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

Aliment Pharmacol Ther 31 , 615–624

Summary

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.     

Immunoglobulins in the skin in dermatitis herpetiformis and their relevance in diagnosis

Eighty skin biopsies from fifty patients with dermatitis herpetiformis (DH) have been examined for immunoglobulin deposits by direct immunofluorescence. IgA was found in all fifty patients. However, in two patients no IgA was detected in their first biopsy, and it is stressed that if the clinical suspicion of DH is high and no IgA is found in a single biopsy, then the biopsy should be repeated. There are two distinct patterns of immunoglobulin deposition in DH. The most common form of deposition is seen in the dermal papillae, termed the 'papillary' pattern. This pattern was the only one present in sixty-seven of the seventy-eight biopsies. A less common pattern is that of a 'continuous' line along the dermo-epidermal junction. This was the only pattern of immunoglobulin deposition in nine of the seventy-eight biopsies. In two biopsies both the papillary and continuous patterns were present. IgA was found in all seventy-eight of the positive biopsies and was the only immunoglobulin detected in sixty-seven biopsies. In addition to IgA, IgM was present in seven biopsies, and IgG in two biopsies. In one biopsy IgM and IgG were present with the IgA. The detection of IgA in the uninvolved skin in patients with DH is a simple test to perform, and at the present time is the most reliable way of establishing the diagnosis     

The ultrastructural changes in the skin in dermatitis herpetiformis after withdrawal of dapsone

The development of skin lesions in patients with dermatitis herpetiformis after the withdrawal of their dapsone therapy was studied with the electron microscope. In control biopsies from patients prior to cessation of treatment, membrane-bound vacuoles were found beneath the basal lamina of the epidermis as previously described. After dapsone withdrawal, there was an apparent increase in the number of vacuoles and occasionally several vacuoles appeared to have coalesced forming an early blister. At this stage, the basal lamina and associated hemidesmosomes were normal although in places there were small discontinuities in the basal lamina. Where the reaction was more intense, vacuoles and cells, mainly eosinophils, were embedded in fibrin de posits. Above this, the basal lamina was usually disrupted with involvement of the basal epidermal cells. These results suggest that the vacuoles do play a part in the formation of the pathological lesion in dermatitis herpetiformis. In addition, the basal lamina is shown to be only secondarily involved. The nature of the vacuoles has still to be elucidated.     

THE ACTION OF CHEMOTHERAPEUTIC AGENTS ON PSORIATIC EPIDERMIS

SUMMARY. —Mitotic counts and histological features have been studied in 35 psoriatic patients prior to treatment, and during treatment with topically applied fluocinolone acetonide, methotrexate, dithranol and coal tar.
Prior to treatment there was considerable variation in the mitotic counts in the 35 biopsies. The granular layer was absent in 10 biopsy specimens, partially formed in small areas in 21, well formed in most areas in 2, and normal in 2. There was no correlation between the mitotic counts and state of the granular layer.
With methotrexate and dithranol treatment the granular layer showed improvement prior to a significant fall in the mitotic counts. With fluocinolone acetonide the improvement in the granular layer appeared at the same time as a significant fall in the mean mitotic count, but the granular layer had completely reformed in 7 of the 9 patients while the mitotic count was still considerably raised compared to uninvolved psoriatic skin. With coal tar the results were not uniform; some patients showed a significant fall in mitotic counts prior to improvement in the granular layer and others first showed improvement in the granular layer.
It is suggested that in clearing psoriasis these drugs have an action other than, or in addition to, inhibiting mitosis.     

EFFECT OF EETINOIC ACID IN PSORIASIS

The effect of topical retinoic acid on the clinical and histological features and mitotic counts of lesions in 12 patients with psoriasis have been studied for a 2-week period. Serial biopsies were performed on lesions treated with retinoic acid in all 12 patients; control lesions treated with unmedicated ointment base were similarly biopsied in 7. There was a significant clinical improvement in 11 of the 12 patients treated with retinoic acid, and in all these patients it was greater than that achieved in the control lesions. Reformation of the granular layer, which was previously absent or only partially formed, occurred in 6 of the 12 psoriatic lesions treated with retinoic acid, but in none of the controls. Mitotic counts for the treated group fell after the 2-week period, but not in the controls. Topical retinoic acid would seem to be of therapeutic value in the treatment of psoriasis. The possible mechanisms of action are discussed.     

Drug Associated Acute Interstitial Nephritis: Clinical and Pathological Features and the Response to High Dose Steroid Therapy

Nine episodes of drug associated acute interstitial nephritis,in seven patients, were treated between 1972 and 1980. The drugsimplicated were cotrimoxazole (three times), ampicillin, Magnapen(amplcillin and flucloxacillin), penicillin, gentamicin, paracetamoland ben-drofluazide. The time from exposure to the onset ofsymptoms ranged from one to 30 days. Presentation was with acuterenal failure, which was non-oliguric in five cases, accompaniedby rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristicinterstitial infiltrate comprising substantial numbers of lymphocytesand plasma cells, with a variable number of neutrophils, eosinophilsand histiocytes. Immunofluorescence was negative in all fourcases studied in the acute phase, and showed scattered depositsof IgG, IgM, IgA and C3 on the tubular basement membrane inone patient during recovery. Significant proteinuria and anabnormal urine deposit were present in all cases, and sevenof nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisoloneand in all there was a response with a diuresis or spontaneousfall in serum creatinine within 72 hrs, and recovery of virtuallynormal renal function. Of two cases who did not initially receivesteroids, one improved more slowly and one developed chronicrenal impairment. Present address: Department of Medicine, Charing Cross Hospital,Fulham Palace Road, London W6 8RF.     

A case of acanthosis nigricans—an investigative approach

A patient with acanthosis nigricans secondary to a metastatic jejunal adenocarcinoma is described. An attempt was made to define the basic epidermal defect and to examine such possible influences as somatotrophin, epidermal growth factor, intestinal peptides and insulin receptors. No evidence to support a hyperproliferative epidermal mechanism was found and the hormonal profile was normal. However, there was an increase in circulating α-MSH and this may have contributed to the pigmentation seen in this patient.     

A comparison of the effect of various topically active steroids on the clinical and histological features of psoriasis

The effect of betamethasone 17-valerate, fluclorolone acetonide, fluocinolone acetonide and formocortal on the clinical and histological features and mitotic counts of psoriatic epidermis have been compared. In five of the six patients studied the preparations were used under polythene occlusive dressings. Biopsies were carried out before treatment and then at varying intervals for a week. All the four steroid preparations appeared effectively to reverse the psoriatic lesion. Betamethasone 17-valerate and fluocinolone acetonide were found to give similar and slightly superior results to fluclorolone acetonide and formocortal on the criteria used in this study. It would appear that at the present time more potent topical steroids would not be of any advantage in the treatment of psoriasis. Drugs with a more selective action on the psoriatic process and without the steroid effect on collagen are required.