Adjuvant therapy of bullous pemphigoid with dapsone

Thirteen patients with recurrent severe widespread recalcitrant bullous pemphigoid (BP) were studied. These patients had been initially treated with prednisone and azathioprine, and clinically responded. However, they frequently continued to have flare-ups or activation of the disease while still on treatment with high doses of these drugs. The addition of dapsone, as an adjuvant to the treatment, helped to produce a complete clinical remission in 12 patients (92%). In addition, there was a statistically significant difference in the median dose of prednisone, before and after the institution of dapsone, and in the maintenance dose of prednisone. Patients were tapered off prednisone more easily than before and did not flare at lower doses of prednisone as previously. It is suggested that, in patients with severe, recalcitrant, recurrent disease, the addition of dapsone to the existing regime of corticosteroids and/or immunosuppressive drugs, may be beneficial. This may be especially valuable to patients in whom corticosteroids have been used for prolonged periods and in whom increasing the corticosteroid dose further may be associated with significant side-effects.     

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.     

Analysis of Neurogenic Contractions Induced by ML-1035 and Other Benzamides in the Guinea-pig Non-stimulated Isolated Ileum

Abstract— 4-Amino-5-chloro-substituted benzamides have been shown to increase gastric motility in-vivo and enhance field-stimulated and peristaltic contractions in-vitro. The present experiments examined the contractile response to a series of benzamides in the guinea-pig non-stimulated ileum. Four benzamides elicited contractions in the isolated ileum which were expressed as a percentage of the contraction induced by 1 μm acetylcholine (% acetylcholine response = 12 ± 2, 19 ± 3, 26 ± 2, 51 ± 3, n= 13, 8, 17, and 21, with EC50 values of 0·85, 1·8, 5·7, and 14·2 μm for cisapride, zacopride, metocloprarmde, and ML-1035 (4-amino-5-chloro-2-((2-methylsulphinyl)-ethoxy)-N-(2-(diethylamino)-ethyl)-benzamide hydrochloride), respectively). ML-1035 contractions were completely blocked by atropine and tetrodotoxin, while ganglionic blockade with hexamethonium was ineffective. Metoclopramide has been reported to sensitize postjunctional muscarinic receptors, however, ML-1035 did not enhance acetylcholine-induced contractions. Tropisetron (ICS 205–930, 1 μm ), caused a parallel rightward shift in the concentration-response curve for both ML-1035 and zacopride (EC50 = 14·2 ± 1·3 and 1·8 ± 0·8 μm in the absence, and 26 ± 2·7 and 6·9 ± 2·3 μm in the presence of tropisetron for ML-1035 and zacopride, respectively) with apparent pK_B values of 5·9 and 6·0 for the respective compounds. 5-Hydroxytryptaminergic receptor desensitization by 2-methyl-5-hydroxytryptamine (5-HT₃) and 5-methoxytryptamine (5-HT₄), attenuated the response to ML-1035. We also examined the effect of the benzamides on [³H]acetylcholine release from longitudinal muscle myenteric plexus preparations; however, these compounds had little effect on basal [³H]acetylcholine release. Thus, the pharmacological data indicate that the benzamides can elicit neurogenic contractions in the non-stimulated ileum by activating postganglionic, cholinergic neurons which is independent of an effect on smooth muscle.     

Benefits and risks of intralesional corticosteroid injection in the treatment of dermatological diseases

Intralesional corticosteroid (CS) injections have been used to treat a variety of dermatological and non-dermatological diseases with variable results. The purpose of the injection is to attain a high concentration of the drug at the diseased site, with minimal systemic absorption. Several CS preparations are available for intralesional injection, although triamcinolone derivatives have gained the widest usage in dermatology. The dose and the interval between injections depend on the type, size and severity of the lesion as well as the response to the previous injections. The most critical issue in the efficacy and also in the development of complications of the injections, is the method of injection. Several local and systemic side-effects have been reported following intralesional injections, but most of them are rare or acceptable. Thus intralesional CS injection is an integral part of the clinical practice of dermatology. Since their introduction in 1951,¹ intralesional CS injections have become an integral part of clinical practice in dermatology. They are used alone or in combination with other therapeutic modalities in the treatment of many skin diseases. The purpose of the injection is to attain a high local concentration of the CS at the diseased site, without significant systemic absorption, thus avoiding the numerous side-effects associated with systemic administration. Intralesional CS injection may he a valuable therapeutic modality in situations where topical CS are not suitable for use, either because of low potency and inefficient epidermal harrier penetration or in clinical conditions associated with epidermal atrophy.     

Immune components (IgA, IgM, IgG, immune cells) of colostrum of Bangladeshi mothers

BACKGROUND: Colostrum is the first defense for neonates. It is rich in immune components including immunoglobulins and viable immune cells. In the present study, human colostrum collected from 105 postpartum mothers was analyzed for its IgA, IgM, IgG levels, and peripheral immune cells. METHODS: Enzyme-linked immunosorbent assay was used to analyze the serum immunoglobulin concentrations. Immune cells were estimated by counting 200 cells. RESULTS: IgA was the dominant immunoglobulin and ranged from 2.84 to 8.69 g/L (mean 5.61 g/L). Mean IgM and IgG concentrations were 0.4 g/L (0.16-0.66 g/L) and 0.095 g/L (0.04-0.15 g/L), respectively. Neutrophil-macrophage (neu-mac) predominated in cell count (59%) followed by lymphocyte-plasma cells (lymph-plasma; 40%). The influence of maternal nutritional status, age, parity and income levels on the colostral immunological factors was studied. No significant association could be traced for immunoglobulin content, suggesting that maternal characteristics do not have any bearing on the immunoglobulin content of colostrum. Mean value of eosinophils was found to be higher among the underweight than the normal mothers (F= 3.143, r=-0.101). Maternal age was positively correlated with eosinophil (F= 3.296, r= 0.162). Concentration of neu-mac had a positive significant correlation with parity (t=-2.07, r= 0.205), while it was negatively significant for lymphocyte-plasma cells (t= 2.073, r=-0.101). However, the correlation coefficients of the immunologic parameters with other maternal characteristics were statistically insignificant. CONCLUSION: Colostrum has enough humoral and cellular elements to protect babies. Therefore, immune protection derived from breastfeeding depends on the immunoglobulin level of the colostrum as well as the amount of colostrum ingested.