Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

INTRODUCTION: Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD. METHODS: A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150). RESULTS: There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated. CONCLUSION: Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.

[Polyposis of the colon and cancer]. / Polipoza na debeloto chervo i rak.

Polyposis of the colon is a colon cancer predisposition syndrome. Familial adenomatous polyposis (FAP) accounts for 1% of the cases of inherited colorectal cancer (CRC). The National Register of inherited CRC and polyposis of the intestines keeps track of 18 patients from 14 families with FAP. Eight of them have been operated of CRC, on 6 patients preventive colectomy with ileorectal anastomosis has been done and four patients refused surgery. Colectomy has been done due to the malignant development also on a female patient with difused juvenile polyposis with adenomatosis. Of three patients under surveillance with the Peutz-Jeghers syndrome, surgery has been done on one female patient with ileus and bleeding large polyps.

[Classifications and prognosis of hepatocellular carcinoma]. / Klasifikatsii i prognoza na khepatotselularniia kartsinom.

In this study are included 78 patients with hepatocellular carcinoma (HCC). In 22 the diagnosis is verified pathologically (obduction), while in the other patients the diagnosis is made by laparoscopy, laparoscopical ultrasonography and morphological verification (through FNAB cytology and/or histology). In 69.2% HCC is associated with cirrhosis. The prognosis of HCC associated with cirrhosis is evaluated through the classification of S. Chevret et all., and is compared to the Child-Pugh scoring system. 38.9% of patients in Chevret's class C score are in class B in the Child-Pugh score, while 25.9% of patients are in class C in both classifications, but Child-Pugh's class C patients are most often in B-C transition. It might be assumed that the prognosis of HCC depends more on the tumor prognosis than on the prognosis of the liver cirrhosis itself. Every classification which does not take in to account the liver function (like TNM system) and the whole characteristics of the tumor, would be incomplete, in some extent, in the prognosis of HCC with cirrhosis. In HCC without cirrhosis, the BCLC classification reflects both the liver function and the tumor characteristics. In BCLC class A patients hepatic resection or transplantation is recommended but hyperbilirubinemia and ascites, which might be seen in A3 and A4 classes contraindicate resection of the liver. All scoring systems define lower HCC stage than it is really found (personal and reference data), so there are no arguments to take classification scores as absolute treatment decision making rules.

Immunological and radioimmunological studies in food allergy.

Experiments in order to induce food allergy were carried out in guinea pigs. The sensitization with egg albumin, pasteurized cow milk and bovine serum albumin provoked anaphylactic shock. The passive cutaneous anaphylaxis, serum antibodies, liver cytochrome P-450 concentration and the anaphylactic shock were determined. Some correlation between the mortality, anaphylactic antibodies and cytochrome P-450 monooxygenase system was established. The morphology of the jejunal mucosa, the activities of the 5 disaccharidases, the number of immunoglobulin secreting cells (Ig SC) and the mastocytes were investigated in 35 patients with food allergy. Normal mucosa was found in 28 cases as well as a significant decrease of the lactase, sucrase and trehalase activities. An increase of IgM and IgG secreting cells and of mastocytes, different electron microscopic changes in the enterocytes (an increased number of lysosomes, appearance of vesicles in cytoplasma, shortening, enlargement and uneven distribution of microvilli) as well as symptoms of functional activity in the plasmocytes and some others were also revealed. The experimental model obtained is similar to that one in humans according to the enteral way of sensitization the high selectivity of the allergic reaction which is of reagin type as the immunoglobulin changes are involved.

[Mastocytes in the human intestinal mucosa]. / Prouchvane na mastotsitite v choveshka chrevna ligavitsa.

A method has been for counting the mastocytes on 0.1 mm2 of intestinal mucosa in patients with chronic enterocolitis, gluten enteropathy, ulcerous colitis in a stage of exacerbation and in controls. The comparison of the results obtained in the separate groups of patients reveal an increased number of mastocytes in gluten enteropathy--mean = 21.01 +/- 6 as compared with the chronic enterocolitis, where mean = 9.79 +/- 3.83 (p = 0.002). Higher values of mastocytes in rectal mucosa were observed in the patients with ulcerous mucosa--mean = 15.83 +/- 4.49 as compared with the control subjects with means = 3.67 +/- 0.99 (p = 0.001). those data admit the participation of mastocytes in the morbid process in patients with gluten enteropathy and with ulcerous colitis.

[Parallel morphological, enzyme and immunological research on the jejunal mucosa in patients with gluten enteropathy, chronic nonspecific enteritis and ulcerative colitis]. / Paralelni morfologichni, enzimni i imunologichni izsledvaniia na ieiunalnata ligavitsa pri bolni s glutenova enteropatiia, khronichen nespetsifichen enterit i iazven kolit.

The results are reported from the study on 120 patients, 30 of them with gluten enteropathy, 50--with chronic unspecified enteritis and 40--with chronic ulcerous colitis. Small intestinal aspiration biopsy was performed to all patients with histomorphological, electron microscopic, enzymatic and immune-fluorescent study. The secretory immunoglobulins in the jejunal juice were studied in 40 patients. Morphological changes, various degrees, were established, that correlate with the increased number of IgG and IgM secretory cells. The exclusion of gluten from the diet in case of gluten enteropathy was followed by normalization of the number and percentage ratio of IgSC and of secretory immunoglobulins. The enzymatic and immune disorders, in chronic unspecific enteritis correlate with the electron microscopic and precede the histologic ones. The role of immune system of small intestine in the etiology and pathogenesis of the various intestinal diseases is discussed.

[Small intestine perfusion. The authors' own method for the simultaneous performance of biopsy and perfusion of the human small intestine]. / Tunkochrevna perfuziia. Sobstven metod za ednovremenno izvurshvane na biopsiia i perfuziia na tunko chervo pri khora.

