Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome--a randomized, double-blind, placebo-controlled study.

BACKGROUND: Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited. AIM: To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS-related abdominal pain/discomfort. METHODS: A total of 412 IBS patients meeting ROME III criteria were included in this double-blind randomized placebo-controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0-100 mm visual analogue scale (VAS) during a 2-week run-in treatment-free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks. RESULTS: The full analysis set included 409 patients (71.4% female: mean age: 46.2 +/- 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups. CONCLUSION: Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.

Serum concentration of interleukin 10, anti-mannan Candida antibodies and the fungal colonization of the gastrointestinal tract in patients with ulcerative colitis.

PURPOSE: There is evidence for the immunomodulation disorders in the response to intestinal flora in inflammatory bowel disease, however, the role of yeasts in the aetiopathogenesis of ulcerative colitis has not been fully clarified. The aim of this study was to assess the serum concentration of interleukin 10 (IL-10), serum levels of anti-mannan Candida antibodies and fungal colonization of the lower part of the gastrointestinal tract in accordance with the clinical course of ulcerative colitis. MATERIAL/METHODS: In 42 consecutive patients with ulcerative colitis serum concentration of IL-10 and anti-mannan Candida antibodies serum levels were measured with ELISA and the quantitative and qualitative fungal cultures of stool samples were performed. RESULTS: In 20 patients IL-10 serum concentration was below the test sensitivity and in 11 patients it ranged between 0.78 and 9.43 (mean 3.38 +/- 2.8) pg/mL. Anti-mannan Candida antibodies were detected in 8 subjects (19.04%). Stool cultures revealed significant fungal colonization in 3 (8.33%) patients with the predominance of Candida albicans. In comparison with mild/moderate UC, IL-10 serum concentration was not higher in patients with severe course of the disease. CONCLUSIONS: The results of our study show that IL-10 serum concentration correlates neither with the disease activity nor with the levels of anti-mannan Candida antibodies and the fungal colonization of the gastrointestinal tract in ulcerative colitis. It seems that IL-10 serum concentration cannot be a universal marker for the assessment of ulcerative colitis activity. Moreover, anti-mannan Candida antibodies and significant fungal colonization are present in the minority of patients with ulcerative colitis suggesting that yeasts have minor, if any, influence on the clinical course of the disease.

Prevalence of lower extremity venous disease in inflammatory bowel disease.

AIM: Inflammatory bowel disease (IBD) has long been considered a risk factor for venous thromboembolism (VTE). Whereas most patients have persistent venous valvular dysfunction following lower extremity deep venous thrombosis (DVT), we hypothesized that patients with IBD would have an increased prevalence of valvular incompetence and changes of chronic DVT (reduced venous caliber with thickened walls) relative to patients with irritable bowel syndrome (IBS) or normal volunteers. METHODS: Subjects with confirmed IBD, clinical features of IBS or normal volunteers underwent complete, prospective duplex ultrasound assessment of their lower extremity venous vascular system. The sonographer performing the venous study was blinded to the clinical diagnosis of the patients. Valvular incompetence was graded as mild, moderate or severe based on accepted criteria. RESULTS: Eighty patients with IBD (ulcerative colitis, UC: 66; Crohn's disease: 14), 80 patients with IBS, and 80 healthy volunteers agreed to participate. One patient with UC was found to have non-occlusive chronic DVT within the left superficial femoral vein. Mild and moderate valvular incompetence was evenly distributed between the 3 groups. No patients met criteria for either acute DVT or severe venous incompetence. CONCLUSION: In patients with IBD, neither valvular incompetence nor chronic venous obstruction are over-represented compared to patients with IBS or normal volunteers. In this prospective assessment of venous physiology by duplex ultrasound, we were not able to confirm prior reports that IBD is a major risk factor for VTE.

Diagnostic difficulties during combined multichannel intraluminal impedance and pH monitoring in patients with esophagitis or Barrett's esophagus.

