[Croatian consensus on the treatment of inflammatory bowel diseases with biologic therapy]. / Hrvatski konsenzus o lijecenju upalnih bolesti crijeva bioloskom terapijom.

Introduction of biologic therapy in clinical practice represented significant progress in the treatment of inflammatory bowel diseases (IBD) because of its proven efficacy and due to the fact that biologics are the first drugs used in the treatment of IBD that can change the natural course of this diseases. At the same time, biologics are very expensive drugs with complex mechanism of action and important side effects and their use requires evidence-based clinical guidelines. These were the reasons that Referral Center of the Croatian Ministry of Health for IBD and the IBD Section of the Croatian Society of Gastroenterology organised Croatian consensus conference that defined guidelines for the treatment of IBD with anti-TNF drugs. The text below includes definitions of IBD, general principles of IBD therapy, comments on the importance of mucosal healing, analysis of reasons for nonresponse and loss of response to anti-TNF drugs, recommendation for the duration of anti-TNF therapy, rules of screening for opportunistic infections prior to anti-TNF therapy, comments on the problems with reproduction in IBD and finally guidelines for the treatment of various phenotypes of IBD including extraintestinal manifestations with anti-TNF therapy.

[Acute plastic bronchitis--case report]. / Akutni odljevni bronhitis--prikaz bolesnika.

Plastic bronchitis is a rare disorder characterized by formation and sometimes dramatic expectoration of bronchial casts. It may occur at any age, but most published cases refer to pediatric population. We report a case of an 81-year-old man hospitalized at intensive care unit, who presented with the appearance of plastic bronchitis type I. He had profuse expectoration of several pieces, a few cm long and up to 1 cm wide, of wormlike reddish-brownish "tissue". Histologically, it was a slimy purulent secretion with abundant fibrin and blood and with cytopathic effect of herpes virus. The pathogenesis of plastic bronchitis is not clear.

[Secondary (AA) renal/bone amyloidosis complicating rheumatoid arthritis]. / Sekundarna amiloidoza (AA) bubrega i kostane srzi u bolesnice s reumatoidnim artritisom.

Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that appears in the context of cancer, chronic inflammation, and chronic infectious disease, including rheumatoid arthritis. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. We present a case of a 52-year-old female patient diagnosed with rheumatoid arthritis at age 27. She was hospitalized due to worsening clinical condition. Physical examination revealed marked peripheral edema in both lower extremities. Laboratory tests showed an increase of inflammatory reactants, anemia, electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was 78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposits that immunoreacted with the antibody against amyloid A protein, thus confirming the diagnosis of secondary amyloidosis.

[Secondary (AA) amyloidosis in Crohn's disease]. / Sekundarna (AA) amiloidoza u bolesnika s Crohnovom bolescu.

Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that occurs in the context of cancer, chronic inflammation and chronic infectious diseases, including inflammatory bowel disease, mainly long-standing Crohn's disease. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. The incidence of the association of secondary amyloidosis in patients with Crohn's disease has been reported to be 0.5%-8%. We present a case of a 39-year-old male patient diagnosed with Crohn's disease at age 21 and submitted to right hemicolectomy because of ileus 17 years before. Thereafter, he was treated with corticosteroids for 15 years and with azathioprine for a short period; in the last three years he was on therapy with mesalazine alone. He was hospitalized due to worsening clinical condition and re-evaluation of the underlying disease. Physical examination revealed marked peripheral edema in both lower extremities. Endoscopic and radiographic examinations confirmed the underlying disease activity. Laboratory tests showed an increase of inflammatory reactants, anemia, hypocalcemia, and severe hypoalbuminemia and hypoproteinemia. He had proteinuria over 24 g/L and creatinine clearance of 66 mL/min, falling within second grade of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposition; deposits immunoreacted with the antibody against amyloid A protein, confirming the diagnosis of secondary amyloidosis. The patient was suggested active induction treatment with corticosteroids and azathioprine to achieve remission of Crohn's disease, thereafter treatment with infliximab, but he did not consent with this therapy at that time. Studies with infliximab have demonstrated a decrease in SAA circulating levels and proteinuria, as well as stabilization of renal function. Amyloidosis is frequently described as a major cause of death in patients with Crohn's disease, with long-term mortality between 40% and 60%. Various therapeutic attempts such as azathioprine, colchicine, dimethyl sulfoxide, infliximab, and elemental diets have been tried but there is no definite treatment for secondary amyloidosis in Crohn's disease. Kidney transplantation may offer the best prospects for patients with Crohn's disease who develop amyloidosis and end-stage renal failure.

