[PSA kinetics after radiotherapy]. / Cinétique de PSA après radiothérapie.

The prostate specific antigen (PSA) is the best marker of the prostate cancer today although not very specific of this pathology. The dynamic interpretation of this marker always has to prevail over that of overtaking a threshold. After radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 microg/L (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 microg/L or more above the PSA nadir, whether or not it is associated with endocrine therapy. The time of appearance of the recurrence and the PSA doubling time after total radiotherapy have a diagnostic value on the nature of the site of recurrence, local or metastatic.

[Biology of primary hyperparathyroidism: selective venous sampling]. / Biologie de l'hyperparathyroïdie primaire: prélèvements veineux étagés.

The diagnosis of primary hyperparathyroidism (PHP) is chemical: high level of Parathormone (PTH) in conjunction with hypercalcaemia. In borderline cases with sub-normal plasma PTH and calcium, an oral calcium load test could allow a differential diagnosis from other causes of high PTH. Imaging is required only for PHP. Selective venous sampling can help in localizing a parathyroid adenoma in difficult cases by PTH cartography in the following situations: imaging in favour of an ectopic mediastinal gland or a deep cervical adenoma, persistent or recurrent PHP after first failed surgery with negative neck exploration or unsatisfactory in case of another hypersecreting gland, PHP well diagnosed with indeterminate imaging, symptomatic PHP with normal PTH and negative imaging. Venous blood sampling performed in a vascular radiological department with a quick PTH assay can reveal an area of maximum secretion potentially linked to a nodule localized by previous ultrasound coupled to scintigraphy, giving thus a "biological imaging" study. The association of imaging and biology is an efficient procedure enabling localization of an area of abnormal PTH secretion and characterization of the level of PTH secretion. The area with the highest gradient of PTH concentration can help to protocol CT and MR examination.

[PSA kinetics after total prostatectomy]. / Cinétique du PSA après prostatectomie totale.

The prostate specific antigen (PSA) is the best marker of the prostate cancer today although not very specific of this pathology. The dynamic interpretation of this marker always has to prevail over that of overtaking a threshold. With the lack of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 microg/L. The type of diminution mono- or biphasic of the marker depends on the chronology of the takings. Faced with residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A recurrence is defined by a value of PSA higher than 0.2 microg/L and confirmed on two successive assays. The time of appearance of the recurrence and the PSA doubling time after total prostatectomy have, with the initial clinical stage and the Gleason score, a diagnostic value on the nature of the site of recurrence, local or metastatic.

Video-assisted thoracoscopic surgery as a first-line treatment for mediastinal parathyroid adenomas: strategic value of imaging.

OBJECTIVE: To present first-line thoracic surgery made possible by localization studies in three patients with ectopic parathyroid adenomas. DESIGN AND METHODS: Three patients with ectopic parathyroid tissue in the mediastinum were examined by ultrasound, technetium-99m sestamibi scintigraphy, computed tomography (CT), and venous catheterization with measurement of parathyroid hormone. Without previous cervical exploration, video-assisted thoracic surgery (VATS) was used in all cases to avoid the need for thoracic open surgical procedures. RESULTS AND CONCLUSIONS: The mediastinal parathyroid glands were all detected at scintigraphy, and CT and venous catheterization were helpful in anatomic and functioning characterization. All pathologic glands were successfully resected, with only one minor complication. VATS can safely remove a deep mediastinal parathyroid adenoma and avoid more aggressive open approaches. In an experienced referral center, systematic and sophisticated imaging studies may accurately identify and localize rare ectopic parathyroid adenomas, and avoid cervical surgery.

Reducing the number of T3 orders in the Paris hospital network: towards better appropriatness of thyroid function test prescription.

