Sumatriptan. An updated review of its use in migraine

Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.     

Vertigo and migraine

Vertigo consists of a variety of syndromes and can be due to many etiologies. One of these causes is migraine, which in our experience is often overlooked, although migrainous vertigo is well known in the literature. Vertigo in migraine can occur as aura or during the headache phase, or independent of the attacks as aura without headache. The aim of this retrospective study was to analyze cases with vertigo and migraine: 23 (8%) of 298 patients with migraine examined in a neurological outpatient department also had rotational vertigo. 48% of these patients had vertigo independent from typical migraine headache. Two types of vertigo were found: permanent vertigo, and vertigo with the characteristics of paroxysmal positional vertigo. 57% of the vertiginous attacks lasted hours, 26% even days, and 17% minutes. Most of the patients had several attacks of vertigo, some involving up to 30 episodes. To recognize migraine as a cause of vertigo has therapeutic implications. Most of our patients with vertigo and migraine showed a good response to antimigraine therapy.     

Coexistence of migraine and idiopathic intracranial hypertension without papilledema

Eighty-five patients with refractory transformed migraine type of chronic daily headache (CDH) had spinal tap as a part of diagnostic work-up. Twelve had increased intracranial pressure without papilledema, transient visual obscurations, or visual field defects. The headache profile of these 12 patients was not different from that of transformed migraine type of CDH. Acute headache exacerbations responded to specific antimigraine agents such as ergotamine, dihydroergotamine (DHE), and sumatriptan, whereas prophylactic antimigraine medications were only partially helpful. Addition of agents such as acetazolamide and furosemide, after the diagnosis of increased intracranial pressure, resulted in better control of symptoms. These observations suggest a link between migraine and idiopathic intracranial hypertension that needs further research. In refractory CDH with migrainous features, a spinal tap to exclude coexistent idiopathic intracranial hypertension without papilledema may be indicated.     

Biological monitoring of exposure to chlorpyrifos by high performance liquid chromatography

Sixteen patients with hypogonadotropic hypogonadism received gonadotropin replacement therapy. Two patients treated with HCG alone showed induction of spermatogenesis 2 and 12 months after the start of treatment. Three subjects receiving combination therapy showed sperm appearance 6-28 months after treatment. The patients showing sperm appearance, whose testicular volume was > or = 4 ml, showed a higher sperm count and impregnated their partners, although no relationship was found between pretreatment testicular volume and sperm appearance. The response to HCG test correlated with sperm appearance after gonadotropin therapy. Sperm appearance was not observed in any subject except for one who showed no response to luteinizing hormone-releasing hormone (LH-RH) test and none of the patients without response of FSH to LH-RH demonstrated any induction of spermatogenesis. In conclusion, the responses to LH-RH test and possibly to HCG test could predict the induction of spermatogenesis after gonadotropin replacement therapy, and a large testicular volume is associated with post-treatment fertility.     

Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies?

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.     

Prediction of efficacy of octreotide therapy in patients with acromegaly

Octreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and 111In-pentetreotide (111In-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 micrograms sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I (IGF-I) were then assayed after 1 month (300 micrograms daily) and 3 months (150-600 micrograms daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 micrograms/L. Twenty-six of 68 patients were subjected to 111In-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GH percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to 111In-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant correlation was found between tracer uptake and GH/IGF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05). In the whole population, the positive predictive value of acute testing, short-term OCT administration, and 111In-penetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH normalization (< 5 micrograms/L) after 3 months of therapy was considered. Moreover, 111-In-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 micrograms/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by 111-In-pentetreotide might better indicate the patients who might effectively benefit from this treatment.     

Influence of long-term human recombinant erythropoietin treatment on secretion of pancreatic polypeptide and gastrin in hemodialysed patients with chronic renal failure

The study aimed to assess the influence of long-term rhu-EPO treatment on secretion of pancreatic polypeptide (PP) and gastrin. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rhu-EPO for 12 months (EPO group), while another nine patients did not receive rhu-EPO (non-EPO group), but were monitored biochemically and clinically as patients of the EPO group. The third group (HD) comparised nine haemodialysed patients with a haematocrit value > or = 30% without rhu-EPO therapy. In all subjects plasma levels of PP and gastrin were estimated before and after administration of a test meal. Patients of the EPO and non-EPO group were examined before and after 6 and 12 months of rhu-EPO therapy (EPO group) or clinical monitoring (non-EPO group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months rhu-EPO therapy was followed by an decrease of basal plasma level of PP and increased response of gastrin to the test meal. After 12 months of rhu-EPO therapy basal plasma level of PP was still lower, the response of PP secretion to a test meal was higher, while that of gastrin secretion lower that the pretreatment ones. Our results suggest, that rhu-EPO treatment exerts effect on secretion of PP and gastrin. These alterations seem not to be related to improvement of the haematological status.     