Helicobacter pylori eradication therapy success regarding different treatment period based on clarithromycin or metronidazole triple-therapy regimens.

BACKGROUND: The study compares the eradication success of standard first-line triple therapies of different durations (7, 10, and 14 days). MATERIALS AND METHODS: A total of 592 naive Helicobacter pylori-positive patients were randomized to receive pantoprazole, amoxicillin, and clarithromycin or metronidazole for 14 days (PACl14 or PAM14), 10 days (PACl10 or PAM10), or 7 days (PACl7 or PAM7). H. pylori eradication was assessed by histological, microbiological, and rapid urease examination. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) analyses have shown no overall statistically significant differences between the eradication success of PACl and PAM treatment groups (ITT p = .308, PP p = .167). Longer treatment duration has yielded statistically significant increase in eradication success for clarithromycin (ITT p = .004; PP p = .004) and metronidazole (ITT p = .010; PP p = .034) based regimens. Namely, PACl10, PACl14, and PAM14 protocols resulted in eradication success exceeding 80% in ITT and 90% in PP analysis. Primary resistance to clarithromycin and metronidazole equals 8.2% and 32.9%, respectively. Prolonging the metronidazole-based treatment duration in patients with resistant strains resulted in statistically significant higher eradication success. CONCLUSIONS: For all antimicrobial combinations, 14 days protocols have led to a significant increase of H. pylori eradication success when compared to 10 and 7 days, respectively. Prolonging the treatment duration can overcome the negative effect of metronidazole resistance. Only PAM14, PACl10 protocols achieved ITT success > 80% and should be recommended as the first line eradication treatment in Croatia.

[Hormonal regulation of gastric secretion and Helicobacter pylori]. / Hormonska regulacija zelucane sekrecije i Helicobacter pylori.

Helicobacter pylori has been recognized as one of the most important factors that lead to chronic changes in the gastric mucosa. These changes have either direct or indirect impact on various intestinal hormones (gastrin, somatostatin, bombensin, cholecystokinin...) which regulate gastric secretion. Gastric secretion enhancement is mostly caused by higher concentration of serum gastrin. The mechanism in which the Helicobacter pylori infection influences the regulation of gastrin and other intestinal hormones is yet to be discovered. It is known that eradication of the Helicobacter pylori infection decreases serum gastrin concentration, thus decreasing gastric secretion and inflammatory changes of the gastric mucosa.

[The urea breath test]. / Izdisajni test ureje.

Helicobacter pylori is infective cause of peptic ulcer and a risk factor for gastric carcinoma. The discovery of the bacterial ed to importance of finding a new reliable and inexpensive diagnostic method for detection of infection before and after eradication therapy. Urea breath test is isotope based test. It has become the most specific and sensitive method in detection of Helicobacter pylori infection, therefore many other isotope based tests become popular in diagnostic of gastrointestinal diseases. Because of its simplicity and no need in using endoscopy in the procedure it is very popular in primary diagnosis and in controlling eradication. It is successfully used in diagnostics of Helicobacter pylori and bacteria eradication success testing, where it is one of most reliable diagnostic methods.

[The rapid urease test]. / Brzi ureazni test.

Today there are many methods in diagnostics of Helicobacter pylori infection. They are divided in two major groups based on using of endoscopy (invasive and non-invasive methods). Helicobacter pylori bacteria are specific because of having very big amounts of urease enzyme that divides urea on NH3 and CO2 which enables environment suitable for survival. Rapid ureas test is based on detecting of the enzyme activity. Because of its simplicity and high sensitivity and specificity it belongs to methods that are used in every day practice in endoscopic laboratories.

[Gastric ulcer and Helicobacter pylori infection]. / Zelucani ulkus i infekcija Helicobacterom pylori.

Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAID) are considered to be the two major risk factors implicated in the development of gastric ulcer. Helicobacter pylori infection related chronic gastritis is known to be the underlying condition which may lead to gastric ulcer. Development of gastric ulcer as the consequence of underlying chronic gastritis is caused by many factors. Treating Helicobacter pylori infection entails the healing of gastric ulcer, it concomitantly prevents recurrences and complications of gastric ulcer, primarily bleeding, and changes the natural course of gastric ulcer disease. Continuation of antisecretory maintenance treatment beyond ulcus healing and eradication of Helicobacter pylori infection is only indicated in risk groups. Patients with gastric ulcer caused by NSAID use are managed with antisecretory therapy.

