Surgical and anesthetic management of paraganglioma diagnosed in a 2nd trimester parturient: Case report.

INTRODUCTION: Neuroendocrine tumors represent a rare entity whose diagnosis is based on clinical, biological and radiological arguments. When they are secreting, they expose the patient to serious complications that can be much more severe during pregnancy and engage the vital prognosis of both the mother and the fetus, which requires multidisciplinary management: anesthesiologist resuscitator - obstetrician - endocrinologist. CASE PRESENTATION: In our article, we report the case of a patient with an estimated pregnancy at 25 weeks of amenorrhea (WA) with a history of 3 miscarriages related to atypical gravid hypertension.The treatment consisted of preoperative medical preparation followed by removal of the paraganglioma and postoperative monitoring. The maternal-fetal evolution was favorable. CONCLUSION: The non-negligible morbi-mortality of this type of tumors require a multidisciplinary management.

Bilateral Lipoadenoma of the Adrenal Glands and Humeral Brown Tumor: An Unusual Association.

Adrenal adenolipomas are rare lipomatous adrenal tumors that can be either functional or not. Only 7 cases have been reported in the English literature so far. However, brown tumors are benign, rare, historical lesions, with histological similarity to giant tumors that can be encountered in 1% of all primary hyperparathyroidism cases. We report the case of an unusual association of bilateral lipoadenoma of the adrenal glands and humeral brown tumor in a 35-year-old patient. He presented to the emergency department with a pathological fracture of the left humerus secondary to a brown tumor. The medical investigations have concluded to primary hyperparathyroidism. The screening for multiple endocrine neoplasia type 1 revealed the presence of bilateral nonsecreting adrenal masses whose anatomopathological study concluded adenolipomas. Adrenal tumors may constitute a part of multiple endocrine neoplasia type 1 in 20 to 40% of cases. In this view, it is necessary to check for the presence of other endocrine gland tumor locations such as primary hyperparathyroidism, neuroendocrine tumors of the duodenum and pancreas, or pituitary adenomas.

Inferior mesenteric artery aneurysm revealed by massif rectal bleeding, case report.

INTRODUCTION: Inferior mesenteric aneurysms are rare, usually asymptomatic. Their diagnostic is challenging based on clinical examination, ultrasonography, and abdominal CT scan; surgery remains the gold standard of treatment. CASE REPORT: In this paper, we will report a clinical case of 62 years old man admitted to the emergency department for massif rectal bleeding due to inferior mesenteric aneurysm fistulization in the transversal colon one month after a left colectomy; the treatment was surgical consisted of a Ligation. CONCLUSION: IMA aneurysm is a rare condition, usually asymptomatic, and it might be revealed by various symptoms, including massif rectal bleeding.

Calcific pancreatitis uncovering a multiple endocrine neoplasia type 1: A case report in compliance with the scare guidelines.

INTRODUCTION: Chronic pancreatitis are mostly linked to alcoholic consumption or biliary lithiasis; and Primary hyperthyroidism (PHPT) is still a very rare association and the exact physiopathology is yet to be fully unveiled to the human knowledge. We present the first case report of a calcific pancreatitis associated with not only PHPT but a multiple endocrine neoplasia (MEN) type 1. CASE PRESENTATION: We report the case of a 52 years old woman suffering from mellitus diabetes consulting the emergency rooms for acute pancreatitis with hyperlipasemia and hypercalcemia whom final imaging discovered a pituitary gland adenoma, a left surrenal adenoma, and a parathyroid adenoma, and for the pancreas it reveiled an acute mild pancreatitis with a background of calcifications, no gallstones, no bone or renal abnormalities; and the parathyroidectomy was performed following the minimally invasive selective technique. DISCUSSION: Calcemia levels testing routinely performed help discover hyperparathyroidism. The associations of chronic pancreatic inflammation to hyperparathyroidism needs to be studied, even if hypercalcemia is prooven to be a risk factor of pancreatitis; the mechanism behind this association is brievely described. parathyroidectomy is the definitive cure for hyperparathyroidism, the technique advances has shown effective localization of the responsible adenoma and the intraoperative testing of parathormon levels after resection decreasing is a very reliable extemporaneous sign for the success of the procedure. CONCLUSION: The endocrine system is synchronized; meaning the injury of one gland should start the search for others. In our case, the first main lead should not have been the acute pancreatitis but her diabetes. In the future we suggest that diabetes primary explorations may need a pancreatic imaging and endocrine explorations even though it could get pricier for the healthcare system, but giving the complications that we could prevent; it is to be considered.

