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Biomedical subjects

P F Plouin

Publications and source records attributed to P F Plouin.

At least 19 recordsLinked to original sources
PubMed2001

The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.

Hereditary paragangliomas are usually benign tumors of the autonomic nervous system that are composed of cells derived from the primitive neural crest. Even though three genes (SDHD, SDHC, and SDHB), which encode three protein subunits of cytochrome b of complex II in the mitochondrial respiratory chain, have been identified, the molecular mechanisms leading to tumorigenesis are unknown. We studied a family in which the father and his eldest son had bilateral neck paragangliomas, whereas the second son had a left carotid-body paraganglioma and an ectopic mediastinal pheochromocytoma. A nonsense mutation (R22X) in the SDHD gene was found in these three affected subjects. Loss of heterozygosity was observed for the maternal chromosome 11q21-q25 within the tumor but not in peripheral leukocytes. Assessment of the activity of respiratory-chain enzymes showed a complete and selective loss of complex II enzymatic activity in the inherited pheochromocytoma, that was not detected in six sporadic pheochromocytomas. In situ hybridization and immunohistochemistry experiments showed a high level of expression of markers of the angiogenic pathway. Real-time quantitative reverse transcriptase (RT)-PCR measurements confirmed that vascular endothelial growth factor and endothelial PAS domain protein 1 mRNA levels were significantly higher (three- and sixfold, respectively) than those observed in three sporadic benign pheochromocytomas. Thus, inactivation of the SDHD gene in hereditary paraganglioma is associated with a complete loss of mitochondrial complex II activity and with a high expression of angiogenic factors.

Adult↗
PubMed2001

[Revascularization of atherosclerotic stenosis of the renal artery. Indications and results].

RISKS: Atherosclerotic renal artery stenosis typically occurs in high risk patients with coexistent vascular disease elsewhere. Patients with atherosclerotic renal artery stenosis may develop progressive renal failure but have a much higher risk of dying with a stroke or a myocardial infarction than of progressing to end-stage renal disease. REVASCULARIZATION RESULTS: Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Percutaneous renal artery angioplasty is the first choice because it is simpler than and as effective as surgical reconstruction. INDICATIONS: Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. Older age, long history of hypertension and a kidney size less than 8 cm are associated with little chance of blood pressure improvement or kidney function recovery. PRACTICAL ATTITUDE: With or without revascularization, medical therapy using antihypertensive agents, statins and aspirin is necessary in almost all cases. Blood pressure and plasma creatinine concentration should be measured every three months. Kidney size and renal artery patency should be assessed yearly.

Arteriosclerosis↗
PubMed2001

Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors.

Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)-II gene, are associated with the malignant phenotype in sporadic adrenocortical tumors. A high risk of recurrence after surgery for adrenocortical tumors is predicted in cases with regional invasion or distant metastases. However, patients with localized tumors also have a high risk of recurrence. Reliable prognostic markers are required to identify subjects at high risk of recurrence. The aim of this study was to assess the prognostic value of three molecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-II gene) by assessing disease-free survival in a large series of adult patients with sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the disease to June 1999 or to death. Malignancy was initially diagnosed in 18 patients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage I: n = 60 and stage II: n = 36) were at risk of recurrence. Histological grade was assessed according to Weiss criteria, and tumors were classified into two groups (Weiss score or=4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and for IGF-II gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univariate analysis (P = 0.001; relative risk, 27), as were histological grade (Weiss score >or=4; P = 0.00001; relative risk, 15), 11p15 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006; relative risk, 18), and overexpression of the IGF-II gene (P = 0.01; relative risk, 5). In a Cox proportional hazards regression model, histological grade (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 21.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of long-term outcome in patients with sporadic adrenocortical tumors. In patients who have undergone curative surgery, routine assessment of these tumor markers is a useful complement to histological scoring for predicting recurrence and guiding decisions for subsequent follow-up and management.

Adolescent↗
PubMed2001

Polymorphic differences from normal in the aldosterone synthase gene (CYP11B2) in patients with primary hyperaldosteronism and adrenal tumour (Conn's syndrome).

