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Biomedical subjects

F Schiele

Publications and source records attributed to F Schiele.

At least 55 records · Page 3Linked to original sources

Seroreactivity to Borrelia burgdorferi antigens in early rheumatoid arthritis: a case-control study.

This study investigates the seroreactivity to Borrelia burgdorferi antigens of patients suffering from rheumatoid arthritis (RA) for < 5 yr. Subjects were matched with controls for age, sex and area of residence in order to minimize the risk of differential exposure to B. burgdorferi. A total of 57 pairs were tested by immunofluorescence assay (IFA) and Western blotting. Only two RA patients showed positive IFA results, and another was positive by Western blot analysis. No significant difference in Lyme seropositivity was detected between cases and controls using either serological test. Furthermore, no significant difference in antibody response was observed to specific or non-specific proteins (e.g. Osp C, 93 kDa protein, flagellin, heat shock proteins). These results do not support the previous suggestions that B. burgdorferi may be involved in the aetiology of RA, or that RA favours the production of antibodies that cross-react with B. burgdorferi proteins.

Adult↗

Planimetry of aortic valve area using multiplane transoesophageal echocardiography is not a reliable method for assessing severity of aortic stenosis.

OBJECTIVE: To assess the reliability of aortic valve area planimetry by multiplane transoesophageal echocardiography (TOE) in aortic stenosis. DESIGN: Study of the diagnostic value of aortic valve area planimetry using multiplane TOE, compared with catheterisation and the continuity equation, both being considered as criterion standards. SETTING: University hospital. PATIENTS: 49 consecutive patients (29 male, 20 female, aged 44 to 82 years, average 66.6 (SD 8.5)), referred for haemodynamic evaluation of an aortic stenosis, were enrolled in a prospective study. From this sample, 37 patients were eligible for the final analysis. METHODS: Transthoracic and multiplane transoesophageal echocardiograms were performed within 24 hours before catheterisation. At transthoracic echo, aortic valve area was calculated by the continuity equation. At TOE, the image of the aortic valve opening was obtained with a 30-65 degrees rotation of the transducer. Numerical dynamic images were stored on optical discs for off-line analysis and were reviewed by two blinded observers. Catheterisation was performed in all cases and aortic valve area was calculated by the Gorlin formula. RESULTS: Feasibility of the method was 92% (48/52). The agreement between aortic valve area measured at TOE (mean 0.88 (SD 0.35) cm2) and at catheterisation (0.79 (0.24) cm2) was very poor. The same discrepancies were found between TOE and the continuity equation (0.72 (0.26) cm2). TOE planimetry overestimated aortic valve area determined by the two other methods. Predictive positive and negative values of planimetry to detect aortic valve area < 0.75 cm2 were 62% (10/16) and 43% (9/21) respectively. CONCLUSIONS: Planimetry of aortic valve area by TOE is difficult and less accurate than the continuity equation for assessing the severity of aortic stenosis.

Adult↗

Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective dose-ranging randomized trial. International Multicentre Hirudin Study Group.

The aim of this multicentre, prospective, randomised, dose-ranging study was to compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023) against intravenous sodium heparin in acute lower limb deep venous thrombosis (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5 +/- 1 days. HBW 023 was given according to body-weight in three dose groups. Thromboembolic disease was assessed by phlebography and ventilation/perfusion (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer patients on HBW 023 developed new V/Q abnormalities during the treatment period, (p = 0.006). There was no difference between the groups in thrombus extension or regression, major bleeding complications or serious adverse events. There were significantly fewer findings of new V/Q mismatch after treatment with HBW 023, and anticoagulant control was superior in these patients.

Adult↗

[Long-term outcome of subvalvular aortic stenoses. A comparative study in adults and children].

The aim of the study was to determine the medium and long-term outcome of discrete subaortic stenosis after surgery: the data of two groups of patients classified according to age (children versus adults) at the time of diagnosis were compared retrospectively. Sixteen patients, with subaortic stenosis, were followed up clinically and by annual echocardiography for an average period of 5.7 +/- 3.6 years (range 1 day to 16 years) and patients in group II were aged 43.6 +/- 6 years (range: 3 to 17 years). Patients in group I were aged 5.4 +/- 4.2 years (range: 37 to 53 years). Four patients from group II had significant aortic incompetence. All but one patient had a membranous stenosis. Seven patients from group I and all in group II underwent surgery during the follow-up period. Four of the 5 adults in Group II were asymptomatic compared with only 1 in group I. Three patients of group II developed left ventricular dysfunction during the preoperative period compared with none in group I. Four patients in group II underwent aortic valve replacement compared with none in group I. Four of the 7 operated patients in group I had recurrence of subaortic stenosis, one of which was a tunnel form. Two reoperations were necessary in group I. There were no recurrences in group II. In conclusion, the poor outcome of adult subaortic stenosis has led to early surgical referral. This attitude should be nuanced in view of the risk of recurrence and of reoperation in childhood.