Treatment of chronic hepatitis C with amantadine

Treatment of chronic hepatitis C infection with interferon has been disappointing, with less than one third of patients achieving a sustained response and most experiencing significant side effects. For these reasons, an open-labeled prospective pilot study was conducted to test the safety and efficacy of the antiviral drug, amantadine, in patients with chronic hepatitis C infection who had previously failed therapy with interferon-alpha 2b. Twenty-two patients with chronic hepatitis C were enrolled into the study and treated with amantadine 100 mg orally twice daily for six months. Control groups included the same cohort followed off therapy for 29-36 months or during therapy with interferon. Serum alanine aminotransferase (ALT) values decreased in 64% (P = 0.01) of patients with amantadine therapy compared to intervals without therapy or to interferon therapy. Twenty-seven percent of patients treated with amantadine had normalization of ALT values and loss of HCV RNA after six months while 18% achieved a sustained response with loss of HCV RNA by PCR six months after discontinuation of amantadine. Therapy with amantadine improved both biochemical and virological markers in patients with hepatitis C who had previously not responded to treatment with interferon.     

Effect of gender and apolipoprotein E genotype on response to anticholinesterase therapy in Alzheimer's disease

BACKGROUND: Anticholinesterase therapies offer modest benefit to subgroups of AD sufferers. However, there has previously been no way of predicting which patients will respond to any of the drugs. OBJECTIVE: To discover if gender and/or apolipoprotein E genotype can be used as predictors of response in the clinical setting. DESIGN: 107 patients from the Bristol Memory Disorders Clinic took part in a double-blinded or open label trial of tacrine therapy for between 3 and 12 months or an open label trial of galanthamine therapy for 3 months. RESULTS: After 3 months of therapy, gender was found to be the only significant influence on the number of responders to anticholinesterase therapy. Men had a 73% greater chance of responding than women (p = 0.012). While ApoE genotype did not modify response to therapy in the short term, there are indications that it may affect response over the longer term (up to 12 months), and also that the initial advantage of male gender may not be maintained after 3 months. CONCLUSION: Gender is likely to be a more powerful determinant of outcome of anticholinesterase treatment than apolipoprotein E status in the short term.     

What is adequate nutrition?

BACKGROUND/AIMS: Retrospective studies have suggested that early loss of serum HCV-RNA predicts sustained response to alpha-interferon treatment in chronic hepatitis C, but the optimal duration of therapy after loss of HCV-RNA is not known. The aims of this study were: a) to prospectively evaluate the effectiveness of HCV-RNA testing after 1 month of alpha-interferon treatment in the prediction of sustained response, and b) to compare the efficacy of 6 and 12 months of therapy in patients with a negative serum HCV-RNA test after the first month of treatment. METHODS: One hundred and thirty patients were administered interferon alpha-2b at doses related to body weight (< or > or = 60 kg) and to HCV genotype: 5 or 8 MU tiw for type 1, and 3 or 5 MU tiw for genotypes non-1. Serum HCV-RNA testing was performed using in-house nested RT-PCR at month 1, at the end of treatment and 6 months afterwards. We considered sustained response to be the maintenance of normal alanine aminotransferase and negativity at serum HCV-RNA testing until the end of follow-up. RESULTS: Sustained response was observed in 2/72 (2.8%) patients with detectable HCV-RNA after the initial month of therapy, in 8/30 (26.7%) patients with early loss of HCV-RNA treated for 6 months and in 20/28 (71.4%) patients treated for 12 months (p<0.01). CONCLUSIONS: Serum HCV-RNA detectability after the first month is strongly associated with a very poor chance of sustained response, and these cases should be offered other treatments. Patients with early loss of HCV-RNA should complete a 12-month treatment, which appeared more effective than a 6-month treatment.     

