[Adrenalectomy for adrenal metastases: is the laparoscopic approach beneficial for all patients?]. / Surrénalectomie pour métastases surrénaliennes: la voie d'abord laparoscopique est-elle bénéfique pour tous les patients ?

INTRODUCTION: Laparoscopy has become the gold-standard approach for excision of benign adrenal tumors but the question of its safety for malignant lesions is still controversial. Our aim was to evaluate the oncologic outcome of laparoscopic adrenalectomy for adrenal metastasis and to look for predictors of a negative surgical outcome. PATIENTS AND METHODS: We retrospectively reviewed the charts of all patients who underwent laparoscopic adrenalectomy for suspicion of adrenal metastasis between 2007 and 2013 at a single academic institution. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Univariate analysis was performed to determine risk factors of negative surgical outcome (positive surgical margins, complications, conversion, significant blood loss) and predictors of RFS and CSS. RESULTS: Thirteen patients underwent 14 laparoscopic adrenalectomies. All patients were operated by a single highly experienced surgeon. Complications occurred in 2 patients (15%): 2 blood transfusions (Clavien-score=2). There were 3 positive surgical margins (21%). Mean length of hospital stay was 4.3 days. Unadjusted RFS and CSS were respectively 48.4% and 83.3% at 1 year, 39.5% and 66.7% at 5 years. In univariate analysis, tumor size was the only risk factor of complication (P=.009) and conversion (P=0.009). Capsule invasion and tumor size were risk factors of positive surgical margins (P=0.01 and P<0.0001). One hundred percent of complications, conversion and positive surgical margins occurred in tumor>7.5 cm on preoperative CT-scan. No predictors of RFS and CSS was found in univariate analysis. CONCLUSION: Laparoscopic adrenalectomy for adrenal metastasis achieves good surgical and oncologic outcomes. When performed by highly experienced surgeon, complications and positive surgical margins occur only in tumors>7.5 cm. These patients may benefit from an open surgical approach.

[Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review]. / Efficacité et tolérance de la stimulation magnétique transcrânienne (SMTr) dans le traitement des dépressions chez le sujet âgé: revue de la littérature.

INTRODUCTION: During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. METHOD: After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. RESULTS: Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater volumes were associated with a poorer response to rTMS. DISCUSSION: Thus, although some studies concluded contradicting results, literature data globally sustain an efficacy of rTMS for depression in the elderly. Several parameters might be associated with greater antidepressant efficacy (higher intensity pulses of rTMS of the left DLPFC; higher number of stimulations or higher number of rTMS sessions). Poorer responsiveness to rTMS may be related to several patients' factors including older age and smaller frontal gray matter volumes; lesions of the white matter pathways connecting the left DLPFC and the left anterior cingulate cortex might explain a poor response to rTMS. Literature data globally confirm that rTMS is safe and does not produce cognitive deficits, even among highly vulnerable patients with clinical evidence of cerebrovascular disease. CONCLUSION: Many questions remain concerning the optimal stimulation parameters, administration protocol, and privileged indications. Thus, the next rTMS studies should be carefully designed to clarify these questions.

Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress.

Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1(-/-) mice is associated with an enhanced gamma-glutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1(-/-) mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.

[Recurrences of bipolar disorders - comparative study of bipolar disorders, recurring depressions and single depressions in a cohort of patients aged over 65 years]. / Récurrences dans les troubles bipolaires - Etude comparative à partir d'une population âgée de 65 ans et plus entre troubles bipolaires, troubles dépressifs récurrents et épisodes dépressifs simples.

