Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment.

BACKGROUND: Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. AIM: To evaluate efficacy and safety of colon-release propionyl-L-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. METHODS: In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18-75; disease activity index (DAI) score 3-10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub-score > 1. RESULTS: Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. CONCLUSION: Propionyl-L-carnitine 1 g/day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).

Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis.

BACKGROUND: Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. AIM: To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. METHODS: A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. RESULTS: The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. CONCLUSION: Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.

[Is subtotal resection of the colon actual for ulcerative colitis in the century of ileal reservoirs?].

The authors describe results of surgical treatment of 112 patients operated for a severe resistant form of ulcerative colitis (UC). In 26 (23.2%) of observations the operations were performed for complications, in 65 (58%)--for hormone-resistent, and in 21 (18.8%)--for hormone-dependent forms of UC. In 80 (71.4%) cases subtotal resection of the colon with ileo- and sigmostomies was fulfilled, in 26 (23.2%) a single stage ablation of all large intestine was fulfilled with the formation of permanent ileostomy and in 5 (5.4%) of observations the first step was finished with the formation of a reconstructive-plastic reservoir anastomosis. The number of complications in the nearest postoperative period was in 12.8% of patients, lethality was 2.3%. The development of a strict strategy of treatment for severe forms of the disease including the present-day using conservative and surgical methods of treatment depending on the individual character of each patient with UC made it possible to minimize the number of postoperative complications and decrease lethality and also to restore anal defecation with good functional results in 30.1% of operated patients.

[The clinicomorphological characterization of segmental lesion in ulcerous colitis].

The authors analyzed the clinical picture in 18 patients with distal lesion of the colon and an inflammatory focus in the cecum (segmentary lesion), and five patients with distal lesion of the colon revealed with endoscopy and pathomorphological signs of inflammation in visually intact cecum. The analysis shows that in a range of cases the extent of lesion in ulcerous colitis (UC) cannot be determined correctly with colonoscopy. An apparent segmentary character of lesion (inflammation in the distal colon and an inflammatory focus in the cecum) is an additional criterion of unfavorable prognosis of transformation into disseminated UC forms. Such patients need application of the same treatment regimens as in patients with disseminated UC forms.

[Surgical treatment of hormone-resistant form of nonspecific ulcerative colitis]. / Khirurgicheskoe lechenie gormonorezistentnoi formy nespetsificheskogo iazvennogo kolita.

From 1990 to 2002 seventy-nine patients with hormone-resistant form of nonspecific ulcerative colitis (NUC) underwent surgery. There were 37 men, 42 women, mean age was 34.4 +/- 3.8 years. Severe form of NUC was in all the patients, total lesion of the colon was in 60.8% cases, subtotal - in 25.3%, and right-sided - in 13.9%. Acute disease was seen in 21 (26.6%) patients, chronic recurrent - in 42 (53.2%), chronic continuous - in 16 (20.2%). Complex intensive treatment including glucocorticoids (prednisolon 2 mg/kg/day) was used in all the patients. Criteria of efficacy were clinical, laboratory and instrumental data (rate of stool, hemodynamics, hyperthermia, pain syndrome, hemoglobin, level of leukocytes and albumin, results of endoscopy and roentgenoscopy). Absence of positive results during 3 weeks was regarded as inefficacy of therapy and indication for surgery. Subtotal resection of the colon with ileostoma or sygmostoma was performed in 68 patients. Detection of resistance to hormones before development of NUC's intestinal complications (intestinal bleeding, toxic dilatation and perforation of colon) permitted to improve results of surgery: number of postoperative complications reduced from 60 to 8 - 9%, lethality - from 21 to 4.6%.

[Potentialities of modern clinical X-ray radiology in the differential diagnosis of tumor and other obstructive diseases of the large bowel]. / Vozmozhnosti sovremennoi klinicheskoi rentgenologii v differentsial'noi diagnostike opukholevykh i drugikh obstruktivnykh zabolevanii tolstoi kishki.

The misdiagnosis rate in defining the cause of obstructive colonic disease is 8.2-24.4%. This is consistent with the fact that every 5 patients with colonic obstruction present difficulties in establishing the nature of a pathological process. The paper provides the results of analysis of clinical and X-ray symptoms in 350 patients with difficult differentially diagnosed cases of narrowing of the rectum and colon. Based on the analysis, the authors identified the basically important X-ray signs that might differentiate tumor stenoses from other obstructive diseases. They also defined the specific X-ray signs of such diseases as infiltrative cancer; extraintestinal cancer involved in the large bowel; inflammatory strictures in ulcerative colitis, diverticulosis, actinomycosis, tuberculosis, intestinal endometriosis, invagination, and other obstructive diseases. The developed differentiated diagnostic criteria could enhance the overall accuracy of X-ray study in this difficult group of patients from 72.7-80% to 93%.

[Diagnosis and treatment of inflammatory infiltrates of the abdominal cavity in Crohn disease]. / Diagnostika i lechenie vospalitelnykh infiltratov briushnoi polosti pri bolezni Krona.

An infiltrate in the abdominal cavity in Crohn's disease does not hinder successful drug therapy in most cases. A positive effect (regression or a marked decrease in the size of the infiltrate) is achieved in 80% of patients, mostly in those with a moderately or mildly severe form of the disease in which a sufficiently prolonged, 10-12-week course of antiinflammatory treatment can be conducted. Combination of prednisolone with azathioprine and antibiotics is most justified. The prednisolone dose is determined by the severity and activity of the disease rather than by the infiltrate. Antibiotics are necessary only in high fever and treatment with them may be limited to 10-14 days in the absence of septicemia. Interrupted seasonal courses of sulfasalazine therapy may fail to prevent exacerbation and, consequently, recurrent infiltrates. These respond readily to repeated drug therapy and do not expand the indications for surgery. Operations were performed on 14 patients, in 11 of them the infiltrate did not recur again.

[Rate of iron (Fe 2+) bacterial oxidation at different temperatures and concentrations of Thiobacillus ferrooxidans cells]. / Skorost' bakterial'nogo okosleniia zheleza (Fe2+) pri razlichnykh temperaturakh i kontsentratsiiakh kletok Thiobacillus ferrooxidans.

The rate of iron oxidation by bacteria Thiobacillus ferrooxidans was measured at different temperatures (5 and 23 degrees C) and concentrations of bacterial cells (10(8)/ml and less). At a cell concentration of 10(7)--10(8)/ml the rate of bacterial oxidation remained at a relatively high level at a lowered temperature. At a low cell concentration (10(6)/ml and less) the rate of bacterial oxidation was reduced at a temperature of 5--6 degrees C.