Effectiveness of mastectomy by response to induction chemotherapy for control in inflammatory breast carcinoma

BACKGROUND: Controversy exists as to the treatment regimen necessary to best provide optimal local control for inflammatory breast carcinoma (IBC). This study was conducted to determine if mastectomy combined with radiotherapy offered any advantages over radiotherapy alone in patients with IBC who had been treated with doxorubicin-based combination chemotherapy. METHODS: A retrospective review of 178 women treated for IBC on doxorubicin-based multimodality therapy protocols between January 1974 and September 1993 was performed. Clinical and histologic response to treatment, time to local recurrence, survival, and ultimate control of local disease were analyzed. Kaplan-Meier analysis was used to examine survival and relapse times, and Fisher's exact test was used to test differences in treatment outcomes. Significance was determined at p < or = 0.05. RESULTS: Median follow-up was 89 months (range 22 to 223 months). Locoregional disease persisted in seven patients and recurred in 44 patients who had been rendered disease free at a median time of 10 months. The mortality rate after a local recurrence (LR) was 98%, and all patients but one with LR developed systemic metastases. Response to induction chemotherapy influenced the incidence of LR, and the amount of residual disease found on histologic examination of mastectomy specimens was highly prognostic for local failure. Patients who underwent mastectomy in addition to radiotherapy had a lower incidence of LR than did patients who received radiotherapy alone (16.3% vs. 35.7%, p = 0.015). CONCLUSIONS: The addition of mastectomy to combination chemotherapy plus radiotherapy improved local control in patients with IBC. The addition of mastectomy to chemotherapy plus radiotherapy improved distant disease-free and overall survival in patients with a clinical complete or partial response to induction chemotherapy. Patients who had no significant response to induction chemotherapy received no survival or local disease-control benefit from the addition of mastectomy to their treatment regimen. These patients should be considered for entry into clinical trials of new treatment regimens.     

Chemotherapy of colorectal carcinoma

The benefit of adjuvant therapy in colorectal cancer (CRC) has been provided in clinical studies that have demonstrated reduction of up to 30% in a 5-year overall mortality in patients (pts.) with TNM stage III (Dukes' stage C) carcinoma. Patients with metastatic CRC are usually in a relatively good condition despite their advanced disease. Therefore, some clinicians wished to withheld the toxicity of chemotherapy until the disease became symptomatic. Others, however, felt it appropriate to treat patients early in the course of the disease. Four clinical trials may be cited addressing this clinical uncertainty (Table 1). Patients receiving chemotherapy had a significantly longer median survival in comparison with only best supportive care. The delay of the carrying out of systemic chemotherapy in patients with metastatic disease decreases the symptom free interval (2 vs. 10 months, p < 0.001), time to disease progression (3 vs. 8 months, p < 0.001) and median survival (14 versus 9 months, p < 0.02) compared to an early start of therapy [7C. Patients with metastatic colorectal cancer benefit from early chemotherapy in terms of survival and quality of life. It is clear that survival is determined by prognostic factors, mainly the performance status, which is a highly significant predictor of therapeutic response and overall survival in advanced colorectal cancer patients. Some authors suggests that the response is a potent and independent prognostic factor of survival, and that response can be used as surrogate marker of survival. Stable disease is a category in therapy response evaluation which is not included in the overall response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In most chemotherapy trials in advanced colorectal cancer patients, about 30-50% had stable disease. One of the possible reasons may be that in colorectal cancer stabilization of disease is a clinically relevant effect of chemotherapy. If we accept that disease stabilization is a clinically relevant effect of chemotherapy, should we continue with chemotherapy after 3 or 4 courses, and for how long, or should we stop treatment according to rules for stable disease, i.e. following 4 courses? The results of on study, which we performed in 99 patients with advanced colorectal cancer, indicate that under category of "stable disease" there are two different subpopulations of patients with quite different symptom responses as an effect of chemotherapy, different time to progression and possible different survival (Graph 1 and Graph 2). It seems that stable disease patients with clinical benefit could be a target group for policy "to treat until disease progression". The tumour response is likely to be positively correlated with improvement in quality of life when a patient is a symptomatic from cancer before the treatment. Stable disease patients without symptom improvement have no benefit from further chemotherapy and in these patients treatment should be stopped. Such selection would spare from toxicity stable disease patients without clinical benefit. We have no data whether different number of chemotherapy cycles in the groups of patients with and without clinical benefit could lead to a bias in survival estimation. Patients who achieved also a stable disease, but who were asymptomatic from the beginning of chemotherapy, and who are still asymptomatic after 4 chemotherapy courses, make a group for which is hard to make decision either to continue or to stop chemotherapy. We have treated and followed-up these stable disease patients as patients without clinical benefit. We have no answer if they could reach better time to progression and/or survival if they had been treated for more than 4 courses. Careful studies in the evaluation of the quality of life in connection with treatment effects for all stable disease subpopulations of patients are warranted. (ABSTRACT TRUNCATED)     

