High serum galectin-3 in advanced melanoma: preliminary results.

BACKGROUND: Galectin-3 (Gal-3) is a member of the family of beta-galactoside-binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo. AIM: To determine whether an increase in serum Gal-3 production could be found in patients with advanced metastatic melanoma. METHODS: We collected 18 sera from patients with AJCC stage IV metastatic melanomas and 20 sera from healthy volunteers. Determination of Gal-3 was performed by ELISA, and in the group of patients with melanoma, these results were compared with the serum lactate dehydrogenase (LDH) and the C-reactive protein (CRP) concentrations. RESULTS: Gal-3 concentration was shown to be significantly higher in the group of patients with melanoma compared with healthy volunteers, and Gal-3 concentration was significantly correlated with both LDH and CRP in the melanoma group. We also selected four patients in the melanoma group for Gal-3 retrospective immunostaining analysis on cutaneous metastases. Two of these patients, who had a higher Gal-3 serum level, showed more intense staining and the other two patients, with a lower serum level of Gal-3, had moderate immunostaining, suggesting that at least part of serum Gal-3 might be produced by metastatic melanoma tissue. CONCLUSIONS: Gal-3 might play a role in melanoma progression and/or inflammation, and warrants further study.

Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage.

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were produced with these three excipients (60% w/w) and theophylline as drug model (40%). On the one hand, in vitro dissolution studies were performed with the rotating paddle method displaying the different release behaviour of these three matrices (immediate release for MCC, steady release for HPMC and sustained release for EC). On the other hand, the evolution of the T2m spin-spin relaxation time in NMR experiments during granules hydration was recorded. NMR findings shore up dissolution data, both depending on interactions between the matrix and water. NMR spectroscopy appears to be a valuable tool for obtaining, at an earlier stage of drug development, more information about drug release mechanism.

Contributions of AMPA and GABA(A) receptors to the induction of NMDAR-dependent LTP in CA1.

The contributions of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and gamma-aminobutyric acid (GABA[A]) receptors in the induction of long-term potentiation (LTP) have been studied in the CA1 region of the rat hippocampus. The results suggest that: (1) in physiological conditions, AMPARs are necessary for the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent LTP since LTP cannot be elicited in the presence of the AMPAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Although a NMDAR-dependent LTP occurs in the presence of a GABA(A) antagonist and high concentrations of divalents cations, blockade of AMPARs leads to a voltage-dependent calcium channels (VDCC)-dependent LTP since its induction is blocked by nifedipine and not by APV. (2) The bicarbonate-induced GABA(A) receptor-mediated depolarizing response is not necessary in the induction of NMDAR-dependent or VDCC-dependent LTP since induction of these two types of LTP were not blocked by acetazolamide or in a nominally bicarbonate-free solution.

[Primary exocrine pancreatic insufficiency in the adult. Presentation of a case]. / Insuffisance pancréatique exocrine primitive de l'adulte. Présentation d'un cas.

The authors report the case of a 37-year-old female complaining of chronic diarrhea since childhood. She had gross steatorrhea and azotorrhea . Pancreatic function tests using secretin and cholecystokinin-pancreozymin stimulation, and analysis of pure pancreatic juice collected under secretin stimulation proved exocrine pancreatic insufficiency. Oral glucose tolerance test was normal. Intestinal absorption tests, small bowel X-ray films and jejunal histology were normal. Brush-border specific enzyme activities were increased. In vitro palmitic acid uptake and esterification in the jejunal mucosa were decreased. There was no pancreatic calcification. Biliary tract was normal. Retrograde pancreatography, pancreatic ultrasonography and tomodensitometry showed no morphologic abnormality. No cause of exocrine pancreatic insufficiency could be detected. A son and a niece of the proband had chronic diarrhea and growth failure. The relationship of the described case with primary lipomatosis of the pancreas in childhood and hereditary exocrine pancreatic insufficiency in CBA/J epi mice is discussed.

[Rupture of an aneurysm of the splenic artery into the pancreas, a rare cause of gastrointestinal bleeding (author's transl)]. / Rupture d'un anévrysme de l'artère splénique dans le pancréas, cause exceptionnelle d'hémorragie digestive par wirsungorragie.

