.

Apolipoprotein (apo) E is an important circulating and tissue protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several apo E variants have been identified. The common coding polymorphism strongly influences the lipid metabolism and the circulating concentration of apo E itself. This polymorphism is at the origin of the implication of apo E in cardiovascular and neurodegenerative diseases, but also of the relation of apo E with longevity. Probably due to its many metabolic and functional consequences, apo E polymorphism has been shown to influence the responses of patients to several drugs (fibrates, statins, hormone replacement therapy, anti-Alzheimer drugs) or environmental interventions (black tea, alcohol, diet). Apo E genotyping may be clinically helpful in defining the risk of patients and their responses to therapeutics. Finally, circulating apo E concentration appears to be altered in diseases and can be modulated by some of the drugs cited above. This parameter can thus also give interesting clinical information and could be a therapeutic target, providing it is validated. At the present time, we cannot exclude that apo E concentration may be the most prominent apo E parameter to be considered in health and disease, while apo E polymorphisms would represent only secondary parameters influencing apo E concentration.

Alleles↗

PubMed1999

Capillary electrophoretic analysis of recombinant human apolipoprotein E. Calibration mode of a protein reference material.

Actual lack of standardization of serum apolipoprotein (apo) E measurements prevents intensive studies on the significance of apoE concentration in clinical chemistry. For this purpose the use of standards calibrated against a common reference material is essential in order to obtain reliable results. The assignment of a certified value to this reference material involves the use of an accurate and non immunological technique. We demonstrate here that capillary electrophoresis in sodium dodecyl sulfate containing gel (SDS-CGE) can be a method of choice. ApoE quantification was performed according to the peak area and a standard solution of purified apoAI. We obtained very close results to that obtained by HPLC of phenylalanine apoE content measurement i.e., 81.6 mg/l versus 84.6 mg/l and concluded that the SDS-CGE analysis is an accurate and reliable method for the certification of an apoE reference material to be used in serum apoE concentration measurements. The SDS-CGE combines advantages of SDS-polyacrylamide gel electrophoresis (high resolving power, rapidity and tolerance of complex sample) with that of quantitative HPLC analysis (accuracy, precision, linearity and speed).

Apolipoprotein E3↗

PubMed1999

Effects of increasing balloon pressure on mechanism and results of balloon angioplasty for treatment of restenosis after Palmaz-Schatz stent implantation: an angiographic and intravascular ultrasound study.

Repeat balloon angioplasty is a widely used therapeutic option for in-stent restenosis, but the optimal balloon inflation pressure has not yet been determined. We used angiography and intravascular ultrasound imaging to assess the mechanism and results of lumen enlargement at various inflation pressures. Thirteen consecutive patients with restenosis post-Palmaz-Schatz stent implantation were submitted to a four-step balloon angioplasty using increasing balloon pressure of 2, 4, 8, and >12 atm. As a global result, the lumen size was only 80% of that observed at stent implantation. Significant changes in angiographic minimal lumen diameter, minimal lumen cross-sectional area, and lumen volume were observed after each step except after the highest-pressure inflation. At low inflation pressure (<8 atm), the decrease in neointimal tissue and the stent over expansion explained the lumen enlargement, whereas after further high inflation pressure (>8 atm), only additional stent over expansion was observed. These results suggest that only moderate balloon inflation pressure (up to 12 atm) is needed for angioplasty of post-Palmaz-Schatz stent restenotic lesions.

Angioplasty, Balloon, Coronary↗

PubMed1999

Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent--a pilot study in the setting of coronary angioplasty.