Gastroesophageal reflux disease (GERD) is one of the most common esophageal diseases in developed countries. It is widely believed that GERD symptoms are caused by acid refluxate within the esophagus, so ambulatory 24 hour pH-monitoring became the gold standard in detecting gastroesophageal reflux. Traditional ambulatory pH monitoring is unable to detect a gastroesophageal reflux with pH >4. The introduction of multichannel intraluminal impedance and pH (MII-pH) brought new possibilities in detecting GERD. In this technique impedance identifies reflux episode whereas pH sensor further characterizes it as either acid (pH <4) or non-acid (pH > or =4). This is a great progress in diagnosing GERD but MII has also some imperfections related to pathological changes in the esophageal mucosa such as esophagitis or Barrett oesophagus, which are connecting with a very low baseline impedance values. Changes in the esophageal mucosa may also impair the esophageal motility and esophageal transit leading to some fluid retention in the esophagus. It should be stressed that very low impedance baseline creates a difficulty in interpreting the MII-pH study. In such a case it might be almost impossible to interpret the study as the interpreter does not see characteristic drop in impedance progressing either orally (reflux episode) or swallow but only almost flat impedance lines. Therefore, future studies are needed to further evaluate this problem.

Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation.

BACKGROUND: WC and NS contributed equally. Non-tuberculous mycobacteria (NTM) frequently colonise patients with end stage cystic fibrosis (CF), but its impact on the course of the disease following lung transplantation is unknown. METHODS: Lung transplant recipients with CF who underwent lung transplantation at our institution between January 1990 and May 2003 (n=146) and CF patients awaiting lung transplantation in May 2003 (n=31) were studied retrospectively. RESULTS: The prevalence rate of NTM isolated from respiratory cultures in patients with end stage CF referred for lung transplantation was 19.7%, compared with a prevalence rate of 13.7% for NTM isolates in CF lung transplant recipients. The overall prevalence of invasive NTM disease after lung transplantation was low (3.4%) and was predicted most strongly by pre-transplant NTM isolation (p=0.001, Fisher's exact test, odds ratio (OR) 6.13, 95% CI 3.2 to 11.4). This association was restricted to Mycobacterium abscessus (p = 0.005, Fisher's exact test, OR 7.45, 95% CI 2.9 to 16.9). While NTM disease caused significant morbidity in a small number of patients after transplantation, it was successfully treated and did not influence the post-transplant course of the disease. CONCLUSION: The isolation of NTM before transplantation in CF patients should not be an exclusion criterion for lung transplantation, but it may alert the clinician to patients at risk of recurrence following transplantation.

Differentiating thrombotic microangiopathies induced by severe hypertension from anemia and thrombocytopenia seen in thrombotic thrombocytopenia purpura.

Thrombotic microangiopathy (TMA) is a recognized complication of malignant hypertension (HTN). Such patients have blood pressures > or = 200/140 mmHg but the condition is defined by the presence of papilledema and is frequently complicated by acute renal failure. Here we report two patients with severe HTN (systolic > or = 180 mmHg or diastolic > or = 120 mmHg), TMA, thrombocytopenia, renal failure, and, in one case, neurological changes (4 of 5 manifestations of the TTP pentad). A 50-year-old male with HTN presented with blurred vision, dizziness, headache, confusion, renal failure, and a TMA (PLT = 39 x 10(9)/L and LD = 2,781 normal <600 U/L). On presentation, BP was 214/133 mmHg and an ophthalmic exam demonstrated no papilledema. With HTN control over 7 days, his platelet count rebounded (220 x 10(9)/L), LD declined (1,730 U/L), and mental status improved. A 60-year-old female with diabetes, HTN, Lupus erythematosus, mild chronic anemia, and thrombocytopenia presented with abdominal pain, shortness of breath, renal failure, and a TMA (PLT = 83 x 10(9)/L and LD = 2,929 U/L). Blood pressures were 180-210/89-111 mmHg and ophthalmic exam demonstrated no papilledema. With HTN control over 8 days, her platelet count rebounded (147 x 10(9)/L), and LD declined (1,624 U/L). Although in both cases a diagnosis of TTP was considered because of overlap with the classic diagnostic pentad, neither received plasmapheresis. TTP is a diagnosis of exclusion, where there is no other likely diagnosis to explain the TMA. In cases of severe HTN (with or without papilledema), the diagnosis of TTP should be held in abeyance until the effect of HTN control can be assessed.

Surgical treatment of constipation.

