Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome.

BACKGROUND: In models of irritable bowel syndrome (IBS), asimadoline, a kappa-opioid agonist, improves pain and abnormal bowel function. AIM: To evaluate the effects of three doses of asimadoline and placebo in subjects with IBS through a double-blind, randomized, placebo-controlled trial. METHODS: Patients were randomly assigned to receive asimadoline 0.15, 0.5, 1.0 mg or placebo BID for 12 weeks. The primary efficacy measure was number of months of adequate relief of IBS pain or discomfort, with a prospective plan to evaluate adequate relief data by entry baseline pain and subtype. Several other endpoints were also evaluated. RESULTS: Five hundred and ninety-six patients were randomized. In the ITT population, statistically significant improvement on the primary endpoint was not seen. However, in diarrhoea-predominant IBS patients with at least baseline moderate pain, asimadoline (0.5 mg) produced significant improvement on total number of months with adequate relief of IBS pain or discomfort (46.7% vs. 20.0%), adequate relief of IBS symptoms (46.7% vs. 23.0%), pain scores (week 12: -1.6 vs. -0.7), pain free days (42.9% vs. 18.0%), urgency and stool frequency (-2.3 vs. -0.3). In patients with alternating IBS, significant improvement was seen on adequate relief endpoints. Asimadoline was well tolerated. CONCLUSION: Asimadoline warrants further evaluation as a treatment for IBS.

Determinants of healthcare-seeking behaviour among subjects with irritable bowel syndrome.

BACKGROUND: Doctor visits for irritable bowel syndrome are associated with high medical costs. Predictors of medical consultation for irritable bowel syndrome remain poorly understood. AIM: To determine factors associated with healthcare seeking for irritable bowel syndrome. METHODS: Subjects from previous US population-based survey were contacted 2 years later. Those who continued to have irritable bowel syndrome were included. RESULTS: 49% of subjects sought medical care for abdominal symptoms in the past year. Healthcare seeking did not differ significantly between males and females, but more females received an irritable bowel syndrome diagnosis. Predictors of irritable bowel syndrome healthcare seeking differed by gender. In multivariate analysis, age > or = 55 years (OR = 2.8, 95% CI: 1.5-5.4), fear abdominal symptoms relates to serious illness (OR = 1.7, 95% CI: 0.95-3.1), decreased bowel movements (OR = 1.8, 95% CI: 0.98-3.2), dyspepsia (OR = 1.7, 95% CI: 0.94-3.2) and pelvic pain (OR = 2.3, 95% CI: 1.2-4.4) were associated with seeking care in females. Among males, being disabled (OR = 11.6, 95% CI: 2.4-56.1) and abdominal cramping (OR =4.3, 95% CI: 1.2-15.4) were associated with seeking care. Healthcare seekers had lower irritable bowel syndrome-related quality of life. Neither pain severity nor mental health status was associated with seeking care. CONCLUSION: Healthcare-seeking behaviour among irritable bowel syndrome patients was determined by presence of comorbidities and extent that irritable bowel syndrome affected quality of life, not physical symptoms or mental health status.

Stability of irritable bowel syndrome using a Rome II-based classification.

BACKGROUND: As there is no biological marker for irritable bowel syndrome, a diagnosis is made using symptom-based criteria. AIM: To evaluate the stability of self-reported symptoms consistent with Rome II-based irritable bowel syndrome classification. METHODS: Irritable bowel syndrome subjects identified in a 2001 population-based study by modified Rome II criteria were re-contacted 2 years later. Data were collected via a web-based questionnaire. RESULTS: Of the 697 subjects, 30% remained in the same irritable bowel syndrome subtype in both surveys, 18.4% changed irritable bowel syndrome subtype and 52% no longer met the irritable bowel syndrome criteria at follow-up. Subjects continuing to meet the irritable bowel syndrome criteria were more likely to have been initially classified in the alternating irritable bowel syndrome subtype and had more psychological impairment and lower irritable bowel syndrome-related quality of life than subjects not fulfilling the irritable bowel syndrome criteria at follow-up. Lack of pain caused more subjects to fall out of the irritable bowel syndrome criteria than the absence of non-painful bowel symptoms. However, the majority of subjects that did not fulfill the pain component of the irritable bowel syndrome criteria continued to report abdominal pain of at least moderate severity. CONCLUSION: In a US population-based follow-up study using modified Rome II criteria, we found irritable bowel syndrome is episodic in nature and current classification is limited in capturing fluctuation of disease over time.

Management of peripheral vascular problems in recipients of cardiac allografts.