Clinical response of localized recurrent periodontitis treated with scaling, root planing, and tetracycline fiber

The purpose of this study was to compare the clinical efficacy of scaling and root planing alone versus tetracycline fiber therapy used adjunctively with scaling and root planing in the treatment of nonresponsive active periodontitis in patients under supportive periodontal therapy. Thirty patients who were receiving supportive treatment and had at least two nonadjacent periodontitis sites with a probing depth of between 4 and 8 mm and bleeding on probing, or had aspartate aminotransferase (AST) levels above 800 microIU in the gingival crevicular fluid in separate quadrants participated in this study. For each patient, the test sites were treated with scaling and root planing plus tetracycline fibers while the control site was treated with scaling and root planing only. Probing depths, clinical attachment levels, gingival recession, AST levels, and bleeding on probing were recorded and subgingival plaque samples were collected at baseline and 1, 3, and 6 months following treatment. At 3 months after treatment, there was a reduction of bleeding on probing and probing depth, and a gain of clinical attachment in both test and control sites. The mean reduction in probing depth of the test sites was 1.38 mm and the attachment gain was 0.8 mm after 6 months. The clinical response obtained at 3 months following therapy was maintained throughout the 6-month follow-up period. However, there were no statistically significant differences between sites treated with scaling and root planing alone and those treated with combined tetracycline therapy. Most of the reductions of probing depths in the fiber group were attributed to gingival recession. The present study did not confirm the efficacy of adjunctive tetracycline fibers in treating nonresponsive sites in maintenance subjects with regard to probing depth reduction or clinical attachment gain. Reinfection of the pockets from untreated sites and extra-crevicular regions may explain the insignificant response to local tetracycline therapy.     

Statistical considerations for design and analysis of a multiperiod crossover study to compare two treatments for migraine headache

The purpose of this paper is to discuss a long-term, multiperiod crossover study to compare two treatments for migraine headache. Principal attention is given to the analysis of an example in which patients randomly received a treatment sequence with test drug for three migraine headaches and placebo for one. An issue that requires attention for this example is the influence of a carryover effect for test drug that was greater when placebo was the subsequent treatment than when test drug was the subsequent treatment. A way to address this issue without excessive loss of power is to consider tests of "total treatment effects," which are weighted averages across headaches of differences between average response to test drug and average response to placebo. Since these weighted averages are linear combinations of treatment effects and carryover effects, their use requires an argument that carryover effects are at least partly a further form of treatment effects. For the example in this paper, this argument is realistic because the test drug could have provided much better relief to migraine headache than other treatment patients might have previously used. A second purpose of the paper is to present some alternative designs for situations like that represented by the example. The structure of variances for alternative specifications for treatment comparison is provided for models of interest for these designs.     

Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.     

Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients

Seven AIDS patients who were receiving suppressive therapy for previously diagnosed cytomegalovirus (CMV) retinitis were offered treatment with protease inhibitors (PIs). Secondary prophylaxis for CMV was discontinued after 3 months of therapy with PIs if patients had >150 CD4 cells/mm3 and a human immunodeficiency virus (HIV) load of <200 copies/mL and if they were negative for CMV as determined by qualitative CMV polymerase chain reaction (PCR). Ophthalmologic exams were done periodically. After a median follow-up of 9 months (range, 9-12), no new episodes of CMV retinitis were observed. CD4 cell counts were >150 cells/mm3 in all cases, HIV loads were <200 copies/mL, and results for qualitative CMV PCRs remained negative. These observations suggest that for selected patients with healed CMV retinitis who have immunologic and virologic evidence of a clinical response to potent combination antiretroviral therapy, temporary discontinuation of a chronic anti-CMV suppressive therapy may not result in further retinal necrosis. However, the long-term immunologic benefit of PIs and hence the safety of prolonged withdrawal of anti-CMV therapy is unknown.     