Rare association of aortoarteritis and pheochromocytoma: A case report.

INTRODUCTION: Pheochromocytoma is an uncommon but treatable cause of secondary hypertension, it may present with a wide variety of manifestations. The coexistence of pheochromocytoma and vascular abnormalities is described but rarely reported entity. PRESENTATION OF CASE: A 36-year-old man was admitted to our hospital for severe hypertension, examination revealed absent femoral pulses with notion of intermittent claudication. Abdominal computed tomography revealed the presence of a right adrenal pheochromocytoma. CT angiogram showed thickening of the thoracoabdominal aortic wall and the proximal portions of some of its branches with stenosis of more than 50% of the origin of the celiac trunk, bilateral occlusion of the external iliac arteries and trunk stenosis of the right renal artery. The Pheochromocytoma was surgically removed. DISCUSSION: Coexistence of pheyochromocytoma and vascular abnormalities especially renal artery stenosis and aortoarteritis seems to be an association rather than a coincidence. CONCLUSION: To the best of our knowledge, the coexistence of pheochromocytoma along with both aortoarteritis and renal artery stenosis has not been reported thus far. The diagnosis, management and potential mechanisms underlying such an association will be discussed in this case.

[A quadricuspid aortic valve passed unnoticed]. / Une quadricuspidie aortique passée inaperçue.

The quadricuspid aortic valve is a rare congenital anomaly that could be silent for a long time. It is mostly isolated but it may also be associated with other malformations, especially anomalies of the coronary artery insertion. It can lead to aortic regurgitation with several degrees of severity, and it should be diagnosed as soon as possible to avoid left ventricular dysfunction and its morbi-mortality. We report the case of a 67-years-old female patient with recent discovery of moderate aortic regurgitation, which has beneficiated from surgical closure of an atrial septal defect in her childhood, and who has never been diagnosed with a quadricuspid aortic valve.

La quadricuspidie aortique est une anomalie congénitale rare dont l'évolution peut rester longtemps silencieuse. Elle est le plus souvent isolée, mais peut parfois être associée à d'autres malformations, dont les anomalies d'insertion des artères coronaires en premier lieu. Elle se complique, le plus souvent, d'insuffisance aortique dont la sévérité est variable, mais qu'il faut savoir diagnostiquer le plus tôt possible afin d'éviter les décompensations ventriculaires gauches et la morbi-mortalité qui en découle. Nous rapportons le cas d'une patiente de 67 ans, ayant bénéficié d'une fermeture chirurgicale de communication interauriculaire dans l'enfance, chez qui le diagnostic de quadricuspidie aortique n'a jamais été soulevé et qui présente une insuffisance aortique modérée de découverte récente.

[Anaphylaxis to protamine during cardiovascular surgery]. / L'allergie à la protamine en chirurgie cardiovasculaire.

Protamine is a polypeptide with low molecular weights that is used widely to reverse heparin anticoagulation during cardiac surgery. Protamine, efficient and relatively sure, can produce multiple adverse reactions after intravenous administration, including pulmonary hypertension, or systemic hypotension leading at times to cardiovascular collapse and death. Physiopathologic mechanisms, underlying these reactions, are not clear. Immunologic and non-immunologic pathways are suggested. Some risk factors expose to protamine's adverse reactions. Preoperative identification of these factors should prompt specific preventive measures. The anesthesiologist and the cardiac surgeon must be vigilant when administrating protamine. Reheparinization and reinstitution of cardiopulmonary bypass should be considered in patients with refractory shock.