AIM OF THE STUDY: To assess the antithrombotic properties of SR90107/ORG31540. a sulfated pentasaccharide, which enhances specifically antithrombin III mediated inactivation of factor-Xa, in a clinical setting known to promote arterial thrombosis, i.e. coronary angioplasty. METHODS AND RESULTS: Percutaneous transluminal coronary angioplasty (PTCA) was carried out with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and 500 mg intravenous aspirin. Heparin was not allowed before, during PTCA, and within 24 h after PTCA. The primary end point was the rate of abrupt vessel closure during and within 24 h after the procedure. The sample size was set at 60 evaluable patients, in order to be able to conclude with a good level of confidence (>95%) that the abrupt vessel closure rate was less than 10%, if less than 3 abrupt vessel closures were observed. Seventy-one patients were included in the study, of whom 10 needed elective stenting, and were not considered as evaluable for efficacy. Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [3.28%, 95% confidence interval (0.4%; 11.4%)]. No major bleeding occurred. The drug plasma concentrations reached 1.91+/-0.39 mg/], 10 min after pentasaccharide injection, and decreased on average to 1. 18+/-0.27 mg/l at 2 h, and to 0.36+/-0.11 mg/l at 23 h after administration of pentasaccharide. Activated clotting time (ACT) and activated partial thromboplastin (aPTT) time remained within normal range. Thrombin-antithrombin complex levels fell from 22+/-17.1 to 4.5+/-3.4 microg/ml, prothrombin fragment 1+2 levels decreased from 2.15+/-1.01 to 1.73+/-0.87, and activated factor VII levels decreased from 43.4+/-16.8 mU/ml to 18.9+/-7.3 mU/ml respectively from baseline to 2 h following injection of the tested drug. CONCLUSIONS: Administration of pentasaccharide led to the inhibition of thrombin generation without modification of aPTT and ACT. The rate of abrupt vessel closure was within range of rates reported in historical series. Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves further investigation.

Adolescent↗

PubMed1998

Production and certification of an enzyme reference material for creatine kinase isoenzyme 2 (CRM 608).

We describe the preparation of a lyophilized material containing purified human creatine kinase 2 (CK-MB), and the certification of its catalytic concentration. The material can be used to verify the comparability of results from different laboratories, for intra-laboratory quality control, or for calibration of the creatine kinase 2 catalytic concentration measurements. The enzyme was purified from human heart by ethanol precipitation and chromatography successively on DEAE-Sephacel and Blue-Sepharose. The purified enzyme had a specific activity of 998.4 U/mg and was > 99% pure on polyacrylamide gel electrophoresis. The material was examined for several possible contaminating enzymes, which were found to be absent. The purified creatine kinase 2 had two subunits (B and M) with molecular masses of 43,650 and 41,700 g/mol, respectively, and an isoelectric point at pH 5.8. The material was prepared by diluting the purified creatine kinase 2 in a matrix containing 25 mmol/L PIPES buffer, pH 7.2, 2 mmol/L ADP, 5 mmol/L 2-mercaptoethanol, 154 mmol/L sodium chloride and 50 g/L human serum albumin, dispensing it into vials and freeze-drying. The batch was shown to be homogeneous. The loss of enzyme activity on storage at -20 degrees C is predicted to be less than 0.18% per annum on the basis of accelerated degradation studies. The catalytic concentration of creatine kinase in samples of the reconstituted material is certified to be 67.2+/-1.8 U/L (1.12+/-0.03 microkat/L) when measured, at 30 degrees C, by the Recommended Method of the International Federation of Clinical Chemistry.

Catalysis↗

PubMed1998

Treatment of in-stent restenosis with high speed rotational atherectomy and IVUS guidance in small <3.0 mm vessels.

The management of in-stent restenosis remains a subject for debate because no one revascularization option is considered the most appropriate. Since a high restenosis rate still occurs after repeat balloon angioplasty, new techniques are attempted in order to reduce this rate. A combination of high speed rotational atherectomy (HSRA) and adjunctive balloon angioplasty is likely to achieve good results. In small (<3.0 mm diameter) vessels, the risk of interaction between the burr and the stent increases. We thus used intravascular ultrasound (IVUS) guidance in the treatment of in-stent restenosis with HSRA in small <3.0 mm small diameter vessels. Nine patients with in-stent restenosis in small vessels were referred for repeat angioplasty. Initial IVUS examination was used to assess the minimal stent struts diameter and to guide the burr size selection. A combination of HSRA and additional balloon angioplasty was performed under IVUS and angiographic guidance. Mean angiographic reference diameter was 2.25 +/- 0.35 mm and mean stent struts diameter was 2.38 +/- 0.20 mm. Burr size was selected approximately 0.5 mm smaller than stent struts diameter and ranged from 1.75 to 2.5 mm, with a 0.88 +/- 0.12 mean burr/artery ratio (range 0.71, 1.08). In two patients, a second larger burr was used. In 4/9 patients, the burr size chosen under IVUS guidance was close to angiographic MLD at stent implantation and thus larger than what would be used without IVUS guidance. Additional balloon angioplasty was decided in all cases, using a 1.1 +/- 0.15 balloon/artery ratio. No complication occurred. Mean relative gain in minimal lumen diameter (MLD) was 94 +/- 90% after HSRA and 54 +/- 34% after balloon angioplasty (total relative gain 180 +/- 100%). IVUS guidance allowed safe management of in-stent restenosis in small vessels using combination of HSRA and balloon angioplasty. Long-term follow-up and comparison with other techniques are necessary to assess whether this technique should be used routinely.