In a 73 year old man, repeated gastrointestinal haemorrhages first attributed to peptic oesophagitis, recurred despite anti-reflux surgery. Upper endoscopy being negative, arteriography was performed which revealed the presence of a fissured aneurysm of the splenic artery. This was successfully treated by left splenopancreatectomy. A communication between the aneurysm and wirsung's duct was found in the operative specimen. This a very rare cause of gastrointestinal bleeding. The diagnosis can be made only by arteriography.

[A case of hepatocholangitis (author's transl)]. / Une observation d'hépaticite (hépato-cholangite).

Inflammation localised to the hepatic duct in the region of the neck of the gallbladder is rare. Regression of the lesions after cholecystectomy authentified its purely inflammatory nature. Its interest comes from possible confusion with carcinoma of the common bile duct. A case of cholangitis with 8 years follow up illustrates these facts and permits a few comments on the pathology of the junction between the cystic duct and the hepatic duct.

[Crohn's disease of the colon. History]. / La maladie de Crohn du côlon. Historique.

During the 18th, 19th, and at the beginning of the 20th century, various observations of inflammatory lesions of the colon and small intestine were published, which were different of tuberculosis to which was at that time attributed every chronical small intestinal inflammatory disease. It was only in 1932, that in a very important paper, Crohn, Ginsburg and Oppenheimer defined the terminal ileitis, afterwards called regional enteritis, and finally more simply Crohn's disease. Twenty years later, in 1952, Crohn's disease of the colon, confused until that date with colonic tuberculosis and with ulcerative colitis, was also identified as a separate entity. Since that time, the number of reported cases has tremendously increased through its is impossible to state whether the incidence of the disease has really increased or whether the diagnosis is done earlier and more precisely. Even today, the exacts limits of the disease are difficult to precise, since the causal agent of the disease is unknown, and that no biological test is completely secure. The present work reports 60 observations of chronic colitis, associated or not with small intestinal inflammation.

[Findings by baryum enema in granulomatous colitis and ileocolitis. A review based upon 60 cases (author's transl)]. / Les signes fournis par le lavement baryté dans les colites et les iléocolites de Crohn. A propos de soixante observations.

Radiological aspects of colonic involvement in 60 patients whose disease has been followed up during several years are described. The typical radiological findings have been observed with their usual frequency. This study also confirmed the persistancy of the radiological findings in the chronic stage and the frequency of recurence in the two first years after surgery. Extension of disease has not been uncommon in the series, even without surgery. This progression was different, according to the initial location of disease: in the case of initial ileal lesion, extension occurred towards the adjacent caecum and right colon in sequence; in the case of initial colitis or ileocolitis lesion, extension occurred at a distance in other colonic segments.

[Haematologic disorders in Crohn's disease (author's transl)]. / Les signes hématologiques de la maladie de Crohn.

Anemia is the most commonly haematologic disorder observed in Crohn's disease. Secondary megaloblastic anemia related to a nutritional deficiency of vitamin B 12 and/or folic acid is a rare condition as well as auto-immune haemolytic anemia. Iron lack microcytic hypochromic anemia is far more frequent. It is probably due to several causes as microscopic or macroscopic haemorrhages, inflammatory syndrome, disturbance of iron absorption. Hyperleucocytis, hypereosinophilia, hypoprothrombinemia related to the inflammatory syndrome and/or lesions of the bowels are frequently observed in such patients. Anyhow, heamatologic disorders seem markedly correlated with the activity of the disease and should be useful in the follow up patients with Crohn's disease.

[Medical mangement of Crohn's disease (author's transl)]. / Traitement médical de la maladie de Crohn.

Medical management of Crohn's disease is above all symptomatic. According to the severeness of the case, treatment varies and may be simple (regimen, antidiarrheic agents and sulfamid drugs) or more sophisticated (continous parenteral alimentation). Sulfamids and antibiotics have a definite although temporary action. Pathogenic medication includes: 1) steroid therapy who is active, but its effects are not long stand; 2) immunosuppressors who allow for the reduction of steroid therapy dosages; 3) immunostimulants as proposed by Geffroy. Among those presently studied are Calmette-Guérin vaccine, either given orally or by scarification, and two anti-parasitic drugs, metronidazole and levamisole. Short term results are good but they worsen with time. The main problem is to know when to discuss surgery. As need be, resection although mutilating, should be timely indicated.