Phase II clinical trial of combined natural interferon-beta plus recombinant interferon-gamma treatment of chronic hepatitis B

BACKGROUND/AIMS: Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis B but only 25-40% of patients will profit from a long-term beneficial response to the currently recommended schedule of 3-6 MU given 3 times a week for 6 months. Clinical trials are therefore needed to investigate alternative modifications of interferon therapy, including combinations of different antivirals or immune modulators in order to improve the therapeutic approach to chronic hepatitis B infection. In a phase II trial we evaluated whether a combination of natural interferon-beta (nIFN-beta) with strong antiviral activity plus recombinant interferon-gamma (rIFN-gamma) with a predominantly immunomodulatory activity is able to increase the response rate compared to historical controls treated with IFN-alpha in a conventional regimen. METHODOLOGY: Forty patients with chronic hepatitis B were included in this trial of combined interferon therapy at a dosage of 6 MU nIFN-beta during week 1 followed by 3 MU for weeks 2-4 plus rIFN-gamma at a daily subcutaneous (s.c.) injection of 150 microg during the entire 4 weeks of the treatment period. Patients entered the trial on the basis of the following criteria: hepatitis B surface antigen (HBsAG), HBeAG and HBV-DNA positive for at least 6 months, HDV, EBV, CMV, anti-HIV negative, and chronic hepatitis proven on biopsy taken within 4 weeks of entry as well as 6 and/or 12 months after interferon therapy. The final diagnosis and classification of chronic hepatitis has been based on guidelines according to a revised classification of chronic hepatitis (Desmet 1994). The post-treatment follow-up was 12 months. RESULTS: The combined interferon therapy achieved complete responses with seroconversion from HBeAG to anti-HBe and a negative HBV-DNA (dot blot) test, as well as normalization of ALT activity in 15 patients, and partial response with negativation of HBV-DNA concomitant to a decrease in aminotransferase activity to near normal levels in 6 patients. Nineteen patients showed no response to viral markers but showed relief of clinical symptoms as well as pronounced decrease of serumtransaminase activity. Grading of liver biopsies demonstrated an improvement of histologic parameters after the interferon regimen in half of the evaluable patients (n=22). Histological response has been quantified by a reduction in the score of histological activity (HAI-index) from 12.6 before to 7.6 after interferon therapy, and in the inflammation and cellular degeneration score (ICD) from 9.9 to 5.2. Histological response, however, failed to show a consistent correlation with serologic response. This medium-dose combination of interferon-beta and interferon-gamma was tolerated very well by the patients, this good tolerability being explained by tachyphylaxis in response to daily interferon doses. No serious side effects or decompensation of liver function were observed during the 4-week period of therapy or the follow-up, despite the special clinical situation where 60% of the patients included in the study presented with histologically proven cirrhosis (35% of them with clinical manifestation of mildly decompensated cirrhosis). CONCLUSIONS: This short-term regimen of combined nIFN-beta + rIFN-gamma therapy in patients with chronic hepatitis B proved to be equieffective to long-term treatment with interferon-alpha and combines high clinical tolerability with good practicability, as it can be administered on an in-patient basis, ensuring close patient monitoring.     

Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of migraine

Homoeopathic remedies for migraine are widely available over the counter, statutorily offered by the national health service in the UK, and apparently popular with patients. Do they work? Sixty-three outpatients with migraine with or without aura by IHS criteria entered a 4-month randomized placebo-controlled, double-blind parallel-groups trial of individualized homoeopathic prophylaxis, the first month being baseline with all patients on placebo. Three patients (4.8%) dropped out, leaving 30 in each treatment group. There were chance differences in attack frequency and severity between the groups at baseline (attacks were more frequent but less severe in the placebo group). Both groups improved on therapy, but neither to a great extent on the primary outcome measure of attack frequency (verum: -19%; placebo: -16%). Reduction was mostly in mild attacks on placebo, more in moderate and severe attacks on homoeopathy. Few adverse events were reported. Overall, there was no significant benefit over placebo of homoeopathic treatment. The course of change differed between groups, and suggested that improvement reversed in the last month of treatment on placebo. On this evidence we cannot recommend homoeopathy for migraine prophylaxis, but cannot conclude that it is without effect.     

Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg dose

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.