BACKGROUND: Bipolar mood disorders, after starting at adulthood, may remain active throughout life, but bipolar disorders may only be revealed in later life. Indeed, Yet few data on bipolar disorders in the elderly have been reported in the litterature. The influence of normal aging on the outcome of the disease as well as the specific prognosis of bipolar disorders in the elderly has occasionally been studied. Eventually Finally, and contrasting with adults, few studies comparing the various subtypes of mood disorders were have been performed in the elderly. OBJECTIVES: We therefore developed a study in patients aged 65 or above, in order to evaluate the course (recurrences) of bipolar disorders, compared to recurring depressions and single depressions, and to determine the influence of recurrences on the outcome of bipolar disorders. METHOD: Patients aged over 65 years were inpatients admitted to the department of psychiatry in 2000 for one of the three previously mentioned diagnoses according to DSM IV. Retrospective data were collected from medical reports. Prospectively, data were collected from the general practitioner of each patient (relying on telephone calls), before statistical analysis was performed. RESULTS: Our study demonstrates a more severe outcome for bipolar disorders compared to recurring depressions and single depressions. Patients with bipolar disorders have a higher prevalence of psychiatric recurrences. Furthermore, the greater the number of previous relapses (or the longer the duration and intensity of the disease), the higher the risk of future new future recurrences both in bipolar disorders and recurring depressions. An age of onset of bipolar disorders before 60 years and more than 5 in-hospital admissions increase the risk of recurrences. CONCLUSION: We originally compare the outcome of bipolar disorders in the elderly, to recurring depressions and single depressions. We confirm the fatal outcome of recurrences in bipolar disorders in old age. Bipolar disorders in the elderly should be considered as a real public health care problem: strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively throughout life.

Effect of insulin treatment on plasma oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients.

OBJECTIVE: In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. RESEARCH DESIGN AND METHODS: Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. RESULTS: Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P<0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1+/-4.7 vs. 24.0+/-5.8 U/mmol, P<0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. CONCLUSIONS: In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.

Restriction and complexity of Mcf2 proto-oncogene expression.

MCF2/DBL is an X-linked proto-oncogene encoding a protein with a yet undetermined function. It can be activated in vitro by loss of 5' sequences in NIH3T3 bioassays; in vivo, deletion of the gene has been found in some hemophilia B patients. PCR analysis of its expression in mouse tissues shows a restriction to the gonads and tissues of neuroectodermal origin. It also identifies an exon encoding 42 amino acids that is alternatively spliced in murine, but not human testis.

Activation of a mcf.2 oncogene by deletion of amino-terminal coding sequences.

The mcf.2 transforming sequence was previously identified by tumorigenicity-assay of the mammary carcinoma cell line MCF-7, molecularly cloned and localized to Xq27 by in situ hybridization. cDNA clones representing both the activated gene and the corresponding portion of its normal counterpart were isolated and their nucleotide sequence determined. Sequence analysis showed that the mcf.2 gene was activated by rearrangement and loss of 5' sequences and no other alteration. Comparison of the mcf.2 nucleotide sequence with the recently published dbl sequence (Eva, A., G. Vecchio, D. Rao, S. Tronick & S. Aaronson (1988) Proc. Natl. Acad. Sci. USA, 85, 2061-2065) revealed that mcf.2 and dbl represent two different activated versions of the same proto-oncogene.

The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor.

Three receptor tyrosine kinases, FLT1, FLK1 and FLT4, contain seven immunoglobin-like domains in their extracellular region and are strongly related by sequence similarities to each other and, to a lesser degree, to the class III receptors CSF1R/FMS, PDGFR, SLFR/KIT and FLT3/FLK2. They constitute a family of receptors putatively involved in the growth regulation of endothelial cells. We describe here the structure and pattern of expression of the human FLT4 gene. Two FLT4 transcripts of 5.8 and 4.5 kb are expressed in the human placenta and several hematopoietic cell lines. In mouse, a 5.8-kb transcript is expressed in a variety of tissues. A translational product 1298 amino acids in length is predicted to be encoded by the largest open reading frame. The FLT4 protein, when transiently expressed in Cos-7 cells and immunoprecipitated with a FLT4-specific rabbit immune serum, has an apparent molecular weight of 170 kDa.

Structure, chromosome mapping and expression of the murine Fgf-6 gene.

The sixth member of the fibroblast growth factor gene family was cloned and analysed in the mouse. It is composed of three coding exons and encodes a putative growth protein of 198 amino acids, possessing a potential signal peptide, and presenting 79% and 93.5% sequence similarity with the mouse Hst/K-fgf and human FGF-6 genes products, respectively. The murine Fgf-6 gene is located in a region distinct from the Int-41 locus and belongs to a linkage group conserved between chromosome 12 in man and chromosome 6 in mouse. It presents an intrinsic oncogenic capacity since it is able to transform cultured fibroblasts. Fgf-6 mRNA levels are developmentally regulated with a peak of expression in the developing fetus at day 15.5 of gestation, moderate levels during late gestation and in the neonate. In the adult, Fgf-6 mRNA can be detected in testis, heart and skeletal muscle.

