The influence of ionizing irradiation (1, 2 and 4 Gy 137Cs) on both the activity of free-radical processes in plasma, formed elements and aorta wall as well as on the character of contractile vascular reactions of isolated rings of thoracic aorta and carotid artery in rabbits has been studied. The experiments were carried out on the 7th day after the whole-body irradiation. The results indicate that simultaneously with the weakening of antioxidant mechanisms both endothelium-dependent and endothelium-independent vascular wall relaxation slightly decreases after 1 Gy exposure. Noradrenaline and KCI-induced contraction is shown to increase. However, these changes are not statistically significant. Irradiation in dose of 2 and 4 Gy considerably decreases endothelium-dependent relaxation. Nitroglycerin-induced relaxation greatly diminishes, KCI- and noradrenaline-induced constriction considerably increases in these conditions. The level of activation of free-radical processes considerably increases too. Thus, already on the 7th day after irradiation significant changes in reactivity of vascular wall are developed. Radiation injures both endothelium and vascular smooth muscle cells. The free-radical processes seem to be the main cause of radiation vascular damage, so there is a pronounced correlation between the changes of vascular contractile properties and the degree of activation of these processes.
The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine.
Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term effects were evaluated with SF-36. SCL-90-R and SF-36 data were compared to age- and gender matched controls.
In the SCL-90-R, clinically significant scores for anxiety, phobic anxiety and depression were found in 55%, 51%, and 44% of the mefloquine group. Substantial acute phase psychotic symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE), and vitality (VT) in the mefloquine group compared to matched controls.
The most frequent acute psychiatric problems were anxiety, depression, and psychotic symptoms. Data indicated that subjects experiencing acute mefloquine adverse side effects may develop long-term mental health problems with a decreased sense of global quality of life with lack of energy, nervousness, and depression.
BACKGROUND: Dry powder inhalers (DPI) have in recent years become a common mode for administration of inhaled corticosteroids for preventive therapy of asthma. Inhaled steroids delivered by DPI achieve increased lung deposition compared with pressurized metered-dose inhalers (pMDI), which is associated with increased therapeutic effect. This may be associated with increased systemic absorption. OBJECTIVE: The purpose of this study was to evaluate the prevalence of adrenal suppression in children using low-dose budesonide given by DPI, as compared with pMDI attached to a large-volume spacer device (pMDI + spacer). METHODS: In an open-labeled crossover study, 15 asthmatic children aged 5 to 15 years received 200 microg of inhaled budesonide twice daily by DPI (Turbuhaler, Astra, Draco AB, Lund, Sweden) and by pMDI + spacer, 1 month each, in a randomized order. Twenty-four-hour urine collections were performed at baseline and at the end of each of the 2 months of the study period, and urinary cortisol and creatinine were measured. RESULTS: Baseline urinary cortisol:creatinine was 0.038 +/- 0.012 microg/mg, similar in both groups. After 1 month of DPI therapy, urinary cortisol:creatinine was reduced by 27 +/- 16% to 0.028 +/- 0.012 microg/mg (P = 0.018). Urinary cortisol:creatinine after 1 month of pMDI + spacer therapy was similar to baseline 0.037 +/- 0.019 microg/mg (P = 0.78). CONCLUSIONS: Treatment of asthmatic children with budesonide 400 microg daily given via a DPI for 1 month was associated with hypothalamic-pituitary-adrenal axis suppression. This effect was not observed with the same dose of budesonide administered via pMDI + spacer. This indicates that systemic absorption might be reduced with pMDI + spacer therapy.
Comment In: Ann Allergy Asthma Immunol. 2002 Dec;89(6):537-912487216
In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.
The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.
The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.
Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.
This study aimed to investigate whether milrinone effect on cardiac muscle contractility undergoes to age-related changes. Experiments were carried out on papillary muscles isolated from right ventricle of Brown Norway rats belonging to two different age groups: 2 month old and 18 month old. The effect of milrinone (10-100 microM) on rat cardiac muscle in vitro preparations was characterized by a reduction of peak developed tension and of contraction duration. Furthermore, the recovery of contractility after a contractile cycle, i.e. the mechanical restitution was faster in the presence of milrinone than in control conditions. All these effects were reduced in preparations from 18 month old rats compared to preparations from 2 month old rats. The decrease of milrinone effect on the mechanical restitution was particularly pronounced. The reduction of the milrinone effects is likely connected with the reduction of the maximal effect of adrenergic stimulation, although the molecular basis of this link is not yet clearly understood.
The inotropic effects of noradrenaline (10(-7)-10(-5) M) and acetylcholine (10(-8)-10(-6) M) were studied in experiments carried out on preparations of the right atria and on papillary muscles of the right ventricle in adult (4-5 months) and old (18-24 months) guinea pigs. An age-related decrease in inotropic noradrenaline effects and the displacement of dose-effect relationships to the right was revealed. Similar changes of the dose-related effects of acetylcholine superfused against the background of noradrenaline action were observed. The direct inotropic action of the acetylcholine did not change with ageing. A lack of the essential atrial-ventricular differences in age-related changes in myocardial reactivity is apparently very significant for support of effective functional coupling of cardiac chambers in ageing.