[Clinical case of the month. Peritonitis after spontaneous rupture of pyonephrosis. A case report]. / Le cas clinique du mois. Péritonite secondaire à la rupture spontanée d'une pyonéphrose dans la grande cavité péritonéale. A propos d'un cas.

Peritonitis after spontaneous rupture of pyonephrosis is a rare complication, usually diagnosed intraoperatively. We report the case of a 35 year old woman who was admited for an acute abdomen. Ultrasound showed features of acute peritonitis, with left pyonephrosis, confirmed by a CT-SCAN. Treatment consisted of laparotomy with nephrectomy and abdominal washing and draining. The outcome was favourable.

Body fluid osmolality and tonicity in preterm infants.

In adult patients, a recent physiological approach for the osmoregulatory system based on body fluid tonicity (the so-called effective osmolality) seems to provide better information on water movements than does the classical body fluid osmolality. To evaluate whether plasma or urinary tonicities could give a better assessment of osmoregulation than plasma and urine osmolalities in sick preterm infants cared for in a NICU. A prospective study was conducted in 30 preterm infants (BW=1284+/-377 g; GA=28.8+/-1.7 weeks). Fifteen consecutive 8-h urine collections were performed for each infant from the 8th h of life (450 periods). A plasma sample was obtained at the end of each urine collection. Sodium, potassium, creatinine, osmolality and tonicity were measured or calculated in urine and blood samples as often as possible. Hypernatremia (PNa=146-149 mmol/l) was observed in seven infants (23.3%) and in 5.9% of the periods. Fifty-three percent of the infants and 20.4% of the periods presented with plasma hyperosmolality (>300 mosmol/kg H2O). The relationship between Posm and PNa was significant, but the clinical relevance was weak (r(2)=0.411; P<0.001). Plasma osmolality (Posm) positively correlated with urine osmolality (Uosm), but did not correlate significantly with CH2O/100 ml GFR. Plasma tonicity (2x(PNa+PK)) positively correlated with both urine tonicity (2x(UNa+UK)) and effective water clearance (EWC/100 ml GFR). On an individual basis, the linear relationship between urine and plasma osmolalities was significantly weaker than the relationship between urine and plasma tonicities. This study suggests that the calculation of plasma and urine tonicities allows a better assessment of water movements in body fluid compartments than plasma and urine osmolalities.

Role of Fas and granule exocytosis pathways in tumor-infiltrating T lymphocyte-induced apoptosis of autologous human lung-carcinoma cells.

We have isolated a cytotoxic T lymphocyte (CTL) clone, Heu161, that reacts specifically with the human autologous lung carcinoma cell line IGR-Heu. We first demonstrated that IGR-Heu lacked Fas-receptor expression and was resistant to CD95-induced apoptosis. To further elucidate the role of Fas in tumor immune surveillance, we have stably transfected IGR-Heu with a Fas-expression vector and isolated CD95-sensitive and -resistant clones. Our data indicated that the resistance of 2 selected Fas-transfected clones to CD95-mediated lysis correlated with down-regulation of caspase-8 or its lack of cleavage and subsequent activation. All Fas transfectants, either sensitive or resistant to anti-Fas agonistic antibody, were as efficiently lysed by the CTL clone as the parental cell line. In addition, neither anti-Fas-blocking antibody nor Fas-Fc molecule inhibited T-cell lysis of Fas-sensitive tumor clone. This cytotoxicity was extracellular Ca(2+)-dependent and abolished in the presence of EGTA, indicating that it was mainly granzyme-mediated. Interestingly, although the caspase inhibitor z-VAD-fmk had no effect on tumor-cell lysis, it efficiently blocked target DNA damage triggered by autologous CTLs via the granule exocytosis pathway, indicating that the latter event was caspase-dependent. The present results suggest that lung carcinoma-specific CTLs use mainly a granule exocytosis-dependent pathway to lyse autologous target cells and that these effectors are able to circumvent alteration of the Fas-triggered intracellular signalling pathway via activation of a caspase-independent cytoplasmic death mechanism.