OBJECTIVE: The hypertension of Conn's syndrome is due to autonomous aldosterone production by a unilateral adrenocortical adenoma. The source of tumour initiation and the reasons for excess aldosterone production as opposed to cortisol are not known, although variations in the promoter region of the gene coding for aldosterone synthase (CYP11B2) might account for the altered rate of aldosterone secretion. DESIGN: In a series (n = 27) of well-characterized Conn's syndrome cases, the aldosterone synthase gene (CYP11B2) was screened by single-strand conformational polymorphism (SSCP) for differences from the consensus sequence. RESULTS: No new mutations were found. The frequencies of two previously described linked polymorphisms, one a change of -344C to T in a putative steroidogenic factor-1 (SF-1) binding site and the other an exchange of intron 2 for that of CYP11B1 (conversion) were measured in tumour and genomic DNA. The frequency of the SF-1 T allele (P < 0.0001) and the conversion allele (P < 0.001) were markedly different between the Conn's syndrome group and the normal controls. However, the frequency did not differ between tumour and genomic DNA in the patient group. CONCLUSION: While it is unlikely that this difference from normal is related to tumour growth, these genotypes may predispose the tumour to aldosterone production.

Adenoma↗
PubMed2001

Presentation and revascularization outcomes in patients with radiation-induced renal artery stenosis.

This study analyzed the initial presentation and revascularization outcomes of patients with radiation-induced renal artery stenosis, a rare complication of therapeutic irradiation. Of 11 patients with renal artery stenosis after irradiation, 7 patients fulfilled the following criteria: normotension before irradiation, radiation dose greater than 25 grays delivered to the renal arteries, associated perirenal radiation-induced lesions, and absence of arterial disease outside the radiation field. The median age at irradiation was 30 years, and the median local irradiation dose was 40 grays. The median time from irradiation to referral was 13 years. All patients were hypertensive at referral, with a median blood pressure (BP) of 171/102 mm Hg and median treatment score of two. The median glomerular filtration rate was 67 mL/min. Two patients had bilateral stenoses and 1 patient had stenosis affecting a single kidney. Stenoses were proximal in 6 patients and truncal in 1 patient, and all had the appearance of atherosclerotic stenosis. Percutaneous transluminal renal artery angioplasty (PTRA) was successful in 5 patients, but required multiple insufflations. PTRA failed in 1 patient, who subsequently underwent an aortorenal bypass. After a median follow-up of 36 months, 2 patients had died of noncardiovascular causes and 4 patients remained hypertensive, with a median BP of 136/85 mm Hg and median treatment score of two. No restenosis occurred, but aneurysms developed at the site of angioplasty in 1 patient. If hypertension occurs even decades after irradiation, a radiation-induced renal artery stenosis should be sought in patients who have undergone abdominal irradiation.

Adult↗
PubMed2001

Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center.

To identify preoperative factors associated with 30-day morbidity and mortality after pheochromocytoma surgery, we carried out an external review of the records of all patients undergoing pheochromocytoma surgery from 1975 to 1997 at a single center. One hundred and forty-seven patients, including 23 with malignant tumors at the time of the first operation, underwent 165 operations. Death, resection of a neighboring organ, further surgery, secondary transfer to an intensive care unit, and any events associated with a surgical stay exceeding 10 days were defined as complications. Mortality and morbidity were 4 of 165 (2.4%) and 38 of 161 (23.6%), respectively. Morbidity included 13 spleen resections and hematomas. Spleen complications were not related to tumor location, but were probably due to the operative strategy used, a transperitoneal complete abdominal exploration including both adrenal glands. Complications were independently associated with preoperative systolic blood pressure [odds ratio (OR), 1.14/cm Hg], urinary metanephrine excretion (OR, 1.18/10 micromol x day), and with the number of operations (repeat vs. first operation OR, 5.36). In conclusion, pheochromocytoma resection consistently involves a risk of complications. Spleen damage should be prevented by complete preoperative localization studies and an elective or laparoscopic surgical approach. Careful blood pressure control should help prevent complications. Patients with high secretion tumors and those undergoing repeat intervention are at high risk of complications and should be referred to centers familiar with pheochromocytoma management.

Adolescent↗
PubMed2000

High levels of tyrosine phosphorylated proto-ret in sporadic phenochromocytomas.

Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neoplasia (MEN)-2 diseases, which account for a minority of pheochromocytomas. We investigated the expression of the RET gene in 14 sporadic tumors harboring no activating mutations. A subset of highly RET-expressing tumors (50%) could be distinguished. They showed RET transcript, protein amounts as well as Ret-associated phosphotyrosine levels similar to those measured in MEN-2A-associated pheochromocytomas. We also determined the GDNF and GDNF family receptor alpha (GFRalpha)-1 transcript levels in tumors and in normal tissues. Whereas the GFRalpha-1 transcripts were detected at similar levels in normal tissues and in tumors, GDNF was frequently found expressed in sporadic tumors at levels several times higher than in controls. These results led us to propose the existence of an autocrine or paracrine loop leading to chronic stimulation of the Ret signaling pathway, which could participate in the pathogenesis of a number of sporadic pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed2000

The long-term effectiveness of preventive strategies for osteoporosis in postmenopausal women: a modeling approach.