Adult↗

PubMed1998

Coronary stent for variant angina: atypical presentation.

Pharmacological therapy remains the treatment of choice for Prinzmetal angina. We report an unconventional approach of coronary artery stenting to treat coronary artery spasm in variant angina refractory to triple drug therapy. Favorable clinical and angiographic results and a negative Ergonovine test, under less aggressive medical therapy, are valuable arguments for stenting. Four-month angiographic follow-up showed absence of intrastent restenosis with a negative Ergonovine test. However, long-term follow-up is necessary before advocating this as a systematic approach.

Adult↗

PubMed1998

Interassay calibration as a major contribution to the comparability of results in clinical enzymology.

OBJECTIVE: Factors contributing to the applicability of interassay calibration of methods measuring enzyme catalytic activities are described. Also discussed are the properties essential for such a material. Similarity of specificity for the methods to be calibrated as well as commutability between the material(s) intended to be used as calibrator are the main criteria to be satisfied. RESULT: Several examples demonstrated that interassay calibration is feasible but a multi-enzyme calibrator with a wide commutability for the most popular methods remains to be developed. This is the project of the IFCC Working Group on Calibrators in Clinical Enzymology (WG-CCE). Several experimental data are also presented that indicate that the temperature at which the reaction is carried out is not a limiting factor in the implementation of interassay calibration in clinical enzymology.

Calibration↗

PubMed1998

Validation of an enzyme calibrator--an IFCC guideline. International Federation of Clinical Chemistry.

OBJECTIVES: The objective of this guideline is to improve standardization in clinical enzymology in order to improve intermethod comparability of patients' results. DESIGN AND METHODS: The reference system, combination of the reference method and the reference material, is used to produce a reference value for a given catalytic activity. Sets of methods are formed of methods exhibiting the same analytical specificity. Materials intended to be used as enzyme calibrators are experimentally checked for their commutability. RESULTS: The transfer of accuracy from the reference value to patients' results is dependent on methods (analytical specificity) and on materials (experimentally assessed commutability). The feasibility of this approach was demonstrated with materials of high level for several enzymes and for each of them for several routine methods. CONCLUSION: Expected advantages of this approach in clinical enzymology are presented.

Calibration↗

PubMed1998

Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up.

OBJECTIVES: This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome. BACKGROUND: Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis. METHODS: Sixty-six patients with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding. RESULTS: Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38+/-18% vs. 31+/-19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases. CONCLUSIONS: These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.

Acute Disease↗

PubMed1998

Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies--with and without intravascular ultrasound guidance. RESIST Study Group. REStenosis after Ivus guided STenting.

OBJECTIVES: We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials. BACKGROUND: The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance. METHODS: After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%). RESULTS: We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean +/- SD) (7.16 +/- 2.48 vs. 7.95 +/- 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 +/- 0.65 mm in Group A vs. 1.70 +/- 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 +/- 2.59 vs. 5.36 +/- 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis. CONCLUSIONS: A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial.

Angioplasty, Balloon, Coronary↗

PubMed1998

Simplified percutaneous mitral valvuloplasty with the Inoue balloon.

