Assessment of hypertrophy in myocardial biopsies taken during correction of congenital heart disease

Myocardial biopsies were obtained from 27 patients undergoing corrective cardiac surgery for congenital heart disease. Normal hearts of 18 autopsied patients were used as reference. The biopsy material was assessed for desoxyribonucleic acid (DNA) concentration and ploidy profile of cell nuclei in order to quantitate myocardial hypertrophy at the time of operation. DNA-concentration decreased significantly with age (r = -0.76; p less than 0.001). Ploidy profile of myocardial nuclei correlated with age: the relative number of diploid nuclei decreased (r = -0.67; p less than 0.001), the relative numbers of tetraploid and octoploid nuclei increased with age (r = 0.58; p less than 0.01 and r = 0.77; p less than 0.001 respectively). At 8 years of age the patients with congenital heart disease reached myocardial DNA-concentrations comparable with those in normal adult hearts. At higher age the patients with congenital heart disease exceeded normal adult values for myocardial DNA-concentration. These findings are interpreted to represent rapid development of hypertrophy with an early onset, reaching at 8 years of age values observed in normal adult hearts. Quantitation of myocardial hypertrophy by DNA-concentration and ploidy profile of nuclei may offer a means to explain some of the factors of influence on the outcome of corrective cardiac surgery for congenital heart disease in relation to its timing. Our data stress the need for preventing irreversible myocardial damage by timely (surgical) therapy.     

The vibratory innocent heart murmur in schoolchildren: A case-control Doppler echocardiographic study

Summary In 810 schoolchildren (aged 5–14 years) the prevalence of a grade 1–3/6 vibratory innocent heart murmur (VIHM) is 41%. Restricted to a grade 2 or 3 VIHM, the prevalence is 14%, decreasing from 21% in the age-class 5–6 years to 8% for children 13–14 years of age. The prevalence of a grade 3 VIHM is 1%. Together with a matched control, 84 children with a grade 2 or 3 VIHM underwent further cardiologic examination including electrocardiography, phonocardiography, and Doppler echocardiography. A positive correlation was found between the presence of a VIHM and higher left ventricular voltages on the ECG, but within the normal range; lower heart rate; smaller diameter of the ascending aorta (AAO); and higher blood flow velocity and higher maximal acceleration of the blood flow in the LVOT and the AAO. In 40% of the children with a VIHM, a systolic aortic valve vibration was seen with a frequency 100 Hz and an amplitude 1 mm, whereas this type of vibration was present in only one case control. No significant difference was found concerning the prevalence of false tendons in the left ventricle, systolic and diastolic diameter of the left ventricle, systolic time intervals, and shortening fraction of the left ventricle. The VIHM is strongly associated with a smaller AAO, with higher velocity and acceleration of the blood flow in the LVOT and AAO, and with a vibratory phenomenon of the aortic valve, pointing towards the LVOT-aortic valve region as the site of origin of the VIHM.     

Identification et analyse des prises de décision dans la chaîne de soins en radiothérapie

This study had two purposes: first, we wanted to understand what role social interactions play in decision-making processes during radiotherapy; second, we aimed to highlight to what extent these decisions can create patient risk. Our analysis focused on the real existing activity which is performed for preparing radiotherapy treatments. We found eight situations in which decision-making is needed: for half of them, interactions among professionals or between professionals and patients have a key role; for all of them, decision-making implies potential risks for patients. These findings stress the importance of taking into account social informal interactions to better understand decision-making and its inherent risks for patients treated with radiotherapy. To conclude, some psychosocial processes that could be involved in these situations are discussed.     

Long-term functional impairment of hemopoietic progenitor cells engineered to express the S1 catalytic subunit of pertussis toxin

OBJECTIVE: A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. METHODS: S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. RESULTS: S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. CONCLUSION: Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo.     

Effect of the circulating renin-angiotensin system on prolactin release in humans

We recently reported that renin, angiotensinogen, and angiotensin-converting enzyme were present in normal human pituitary lactotroph cells and PRL-secreting adenomas. Angiotensin-II and -III have also been shown to modulate PRL release in vitro. The present study was designed to determine whether angiotensin modulates PRL secretion in vivo. In 36 hypertensive patients with widely varying renin levels, active renin and basal PRL levels did not correlate. In 10 normal volunteers, both a sustained infusion of angiotensin-II and a graded infusion of angiotensin-III induced a 2- to 3-fold increase in aldosterone levels, but had no effect on PRL secretion. Administration of the angiotensin-converting enzyme inhibitor captopril had no effect on PRL circadian rhythm in 10 normal subjects or on PRL concentrations in 11 patients with PRL-secreting adenomas. Cross-over administration of placebo and captopril did not affect the peak PRL level measured after TRH treatment in 10 hypertensive men (placebo, 43.1 +/- 5.4; captopril, 40.0 +/- 6.2 micrograms/L; P = NS) or the rise in PRL induced by doperidone in 6 normal women (placebo, 129.5 +/- 16.2; captopril, 150.0 +/- 35.7 micrograms/L; P = NS). Further, administration of enalapril for 30 days to 6 hypertensive patients did not alter basal PRL concentrations or the peak concentrations induced by TRH. These data indicate that in humans the circulating renin-angiotensin system does not interact with diurnal PRL release or with the response to TRH or domperidone.     