In vitro thyroid function tests are among the most frequently prescribed laboratory procedures. Serum triiodothyronine (T3) tests are seldom necessary as a first-level measurement. Our objectives were to measure the proportion of T3 measurements relative to all in vitro thyroid function tests in a large hospital network and to investigate the contributions of various interventions to change prescribers'behavior. We performed two cross-sectional surveys in 1995 and 1998 in the 50 Paris University hospitals. Questionnaires were mailed to the heads of the 30 laboratories performing thyroid function tests. One-month orders of free and total thyroxine, free and total T3 and thyrotropin were recorded; changes in T3 measurement orders between the two periods were estimated and association with interventions were expressed as odds ratios and 95% confidence intervals. Twenty-five heads of laboratory responded to both surveys. In 1995, T3 measurements constituted 21% of in vitro thyroid function test ordering, which seems to us exceedingly high. The decrease in T3 measurement ordering observed in 1998 (15% of thyroid function test ordering) was independently associated with multiple behavioral changes: educational interventions, structured test form use and year of prescription.

[Utility of BNP measurement in the emergency room in patients with suspected unstable angina with a normal ECG]. / Utilité du dosage du BNP aux urgences chez les patients suspects d'angor instable avec ECG normal. A propos de 120 patients.

Unstable angina is a serious condition, difficult to diagnose in the emergency room. Clinical, electrocardiographic and biological signs (increased troponine) are not sensitive. The authors set out to assess whether measuring B natiuretic peptide in the emergency room was more sensitive for identifying symptomatic coronary lesions. One hundred and twenty patients admitted to the emergency room for chest pain compatible with the diagnosis of unstable angina and a normal ECG were included in this prospective study. All patients underwent coronary angiography during their hospital admission. The sensitivities of troponine at a threshold of 0.4 ng/ml and of brain natiuretic peptide (BNP) at a threshold of 10 pg/ml in this population were 66% and 92% respectively. The use of troponine and BNP together provided better results than troponine and BNP alone for the identification of patients with chest pain with significant coronary lesions.

[Diagnosis of ectopic mediastinal parathyroid adenomas: value of cardiac MRI]. / Diagnostic des adénomes parathyroïdiens ectopiques médiastinaux: apport de l'IRM cardiaque.

Primary hyperparathyroidism is due to an adenoma in 85% of cases. In 10% of cases, the parathyroid adenoma may be in an ectopic location. Ten per cent of these ectopic adenomas are located in the mediastinum. Imaging modalities performed in persistent or recurrent hyperparathyroidism include ultrasound, MIBI scintigraphy, venous blood sampling, helical CT and MRI. The authors report 3 cases of ectopic adenoma located in the mediastinum, where pre-operative diagnosis was confirmed using cardiac MRI sequences.

[New biological markers for acute coronary artery disease]. / Nouveaux marqueurs biologiques des syndromes coronariens aigus.

Cardiac markers are now considered as useful indexes for the diagnosis of myocardial ischemia and prediction of future events. Measurements of creatine kinase (CK) and MB enzymes have been considered as the gold standard in the past, but they lack sensitivity and specificity. Troponin has progressively gained acceptance as the new standard. Troponin assay is now widely available and several authors have demonstrated its diagnostic accuracy, predictive value, and capacity to predict prognosis and guide therapy in acute coronary artery disease. Further evaluations have however opened the perspective of more sensitive markers which may also exhibit more prompt elevation. B-type natriuretic peptide (BNP) is secreted during myocardial ischemia in response to increased overload pressure. BNP rises immediately after ischemic events and may be more sensitive than other cardiac markers, including troponin. Moreover, new techniques allow immediate determination. BNP therefore would be of great interest for the diagnosis and management of myocardial ischemia. New markers may allow determination of coronary plaque fissuring and detection of coronary disease at a preclinical phase.

Altered myosin isoform expression in rat skeletal muscles induced by a changed thyroid state.