Constipation is a common symptom in clinical practice. Definition of constipation includes abnormal bowel frequency, difficulty during defecation and abnormal stool consistency. There are many classifications of constipation based on constipation etiology (constipation in healthy people caused by life style, constipation as a symptom of digestive tract diseases, secondary constipation in the course of systemic disorders or associated with drugs) and/or constipation mechanisms (functional, mechanical). The numerous disorders leading to constipation make often diagnostic management difficult and complicated. Treatment of constipation includes dietary and behavioral approaches, pharmacologic therapy and in selected patient surgical treatment. Surgical treatment is recommended in young patients with severe slow transit constipation refractory to conservative treatment. Confirmation of indication to surgical treatment requires studies of colonic and anorectal function (colonic transit studies, anorectal manometry, studies of defecation). Preferred surgical technique is colectomy with ileorectal anastomosis. Authors reported good results and patient satisfaction in 50-100 percent of cases. Postoperative complications include intestinal obstruction, abdominal pain, flatulence, diarrhea.

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Outcomes of intensive care unit care in adults with cystic fibrosis.

Cystic fibrosis (CF) causes progressive respiratory failure and death in more than 90% of patients. Mechanical ventilation has been discouraged in CF because of poor outcomes, but improved survival and the availability of lung transplantation have increased the indications for care of CF patients in the intensive care unit (ICU). We studied the outcomes of all CF patients admitted to the University of North Carolina Hospitals Medical ICU from January 1990 through December 1998. Seventy-six patients, ranging in ages from 17 to 45 yr (mean: 27 yr), and of whom 53% were female, had 136 admissions for exacerbations of CF with respiratory failure (RF, n = 65), hemoptysis (n = 33), antibiotic desensitization (n = 30), pneumothorax (n = 3), or other reasons (n = 5). Eighty-six percent of the patients with hemoptysis and all of those with desensitization and pneumothorax were alive 1 yr after ICU discharge. Of the 42 patients with RF, 37 (88%) required assisted ventilation. Twenty-three (55%) of the patients with RF survived to ICU discharge and 19 (45%) died. Seventeen (40%) of the patients with RF received lung transplants and 14 were alive 1 yr later. Without transplantation, three (7%) of the patients with RF were alive and three (7%) were dead 1 yr later. Sex, body mass index, and respiratory bacteria did not correlate with survival. We conclude that ICU care for adults with CF who have reversible complications is appropriate and effective. Ventilatory support is appropriate for some transplant candidates.

[Multimodal evoked potentials in malabsorption syndrome]. / Multimodalne potencjaly wywolane w zespolach zlego wchlaniania.

The multimodal evoked potentials (visual, somatosensory and auditory brainstem) in 23 patients with malabsorption syndrome of different origin were investigated. The diagnosis of the disease was confirmed on the basis of histological examination and result of D-ksyloza test. The control group consisted of 30 healthy persons. Examination of visual evoked potentials revealed significant prolongation of latency of P 100 component in examined group in comparison with controls. Latency of N13 and N20 of somatosensory evoked potentials in patients with malabsorption syndrome were also significantly prolonged when compared to controls, otherwise transit time to cortex (TTC) was merely prolonged. Auditory brainstem potentials were also abnormal. Changes involved prolongation of latency of I, III and V responses and prolongation of interpeak latencies of I-III, III-V, I-V as well. The amplitudes of the examined evoked potentials between patients and controls did not differ significantly. On the basis of obtained results in was pointed out that different specific afferent systems are affected in patients with malabsorption syndrome what seems to be connected with vitamin's deficiency, especially B12 and E. Authors conclude that multimodal evoked potentials examinations are useful in the diagnosis and monitoring of the disease, specially in subclinical cases.

Efficacy and tolerability of mesalazine foam enema (Salofalk foam) for distal ulcerative colitis: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Rectal formulations of mesalazine are the treatment of choice in mildly to moderately active ulcerative colitis. A new foam formulation of mesalazine was developed to improve both drug delivery and patient acceptance. METHODS: In this multicentre, randomized, double-blind, parallel-group study, 111 patients with mildly to moderately active proctitis, proctosigmoiditis, or left-sided ulcerative colitis received mesalazine foam enema or placebo enema (2 g mesalazine per day) for 6 weeks. Disease activity was monitored on the basis of the Clinical Activity Index, Endoscopic Index, Histological Index, and global efficacy assessment by the investigators. Safety assessments included the recording of adverse events, laboratory variables and vital signs. RESULTS: Clinical remission was more frequent in the mesalazine group than the placebo group (65% vs. 40%; P=0.0082), particularly in patients with mild disease and patients with proctosigmoiditis. The frequency of patients with an endoscopic remission was higher in the mesalazine group (57%) than in the placebo group (37%). Similarly, 59% of patients receiving mesalazine but only 41% of those receiving placebo showed an improved Histological Index. The foam enemas were generally well-tolerated, and no treatment-related changes on laboratory variables and vital signs were noted. CONCLUSIONS: Mesalazine foam enema was well-tolerated and was more effective than placebo in the treatment of patients with distal ulcerative colitis.