Adolescent↗

Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is a rare but severe complication of heparin therapy that can result in severe venous or arterial thromboembolic events and whose treatment remains partially unanswered. Recombinant hirudin is potentially effective as an antithrombotic treatment in the management of heparin-induced thrombocytopenia, given its potent antithrombin effects without known interaction with platelets. We report the results obtained with intravenous recombinant hirudin (HBW 023) administered on a compassionate basis to patients suffering from heparin-induced thrombocytopenia. Six patients suffering from heparin-induced thrombocytopenia were submitted to intravenous recombinant hirudin (HBW 023) administered at a dose of 0.05 mg/kg/hr after an initial bolus injection of 0.07 mg/kg in the case of a venous thromboembolic event, and at a dose of 0.15 mg/kg/hr with the same initial bolus injection in the case of an arterial thromboembolic event. Whenever possible, oral anticoagulation with acenocoumarol was introduced at the same time as recombinant hirudin, which was interrupted as soon as the international normalized ratio reached 3. Clinical events, particularly thromboembolism and bleeding, were noted; activated partial thromboplastin time (aPTT), and platelet count were assessed throughout the administration of recombinant hirudin. Heparins responsible for heparin-induced thrombocytopenia were porcine sodium or calcium heparinate in four cases, nadroparin in one case, and enoxaparin in one case. Thrombocytopenia was discovered on routine systematic platelet count in two patients and after the occurrence of arterial and venous thromboembolism in two patients, respectively. After discontinuation of heparin and the onset of recombinant hirudin, clinical evolution was uneventful in all patients, with no recurrence of thromboembolism, limb amputation, or hemorrhagic complication. The aPTT ratio varied from 1.8 to 3.5 (median 2.4) throughout administration of recombinant hirudin. Platelet count rose from nadir (median value 60 x 10(9), 15 to 90) to above 100 x 10(9)/L in every patient within 3-6 days (median 5), after discontinuation of heparin. Intravenous administration of recombinant hirudin ensured safe anticoagulation in patients with heparin-induced thrombocytopenia and made it possible to wait for oral anticoagulation to become efficient and platelet count to return to normal values without occurrence or recurrence of thromboembolism.

Aged↗

Lipid and lipoprotein genetic variability: an important contribution from the French health examination centers.

OBJECTIVE: To assess lipid and lipoprotein genetic variability in the French Population. METHODS: Many health examination centers are covering a great part of France (700,000 individuals are examined in 54 centers every year). Each citizen has the right to have a personal examination every 5 years. This unique system was modified in 1992, and we are presenting our 25-year experience focusing on the results we have more recently obtained in the lipid and lipoprotein field. RESULTS: First of all, the 600 items of information collected on every patient coming to our Center give us the data and facilitate the development of the theory of reference values. Having mastered the analytical variations, we studied the biological variations. Age, sex, overweight, tobacco, alcohol, and drugs are the main factors we should control for obtaining reference values. More recently, the genetic part in the production of reference values has become of greater importance, particularly for apolipoproteins. Apolipoprotein E is an important lipoprotein for which the two frequent mutations influence the level of circulating Apolipoprotein E. The risks linked to these alleles are also very different in cardiovascular disease and extremely important (for epsilon 4) in Alzheimer's Disease. Apolipoproteins B and A-IV also have interesting polymorphisms, but currently have no systematic applications in clinical chemistry. The familial recruitment we have in Nancy also permitted us to constitute a large tool "La Cohorte Stanislas." CONCLUSION: The thousand families recruited will be followed for 10 years. It is an open tool for collaboration.

Adult↗

Usefulness of reference materials in calibration of enzyme activities.

alpha-Amylase, alkaline phosphatase and gamma-glutamyltransferase were studied in a multicentre evaluation. Analyses were performed on different patient samples. Each enzyme was assayed in two different laboratories at both 30 and 37 degrees C, with widely used reagent kits and with the IFCC reference method (if in existence). Results differed considerably according to the measurement procedure. Data also showed that it was not possible to employ a constant conversion factor for one enzyme and different techniques between 30 and 37 degrees C. Calibration with three reference materials extensively improved the intermethod consistency for most of the tested measurement procedures. It was possible to transfer accuracy from the method used for the certification of the reference material to routine procedures, by using the reference material as calibrator. Temperature did not seem to be a crucial variable for the implement of the enzyme calibrator approach.