The analysis of advantages and disadvantages of the technique and principles of the methods of small intestinal perfusion, used by various authors in the studies on resorption processes, provided grounds the authors to develop their own method. The system for infusion and aspiration by a combined probe is described. Details about the composition of perfusion solution, the technique of the study and calculation of resorption rate are reported. The advantages of the method are as follows: simultaneous performance of small intestinal glucose perfusion and biopsy of small intestine, good tolerance by the patients and availability of the elements needed for the construction of the probe and system for infusion and aspiration. The mean glucose resorption rate was 814,07 mumol/min/30 cm in 9 subjects with no small intestinal diseases and with normal histomorphological picture of small intestinal mucosa.

[Parallel morphological and functional research on chronic enterocolitis patients using the authors' own method for the simultaneous performance of perfusion and biopsy of the small intestine]. / Paralelni morfologichni i funktsionalni izsledvaniia pri bolni s khronichen enterokolit s pomoshtta na sobstven metod za ednovremenno izvurshvane na perfuziia i biopsiia na tunko chervo.

Thirty two patients were studied with chronic enterocolitis and 9 patients without any small intestinal diseases, with normal histomorphological picture of small intestinal mucosa--control group. The method of simultaneous performance of perfusion and biopsy of small intestine was used. Glucose resorption rate in small intestine was studied and histomorphological, electron--microscopic and enzymologic (disaccharidases) studies were carried out on jejunal mucosa. Data about chronic enterocolitis without atrophy were established in 17 patients, in 10--initial partial atrophy, in 5--advanced partial and subtotal atrophy of jejunal mucosa. Reduced glucose resorption rate was established in small intestine in the patients with chronic enterocolitis as compared with that of the control group. Glucose resorption rate correlates with the severity of the histomorphological changes in small intestinal mucosa. Disturbed resorption rate was established via jejuno--perfusion in patients with clinically not manifested syndrome of malresorption and absence of histomorphological changes in small intestinal mucosa, but with established ultrastructural changes in enterocytes.

[Whipple disease: clinical and immunohistologic findings in 2 cases]. / Der Morbus Whipple: Klinische und immunhistologische Befunde in zwei Fällen.

Two cases with typical clinical and histological manifestations of Whipple's disease were reported. Peroral jejunal biopsies were studied in the florid stage and during remission achieved by tetracycline therapy. A complete absence of immunoglobulin-containing cells (Ig-CC) and an increased number of mast cells in the mucosa were established in one of the cases. A 5-fold decrease of the mucosal Ig-CC was found by immunofluorescent morphometry in the second case. An increased Ig-CC number and histological restitution of the mucosa were shown in the first case during remission, whereas histological alterations and decreased Ig-CC number persisted in the second case despite of clinical improvement. The HLA-locus B27 was not available in the reported cases.

[Correlation between immunoglobulin-secreting cells and secretory immunoglobulins in the small intestine in chronic intestinal diseases]. / Korelatsiia mezhdu imunoglobulin-sekretirashtite kletki i sekretornite imunoglobulini v tunkite cherva pri niakoi khronichni chrevni zaboliavaniia.

A total of 45 patients were studied: seven with gluten enteropathy and 38 with chronic unspecific enteritis. Histological and immunefluorescent studies were performed and to a part of the cases--enzymatic and electron-microscopic investigations of the jejunal mucosa. An increased number of immuneglobulin -secreting cells was established in the non-treated patients with gluten enteropathy, growing with age. In the cases with chronic unspecific enteritis with a manifested clinic, a tendency to decrease of the number of IgSC was observed, with growing percentage of IgG-SC and the values of the secretory IgG. There was no correlation between the intraepithelially located lymphocytes and those in the chorion, as well as between the duration of the disease, number and percentage distribution of Ig-SC.

[Case of a patient with liver cirrhosis and Silvestrini-Corda syndrome]. / Sluchai na bolen s chernodrobna tsiroza i sindrom na Silvestrini--Corda.

A case with alcoholic cirrhosis of liver is described that was combined with manifested gynecomastia, atrophia of testes and impotence--Silvestrini--Corda syndrome. Changes in the endocrine state of the patient were established--a tendency to reduced estrogens in plasma (estradiol), increased blood cortisol and reduced excretion of its metabolites in urine. The case is of clinical interest because the severe alcoholic hepatic lesion became the cause of the affection of endocrine state and in this way led to manifested classical syndrome of Silvestrini--Corda.

Nodular lymphoid hyperplasia of the jejunal mucosa associated with hypogammaglobulinemia. Increased number of mast cells in the jejunal mucosa.

A case with nodular lymphoid hyperplasia of the jejunal mucosa associated with hypo- and dysgammaglobulinemia, increased susceptibility to infections, recurrent giardia invasions, absence of plasma cells in the bone marrow and jejunal mucosal stroma and extremely increased number of mucosal mast cells has been described. The latter was supposed to be an essential morphological feature of the syndrome, that is due to a "secondary" response to repeated giardia invasions in a condition of impaired humoral but presumably normal cellular immune response. Some of the tinctorial properties of intestinal mucosal mast cells were discussed.

[Gluten enteropathy--epidemiologic, clinical, morphologic and enzymatic study]. / Glutenova enteropatiia--epidemiologichno, klinichno, morfologichna i enzimno prouchvane.

The results from the clinical, morphological and enzymatic studies are reported upon the jejunal mucosa and the effect of a gluten-free diet among a group of 60 patients with gluten enteropathy and 5 patients with idiopathic steatorrhea. The significance of light microscopic and electronmicroscopic studies are discussed in details in making the diagnosis, differential diagnosis and assessment of the results from the treatment of gluten enteropathy.