Based on data from the literature, we have developed a computer-based simulation model to compare the long-term effectiveness of different preventive strategies of osteoporotic fractures. The Markov model comprises 25 states, including states which describe women distributed according to three levels of fracture risk, fractures states, post-fracture states and a death state. We chose eight standard preventive strategies, which we compare with the 'No Treatment' reference strategy. The first two strategies consist in treating all 50-year-old women for 5 or 10 years with hormone replacement therapy (HRT). Strategies 3 and 4 aim at assessing a 5-year course of treatment with bisphosphonates in osteopenic and osteoporotic 65- or 75-year-old women. Strategies 5 and 6 combine 5 years of HRT in all 50-year-old women with 5 years of bisphosphonates in osteopenic and osteoporotic women at 65 or 75 years. The last two strategies simulate 10 years of HRT in all 50-year-old women, followed by strategy 3 or strategy 4. Simulated life expectancy and mean ages of fracture occurrence fit well with the observed data. All the preventive strategies tested reduced the number of fractures. Early 10-year HRT in all women, plus 5 years of bisphosphonates in women at risk of fractures at 65 or 75 years, are the most effective strategies, with an 18.4-19.0% reduction in all fractures, and a 25.6-26.1% reduction in the number of hip fractures. Strategy 2 has a similar outcome, thus demonstrating the value of treatment started early and sustained over a long period. The strategies implemented later, S3 and S4, only concern women at risk (i.e., osteopenic or osteoporotic), and are less effective, with a 1.5-2.1% decrease in all fractures. The combined strategies, S5 and S6, produce intermediate results: a 12.9-13.5% reduction in the number of all fractures and a 17.5-17.9% reduction in hip fractures.

Aged↗
PubMed2000

Atherosclerotic renal artery stenosis: surgery, percutaneous transluminal angioplasty, or medical therapy?

Atherosclerotic renal artery stenosis typically occurs in high-risk patients with coexistent vascular disease elsewhere. Patients with atherosclerotic renal artery stenosis may develop progressive renal failure but have a much higher risk of dying of stroke or myocardial infarction than of progressing to endstage renal disease. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or an increase in plasma creatinine levels during angiotensin converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive agents, statins, and aspirin is necessary in almost all cases.

Angioplasty, Balloon↗
PubMed2000

[Recent progress in the diagnosis, prognostic evaluation and treatment of pheochromocytomas].

INTRODUCTION: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. CURRENT KNOWLEDGE AND KEY POINTS: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. FUTURE PROSPECTS AND PROJECTS: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect.

Adrenal Gland Neoplasms↗
PubMed2000

Comparison of nurse- and physician-determined clinic blood pressure levels in patients referred to a hypertension clinic: implications for subsequent management.

BACKGROUND: When measuring BP, the physician induces a transient pressor response triggered by an alarm reaction. This 'white-coat effect' can influence therapeutic decisions. Whether it depends on the characteristics of the physician has not been evaluated. OBJECTIVE: To assess the 'white-coat effect' induced by several physicians in a large sample of patients, using the blood pressure measured by trained nurses as a reference. SETTING: Referral hypertension clinic. METHODS: Patients were selected for the study if they had been referred for the first time to the clinic and if they had had their supine systolic/diastolic blood pressure measured by a trained nurse (mean of the last two of three measurements taken every 1 min by an oscillometric device) and a physician (auscultatory method using a standard mercury sphygmomanometer). Physicians were included in the study provided they had seen at least 25 patients during the study period. The between-physician difference was assessed using linear regression analysis. Physician blood pressure was the dependent and nurse blood pressure was the independent variable. RESULTS: From 1 January 1997 to 15 September 1997, 1062 patients (50% male, aged 52 +/- 14 years), seen by 10 physicians (26-187 patients per physician) and one nurse were included for analysis. The mean systolic/diastolic blood pressure for physicians was 162 +/- 27/ 97 +/- 15 mmHg and that for the nurse was 155 +/- 24/ 88 +/- 14 mmHg. The nurse-physician differences were -6 mmHg (range -67 to +66) for systolic and -8 mmHg (-44 to +31) for diastolic blood pressures. Major differences were observed between individual physicians. Intercepts of the physician blood pressure versus nurse blood pressure relationship ranged from 0.1 -60.7 mmHg for systolic and from 13.3-55.3 mmHg for diastolic pressures. The slopes of this relationship differed less between physicians for systolic (0.72-1) than for diastolic pressures (0.56-0.97). There was no difference between the patients seen by physicians in patients' age, sex, tobacco consumption, anti-hypertensive treatment or target-organ damage. CONCLUSION: Large between-physician differences exist in the magnitude of the white-coat effect that cannot be explained by patient characteristics. Physicians should therefore not make any decisions based on blood pressure measured manually during a first encounter.