Alkaline Phosphatase↗

[Subcutaneous recombinant hirudin in the treatment of deep venous thrombosis. A pharmacokinetic study].

Recombinant hirudin (HBW 023) has a pure and specific antithrombotic activity. It could be more effective than heparin in the treatment of deep venous thrombosis. Its half life is about three hours when administered intravenously which requires continuous infusion whereas subcutaneous administration can ensure stable plasma concentrations and antithrombotic activity over a period of approximatively 12 hours. The aim of the study was to check the safety and clinical and radiographic efficacy of recombinant hirudin administered subcutaneously to patients with recent deep venous thrombosis and to analyse the pharmacokinetics of the product and its effects on tests of coagulation. Ten patients were treated with 0.75 mg/kg of subcutaneous recombinant hirudin twice a day for 5 days. Anticoagulation was performed with standard heparin and acenocoumarol. Bilateral phlebography, pulmonary angiography or ventilation and perfusion scintigraphy were carried out before and on the 5th day of recombinant hirudin treatment. The activated cephalin time and standard anticoagulant tests and the plasma kinetics of recombinant hirudin were assayed between the 1st and 12th hour on the first and fifth days of treatment. The clinical course was simple in all but one patient who had a recurrence of pulmonary embolism on the 4th day justifying thrombolytic treatment. No haemorrhagic complications or secondary biological effects were observed. On the 5th day, control phlebography was unchanged or improved in all patients. The peak plasma concentration of recombinant hirudin was observed between the 3rd and the 4th hour following subcutaneous injection. The activated cephalin time was increased in parallel with increased concentrations of recombinant hirudin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Improvement of result coherence in clinical enzymology: multicenter study of gamma-glutamyltransferase, alkaline phosphatase and amylase activities].

We report here on the results of a multicenter study of three enzyme activities (gamma-glutamyltransferase, alkaline phosphatase and amylase). For each activity, measurements were performed in two laboratories on different series of patients' specimens under routine conditions, at 30 and 37 degrees C, with techniques frequently used in France and with the IFCC reference method, when it exists. For each technique, precision was acceptable, but results differed considerably according to the technique used. The study also showed that for different techniques it is not possible to use a single transformation factor for activities between 30 and 37 degrees C. Patients' results determined by two techniques often showed a constant relationship. Groups of techniques that determined the same catalytic activity in patients' specimens were identified, whereas other techniques did not have this property. Several preparations, including reference materials produced by the Community Bureau of Reference (European Community, Brussels) and ten commercial secondary materials were tested for similar behaviour as compared to patients' samples. Results show the commutability of reference materials within a group of techniques indicating that they can be used as calibrators. This was seldom the case for the commercial secondary materials and we did not find any such material suitable for calibration of the three enzymatic activities. The present study demonstrates that with defined techniques and validated calibrators it is possible to reduce considerably differences between results obtained with different techniques at different temperatures and in different laboratories.

Alkaline Phosphatase↗

[Efficacy and safety of thrombolytic therapy in the elderly with severe pulmonary embolism].

Thrombolytic therapy leads to more rapid dissolution of thrombi in severe pulmonary embolism than conventional heparin therapy but is considered with much reserve in elderly patients because of the risk of haemorrhage, which is thought to be potentially greater in these subjects. The object of this study was to assess the efficacy and safety of thrombolytic therapy in patients over 70 years of age with severe pulmonary embolism, compared with patients under 70 years of age with the same condition. Eighty-nine patients with severe pulmonary embolism (Miller score > 17/34) were prescribed thrombolytic therapy in the absence of a contraindication without taking age into consideration. Fifty-three were under 70 years of age (54 +/- 15; range: 18 to 70 years) and 36 were over 70 years of age (78 +/- 5; range: 71 to 88 years). Apart from age, there was no difference in the clinical presentation of the two groups. Thrombolytic therapy was initiated with streptokinase 100,000 IU/hr for twelve hours after an initial bolus of 250,000 IU or with urokinase or plasminogen tissue activator in cases with a contraindication to streptokinase. An uncomplicated course was observed in the same percentage of cases in the two groups. The Miller score and mean pulmonary pressures fell in the same way in the two groups. Three patients died during the hospital period, two aged under 70 (3.7%) and one over 7 years of age (2.7%). Major bleeding occurred in 3 subjects under 70 (5.6%) and 5 subjects over 70 (13.8%) (p = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Complications of percutaneous mitral valvuloplasty; comparison of the double balloon and the Inoue techniques].