The aim of our study was to find out, which are the thyroid linked mechanisms responsible for the changes in myosin isoform composition which accompany endurance training (ET) in rodents. We studied the interaction between ET and altered sedentary group with no thyroid treatment or Se group. Six groups of rats were compared: (1) a trained group with no thyroid treatment or T group; (2) a thyroid state in rats; (3) a sedentary group rendered hypothyroid with 6-n-propyl thio uracil (H); (4) a sedentary group rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (St); (5) trained rats rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (Tt) and (6) a trained group kept euthyroid with T3 (150 ng kg(-1) every other day for 4 weeks) (Te). In each group myosin isoform composition was determined in five muscles, three locomotor muscles: (1) extensor digitorum longus, (2) superficial lateral gastrocnemius, (3) deep medial gastrocnemius, (4) an antigravity muscle, the soleus and (5) a rhytmic respiratory muscle, the crural diaphragm. Different muscles responded in a specific way to variations of the thyroid state and training.

Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study.

It is well known that atrial fibrillation can lead to heart failure, and is attributed to rapid ventricular rate (tachycardia-induced cardiomyopathy). Some recent studies suggest the possible existence of an intrinsic left-ventricular factor related to atrial fibrillation, irrespective of other elements. In order to demonstrate the implication of this factor, we measured B-type Natriuretic Peptide, known as a functional marker of left-ventricular dysfunction, in 40 consecutive patients with chronic non-valvular atrial fibrillation, with low ventricular rate and absence of clinical heart failure or echocardiographic left-ventricular dysfunction. In all patients, Brain Natriuretic Peptide (BNP) plasma level was high and dramatically decreased 24 h after external electrical cardioversion (61.4 pg/ml before cardioversion, 23.5 pg/ml 1 day after cardioversion, P<0.002). Our study demonstrates that atrial fibrillation, in absence of high ventricular rate, induces an asymptomatic cardiac alteration that is not detectable by echocardiography.

Myocardial contractile reserve under low doses of dobutamine and improvement of left ventricular ejection fraction with treatment by carvedilol.

To examine the ability of myocardial contractile reserve (MCR) assessment to predict the improvement of left ventricular ejection fraction with treatment by carvedilol, a prospective study was undertaken in 85 patients with chronic heart failure and left ventricular ejection fraction < 45%. Low dose dobutamine echocardiography (DSE), a 6-min walk test and measured brain natriuretic peptide (BNP) were assessed in all the patients. Patients were separated into two groups. Group A were patients without any myocardial reserve and group B patients with a myocardial contractile reserve defined as an increment of more than 20% of the resting left ventricular ejection fraction during dobutamine infusion. The two groups differed for percentage of ischemic cardiomyopathy (67.8 in group A vs. 29.7% in group B P = 0.028), 6-min walk test performance (respectively, 343 vs. 415 meters P < 0.05) and BNP plasma levels (respectively, 184.5 vs. 70.1 P < 0.02) but not for left ventricular ejection fraction or NYHA class. During DSE, MCR and heart rate variation was higher in group B than in group A. At the end of the follow up, LVEF increased and NYHA class decreased in group B but not in group A. In multivariate analysis the existence of MCR could predict the improvement of LVEF with treatment by carvedilol. In our study, studying MCR could help to predict patients who will improve their LVEF with carvedilol prior to the administration of the treatment.

Brain natriuretic peptide blood levels in the differential diagnosis of dyspnea.

STUDY OBJECTIVES: In dyspneic patients without left ventricular enlargement, it may be difficult to differentiate between obstructive lung disease and diastolic heart failure. Determination of plasma brain natriuretic peptide (BNP) levels, known to increase with ventricular stretch, may be of clinical relevance in this situation. We compared the discriminant power of BNP blood levels and of echocardiography in patients with either chronic obstructive lung disease or diastolic heart failure. PATIENTS: Twenty-six New York Heart Association class III dyspneic patients with normal left ventricular systolic function were enrolled: 17 patients with chronic obstructive lung disease and 9 patients with unequivocal diastolic heart failure. RESULTS: Echocardiographic data were unable to accurately differentiate between the two groups, whereas BNP levels were significantly and markedly higher in patients with diastolic heart failure when compared to those with obstructive lung disease (224 +/- 240 pg/mL vs 14 +/- 12 pg/mL, p < 0.0001). CONCLUSIONS: These preliminary results warrant a prospective, large-scale evaluation of the value of BNP assay for determining diastolic dysfunction, a common cause of dyspnea in elderly patients, and differentiating it from other diagnoses such as obstructive lung disease.