Primary lymphoma of the thyroid gland. Diagnostic and therapeutic discussion. Apropos of 4 cases

Non Hodgkin lymphomas (NHL) of the thyroid are rather uncommon and account for about 7.7 p.100 of the tumours of the gland. They are remarkable by their usual occurrence in patients with Hashimoto's disease and by controversy about their therapy. The clinical features and the course of four additional cases occurring in four female patients (ages ranged from 61 to 73 years) are reported. The clinical picture was that of a quickly growing diffuse or multinodular goiter, squeezing surrounding neck structures. Antithyroid antibodies were present in 3 cases; microscopical examination showed cytologic features of lymphocytic thyroiditis. Two patients died within a few months, the follow-up is about two years for the others. Two main problems are discussed. First, NHL of the thyroid usually occurs in patients with Hashimoto's disease: how to confidently recognize lymphomas by fine needle biopsy in such cases? Second, which is the best treatment? The authors think that lymphomas of the thyroid have to be considered rather as lymphomas than thyroid tumours. Therefore the cure of the disease may need chemotherapy, in some cases associated with radiotherapy according to careful staging and grading in each case.     

Isoprenoid biosynthesis in the diatoms Rhizosolenia setigera (Brightwell) and Haslea ostrearia (Simonsen)

Isoprenoid biosynthesis in the widespread diatomaceous algae, Rhizosolenia setigera (Brightwell) and Haslea ostrearia (Simonsen), results not only in the production of diterpenoids, triterpenoids, and sterols but, unusually for diatoms, also in the production of sesterterpenoids. By using 13C and 2H isotopic labeling techniques followed by NMR and mass spectrometry, specific inhibition of mevalonate (MVA) and methylerythritol (MEP) pathways, and comparison with the natural 13C/12C isotope ratios of the lipids, the different biosynthetic pathways of the sesterterpenes and other isoprenoids have now been determined. Surprisingly, whereas the sesterterpenes (Delta(7(20))-haslenes) in R. setigera were made by the MVA pathway, as were the related triterpenoid rhizenes and desmosterol, in H. ostrearia the structurally similar Delta(6(17))-haslenes and the major sterol, 24-ethylcholest-5-en-3beta-ol, were instead biosynthesized by the MEP route. Phytol was biosynthesized in both diatoms by the MEP route. Subfractionation of R. setigera cells revealed that although phytol was located in the chloroplasts, the haslenes, rhizenes, and sterols were present in the cytoplasm. The observations described here for R. setigera and H. ostrearia show that terpenoid biosynthesis in diatoms is species-dependent and cannot simply be grouped according to structural type. Triterpenes appear to be made by the MVA route as in higher plants, whereas sesterterpenes and sterols can be made by either the MVA or MEP routes. In neither organism were the isoprenoids biosynthesized by leucine metabolism. Sesterterpene and triterpene biosynthesis in diatoms has not been investigated previously.     

Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with subclinical autonomous cortisol hypersecretion: a prospective clinical study

BACKGROUND: Incidentally discovered adrenal tumours are frequently associated with subclinical autonomous cortisol hypersecretion of unknown origin. Aberrant hormone receptors have been observed in case reports of overt Cushing's syndrome. The question arises as to whether such receptors may be present in the functioning adrenal incidentaloma, which is common and might be a subclinical stage of Cushing's syndrome. PATIENTS AND METHODS: Twenty-one consecutive patients with a unilateral incidentaloma, the biochemical features of subclinical cortisol hypersecretion and/or the scintigraphic features of an autonomously functioning adrenal adenoma were investigated for plasma cortisol responses to various stimuli: upright posture, meal, combined hypothalamic-hormones, the vasopressin analogue terlipressin, glucagon, angiotensin II, the serotonin 5-HT4 agonist cisapride, and ACTH. Six normal controls were similarly investigated. All subjects were studied during 8 mg per day dexamethasone in order to avoid any ACTH-dependent variation of plasma cortisol. RESULTS: The most constant responses in adrenal incidentalomas were observed after stimulation by terlipressin (18/20 patients, 28-415% cortisol increase) and cisapride (17/21 patients, 25-364% cortisol increase). Eighteen out of 21 patients responded to several stimuli (cortisol increase >or= 25%), and all responded to at least one stimulus other than ACTH, while such responses were absent in the controls. Plasma ACTH remained suppressed in all subjects throughout the study. CONCLUSIONS: Aberrant membrane receptors detected by in vivo stimulation tests appear to be common in autonomously functioning unilateral adrenocortical adenomas. These receptors may be involved in the modulation of cortisol secretion in adrenal incidentaloma, with potential therapeutic consequences for the control of subclinical cortisol hypersecretion.     

Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study

OBJECTIVE: The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis. DESIGN: Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and 3 with MEN 2B (from 3 families). METHODS: Medullary thyroid carcinoma (MTC) was diagnosed by measuring plasma calcitonin in basal conditions or after pentagastrin stimulation. The search for pheochromocytoma consisted of clinical evaluation, 24 h determination of urinary catecholamines and adrenal imaging. The mean age at genetic diagnosis of MEN 2 was 14.0+/-7.0 years, the mean duration for the follow-up was 7.6+/-2.8 years. RESULTS: All 87 patients had a MTC detected at the same time as the genetic diagnosis was made. Urinary catecholamine measurements led to the diagnosis of pheochromocytoma and a combination of imaging techniques enabled the correct localization of both unilateral or bilateral adrenal involvement. Pheochromocytoma was detected simultaneously with MTC in only seven patients, and seven others were detected throughout the follow-up. Of the 14 patients with pheochromocytoma, 11 had bilateral involvement: nine were initially bilateral and two became so during follow-up. CONCLUSION: This study demonstrates that in MEN 2, MTC is the lesion which appears earliest. Pheochromocytoma develops later during the evolution of the disease, and necessitates regular clinical and biological monitoring throughout follow-up. Determination of urinary and/or plasma catecholamines and metanephrines should be performed to detect pheochromocytoma. Imaging techniques lead to the detection of both unilateral and bilateral pheochromocytoma, thus making video-assisted laparoscopic adrenalectomy possible.     

Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.