Lung transplantation for cystic fibrosis: effective and durable therapy in a high-risk group.

BACKGROUND: The purpose of this study was to review our experience with lung transplantation in patients with end-stage cystic fibrosis. METHODS: Eight-two patients with cystic fibrosis have undergone bilateral lung transplantation (n=76) or bilateral lower lobe transplantation (n=6) since October 1990. RESULTS: Actuarial survival for the entire cohort is 79% at 1 year and 57% at 5 years. The development of bronchiolitis obliterans syndrome is the leading cause of death after the first year. Freedom from bronchiolitis obliterans syndrome is 84% at 1 year and 51% at 3 years. Pulmonary function tests improve dramatically in recipients. There was no association between death within 1 year and recipient age, weight, graft ischemic time, cytomegalovirus seronegativity, or the presence of pan-resistant organisms. Similarly, there was no association between the development of bronchiolitis obliterans syndrome within 2 years and ischemic time, number of rejection episodes, cytomegalovirus seronegativity, or the presence of panresistant organisms. CONCLUSIONS: Despite their poor nutritional status and the presence of multiply resistant organisms, patients with cystic fibrosis can undergo bilateral lung transplantation with acceptable morbidity and mortality.

Saprophytic fungal infections and lung transplantation--revisited.

BACKGROUND: Fungal infections cause serious morbidity and death in lung transplant recipients. Some centers exclude and others will prophylactically treat patients with evidence of Aspergillus colonization. METHODS: Of 126 patients undergoing lung transplantation at the University of North Carolina since January 1990, five patients have died because of invasive Aspergillus and other saprophytic fungal infections. Those cases are reviewed looking for common predisposing factors, including any evidence of prior colonization. In addition, all preoperative and postoperative culture data on all transplant recipients were retrospectively examined to define the prevalence of preoperative and postoperative Aspergillus colonization in 121 patients with and without cystic fibrosis, none of whom had development of significant fungal disease. RESULTS: Fifty-two percent of 65 patients with cystic fibrosis were colonized with Aspergillus before operation, and 40% after operation at some time. None had development of significant Aspergillus infections, and none received prophylactic antifungal therapy. Most of the deaths from deep-seated fungal infections have been in patients without cystic fibrosis with no evidence of preoperative colonization. These patients had evidence of severe obliterative bronchiolitis, bacterial infections, persisting cytomegalovirus disease, or other major organ failure. CONCLUSION: The rationale for excluding patients or for giving amphotericin in the perioperative period in those patients who are colonized before surgery is questioned.

Seizures in lung transplant recipients.

PURPOSE: We wished to assess organ transplant recipients, who incur a significant risk for seizures. METHOD: We reviewed 85 lung transplants performed in 81 patients at the University of North Carolina hospitals between 1991 and 1994. All patients were reviewed for age, reason for transplant, detailed description of seizures, neurological examination, medications, and laboratory results, including cyclosporine level, EEG, and brain imaging. RESULTS: Eighteen of 81 (22%) patients experienced seizures. Patients aged < 25 years had the greatest risk of seizures and 15 of the 18 patients had cystic fibrosis. Sixteen of the 18 (89%) patients, by history, had partial-onset seizures. Eleven of the 18 (61%) patients had seizures < or = 10 days after initiation of intravenous methylprednisolone for allograft rejection. Two patients had seizures associated with sustained hypertension: 1 of these patients was simultaneously being treated for rejection. Four patients had strokes (1 before transplant) and seizures. Two patients were receiving imipenem. Magnetic resonance imaging (MRI) of the brain demonstrated areas of increased T2 signal in 8 of 9 patients. CONCLUSIONS: Our findings demonstrate multiple etiologies for seizures in our transplant recipients. However, we believe that patients, especially those aged < 25 years, being treated with intravenous methylprednisolone for rejection may be at increased risk of seizures. We hypothesize that the focal loss of blood-brain barrier (BBB) may play a significant role in the development of partial seizures in lung transplant recipients.