Five hundred and twenty consecutive heart transplant cases (458 adult, 62 pediatric) were reviewed to assess the impact of peripheral vascular problems. Peritransplant interventions requiring vascular cannulation (e.g., intraaortic balloon pump procedures, catheterization of the right and left sides of the heart, femoral bypass) resulted in 10 complications that necessitated nine surgical procedures. Five aortic aneurysms (three infrarenal and two suprarenal) were resected. There was one death unrelated to the aneurysm resection. Sixteen patients had evidence of peripheral vascular disease (PVD). There were three deaths in this group, none directly related to the PVD. Three patients required vascular reconstruction (axillobifemoral, bilateral femoral distal and popliteal endarterectomy) in the posttransplant period, all for advanced ischemic symptoms. Except for one patient in whom ischemia-related ulcers developed on the heels, all patients had improved or stable symptoms that did not require intervention. There were no limb losses or vascular infections. We conclude that despite the rigors of posttransplant immunosuppression, patients with stable manifestations of PVD may successfully undergo heart transplantation and subsequent vascular reconstruction, when indicated, without prohibitive risk.

Hepatobiliary complications of polyarteritis nodosa.

Although polyarteritis nodosa (PAN) may result in thrombosis or aneurysm formation in any organ in the body, hepatobiliary complications are unusual. We reviewed seven cases that demonstrated the diagnostic difficulties and therapeutic options available in the management of hepatobiliary PAN. No consistent sign that indicated the severity of hepatobiliary PAN could be identified. In cases of thrombotic PAN, acalculus cholecystitis usually could be diagnosed preoperatively. Early tissue diagnosis and aggressive intervention are required for appropriate patient treatment. If the diagnosis is unclear, a preoperative muscle or skin biopsy specimen is often helpful in establishing a tissue diagnosis of PAN, even if no obvious pathologic condition is evident. Patients who undergo celiotomy for acalculus cholecystitis or peritoneal signs of an unclear origin should have tissue specimens (gallbladder wall, liver, or omentum) submitted for pathologic study. Angiography may be diagnostic preoperatively or when results of biopsies are equivocal. In addition, early angiography can define the extent of visceral involvement and permit control by embolization of hemorrhage secondary to aneurysm rupture. Awareness of the possibilities of thrombotic, ischemic, or bleeding complications from PAN allows more aggressive and rapid management of abdominal complaints, especially in patients who are receiving immunosuppressant therapy.

The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms.

As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution. A prospective clinical study was undertaken to assess the validity of this policy. One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989. All patients underwent CT scanning as an initial evaluation. Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease. During this period 19 patients (19%) underwent both CT scanning and angiography. The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4). Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation. No patient was adversely affected by elimination of angiographic evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated.

A ten-year experience with bacterial aortitis.

Twenty-one patients with bacterial aortitis were treated in four institutions over a 10-year period. Clues to the diagnosis were a pulsatile mass; fever; positive blood culture; CT scan revealing aortic nodularity, an aneurysm of irregular configuration, or air in the aortic wall; and angiography revealing a lobulated aneurysm. The most commonly identified organisms were Salmonella and Staphylococcus. Excision with in situ repair was performed in nine patients; 11 patients underwent extraanatomic bypass grafting with aortic ligation. In situ graft repair was performed when the infected aorta could be removed entirely or when the thoracic or suprarenal aorta was involved. Axillofemoral bypass grafting was used when infection was extensive. There were eight disease-related deaths. No graft infections were encountered in patients who survived.

Evaluation of surgical response in renovascular hypertension using angiotensin II blockade.

The mechanisms involved in residual or recurrent hypertension following operation to correct renal artery stenosis were studied in 10 patients by performing angiotensin II blockade with Saralasin (Sarcosine, alanine, angiotensin II) before and after operation. Peripheral renin and renal vein renin determinations, angiography, and renography were done as well. The limitations of renin determinations are cited and the application of angiotensin II blockade as a specific method of detecting renin-dependent hypertension before and after operation are presented. Saralasin infusion under the controlled conditions of our study proved to be a sensitive method for detection of renin-dependent hypertension. The results of Saralasin infusion correlated closely with peripheral and renal vein renin determinations. Thus angiotensin II blockade before and after operation may supercede more invasive and less specific diagnostic methods.

Staphylococcal infections.

All the forms of staphylococcal infections require cooperation among microbiologists, immunologists and clinicians. In case of any acute staphylococcus process, the curative tactics is based on an effective chemotherapy sometimes completed by a radical surgical intervention. In case of chronic forms, however, the antibiotics therapy is considered to be problematic. It is the specific immunotherapy by means of specific vaccine with polyvalent action, containing all pathogenetically significant antigens, that is considered by the authors to be a reliable base of the therapy of chronic staphylococcus infections. The specific polyvalent phage lysate is used for local application. It has to be pointed out that this therapy requires a complex curative regimen, i.e. regulation of the deficiency of serum immunoglobulines, administration of antibiotics, amelioration of the tissue trophism of the area concerned, suitable therapy by means of vitamines and diet. If necessary, surgical technique and tactics are an important part of the entire complex curative method.