A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells, endothelial cells and platelets.

The architecture of lymphoid microenvironments depends upon complex interactions between several stromal cell types. We describe in this report the cloning of a cDNA which encodes a novel membrane molecule containing two external Ig-like domains. It is expressed at the junction between endothelial cells including HEV. It is also expressed by platelets and MHC class II+ antigen presenting cells in thymic medulla and T-cell areas in peripheral lymphoid organs. These cells which lack in RelB-deficient mice include tissue-derived dendritic, epithelial cells and macrophages. Thus, this molecule might contribute to the organization of cell junctions in different microenvironments.

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.

Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice.

Pantetheinase (EC 3.5.1.-) is an ubiquitous enzyme which in vitro has been shown to recycle pantothenic acid (vitamin B5) and to produce cysteamine, a potent anti-oxidant. We show that the Vanin-1 gene encodes pantetheinase widely expressed in mouse tissues: (1) a pantetheinase activity is specifically expressed by Vanin-1 transfectants and is immunodepleted by specific antibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantetheinase activity in kidney and liver; (4) in these organs, a major metabolic consequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. Since the Vanin-1 molecule was previously shown to be involved in the control of thymus reconstitution following sublethal irradiation in vivo, this raises the possibility that Vanin/pantetheinase might be involved in the regulation of some immune functions maybe in the context of the response to oxidative stress.

Characterization of a murine glyceraldehyde-3-phosphate dehydrogenase pseudogene.

A mouse cDNA clone from the ubiquitous glycolysis enzyme Gapdh was isolated from a testis library and sequenced. The gene presents abnormalities indicating that it is a pseudogene. It is expressed as a 1.9 kb minor transcript.

A radiologic index of pulmonary arterial hypertension.

A new radiologic index indicative of pulmonary artery hypertension is presented. It was obtained by measuring the horizontal distances from the midline to the first divisions of the right and left pulmonary arteris, and dividing the sum of these distances by the maximum transverse diameter of the thorax. The index was significantly different in groups with and without pulmonary hypertension and was abnormal (above 38 percent in 111 of 150 patients with cardiovascular disease and pulmonary arterial hypertension (PAH). None of the cases with increased pulmonary flow from cardiac shunts but normal PAP had an anbormal index. Thus, an abnormal index suggested PAH but correlated poorly with the extent of hypertension.

[Relation between serum levels and inotropic effect of digoxin in advanced cardiac failure during long-term treatment]. / Relation taux sérique - effet inotrope de la digoxine dans l'insuffisance cardiaque avancée lors d'un traitement au long cours.

The aim of this study was to determine the relationship of digoxin serum levels to their inotropic effects in advanced cardiac failure during long-term therapy with different dosages. The study was based on the analysis of left ventricular systolic time intervals (STI) measured at 97 follow-up appointments of 20 patients in advanced, stable cardiac failure over an average period of 37 days. The dosage of digoxin was varied at successive consultations so that the serum digoxin levels reached 0.50 ng/ml on at least one occasion. The serum digoxin levels (SD) varied between 0 and 4 ng/ml. Four levels of SD were individualised: A) "control" SD less than 0.25 ng/ml (22 consultations); B) SD: 0.25 to 1 ng/ml (n = 25); C) SD: 1.0 to 2.0 ng/ml (n = 29); D) SD greater than 2 ng/ml (n = 21) including 6 cases with clinical and/or ECG signs of digoxin toxicity. A progressive significant shortening of the electromechanical systolic index (Q-S2 I) was observed up to levels of 2 ng/ml (B and C, -18 ms and -28 ms respectively). The same phenomenon was observed with the ejection time index (ETi) and pre-ejection time index (PETi) (-7 ms and -14 ms; -11 ms and -15 ms respectively) compared to the basal values. At SD greater than 2 ng/ml the reduction remained stable and then started to decrease (positive difference between C and D). These changes were observed in the absence of significant variations of the heart rate. There was a significant linear relationship between the variations of the STI and SD in 15 out of 18 patients (in whom the regression could be calculated, these patients having attended at least 3 appointments). These linear relationships were observed for the Q-S2 i (11-18), the ETi (9-18) and/or PETi (10-18). An unexpected increase in the pre-ejection period was observed in 2 patients. In conclusion, a linear relationship has been shown between SD and inotropic effect which is particularly noticeable at SD levels less than 2 ng/ml. When SD is greater than 2 ng/ml, further increases in SD are associated with smaller variations of the STI. On the other hand, a significant inotropic effect is observed with small doses and SD levels less than 1 ng/ml. This inotropic effect persists unchanged at long-term.