Percutaneous mitral valvuloplasty is a non-surgical procedure for treating mitral stenosis. There are two techniques of performing this procedure, the double balloon and the Inoue techniques. The aim of this study was to compare the immediate complications of percutaneous mitral valvuloplasty in two consecutive series of unselected patients undergoing the double balloon (131 patients) and the Inoue (131 patients) techniques. The two series were comparable before valvuloplasty with respect to demographic, clinical, echocardiographic and haemodynamic criteria. The increase in valvular surface area and the decrease in pressure gradient after valvuloplasty were not significantly different (1.1 +/- 0.2 to 1.95 +/- 0.5 cm2 in the Inoue series and 1.0 +/- 0.2 to 1.95 +/- 0.5 cm2 in the double-balloon series; 12 +/- 3 to 5 +/- 2 mmHg in the Inoue series and 13 +/- 4 to 5 +/- 2 mmHg in the double-balloon series for the mean transvalvular pressure gradient). A good immediate result was defined as a valve surface are > 1.5 cm2 and < or = 2 + mitral regurgitation after the series, and this was obtained in 78% of cases in both series. Severe mitral regurgitation (3 +) requiring immediate or elective mitral valve replacement was observed in 7 cases in the Inoue series and in 5 cases in the double-balloon series (NS). One cerebral embolism occurred in the double balloon series and two systemic embolisms, one cerebral and one coronary, in the Inoue series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The Y graft: myocardial revascularization with both internal thoracic arteries. Evaluation of eighty cases with coronary angiographic assessment.

The use of bilateral in situ internal thoracic arteries is restricted by the risk of sternal devascularization, the length of the pedicle, and the necessity to avoid crossing the midline. The aim of this study is to evaluate Y grafts achieved by anastomosing the proximal end of the free right internal thoracic artery to the side of the attached left internal thoracic artery. Y grafts were performed in 80 patients, aged 41 to 74 years (mean age 58.6 years) between May 1991 and September 1992. Two different techniques were used. Thirty-four patients were included in group 1 and 46 in group 2. Seventy-nine grafts were performed from the left internal thoracic artery to the left anterior descending artery. The right internal thoracic artery was anastomosed to the diagonal artery (5 times), the marginal branch (67 times), the circumflex artery (7 times) and the right coronary artery (2 times). Seventy-five complementary saphenous vein bypasses were performed in 58 patients. Operative mortality was 2.5%. Two patients had perioperative myocardial infarcts (2.5%) on nonbypassed sites. Three patients had sternal wound infections (3.7%). Sixty-two patients (80%) were reexamined by angiography at month 6-25 in group 1 and 37 in group 2. Sixty left internal thoracic artery bypass grafts (97%) were patent versus 39 right internal thoracic artery bypass grafts (63%). In group 1, 23 of 25 left internal thoracic artery bypass grafts were patient (92%) versus 12 right internal thoracic artery grafts (48%). In group 2, all 37 left internal thoracic artery bypass grafts were patent (100%) versus 27 right internal thoracic artery grafts (73%). With this procedure, particular attention must be paid to the length of the right internal thoracic artery, and extensive training is required.

Adult↗

A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis.

BACKGROUND: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis. METHODS: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5. RESULTS: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Marder score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5. CONCLUSIONS: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.

Adolescent↗

Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: a comparison with nonelderly patients.