[Brain natriuretic peptide and heart failure]. / Brain natriuretic peptide et insuffisance cardiaque.

Brain natiuretic peptide (BNP) is a hormone secreted specifically by the left ventricular myocytes. Its concentration is correlated with the severity of symptomatic or asymptomatic left ventricular dysfunction. The measurement of BNP has several applications from the screening of populations to the monitoring of the effects of treatment and the evaluation of the prognosis of cardiac failure. The emergence of new methods of rapid measurement will enable its usage as a routine investigation in the near future. Large scale clinical trials are, however, required to confirm the hopes raised by this new marker of left ventricular dysfunction.

Biochemical markers (without markers of infection) of the risk of preterm delivery. Implications for clinical practice.

BACKGROUND: New biochemical markers for the risk of spontaneous preterm birth (SPB) give a more precise and earlier diagnosis than the usual ones. We reviewed the data about the principal markers. RESULTS: Using studies with good methodology and a large number of subjects, we observe that the predictive value of these new markers is somewhat higher than those of the usual markers. Fetal fibro-nectin (FNf) and cervical ultrasound undeniably improve the identification of patients at risk of preterm birth, both in the general population and in these threatened preterm delivery. However no management has yet been demonstrated efficacious, especially in a general population so any recommendations for their systematic utilisation is premature. Other biochemical markers (salivary estriol, serum CRH, etc.) are still under assessment and should not be used outside research protocols. IMPLICATION FOR PRACTICE: It is appropriate to integrate either FNf or cervical ultrasound into daily clinical practice for patients with signs of preterm labor. These new indicators are of special use when the diagnosis is uncertain with the standard markers (uterine contractions, digital examination). Among these patients, they should reduce the number of hospitalizations and of useless treatments, because of their good negative predictive value. At the same time, for patients poorly 'labeled' by the clinical examination, they should allow the application of intensive management (intravenous tocolysis, corticoids, in utero transfers). CONCLUSION: Future studies should evaluate these tests in everyday practice. The objective is not to predict preterm birth but to prevent either it or its negative consequences. This goal will be met when we have an effective treatment, without associated adverse effects, to offer patients after a positive test result.

Unilateral neck exploration under local anesthesia: the approach of choice for asymptomatic primary hyperparathyroidism.

BACKGROUND: Conventional parathyroidectomy involves a bilateral neck exploration with the patient under general anesthesia with a thorough search for all parathyroid tissue. The purpose of this study was to assess the efficacy and safety of unilateral neck exploration under local anesthesia in patients with asymptomatic primary hyperparathyroidism (first-degree hyperparathyroidism). METHODS: Of 679 patients who underwent parathyroidectomy for first-degree hyperparathyroidism from July 1989 to June 1997, 230 asymptomatic patients underwent unilateral neck exploration under local anesthesia. Selection criteria for this approach included the successful identification of a solitary parathyroid adenoma on preoperative imaging, no thyroid disease, and no family history of multiple endocrine neoplasia. Intact parathyroid hormone levels were monitored during the operation. RESULTS: Total serum calcium levels were normal in 220 patients (96%) 3 to 6 months after surgery. Ten patients (4%) experienced persistent hypercalcemia, 8 of whom had multiple gland disease and 2 of whom had false-positive imaging. Two of these patients underwent bilateral neck exploration under general anesthesia and were cured, although 8 patients remained asymptomatic and were followed up non-operatively. The mean operating time was 30 minutes (range, 12-65 minutes). There were two complications (0.87%) including one wound hematoma and one transient recurrent laryngeal nerve palsy. CONCLUSIONS: Unilateral neck exploration under local anesthesia is an efficacious and safe approach to the treatment of first-degree hyperparathyroidism and should be considered in all patients with asymptomatic disease.