[Gastroesophageal reflux disease and Helicobacter pylori infection]. / Gastroezofagealna refluksna bolest i infekcija Helicobacterom pylori.

Gastroesophageal reflux disease (GERD) is one of the common diseases of the upper gastrointestinal system. It is present in the whole world population, especially frequent in the developed countries. It evolves from pathological reflux which exposes the esophagus to the gastric contents which must overcome esophageal defense system. Many factors have been found to be involved in the pathogenesis of GERD; the most important one is the relaxation of the lower esophageal sphincter. Intensity of the disease is proportional to the amount of gastric contents refluxing from the stomach and the duration of esophageal exposure to this contents. GERD is currently in the spotlight because of its special significance in the development of very specific disease in the lower part of the esophagus--Barrett's esophagus, as well as esophageal adenocarcinoma which has lately been increasing in prevalence. Today, unrecognized and inadequately cured GERD is known to be a high risk factor for adenocarcinoma of the esophagus. In recent years the relation between GERD and Helicobacter pylori infection has been the topic of investigation by many prominent researchers. Therapy of GERD is based on inhibition of acid secretion. There are many different therapeutic agents available, however, proton pump inhibitors (PPI) are considered to be the most effective in the treatment of this disease.

[Helicobacter pylori and malignant diseases of the stomach]. / Helicobacter pylori i maligne bolesti zeluca.

The association between Helicobacter pylori infection and gastric malignancies, cancer and MALT lymphoma, has been suggested through several lines of evidence during the last decade. Although unresolved issues still cast doubts on the real weight of these association, in the sequence of events that leads to gastric cancer or lymphoma, Helicobacter pylori appears to play a prominent role in the very initial steps as causative agent of chronic gastritis. The subsequent events in the sequence--atrophy, intestinal metaplasia, dysplasia and cancer are multifactorial involving environmental agents, host response and characteristics of the bacterial strain itself. Recognition of the causal role of Helicobacter pylori infection in the cancer induction theoretically presents tools for its prevention. The ongoing studies will show in the future whether eradication or prevention of infection are followed by a reduction in risk of cancer. Lymphomas arising from gastric mucosa-associated lymphoid tissue (MALT) may be a clonal evolution starting from the infection. In low-grade gastric MALT lymphoma cure of the infection induces complete remission in the majority of patients. Longer follow-up investigations are necessary to determine if remissions indicate a cure of the disease.

[Helicobacter pylori--overview of therapy]. / Helicobacter pylori--pregled terapijskih mogucnosti.

The clinical significance of Helicobacter pylori infection in the etiopathogenesis of many gastroduodenal disorders, especially peptic ulcer disease and current awareness of the benefits of its eradication has entirely changed the current treatment of these diseases. Eradication was already defined as the disappearance of Helicobacter pylori from the gastric mucosa (finding negativization) confirmed at least 4 weeks (or later) after completed antibiotic eradication therapy. The regimen has to be simple, cheap and tolerable so that the patient could carry it out completely and as easy as possible (good compliance is required). The success of Helicobacter pylori eradication, evaluated by the strict "intention-to-treat" criteria, has to be higher than 80%. Current modern therapy should be triple and not longer than 7 days. One of three proton pump inhibitors is recommended as the antisecretory component (omeprazole, pantoprazole or lansoprazole). Two of three following antibiotis is added to this therapy: metronidazole/tinidazole, clarithromycin or amoxicillin. Treatment failure and growing number of antimicrobial resistant Helicobacter pylori strains require new ways of therapy and more effective drugs. Our results of 7-, 10- and 14-day therapy consisting of omeprazole, amoxicillin and metronidazole are poorer than those of drug combination including clarithromycin instead of amoxicillin. The results of Clinical Hospital "Merkur" showed that combination of amoxicillin, metronidazole and pantoprazole was more effective than the same combination with omeprazole, and the opposite was true for metronidazole and azithromycin combined with omeprazole and pantoprazole, respectively. The results of other medical centers prescribing the same eradication protocols were completely different. The differences are probably caused by poor patient compliance.