A case of acute hepato-renal failure which developed after the oral intake of rifampicin is reported. Allergic reaction on the drug was accompanied by chill, weakness, paraesthesia, skin itch and facial swelling. The case described in the article appears to be all the more interesting due to the fact that severe lethal complication has developed in patient who had a history of allergic reactions on rifampicin.
Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barré syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy.
The results of clinical trials have shown that the general level of side-effects is substantially lower with zimeldine than with tricyclic antidepressants. Data from ordinary clinical usage in Sweden and the U.K. (as opposed to clinical research experience) shows a similar picture. Hypersensitivity reactions, characterized by fever, myalgia and/or arthralgia, and transient increases in transaminases, occur in approximately 1.5% of patients. In rare cases potentially serious neuropathies have been reported.
Asthma is considered to be a chronic inflammatory response of the airways characterized by a leukocyte infiltration into the lungs. Whereas lymphocytes and macrophages are involved in the initiation and propagation of inflammation, both neutrophils and in particular eosinophils are considered to play major effector roles. Therefore, allergic animal models in various species have been established to assess leukocyte infiltration by bronchoalveolar lavage (BAL) of antigen-sensitized and antigen-challenged animals as an inflammatory parameter in asthma pharmacology. Differential leukocyte counts in BAL fluids are routinely assessed by visual microscopic analysis of stained slides after cytocentrifugation. This procedure is very time-consuming, and the underlying standard morphological criteria may vary between different observers. In the present paper, we propose an alternative automatic method for leukocyte differentiation in BAL fluids from ovalbumin-treated guinea pigs and Brown-Norway rats using Cobas Helios 5Diff from Hoffmann-La Roche. BAL samples are directly applied to the analyzer and are automatically mixed with "Eosinofix," which stabilizes leukocyte membranes and specifically stains eosinophils. By a combination of electric (resistance) and optical (light scatter) analysis, the lymphocytes, monocytes/macrophages, neutrophils, and eosinophils are discriminated and the total leukocyte numbers are obtained. For both animal species we found high correlations for all leukocyte populations by comparing the results obtained with Cobas Helios 5Diff and conventional microscopic analysis. The major advantage of the automatic method is the much lower (about one-third) time requirement.
Carboplatin-based regimens have demonstrated activity in pediatric patients with low-grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy.
The objectives of this study were to describe the prevalence, characteristics, and management of Cb HSR and to detail their impact on outcome. The authors conducted a comprehensive, national, retrospective review of children who were diagnosed with LGG between 1985 and 2004 and received treatment with carboplatin.
One hundred five patients from 10 Canadian centers were included. The median patient age at diagnosis was 3.5 years (range, 0.3-16.8 years), and 33 patients (31.4%) had neurofibromatosis type 1. Carboplatin was administered monthly in 46 children and weekly in 59 children. Forty-four patients (41.9%) developed Cb HSR after a median of 10.5 infusions (range, 3-39 infusions). Cb HSR occurred significantly earlier among children on the weekly schedule (4.4 months vs 9.1 months; P = .02). The first allergic reaction was grade I or II in 36 patients (82%). The cumulative incidence of Cb HSR increased with the number of infusions, and there was no evidence of a plateau. The only predictive factor was being a girl rather than a boy (P = .02). Thirty-four of 44 patients with Cb HSR were re-exposed to carboplatin, and 24 of 34 patients (70.5%) had recurrent Cb HSR. A desensitization approach did not provide any advantage compared with premedication alone for altering Cb HSR. The median number of additional Cb infusions delivered was 4 (range, 0.5-34 infusions). The effect of Cb HSR on the 5-year progression-free survival rate was not statistically significant (P = .1).
Forty-two percent of children with LGG who received carboplatin regimens experienced Cb HSR. Most rechallenged children had recurrent Cb HSR despite Cb HSR-altering regimens. Cb HSR did not have an impact on progression-free survival.
Because minocycline can cause serious adverse events including hypersensitivity syndrome reaction (HSR), serum sicknesslike reaction (SSLR), and drug-induced lupus, a follow-up study based on a retrospective review of our Drug Safety Clinic and the Health Protection Branch databases and a literature review was conducted to determine if similar rare events are associated with tetracycline and doxycycline. Cases of isolated single organ dysfunction (SOD) attributable to the use of these antibiotics also were identified.
Nineteen cases of HSR due to minocycline, 2 due to tetracycline, and 1 due to doxycycline were identified. Eleven cases of SSLR due to minocycline, 3 due to tetracycline, and 2 due to doxycycline were identified. All 33 cases of drug-induced lupus were attributable to minocycline. Forty cases of SOD from minocycline, 37 cases from tetracycline, and 6 from doxycycline were detected. Hypersensitivity syndrome reaction, SSLR, and SOD occur on average within 4 weeks of therapy, whereas minocycline-induced lupus occurs on average 2 years after the initiation of therapy.
Early serious events occurring during the course of tetracycline antibiotic treatment include HSR, SSLR, and SOD. Drug-induced lupus, which occurs late in the course of therapy, is reported only with minocycline. We theorize that minocycline metabolism may account for the increased frequency of serious adverse events with this drug.
An outline is given of the data on human health effects that are needed as a foundation for the administration of legislation on chemical substances and products. Danish data on mortality and morbidity from acute poisoning and some published clinical studies are presented. Serious problems may persist in subgroups of the population and the prevention of acute poisoning is still a basic aim of this legislation. Allergic reactions to chemicals are discussed. Not all sensitized individuals can be protected but steps should be taken to prevent contact with the sensitizing agents that are of the greatest public health importance. Chronic health effects following exposure to chemicals have influenced the recent strengthening of regulations but carcinogenic risks especially are extremely difficult for administrative and political systems to handle in an approximately rational way. While we are reducing the use of suspected carcinogenic chemicals our populations must, however, be given a greater appreciation of the cancer risk problem, particularly the fact that we cannot eliminate all cancer risks. Biological monitoring of human populations is a necessary supplement to the traditional registration of diseases as part of our health surveillance systems. Fortunately our societies have been able to pay increasing attention to the long-term public health consequences of exposures to chemical factors in our environment.