Vaccines without thiomersal: why so necessary, why so long coming?

The inorganic mercurial thiomersal (merthiolate) has been used as an effective preservative in numerous medical and non-medical products since the early 1930s. Both the potential toxicity of thiomersal and sensitisation to thiomersal in relation to the application of thiomersal-containing vaccines and immunoglobulins, especially in children, have been debated in the literature. The very low thiomersal concentrations in pharmacological and biological products are relatively non-toxic, but probably not in utero and during the first 6 months of life. The developing brain of the fetus is most susceptible to thiomersal and, therefore, women of childbearing age, in particular, should not receive thiomersal-containing products. Definitive data of doses at which developmental effects occur are not available. Moreover, revelation of subtle effects of toxicity needs long term observation of children. The ethylmercury radical of the thiomersal molecule appears to be the prominent sensitiser. The prevalence of thiomersal hypersensitivity in mostly selected populations varies up to 18%, but higher figures have been reported. The overall exposure to thiomersal differs considerably between countries. In many cases a positive routine patch test to thiomersal should be considered an accidental finding without or, probably more accurately, with low clinical relevance. In practice, some preventive measures can be taken with respect to thiomersal hypersensitivity. However, with regard to the debate on primary sensitisation during childhood and renewed attention for a reduction of children's exposure to mercury from all sources, the use of thiomersal should preferably be eliminated or at least be reduced. In 1999 the manufacturers of vaccines and immunoglobulins in the US and Europe were approached with this in mind. The potential toxicity in children seems to be of much more concern to them than the hidden sensitising properties of thiomersal. In The Netherlands, unlike many other countries, the exposure to thiomersal from pharmaceutical sources has already been reduced. Replacement of thiomersal in all products should have a high priority in all countries.

Ranitidine does not affect psoriasis: a multicenter, double-blind, placebo-controlled study.

BACKGROUND: Data from open studies suggest that ranitidine has a beneficial effect on psoriasis and is well tolerated. OBJECTIVE: Our purpose was to determine the effectiveness of ranitidine in a 24-week, multicenter, double-blind, placebo-controlled, dose-comparing study of 201 patients with psoriasis. METHODS: Patients with moderate to severe psoriasis who had stopped systemic antipsoriatic therapy, including PUVA and UVB, for at least 10 weeks were included. After a washout period of 2 weeks, patients were randomly allocated to use either ranitidine, 150 mg twice a day; ranitidine, 300 mg twice a day; or placebo for up to 24 weeks. Assessment with the Psoriasis Area and Severity Index was performed at weeks 3, 6, 9, 12, 18, and 24 after randomization. Reduction of the Psoriasis Area and Severity Index score by 70% at the completion of the study was considered a treatment success. RESULTS: The success rates at week 24 in the 300 mg, 600 mg, and placebo groups were 11%, 5%, and 12%, respectively. No significant differences were observed between the three treatment groups at any stage of the study. CONCLUSION: This study provides strong evidence that ranitidine does not affect the skin disease in patients with psoriasis.

Sensitization to thimerosal (Merthiolate) is still present today.

The results on thimerosal (Merthiolate) hypersensitivity of a retrospective study, together with the relevant data on thimerosal hypersensitivity referred to in the literature up to 1993, are presented. Positive patch test reactions to thimerosal (0.1% pet.) were observed in 32 (1.3%) of 2461 adult patients with suspected contact allergy examined in the period 1987-1992. 20 (0.8%) patients had a solitary positive patch test to thimerosal. The observed incidence is low. Clinical symptoms related to thimerosal hypersensitivity were observed in only 3 patients. The collected results are discussed with emphasis on the clinical implications of sensitization to thimerosal. It appears that a positive patch test to thimerosal is frequently clinically irrelevant.

Subcutaneous injection or infusion of gonadotropin releasing-hormone agonist buserelin in the treatment of enlarged uteri harboring leiomyomata.

Thirteen women with symptomatic enlarged leiomyomatous uteri completed 6 months treatment with the gonadotropin releasing-hormone agonist (GnRH-a) buserelin, 600 micrograms daily subcutaneously (s.c.). Seven patients received injections (200 micrograms thrice daily, I-group) and six infusion by pump (50 micrograms.min-(1).2 h-(1). P-group). Residual uterine volumes after 6 months therapy were comparable in both study groups (I-group median 37%, range 23 to 74%; P-group median 49%, range 30 to 69%), as were estradiol levels. Symptoms were well controlled within short time. Six months posttreatment follow-up revealed uterine regrowth to pretreatment dimensions in all but 1 patient with recurrence of symptoms in most women. During therapy, several biochemical indices of bone metabolism were significantly elevated, reflecting an increased bone resorption; they were restored within 3 months after cessation of therapy, except for alkaline phosphatase. Triglycerides and HDL-cholesterol did not change during study; cholesterol was slightly, but significantly elevated after 6 months therapy. GnRH-a buserelin, 600 micrograms daily by s.c. injection or infusion is equally effective in reducing enlarged leiomyomatous uteri. Discontinuation of therapy is followed by uterine regrowth with recurrence of symptoms in most women. The present mode of therapy seems to be beneficial as an adjunct before myomectomy, or in advancing menopause in symptomatic, climacteric women.

Pharmacokinetics and endocrine effects of the LHR analogue buserelin after subcutaneous implantation of a slow release preparation in prostatic cancer patients.

The pharmacokinetics and endocrine effects of the LHRH analogue buserelin [D-Ser(TBU)6-LHRH], released from biodegradable implants, were studied in 14 patients with stage C and D prostate cancer. Six patients received a subcutaneous implant of 3.3 mg buserelin monthly, and 8 patients received a subcutaneous implant of 6.6 mg buserelin every two months. Serum levels of buserelin decreased rapidly immediately after implantation. After 1-2 weeks a more gradual decline occurred, while in the two-monthly treated group a third phase of the elimination curve started after 5 weeks. Mean serum buserelin levels just before the next implantation in the two groups were not different. Urinary excretion of buserelin followed the same pattern. Serum LH levels in both groups became non-detectable 2 weeks after the first implant. This decrease of LH levels was accompanied by a suppression of serum testosterone to concentrations below 1 nmol/l (castration level). Side effects were not different from those observed with the intranasal application of buserelin. It is concluded that the subcutaneous application of buserelin is an easily administered form of treatment which has more profound and more reliable endocrine effects when compared with the intranasal administration of the drug. The greatest advantage of the new preparation is that the intervals between applications may be prolonged to at least 2 months.