[Thyroid hormone determination at the Public Assistance Hospital of Paris: ordering, costs and opinions of physicians qualified in endocrinology]. / Les dosages hormonaux thyroïdiens à l'Assistance Publique-Hôpitaux de Paris: prescriptions, coût et opinions des médecins qualifiés en endocrinologie.

OBJECTIVES: To determine the distribution of orders for hormonal tests assessing thyroid function in a hospital setting. To collect the opinion of physicians specialized in endocrinology concerning free triodothyronine (FT3) assessment. METHODS: Using a cross-sectional survey numbers of free thyroxine (FT4), total T4 (TT4), FT3, total T3 (TT3), and TSH tests were collected from the heads of laboratory assessing thyroid function in June 95 at the Assistance Publique-Hôpitaux de Paris (AP-HP). Cost for these tests was estimated. The physicians of the AP-HP specialized in endocrinology were asked through a questionnaire for circumstances justifying FT3 test ordering. RESULTS: Twenty-eight laboratories (93%) responded: 28455 measurements (TSH: 43%, FT4: 33%, TT4: 2%, FT3: 20%, TT3: 2%) were performed and were valued at 3.4 million French Francs. Proportions of T4 (36%) and T3 (20%) tests were lower in hospitals with an inpatient department of endocrinology than in hospitals with an outpatient clinic with specialists in endocrinology (T4: 36%; T3: 27%) or with no endocrinology unit (T4: 33%, T3: 27%); proportion of TSH tests was higher in hospitals with an inpatient endocrinology unit (respectively 44%, 40%, 32%). Forty-two endocrinologists (76%) from 21 departments answered. Follow-up of treatment with amiodarone and euthyroid sick syndrome were considered the only conditions justifying FT3 test ordering. CONCLUSION: Though the opinion of physicians specialized in endocrinology was not uniform regarding recommendations for TT3 or FT3 tests as a first-line measurement, the cost of these tests has been estimated at 650 thousand Francs for a month at the AP-HP.

Technetium-99m sestamibi scintigraphy, magnetic resonance imaging and venous blood sampling in persistent and recurrent hyperparathyroidism.

Surgical treatment for primary hyperparathyroidism (HPT) is effective in 90% of cases. Recurrent or persistent HPT occurs in 10% of cases. Parathyroid imaging is indicated to confirm and locate an abnormal gland before reoperation. The aim of this study was to evaluate whether the combination of 99Tcm sestamibi scintigraphy, MRI and venous blood sampling (VBS) improved the overall sensitivity for abnormal parathyroid gland detection. 18 patients with recurrent or persistent HPT underwent sestamibi scintigraphy (n = 18), MRI (T1 weighted and STIR sequences) (n = 18) and venous blood sampling (n = 12) at different sites (internal jugular veins, innominate veins, and superior vena cava). All patients underwent surgical exploration. MRI yielded positive results in 15 cases (sensitivity 88%), sestamibi scintigraphy in 14 cases (83%) and VBS in 10 cases out of 12 (83%). Combined results of MRI, sestamibi and VBS yielded positive results in 16 cases (94%). The combination of MRI, sestamibi scintigraphy and VBS improved accuracy in detecting abnormal parathyroid glands before reoperation.

[Role of selective venous catheterization with assay of parathormone 1-84 in the treatment of persistent hyperparathyroidism]. / Place du cathétérisme veineux étagé avec dosage de la parathormone 1-84 dans le traitement de l'hyperparathyroïdie persistante.