Promoter structure and cell cycle dependent expression of the human methylpurine-DNA glycosylase gene.

The methylpurine-DNA glycosylase (MPG) gene coding for human 3-methyladenine (3-meAde)-DNA glycosylase functions in the first step of base excision repair (BER) to remove numerous damaged bases including 3-meGua, ethenoadenine, and hypoxanthine (Hx) in addition to 3-meAde. In this report, we identify the length of the minimal MPG promoter region, demonstrate the involvement of several transcription factors in expression of the MPG gene, and determine the point at which transcription initiates. We also demonstrate that control of MPG expression is linked to MPG activity. To initiate studies on how the MPG functions with the ensemble of BER genes to effect repair, we have investigated the cell cycle control of MPG and other BER genes in normal human cells. Steady-state mRNA levels of MPG, human Nth homologue (NTH), and uracil-DNA glycosylase (UDG), DNA glycosylases, and human AP site-specific endonuclease (APE), an endonuclease incising DNA at abasic sites, are cell cycle dependent. In contrast, expression levels of genes coding for human 8-oxoguanine-DNA glycosylase (OGG1) and TDG DNA glycosylases, and omicron 6-methylguanine-DNA methyltransferase (MGMT) gene, and the RPA4 subunit gene do not vary with cell cycle. These observed cell cycle dependent differences might reflect distinct roles of individual BER proteins in mutation avoidance.

3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins.

Human 3-methyladenine-DNA glycosylase (MPG protein) initiates base excision repair by severing the glycosylic bond of numerous damaged bases. In comparison, homologues of the Rad23 proteins (hHR23) and the hXPC protein are involved in the recognition of damaged bases in global genome repair, a subset of nucleotide excision repair. In this report, we show that the hHR23A and -B also interact with the MPG protein and can serve as accessory proteins for DNA damage recognition in base excision repair. Furthermore, the MPG.hHR23 protein complex elevates the rate of MPG protein-catalyzed excision from hypoxanthine-containing substrates. This increased excision rate is correlated with a greater binding affinity of the MPG protein-hHR23 protein complex for damaged DNA. These data suggest that the hHR23 proteins function as universal DNA damage recognition accessory proteins in both of these major excision repair pathways.

Interaction of the recombinant human methylpurine-DNA glycosylase (MPG protein) with oligodeoxyribonucleotides containing either hypoxanthine or abasic sites.

Methylpurine-DNA glycosylases (MPG proteins, 3-methyladenine-DNA glycosylases) excise numerous damaged bases from DNA during the first step of base excision repair. The damaged bases removed by these proteins include those induced by both alkylating agents and/or oxidizing agents. The intrinsic kinetic parameters (k(cat) and K(m)) for the excision of hypoxanthine by the recombinant human MPG protein from a 39 bp oligodeoxyribonucleotide harboring a unique hypoxanthine were determined. Comparison with other reactions catalyzed by the human MPG protein suggests that the differences in specificity are primarily in product release and not binding. Analysis of MPG protein binding to the 39 bp oligodeoxyribonucleotide revealed that the apparent dissociation constant is of the same order of magnitude as the K(m) and that a 1:1 complex is formed. The MPG protein also forms a strong complex with the product of excision, an abasic site, as well as with a reduced abasic site. DNase I footprinting experiments with the MPG protein on an oligodeoxyribonucleotide with a unique hypoxanthine at a defined position indicate that the protein protects 11 bases on the strand with the hypoxanthine and 12 bases on the complementary strand. Competition experiments with different length, double-stranded, hypoxanthine-containing oligodeoxyribonucleotides show that the footprinted region is relatively small. Despite the small footprint, however, oligodeoxyribonucleotides comprising <15 bp with a hypoxanthine have a 10-fold reduced binding capacity compared with hypoxanthine-containing oligodeoxyribonucleotides >20 bp in length. These results provide a basis for other structural studies of the MPG protein with its targets.