Adolescent↗
PubMed2000

Renal arteries in patients at risk of renal arterial stenosis: multicenter evaluation of the echo-enhancer SH U 508A at color and spectral Doppler US. Levovist Renal Artery Stenosis Study Group.

PURPOSE: To assess SH U 508A in the diagnosis of suspected renal arterial stenosis by means of ultrasonography (US) and to confirm the safety of SH U 508A in a clinical setting. MATERIALS AND METHODS: A randomized crossover study was performed in 198 patients from 14 European centers who were referred for renal arterial angiography because they were suspected of having renal arterial stenosis. All patients underwent nonenhanced and SH U 508A-enhanced Doppler US of the renal arteries. Doppler criteria included measurement of renal arterial peak systolic velocity (threshold, 1.4-2.0 m/sec) in all centers and renoaortic ratio (threshold, 3.0-3.5) in nine. RESULTS: The number of examinations with successful results increased following enhanced Doppler US examination--160 (83.8%) compared with 122 (63.9%) with nonenhanced Doppler US (P = .001), including patients with obesity or renal dysfunction. Renal arterial stenosis (> or =50%) was detected at angiography in 72 patients. Results at enhanced Doppler US were in agreement with results at angiography more often than with results at nonenhanced Doppler US in the diagnosis or exclusion of renal arterial stenosis (P = .001). For patients examined with nonenhanced and enhanced Doppler US, sensitivity (80.0% and 83.7%, respectively) and specificity (80.8% and 83.6%, respectively) remained unchanged. There were no clinically important adverse events following use of SH U 508A. CONCLUSION: In patients suspected of having renal arterial stenosis, SH U 508A increased the number of diagnostic renal arterial Doppler studies.

Adult↗
PubMed2000

[Can the degree of renal artery stenosis be automatically quantified?].

The objective of the reported study is to validate a computer system, QUASAR, dedicated to the quantification of renal artery stenoses. This system estimates automatically the reference diameter and calculates the minimum diameter to compute a degree of stenosis. A hundred and eighty images of atheromatous stenoses between 10% and 80% were collected from two French independent protocols. For the 49 images of the EMMA protocol, the results from QUASAR were compared with the visual estimation of an initial investigator and with the results from a reference method based on a panel of fixe experienced experts. For the 131 images of the ASTARTE protocol, the results from QUASAR were compared with those from a semi-automatic quantification system and with those from a system based on densitometric analysis. The present work validates QUASAR in a population of narrow atheromatous stenoses (> 50%). In the context of the EMMA protocol, QUASAR is not significantly different from the mean of the fixe experts. It is unbiased and more precise than the estimation of a single investigator. In the context of the ASTARTE protocol, there is no significant difference between the three methods for the stenoses higher than 50%, however, globally, QUASAR surestimates significantly (up to 10%) the degree of stenosis.

Aged↗
PubMed2000

[Hypertension and primary hyperaldosteronism].

Hypokalaemic hypertension or resistant hypertension justify investigation for primary hyperaldosteronism. The first step of this investigation is to exclude the ingestion of liquorice, alkalis and diuretics. The second is to make sure that the treatment is compatible with the hormonal tests and that the natriuresis and kaliuresis are normal. The diagnosis then depends on an increased plasma or urinary concentration of aldosterone with a low plasma renin activity. The adenoma of Conn is present in 2/3 of cases and surgically curable, and should be distinguished from adrenal hyperplasia which is treatable with distal diuretics. This is a diagnosis which requires computerised tomography or, when inconclusive, demonstration of unilateral secretion of aldosterone. Adrenalectomy, usually by coelioscopy, is indicated in Conn's adenoma when the patient is young and the hypertension severe or recent. Surgical abstention is strongly advised in cases of adrenal hyperplasia.

Adenoma↗