BACKGROUND: Percutaneous mitral valvuloplasty with the Inoue balloon is conventionally performed with double vascular access: arterial and venous. However, in patients with a good echogenic window it may be performed with venous access only and the procedure monitored by 2D-echocardiography and colour flow mapping. This should result in early ambulation and hospital discharge with reduced arterial complications. AIMS: To compare retrospectively the immediate results of percutaneous mitral valvuloplasty with the Inoue balloon in two groups of patients: Group I: venous access only (no arterial access, n = 102) and Group II: conventional double vascular access (arterial and venous access, n = 275). METHODS AND RESULTS: The baseline characteristics of the two groups were comparable for age, sex, clinical, echocardiographic, radiological and haemodynamic variables. The mitral valve area (Group I: 1.1 +/- 0.3 to 1.85 +/- 0.5 cm2 vs Group II: 1.05 +/- 0.2 to 1.85 +/- 0.5 cm2, P = ns) and transmitral gradient (Group I: 11 +/- 4 to 4.7 +/- 2 mmHg vs Group II: 12 +/- 4 to 4.8 +/- 2 mmHg, P = ns) before and after mitral valvuloplasty were not statistically different. A good immediate result, defined as mitral valve area > 1.5 cm2 and mean mitral gradient < 5 mmHg with mitral regurgitation < or = 2+ at the end of the procedure, was observed in 77% of the cases in the venous-only group and 79% in the double access group (P = ns). The incidence of severe mitral regurgitation (Grade III or IV) was not statistically significant. Procedural duration (71 +/- 24 min vs 109 +/- 26 min, P < 0.01), fluoroscopic time (12.5 +/- 5.5 min vs 18.5 +/- 6 min, P < 0.01) and hospital stay (2.8 +/- 1.5 days vs 4.8 +/- 2.6 days, P < 0.001) were significantly shorter in the venous-only group than in the conventional Inoue series. CONCLUSION: Single venous access balloon mitral valvuloplasty is as equally safe and effective as double vascular access. The additional advantages of single venous access are shorter procedural duration, fluoroscopic time and hospital stay. We recommend that it be performed by an experienced operator (minimum of 100 trans-septal punctures) in patients without major thoracic deformity and a good echogenic window.

Adult↗

PubMed1998

Predictors of event-free survival after percutaneous mitral commissurotomy.

OBJECTIVE: To assess the long term functional result after percutaneous mitral commissurotomy and identify the predictors of event-free survival following 10 years of experience. DESIGN: Analysis of clinical, echocardiographic, and haemodynamic variables at baseline and after the procedure by univariate and multivariate analyses (Cox model). SETTING: University hospital. PATIENTS: 532 consecutive patients receiving percutaneous mitral commissurotomy in the same institution. RESULTS: The mean (SD) follow up was 3.8 (4.0) years. Survival at 3, 5, and 7.5 years was 94%, 91%, and 83%, respectively; event-free survival was 84%, 74%, and 52%. Mitral valve anatomy was identified as the strongest independent predictor of event-free survival. Age, cardiothoracic ratio, mean pulmonary artery pressure, and mean echocardiographic mitral gradient after commissurotomy were also found to be independent predictors of long term functional results. Event-free survival was 92%, 84%, and 70% at 3, 5, and 7.5 years in patients with favourable anatomy (echo score = 1), 86%, 73%, and 34% in patients with intermediate anatomy (echo score = 2), and 45%, 25%, and 16% in patients with unfavourable anatomy (echo score = 3). In patients aged < or = 65 years, the event-free survival rate was 80%, 70%, and 45% at 3, 5, and 7.5 years v 52%, 38%, and 17% in patients aged > 65 years. CONCLUSIONS: The anatomical form of the mitral valve and the patient's age were the most powerful predictors of event-free survival. Patients with intermediate or unfavourable anatomy and those aged > 65 years have low 5 and 7.5 year event-free survival rates. This must be taken into account when discussing the indications for percutaneous mitral commissurotomy; immediate mitral valve replacement is a reasonable alternative to balloon mitral commissurotomy in patients with higher risk of functional deterioration after the procedure.

Age Factors↗

PubMed1998

Biological effects of eleven combined oral contraceptives on serum triglycerides, gamma-glutamyltransferase, alkaline phosphatase, bilirubin and other biochemical variables.

The objectives of this paper are to update and quantify the biological effects of the most commonly used oral contraceptives (OC) on 15 biochemical tests currently determined in clinical laboratories and to compare these effects between the different types of OC. The sample population was constituted by 1604 women using combined OCs and the control group comprised 3466 women in the same age range not taking medication. Women taking OC were divided into 11 groups according to the estrogen/progestogen combination. The effects of OCs were studied after adjustment for age, weight, height, body mass index and alcohol and tobacco consumption. The changes observed with the new progestogens were less important than in the past. In comparison with the controls, the mean serum triglyceride concentration was significantly increased by +8.5% to +36.0% (p<0.05 to p<0.001) in each group while those of total cholesterol and gamma-glutamyltransferase were increased only in 3 and 4 estrogen/progestogen combinations respectively. Conversely, the mean concentrations of alkaline phosphatase, total bilirubin, phosphate and albumin were significantly decreased. Using a discriminant analysis, three main groups according to the type of progestogen were defined: cyproterone acetate, DL-norgestrel and levonorgestrel, and all other progestogens. The changes in serum triglyceride concentration induced by OC intake must be considered by the clinician and are useful for taking a clinical and risk decision in an individual woman.