Short-term vasomotor adjustments to post immersion dehydration are hindered by natriuretic peptides.

Many studies have described the physiology of water immersion (WI), whereas few have focused on post WI physiology, which faces the global water loss of the large WI diuresis. Therefore, we compared hemodynamics and vasomotor tone in 10 trained supine divers before and after two 6h sessions in dry (DY) and head out WI environments. During each exposure (DY and WI) two exercise periods (each one hour 75W ergometer cycling) started after the 3rd and 5th hours. Weight losses were significant (-2.24 +/- 0.13 kg and -2.38 +/- 0.19 kg, after DY and WI, respectively), but not different between the two conditions. Plasma volume was reduced at the end of the two conditions (-9.7 +/- 1.6% and -14.7 +/- 1.6%, respectively; p < 0.05). This post-WI decrease was deeper than post DY (p < 0.05). Cardiac output (CO) and mean arterial blood pressure were maintained after the two exposures. Plasma levels of noradrenaline, antidiuretic hormone and ANP were twofold higher after WI than after DY (p < 0.05). After DY total peripheral resistances (TPR) were increased (p < 0.05) and heart rate (HR) was reduced (p < 0.05). After WI there was a trend for a decrease in stroke volume (p = 0.07) with unchanged TPR and HR, despite more sizeable increases in plasma noradrenaline and vasopressin than after DY. We hypothesized that the higher levels of plasma natriuretic peptides after WI were likely counteracting the dehydration-required vasomotor adjustments.

[Penicillium chrysogenum endophthalmitis: a case report]. / Endophtalmie à Penicillium chrysogenum: à propos d'un cas.

We report a case of Penicillium chrysogenum endophthalmitis after penetrating ocular trauma in a 9-year-old child, describing the initial management and the therapeutic adaptation after biopsy culture. After a review of endophthalmitis treatment, we discuss mycotic endophthalmitis treatment and recommend the use of intravitreal antibiotics. In this case, we used amphotericin B to treat the fungal disorder with success.

[Ocular metastasis of cutaneous melanoma]. / Métastase oculaire d'un mélanome cutané.

We report a case of vitreal metastases from cutaneous melanoma. We describe the clinical findings and the histological aspects of the lesions, which allows us to discuss the diagnosis of masquerade syndrome and highlight the diagnostic importance of vitreous biopsy.

[Negative relation between sodium intake and prolactinaemia in the normal subject (author's transl)]. / Absence d'influence de la ration sodée sur la prolactinémie de l'homme normal.

The different effects of sodium regimens administered over a period of five days were studied in 18 normal men, aged 21 to 27 years. As the dietary sodium increased, there was a parallel increase in osmolality, plasma volume, reabsorption of free water, and secretion of antidiuretic hormone. However, there was a decrease in plasma renin activity, plasma aldosterone and urine aldosterone. All of these parameters correlated significantly with the urinary sodium. Plasma prolactin did not appear to be influenced by low, normal or high sodium regimens; its values being 3.1 +/- 1.1, 2.9 +/- 1.7, 2.7 +/- 1.2 ng/ml respectively at 9 AM in an upright position. Once more, there does not exist any correlation between the plasma prolactin levels and the parameters mentioned above. In conclusion, variations in dietary sodium do not influence plasma prolactin levels in the normal human being.