The effect of chemotherapy on the growing skeleton

With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age.     

Door-to-ECG time in patients with chest pain presenting to the ED

OBJECTIVE: To describe time to electrocardiogram (ECG) acquisition, identify factors associated with timely acquisition, and evaluate the influence of time to ECG on adverse clinical outcomes. METHODS: We measured the door-to-ECG time for emergency department patients enrolled in prospective chest pain registry. Clinical outcomes were defined as occurrence of myocardial infarction or death within 30 days of the visit. RESULTS: Among patients with acute coronary syndrome (ACS), 34% and 40.9% of patients with non-ST-elevation ACS and ST-elevation myocardial infarction (STEMI), respectively, had an ECG performed within 10 minutes of arrival. A delay in ECG acquisition was only associated with an increase risk of clinical outcomes in patients with STEMI at 30 days (odds ratio, 3.95; 95% confidence interval, 1.06-14.72; P = .04). CONCLUSION: Approximately one third of patients with ACS received an ECG within 10 minutes. A prolonged door-to-ECG time was associated with an increased risk of clinical outcomes only in patients with STEMI.     

Nitric oxide and neopterin in bipolar affective disorder

BACKGROUND: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. METHODS: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression and healthy controls. As an index of NO synthesis, the ratio of the amino acids citrulline and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. RESULTS: The results indicate that both neopterin and the Cit-Arg ratio are decreased in bipolar affective patients, irrespective of their symptomatic status. In addition, an association between the values of the Cit-Arg ratio and the neopterin level was observed, which is suggestive for a low tetrahydrobiopterin activity. CONCLUSION: NO formation may be endangered in bipolar affective disorder.     

Therapeutic treatment with heat-killed Mycobacterium vaccae (SRL172) in a mild and severe mouse model for allergic asthma

The hypothesis that a lack of early childhood bacterial infections would favor the development of allergic disease suggests that bacteria can be used as a potential treatment for allergic asthma. Therefore, in this study, we investigated the therapeutic potential of heat-killed Mycobacterium vaccae in two mouse models of allergic asthma. For this purpose, mice were sensitized i.p. with ovalbumin/alum (severe model) or ovalbumin alone (mild model) and challenged on days 77, 80 and 83 by inhalation of either ovalbumin or saline aerosols. Treatment of mice with M. vaccae (s.c. 10⁷ or 10⁸ colony-forming units) on days 56 and 63, however, did not reduce airway hyperresponsiveness and eosinophilia, IgE and interleukin-5 production 24 h after ovalbumin challenge in either mouse model. We therefore conclude that treatment of sensitized mice with M. vaccae before allergen exposure is not able to reduce the allergic and asthma-like response in a mild and a severe model of allergic asthma.     

Detecting recurrent laryngeal carcinoma after radiotherapy: room for improvement

Detecting recurrent laryngeal carcinoma after radiotherapy for a primary tumour can be difficult. Early detection however, is an important prognostic factor. Although a biopsy should be performed in case of clinical suspicion, repeated negative biopsies do not exclude the presence of viable tumour. The trauma caused by biopsies in irradiated tissue may initiate infection, further oedema and failure to heal. We investigated these problems and evaluated the current care and its usefulness. A survey of the current practice concerning diagnostic procedures for detecting recurrent laryngeal carcinoma after radiotherapy in the major institutions treating head and neck cancer in The Netherlands was performed by means of a questionnaire. Furthermore, we performed a comprehensive analysis of the extent and yield of diagnostic work-up in a cohort of patients clinically suspected of a recurrence, who had undergone direct laryngoscopy between 1986 and 1998 in our institution, with a follow-up of at least 6 months. In case of suspected recurrence, 94% of the departments use direct laryngoscopy under general anaesthesia with the taking of biopsies as a diagnostic technique. Imaging does not play an important role. In our department 207 laryngoscopies were evaluated in 131 patients. In 70 patients the first laryngoscopy was negative. Of these initial negative laryngoscopies, 22 (31%) turned out to be false negative within 6 months. Thirty-seven patients remained disease free. They underwent 65 unnecessary laryngoscopies to come to this conclusion. In the decision to perform direct laryngoscopy, the conventional work up leaves room for improvement. Too many unnecessary laryngoscopies are performed. New imaging techniques such as FDG-PET or new applications of CT or MRI may improve the yield of direct laryngoscopy.