Repair of DNA alkylation damage.

Alkylation damage of DNA is one of the major types of insults which cells must repair to remain viable. One way alkylation damaged ring nitrogens are repaired is via the Base Excision Repair (BER) pathway. Examination of mutants in both BER and Nucleotide Excision Repair show that there is actually an overlap of repair by these two pathways for the removal of cytotoxic lesions in Escherichia coli. The enzymes removing damaged bases in the first step in the BER pathway are DNA glycosylases. The coding sequences for a number of methylpurine-DNA glycosylases (MPG proteins) were cloned, and a comparison of the amino-acid sequences shows that there are some similarities between these proteins, but nonetheless, compared to other DNA glycosylases, MPG proteins are more divergent. MPG proteins have been purified to homogeneity and used to identify their substrates ranging from methylating agents to deamination products to oxidatively damaged bases. The ligation-mediated polymerase chain reaction has been used to study the formation of alkylation damage, and its repair in mammalian cells. We have studied DNA damage in the PGK1 gene for a series of DNA alkylating agents including N-methyl-N'-nitro-N-nitrosoguanidine, Mechlorethamine, and Chlorambucil and shown that the damage observed in the PGK1 (phosphoglycerate kinase 1) gene depends on the alkylating agent used. This report reviews the literature on the MPG proteins, DNA glycosylases removing 3-methyladenine, and the use of these enzymes to detect DNA damage at the nucleotide level.

Hepatic storage and transport of n-3 and n-6 polyunsaturated fatty acids by very-low-density lipoproteins in growing rats fed low- or adequate-protein diets with sunflower, soybean, coconut, and salmon oils.

Protein and essential fatty acid (EFA) deficiencies may both occur in chronic malnutrition and have common symptoms. To determine the interactions between dietary protein intake and EFA availability, rats were fed purified diets containing 20% or 2% casein and 5% as one of four fats (sunflower, soybean, coconut, or salmon oil) that differed particularly in their n-6 and n-3 polyunsaturated fatty acids (PUFAs). Protein malnutrition enhanced hepatic triacylglycerol and cholesterol concentrations while decreasing hepatic protein and phospholipid contents and mass and components of very-low-density lipoprotein (VLDL). The ratio of PUFAs to saturated fatty acids (SFAs) was consistently depressed by protein malnutrition in liver and VLDL triacylglycerol and phospholipid. Total n-6 and n-3 fatty acids were diminished by protein malnutrition, except with salmon oil, with which a decrease in 20:5n-3 was compensated for by an increase in 22:6n-3. The ratio of 20:4n-6 to 18:2n-6 was enhanced in liver phospholipid and VLDL triacylglycerol, and modified little in liver triacylglycerol. Generally, the ratio of 20:3n-9 to 20:4n-6, an index for EFA deficiency, was raised with protein malnutrition in liver triacylglycerol and phospholipid and in VLDL triacylglycerol. The extent of changes in each fatty acid proportion varied according to the oil fed. Overall, VLDL-apolipoprotein concentrations were, in general, strongly reduced with protein malnutrition. In conclusion, protein malnutrition may accelerate marginal EFA deficiency and decrease long-chain PUFA bioavailability and thus increase EFA requirement.

A synthetic peptide from the human immunodeficiency virus type-1 integrase exhibits coiled-coil properties and interferes with the in vitro integration activity of the enzyme. Correlated biochemical and spectroscopic results.

Integration of the human immunodeficiency virus (HIV-1) DNA into the host genome is catalysed by a virus-encoded protein integrase. Here, we report some of the structural and functional properties of two synthetic peptides: integrase-(147-175)-peptide reproducing the residues 147-175 (SQGVVESMNKELK159KIIGQVRDQAEHLKTAY) of the HIV-1 integrase, and [Pro159] integrase-(147-175)-peptide where the lysine 159 is substituted for a proline. Circular dichroism revealed that both peptides are mostly under unordered conformation in aqueous solution, contrasting with the alpha-helix exhibited by residues 147-175 in the protein crystal structure. In a weak alpha-helix-promoting environment, integrase-(147-175)-peptide self-associated into stable coiled-coil oligomers, while [Pro159] integrase-(147-175)-peptide did not. This property was further confirmed by cross-linking experiments. In our in vitro experiments, only integrase-(147-175)-peptide was able to reduce the integration activity of the enzyme. We propose that the inhibitory activity shown by integrase-(147-175)-peptide is dependent on its ability to bind to its counterpart in integrase through a peptide-protein coiled-coil structure disturbing the catalytic properties of the enzyme.

Binding of Net-Fla, a netropsin-flavin hybrid molecule, to DNA: molecular mechanics and dynamics studies in vacuo and in water solution.

We have studied the binding of the hybrid netropsin-flavin (Net-Fla) molecule onto four sequences containing four A. T base pairs. Molecular mechanics minimizations in vacuo show numerous minimal conformations separated by one base pair. 400 ps molecular dynamics simulations in vacuo have been performed using the lowest minima as the starting conformations. During these simulations, the flavin moiety of the drug makes two hydrogen bonds with an amino group of a neighboring guanine. A 200 ps molecular dynamics simulation in explicit water solution suggests that the binding of Net-Fla upon the DNA substrate is enhanced by water bridges. A water molecule bridging the amidinium of Net-Fla to the N3 atom of an adenine seems to be stuck in the drug-DNA complex during the whole simulation. The fluctuations of the DNA helical parameters and of the torsion angles of the sugar-phosphate backbone are very similar in the simulations in vacuo and in water. The time auto-correlation functions for the DNA helical parameters decrease rapidly in the picosecond range in vacuo. The same functions computed from the water solution molecular dynamics simulations seem to have two modes: the rapid mode is similar to the behavior in vacuo, and is followed by a slower mode in the 10 ps range.

Alternate strand DNA triple helix-mediated inhibition of HIV-1 U5 long terminal repeat integration in vitro.

Integration of the human immunodeficiency virus (HIV) DNA into the host genome is an obligatory process in the replicative life cycle of the virus. This event is mediated in vitro by integrase, a viral protein which binds to specific sequences located on both extremities of the DNA long terminal repeats (LTRs). These sites are highly conserved in all HIV genomes and thus provide potential targets for the selective inhibition of integration. The integrase-binding site located on the HIV-1 U5 LTR end contains two adjacent purine tracts on opposite strands, 5' . . . GGAAAATCTCT-3'/3'-CCTTTTAGAGA . . . 5', in parallel orientations. A single strand oligonucleotide 5'-GGTTTTTGTGT-3' was designed to associate with these tracts via its ability to form a continuous alternate strand DNA triplex. Under neutral pH and physiological temperature, the oligonucleotide, tagged with an intercalator chromophore oxazolopyridocarbazole, formed a stable triplex with the target DNA. The occurrence of this unusual triplex was demonstrated by both DNase I footprinting and electron microscopy. The triplex inhibits the two steps of the integrase-mediated reactions, namely, the endonucleolytic cleavage of the dinucleotide 5'-GT-3' from the 3' end of the integration substrate and the integration of the substrate into the heterologous target DNA. The midpoints for both inhibition reactions were observed at oligonucleotide concentrations of 50-100 nM. We believe that these results open new possibilities for the specific targeting of viral DNA LTR ends with the view of inhibiting integration under physiological conditions.