From March 1993 to October 1994, 12 patients operated for persistent hyperparathyroidism had preoperative catheterization of large cervical and mediastinal veins (CLCMV) with determination of serum concentration of intact parathyroid hormone. Other localization procedures included: ultrasonography (US, n = 9), computed tomography (CT, n = 8), magnetic resonance imaging (MRI, n = 5), and sestamibi radionuclide imaging (MIBI, n = 9). A (1-84 PTH) gradient of 1-84 PTH was demonstrated in all patients, localizing a lesion in the neck (n = 9) or in the mediastinum (n = 3). An adenoma was found in nine patients either in the neck (n = 6) or in the mediastinum (n = 3), and 2 patients had glandular hyperplasia. Two patients remained hypercalcemic despite the removal of parathyroid tissue during CLCMV-guided reexploration. An other patient underwent unsuccessful neck reexploration. The sensitivity of other procedures was lower: US: 22%, CT: 50%, MRI: 60%, and MIBI: 66.5%. After a median follow-up of 13 months, 9 patients were cured of their hyperparathyroidism (75%) and 3 had persistent hypercalcemia. Our results suggest that CLCMV with 1-84 PTH measurement is the most accurate localization procedure in persistent hyperparathyroidism.

Values of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of 1-84 PTH for unilateral neck exploration of primary hyperparathyroidism.

Unilateral neck exploration (UNE) is a controversial approach to the treatment of primary hyperparathyroidism (PHP), and most surgeons favor bilateral neck exploration. The aim of this study was to assess the value of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of urinary cyclic AMP (UcAMP) or 1-84 PTH in 200 patients undergoing unilateral neck exploration under local anesthesia. Conditions for UNE were (1) a presumed solitary adenoma detected by ultrasonography, (2) no thyroid disease, and (3) no family history of PHP or multiple endocrine neoplasia. Patient's consent was obtained for conversion to bilateral exploration according to surgical and biologic findings. Sensitivity of ultrasonography was 92.5%. Sestamibi scintigraphy, performed in 70 patients, was less sensitive than ultrasonography (80%). Persistent PHP was accurately detected by intraoperative measurement of UcAMP or 1-84 PTH in all cases. At follow-up, 96.0% of the patients were cured either after unilateral neck exploration only (90.5%), or after conversion into bilateral exploration. Ultrasonography and intraoperative measurement of 1-84 PTH allow unilateral neck exploration with excellent results in a selected group of patients with PHP.

Respiration of amniotic fluid in near-term foetal rabbit.

OBJECTIVE: To examine the existence of amniotic fluid inhalation in foetal rabbit near term. STUDY DESIGN: Rabbit red cells labelled with 51 radio-chromium (Cr51-S1: Injectable solution sodium chromate, volumic activity: 74 MBq/ml; Cis-BioInternational, France) were injected into the amniotic sac of 24 New Zealand White foetal rabbits (mean gestation: 31 days) at day 25 per-laparotomy. At day 26, just prior to caesarean section, human serum albumin labelled with 125 radio-active iode (125I-HSA) (SERALB-125: human serum albumin labelled with radioactive Iode 125, volumic activity: 185 kBq/ml, Cis-BioInternational, France) was injected into each amniotic sac. The lungs, digestive tracts, kidneys and liver were excised separately and radioactivity counted in each organ. RESULTS: On day 26 of gestation, the 51Cr-RC radioactivity rate per gram of tissue in lungs, digestive tract amniotic fluid, liver and kidneys were respectively 1.66 +/- 2.8%, 1.15 +/- 1.6%, 0.015 +/- 0.02% and 0.04 +/- 0.07% of the total amount of radioactivity injected into the amniotic sac at day 25. The lungs' radioactivity was significantly higher than liver (t = 2.94, P < 0.01) or kidneys radioactivity (t = 2.38, P < 0.05). The 125I-HSA injected just prior to caesarean section at day 26 was not found in any foetal organ. CONCLUSIONS: Lung radioactivity is not related to gasps induced by caesarean section, or to a vascular diffusion since lung radioactivity was significantly higher than liver or kidneys' radioactivity. The results of these series of experiments demonstrate that amniotic fluid inhalation does exist in foetal rabbit near term.