Atrial anastomotic thrombus causes neurologic deficits in a lung transplant recipient.

Pulmonary thrombus formation in the region of atrial anastomosis following lung transplantation has been reported by several authors. Such patients typically present immediately after surgery with significant hemodynamic compromise causing pulmonary edema and hypoxemia. We describe a patient who presented with bilateral neurologic deficits 4 and 6 weeks after lung transplantation. Despite a normal transthoracic echocardiogram, transesophageal echocardiography (TEE) detected a large left atrial thrombus adherent to the atrial anastomosis. This thrombus was treated with intravenous heparin and subsequently warfarin. After 3 weeks, a repeat TEE demonstrated complete resolution of the lesion. This case demonstrates that postoperative left atrial and pulmonary venous thrombi may provide the basis for serious patient morbidity without hemodynamic or radiographic clues to their presence, that TEE is superior to transthoracic echocardiography for detecting left atrial thrombi, and that such lesions can respond to medical management alone.

Acute and chronic lung allograft rejection during pregnancy.

Young women who undergo lung transplantation may regain normal fertility and become pregnant. Currently, little is known about the outcome of pregnancy after lung transplantation. We present a case of pregnancy after bilateral lung transplantation complicated by acute and chronic allograft rejection, resulting in irreversible loss of lung function.

[The effect of cimetidine and famotidine on esophageal motility]. / Wplyw cymetydyny i famotydyny na motoryke przelyku.

An effect of cimetidine and famotidine on the lower esophagus sphincter pressure and esophageal body motility has been investigated. The studies involved 30 patients with duodenal ulcer. The lower esophagus sphincter pressure, mean force and mean duration of spasms as well as wave transmission velocity in esophageal body, 1-13 cm above the sphincter, have been recorded with Polyphysiograph R-611. The lower esophagus sphincter pressure and esophageal body motility have been recorded 15 minutes prior to and following the administration of 200 mg cimetidine or 20 mg famotidine. It was shown that cimetidine has net changed the lower esophagus sphincter pressure and esophageal body motility parameters. Famotidine increased the lower esophagus sphincter pressure from the initial 2.31 +/- 1.19 kPa to 3.51 +/- 1.61 kPa (p < 0.05) and had no effect on the esophageal body motility parameters. It may be concluded that within H2-receptor antagonists famotidine may be considered a drug of choice in the treatment of gastroesophageal reflux.

[Manometric examination in diagnosis of esophageal motility disorders]. / Badania manometryczne w diagnostyce zaburzen czynnosciowych przelyku.

Indications to manometric measurements in patients complaining for esophageal disorders are discussed. Such symptoms most frequently include: dysphagia, heartburn, and angina-like pain after exclusion of the coronary artery disease. Radiological and endoscopic examinations should precede esophageal motility measurements to eliminate organic causes of patients' complaints. Initial manometric measurements may be repeated after the application of pharmacologic stimuli or functional tests. Most frequent esophageal motor disorders have been described.

Analysis of cystic fibrosis referrals for lung transplantation.

Patients with cystic fibrosis (CF) are being considered in increasing numbers as candidates for lung transplantation, despite earlier concerns that their nutritional status and the infective nature of their lung disease would contribute to increased morbidity and mortality. We undertook a retrospective analysis of patients with CF referred for consideration of lung transplant to identify factors that helped to select suitable transplant candidates and to identify characteristics that predicted death while on the waiting list. Analysis of 95 referred patients with CF demonstrated a high rate of suitability (78%) by our criteria. The mean weight of listed patients with CF was 77% predicted, and the mean FEV1 was 20% predicted. Sixteen percent of listed patients with CF died awaiting transplant. The FEV1 of these patients was significantly lower than that of patients who survived to transplant. This study implies that patients with CF are being referred for transplant late in the course of their disease. Earlier referral may lead to an increase in the number of patients with CF undergoing successful lung transplantation.