Adolescent↗

PubMed1998

Biological variations and genetic reference values for apolipoprotein E serum concentrations: results from the STANISLAS cohort study.

Serum apolipoprotein (apo) E concentrations were determined by immunoturbidimetry in 4284 subjects from 4 to 71 years of age and belonging to 1003 nuclear families recruited for the STANISLAS cohort study between January 1994 and August 1995. Values for apo E ranged from 16 to 169 mg/L, with a geometric mean +/- SD values of 46.6 +/- 13.8 mg/L in the overall sample. The interindividual variability varied from 24.6% to 32.0% among family members. Females exhibited higher apo E values than males until the age of 17-26 years. Conversely, after the age of 26 years, serum apo E concentrations were higher in men than in women. Biological factors affecting serum apo E concentrations were described in fathers, mothers, sons, and daughters and explained up to 32.0% of the apo E variability in daughters and 19.0% in fathers. The main biological factors affecting apo E concentrations were the following: apo E polymorphism, waist-to-hip ratio, oral contraceptive intake, puberty, body mass index, age, and gender. Given the importance of apo E polymorphism in the regulation of apo E concentrations, we recommend the use of genetic-based reference values for the clinical interpretation of serum apo E concentrations.

Adolescent↗

PubMed1997

Gene transfer technologies for the production of enzyme and protein reference materials.

To maintain the success of recommended methods and to allow comparison among various methods of enzyme analysis, enzyme reference materials are required, having catalytic properties as close as possible to those of the corresponding human enzymes. Though human sources are preferable, ethical reasons require the extraction and purification from animal tissues. By providing theoretically unlimited amounts of material, gene transfer technologies and mass culture can overcome the need of human or mammalian tissues. We have used these technologies to produce human gamma-glutamyltransferase (GGT) and pancreatic lipase (PL) in various types of host cells. Different strategies were tested, especially for GGT, depending on the inherent properties and requirements of the human enzyme. Expression and purification protocols were optimized, yielding good amounts of recombinant enzymes which share many physico-chemical and catalytic features with their natural counterparts. Kinetic constants and catalytic behavior were very similar, demonstrating the usefulness of these products as reference materials. We assume recombinant DNA technologies could be successfully applied to most enzymes or proteins assayed in clinical chemistry laboratories.

Animals↗

PubMed1997

Streptokinase vs alteplase in massive pulmonary embolism. A randomized trial assessing right heart haemodynamics and pulmonary vascular obstruction.

OBJECTIVE: The aim of the study was to test the efficacy of recombinant tissue plasminogen activator and streptokinase in massive pulmonary embolism, the primary endpoints being haemodynamic improvement and thrombus lysis, and the secondary endpoints efficacy and safety. DESIGN: Fifty patients with massive pulmonary embolism were randomly allocated either to a 100 mg 2 h infusion of recombinant tissue plasminogen activator followed by a 20 IU.kg-1.h-1 infusion of heparin, or to a 100,000 IU.h-1 12 h infusion of streptokinase after a initial bolus of 250,000 IU over 15 min, followed by heparin infusion of 10 IU.kg-1.h-1. Total pulmonary resistance and right ventricular ejection fraction were monitored over a 12 h period. Pulmonary vascular obstruction was assessed at 24 to 48 h and 10 days after thrombolytic therapy. RESULTS: Thrombolysis occurred more rapidly with recombinant tissue plasminogen activator than with streptokinase, but without any significant difference in terms of right heart haemodynamics at 12 h or in improvement of pulmonary vascular obstruction at 24-48 h or at 10 days. There was no significant difference in bleeding complication rates and no patients suffered intracranial haemorrhage. CONCLUSION: These results proved that, when the full dose of streptokinase has been given over 12 h, its efficacy is as good as that of 2 h of recombinant tissue plasminogen. A further trial aimed at comparing recombinant tissue plasminogen activator and streptokinase infused over a 2 h period is needed to determine whether a similar efficacy can be obtained.

Aged↗