OBJECTIVES: The aim of the study was to prospectively estimate the safety of thrombolytic therapy in elderly patients with massive pulmonary embolism in comparison with that in nonelderly patients. BACKGROUND: In massive pulmonary embolism, lysis of thrombi can be achieved faster with thrombolytic therapy than with conventional heparin therapy, but it is administered with great caution in elderly patients because the risk of bleeding is thought to be higher than in nonelderly patients. Yet, thrombolytic therapy might be of value in elderly patients also, in allowing potentially more rapid improvement than is achieved with conventional heparin therapy. METHODS: Eighty-nine patients with massive pulmonary embolism defined as Miller score > or = 17/34 underwent thrombolytic therapy without consideration of age if they had no contraindication for such treatment. Fifty-three patients were < or = 70 years old (mean age +/- SD 54 +/- 15 years; range 18 to 70), and 36 patients were > or = 71 years old (78 +/- 5 years; range 71 to 88). Except for mean age, there were no significant differences between the two treatment groups, particularly in terms of clinical presentation, average Miller score and pulmonary artery pressure regimen. Thrombolytic therapy was administered in the form of streptokinase at a dose of 100,000 IU/h over 12 h, with an initial injection of 250,000 IU over 15 min. Heparin was introduced 12 h after initiation of thrombolytic therapy. Urokinase or tissue-type plasminogen activator was used only in case of contraindication to streptokinase. RESULTS: The frequency of uncomplicated clinical course was the same in both treatment groups. Surgical embolectomy was necessary in three nonelderly patients (5.6%) and one elderly patient (2.7%). Changes in pulmonary pressure regimen and Miller score were identical in both groups. Three patients died during the in-hospital course: two nonelderly patients (3.7%) and one elderly patient (2.7%). Minor bleeding occurred in five nonelderly (9.4%) and five elderly (13.8%) patients (p = 0.74). Major bleeding was observed in three nonelderly (5.6%) and five elderly (13.8%) patients (p = 0.29). Bleeding subsequent to early invasive procedure accounted for six (75%) of eight patients with major bleeding: two nonelderly patients (one of whom died) and four elderly patients. No intracranial hemorrhage was observed. No predisposing factor for bleeding was identified, except the need for early vascular access for pulmonary angiography through the femoral approach or for percutaneous insertion of an intracaval device for partial interruption of the inferior vena cava. CONCLUSIONS: Thrombolytic therapy administered for massive pulmonary embolism in patients free of contraindication yields similar results and carries a similar risk for bleeding complications in elderly compared with nonelderly patients. Limiting early invasive procedures may result in less frequent major bleeding complications.

Adolescent↗

Concentration and hydroxyapatite binding capacity of plasma osteocalcin in chronic alcoholic men: effect of a three-week withdrawal therapy.

Plasma concentrations of osteocalcin (OC) were studied in 40 chronic alcoholic men (age range: 21-56 years) before and after 3 weeks of ethanol withdrawal therapy and in 50 non-alcoholic controls selected in respect to age and sex. Plasma OC level in alcoholic subjects was significantly lower than in the controls (3.0 +/- 2.6 micrograms/l and 4.7 +/- 2.8 micrograms/l, respectively). After 21 days of withdrawal therapy, plasma OC level was significantly higher than at the day of admission (5.8 +/- 3.5 micrograms/l, P < 0.001). This level was not statistically different from that of the controls. We also demonstrated that the hydroxyapatite binding capacity of plasma OC before as well as after the withdrawal period was not different from that of the controls. The acetaldehyde adduction of purified bovine OC in vitro did not change any of its immunoactivity and hydroxyapatite binding capacity. The results emphasize the fact that the decrease of plasma osteocalcin in chronic alcoholics is reversible within 3 weeks of alcohol withdrawal and that the circulating protein seems to be similar to that present in controls.

Acetaldehyde↗

Application of gene transfer technologies to the production of enzyme reference materials: example of gamma-glutamyltransferase.

Protein reference materials are traditionally prepared by purification from mammalian or human tissues. The supply of these tissues is limited; consequently, there is a growing need for applied molecular and cellular biology technologies for the production of human recombinant proteins. This is especially true when only small amounts of the proteins are available in the tissues. We review the current knowledge necessary for high-level production of such proteins in different heterologous expression systems, using our data on gamma-glutamyltransferase (EC 2.3.2.2) as an example. We describe the steps required to achieve the expression of enzymes and other proteins in Escherichia coli, yeast, or mammalian cells. We list many of the problems investigators may face in preparing recombinant proteins, and provide information on selecting the most appropriate system as well as the most favorable experimental conditions. Depending on the expression system, recombinant proteins can potentially be obtained for most, if not all, enzymes of interest in clinical chemistry, and such proteins should possess characteristics very similar to those of the corresponding human native proteins. Studies suggest that these products can be used as reference materials in clinical chemistry laboratories.

Animals↗

The role of genetics in defining reference values and health status.

Since its establishment, the Center for Preventive Medicine in Vandoeuvre-les-Nancy, France, performed specific studies on healthy humans, and its approach was very useful for defining reference values. Prevention should extend its interest to chronic diseases. The majority of important adult disorders are partially genetically determined. Genetic markers are also useful as exclusion or as partition criteria in the production of reference values. Results are presented that were obtained for apolipoproteins E, B and AIV, frequencies of these polymorphisms in the Lorraine population, and relationships between these polymorphisms and lipid metabolism-related parameters. Health checkup centers, in particular those involved in family screening, are well suited for resembling many data concerning environmental factors: tobacco consumption, alimentation habits, or alcohol and drug consumption. Simultaneous determination of genetic markers could allow the determination of an individual's susceptibility or resistance to developing a disease and to prepare a preventive action.

Environmental Exposure↗