[Surgical treatment of Crohn disease of the colon. (38 cases) (author's transl)]. / Le traitement chirurgical de la maladie de Crohn colique. A propos de 38 observations.

From 1959 to december 1972 thirty-eight patients out of sixty having Crohn disease of the colon alone or with ileal and/or rectal involvement were operated upon. We had four post-operative deaths and one a long time after the intervention, but in relation with the initial Crohn disease. These thirty-eight patients had sixty-seven operations. Only fifty-five per cent of the operated on patients did not have any complications. Twenty-three patients had recurrence of the disease, seven of them were re-operated for this first recurrence, two of them for a second recurrence and one of these two last patients had a third recurrence. That makes twenty-seven recurrences out of forty-three resections. Among these twenty-seven recurrences, in at least seventeen cases, resection was not large enough or was not radical. Three quarters of the recurrences appear during the first year. The more exposed interventions to recurrences are left hemi-colectomies (two out of two) and total colectomies with ileo-rectal anastomosis (six out of eight). The ones that give less recurrences are total colo-protectomies or subtotal colectomies (one recurrence out of nine). Indications for the different types of interventions are analysed. Management of the rectum in Crohn disease of the colon is difficult. Procedures applied for toxic megacolon are equally very critical.

[Extra intestinal manifestations of Crohn's disease (author's transl)]. / Manifestations extra-intestinales de la maladie de Crohn.

The extra intestinal manifestations of Crohn's disease (CD) are not devoid of interest. They can, by themselves, aggravate the CD. Some of them have to be searched systematically (urinary complications, spondylarthritis and sacro-iliac arthritis). Amongst our 60 cases of Crohn's disease of the colon or of the ileon and colon, articular manifestations were the most frequent: arthralgias 25 cases (42%), true arthritis 17 cases (28%), spondylarthritis 5 cases, aacro-ileitis 9 cas (13%), finger hippocratism 11 cases (18%). In second cause, the cutaneous manifestations: 29 cases (48%) among which 6 cases (10%) of erytheme nodosa and 9 cases of allergic troubles (15%). Then came ocular troubles (5 cases), jaundice (5 cases). We observed 4 renal lithiasis and an hepatic sarcoïd granuloma revealed by the liver biopsy. Some complications were the local consequence of a local disease (hydronephrosis). Others represented the distant repercussion of a severe chronical intestinal disease. Some were true extra-intestinal localisations of the disease (perineal ulcerations and para-stomal ulcerations). Finally some complications, though non specific of Crohn's disease, evolued in parallel to it (some articular, ocular; dermatologic complications). In some cases they were anterior by several months or years to the intestinal symptoms of Crohn's disease, which suggests the existence of common etiological factors, especially genetical.

Effects of somatostatin on the external secretion of the pancreas of the rat.

The effects of somatostatin on the secretions of the exocrine pancreas were studied in anesthetized and conscious fistula rats. Somatostatin resulted in a dose-dependent decrease of basal secretion (flow, bicarbonate, protein) in conscious rats. In anesthetized rats, basal secretion was initially augmented by bolus injections of 10 to 50 microgram per kg and was subsequently decreased by venous infusions of somatostatin at 1.5 to 100 microgram.kg-1.hr-1. This inhibition, which was poorly dose dependent, was greater for protein secretion than for that of water and electrolytes. Somatostatin inhibited caerulein-stimulated protein secretion by 40 to 50% but had no effect on secretion stimulated by exogenous and endogenous secretin. Somatostatin markedly inhibited secretion stimulated by 2-deoxyglucose and by electrical stimulation of the vagus nerves in a dose-dependent fashion (protein and bicarbonate exhibited a maximal inhibition of 85%). Acetylcholine-stimulated secretion was also inhibited by somatostatin, but the maximal inhibitions observed were only 505 for protein and 60% for bicarbonate. These findings agree with the hypothesis that somatostatin infusion leads to both a decrease of acetylcholine release at nerve endings and to a direct inhibition at the level of pancreatic effector cells.