Acute Hepatic Porphyrias: Review and Recent Progress.

The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%-3%). Here we provide an updated review of relevant literature and discuss recent and emerging advances in treatment of these disorders. Symptomatic attacks occur primarily in females between 14 and 45 years of age. AHP is diagnosed by finding significantly elevated levels of porphyrin precursors ALA and porphobilinogen in urine. Acute attacks should be treated promptly with intravenous heme therapy to avoid the development of potentially irreversible neurologic sequelae. All patients should be counseled about avoiding potential triggers for acute attacks and monitored regularly for the development of long-term complications. Their first-degree relatives should undergo targeted gene testing. Patients who suffer recurrent acute attacks can be particularly challenging to manage. Approximately 20% of patients with recurrent symptoms develop chronic and ongoing pain and other symptoms. We discuss newer treatment options in development, including small interfering RNA, to down-regulate ALA synthase-1 and/or wild-type messenger RNA of defective genes delivered selectively to hepatocytes for these patients. We expect that the newer treatments will diminish and perhaps obviate the need for liver transplantation as treatment of these inborn metabolic disorders

Renal Failure Affects the Enzymatic Activities of the Three First Steps in Hepatic Heme Biosynthesis in the Acute Intermittent Porphyria Mouse

Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure

Etude expérimentale de l'opalescence critique

Dans le présent article sont décrits un procédé de remplissage des tubes pour l'étude de l'état critiqne, une étuve électrique à température constante et les résultats de mesures photométriques faites sur cinq liquides purs (éther ordinaire et éthers acétiques homologues). L'intensité de l'opalescence critique varie en raison inverse de la différence entre la température d'observation et la température critique. Depuis son début jusqu'à 0,15°C environ de la température critique, elle est inversement proportionnelle à la quatrième puissance de la longueur d'onde. Au-dessous de cette limite, elle est inversement proportionnelle au carré de la longueur d'onde. L'opalescence varie avec le remplissage des tubes, suivant une loi parabolique analogue à la loi de variation de la température critique avec ce remplissage. Dans une série de corps homologues, l'opalescence est plus intense et sa durée est plus longue à mesure que le poids moléculaire augmente. Une série de mesures absolues du nombre N ont donné les valeurs moyennes 58.10^(22) et 60.10^(22). L'application de la photographie a permis d'étudier la variation de l'opalescence avec la nature de la phase et le sens du passage d'une phase à l'autre; la spectrophotométrie photographique a permis de vérifier une partie des résultats obtenus par mesures visuelles directes

Jejunoileal Crohn's disease: a case-control study.

AIMS: Jejunoileitis might be a severe form of Crohn's disease (CD). The aim of the study was to evaluate clinical characteristics, therapeutics modalities and long-term outcome in CD patients with jejunoileitis (CDJI). METHODS: All patients with CDJI followed in the department of Gastroenterology from 1963 to 1999 were included and compared to matched (on Year of CD diagnosis) CD controls without jejunoileitis. Data were obtained from retrospective review of medical charts. RESULTS: Eighteen patients with CDJI were compared to 36 matched CD controls. Median follow-up was 7.65 Years in both groups. At time of CDJI diagnosis the following signs were significantly more frequent in patients with jejunoileal CD than in controls: malnutrition (39% vs 3%), pain suggesting obstruction (33% vs 8%), vomiting (28% vs 5%). Patients with CDJI were more frequently male: M/F ratio=2.0/1.1 (P=0.33). Upper digestive involvement (esophagus, stomach and duodenum) (67% vs 36%, P=0.04) and small intestine strictures (61% vs 19%, P=0.06) were more frequent in CDJI. Initial management was more "aggressive" in CDJI than in controls: steroids in 62% vs 30%, azathioprine in 39% vs 3%, total parenteral nutrition in 28% vs 8% and surgery in 33% vs 17%. During follow-up, the need for azathioprine therapy and surgery were more frequent in CDJI than in controls (extensive small bowel resection in two patients). In 10 of 18 patients, jejunoileitis involvement was diagnosed with a median delay of 3.6 Years (range: 0.5-14.5) after CD diagnosis and at time of CD diagnosis in the 8 others; outcome after CDJI diagnosis was similar in these 2 groups. CONCLUSION: The main revealing signs of jejunoileitis in CD patients are obstruction and malnutrition. Patients with CDJI require more often azathioprine and surgery than CD patients without jejunoileitis. Jejunoileitis is a severe form of CD more frequently complicated by extensive small bowel resection

Recherches sur l'émission spectrale des arcs à mercure en quartz

Nous nous sommes proposé de déterminer, pour des modèles d'arcs à vapeur de mercure en quartz très différents, fonctionnant sous des régimes très variés les intensités relatives des principales raies émises. Bien que nous n'ayions exécuté actuellement qu'une partie de notre programme, il apparaît que nos résultats complètent en les confirmant, ceux des travaux antérieurs. Nous avons trouvé notamment, avec six arcs, en étendant les mesures depuis le doublet jaune jusqu'à la raie de résonahce (2 536 Å), que : 1° pour un même arc, l'intensité d'une raie émise change notablement avec le régime principalement avec la tension aux bornes ; 2° pour deux arcs différents. et pour la même raie spectrale, une variation identique de régime ne produit pas le même changement dans l'émission

Un appareil de pulvérisation cathodique permettant d'obtenir des couches dont la densité est contrôlée pendant la formation

The deposits are prepared by cathodic sputtering. The optical density of the deposits is measured during the sputtering (a beam of light passes through the target plate and the metallic cathode which is perforated for this purpose). The apparatus also provides a control of the purity of the gas in the region where the sputtering takes place

Mesure de la douleur aux urgences (effet sur la qualité de la prise en charge des patients et sur leur satisfaction)

La douleur est un motif de consultation fréquent dans les services d'urgences médico-chirurgicales. Toutefois la qualité de sa prise en charge est insuffisante...PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF