The effects of theophylline on 661-1661-1661-1on polymorphonuclear leukocytes of asthmatic children and juveniles

The density (B_max) and affinity (K_D) of ₂-adrenoceptors in polymorphonuclear leukocytes (PMN) were measured in 29 children and juveniles with mild or moderate asthma and in 25 healthy control subjects using the highly specific radioligand (±)-¹²⁵I-cyanopindolol. No significant difference in B_max was found between asthmatic subjects without medication and the control group. The asthmatic subjects were divided into four different groups by their actual medication: no medication, adrenergics, theophylline, adrenergics plus theophylline. Analysis of variance revealed highly significant differences between these groups for B_max (P=0.0016) but not for K_D. In asthmatics on adrenergic therapy B_max was significantly lower (995±415) than in asthmatics without medication (1660±521;P=0.008). In contrast, B_max in asthmatics on theophylline therapy was significantly higher (2137±231;P=0.009) than in the controls. B_max was average in the group of asthmatics treated with both adrenergics and theophylline (1619±547). It is concluded that in asthmatic subjects therapy with theophylline increases the density of ₂-adrenoceptors and partly prevents their down-regulation induced by adrenergic therapy.     

Status of determining the transepithelial potential difference (PD) of the respiratory epithelium in the diagnosis of mucoviscidosis

Patients with cystic fibrosis (CF) have an increased transepithelial electrical potential difference (PD) on the respiratory mucosa. In an attempt to investigate the diagnostic value of this measurement 12 patients with CF, 15 first degree relatives and 38 controls were studied. A nasal recording electrode and a reference electrode placed subcutaneously in the left upper arm were used. The recorded values of nasal PD were significantly (p less than 0.0001) higher (-61 mV +/- 7) than in subjects without cystic fibrosis (-21 mV +/- 6) and in CF relatives (-25 mV +/- 8). There was an overlap in values measured on the lip and on the tongue of subjects with and without cystic fibrosis. No differences in nasal PD were noted between male or female subjects. Transepithelial potential difference declined slightly with age. In addition, a superfusion with amiloride as inhibitor of sodium transport induced a 62% reduction in nasal PD in a cystic fibrosis patient as compared to a healthy subject (31%). These results as well as the good reproducibility (r = 0.99) demonstrate that the measurement of transepithelial potential difference on the nasal mucosa could be an additional diagnostic tool in cystic fibrosis.     

Type I allergy to egg and milk proteins: comparison of skin prick tests with nasal, buccal and gastric provocation tests

Provocation tests with egg or milk antigens were performed on symptomatic patients or those who were skin prick test positive to these antigens. Skin test positive patients responded immediately in 12/13 to nasal, in 7/15 to buccal and in 5/15 to gastric provocation tests. An immediate gastric response was within 1 h. The threshold dose for a positive result showed that tissue sensitivity from greatest to least was in the order: skin, nasal, buccal and gastric. None of the skin test negative group responded to any of the provocation tests. The results, particularly the nasal provocation, validate the skin prick test as a sensitive measure of type I allergy to defined foods. The relative insensitivity of buccal and gastric mucosae may explain positive skin test responses in asymptomatic subjects.     

Primary hyperparathyroidism, psychiatric manifestations, diagnosis and management

Mental manifestations of primary hyperparathyroidism simulate a wide spectrum of psychiatric disorders. Definitive surgical treatment results in long-lasting full recovery. The 2 cases presented demonstrate this. The clinical diagnostic and therapeutic aspects of primary hyperparathyroidism, with an emphasis on neuropsychiatric manifestations, are discussed. Early diagnosis of hypercalcemia can prevent unnecessary and potentially harmful treatment with antidepressive, anxiolytic or antipsychotic drugs, which can further depress the cognitive state of the patients, and can aggravate the mental symptoms.     

Enzyme-linked immunosorbent assay of allergen-specific IgG antibodies in bee sting allergic patients hyposensitized with pure bee venom

Summary An ELISA is presented for detection of IgG antibodies to bee venom. By this method, sera of 11 bee sting allergic patients, who were treated with rapid hyposensitization with pure bee venom, were tested. The highest antibody titers were observed after 30 days of treatment, a maximum rise of 7.4±1.5 log 2-titer steps. Pure bee venom is shown to be more potent immunologically than whole body bee extract. Prediction of the clinical success, measured by tolerance to a bee sting challenge, is not yet possible using venom specific IgG determinations.This work was supported by the Deutsche Forschungsgemeinschaft, grant UR 12/2     

Polypharmacy in elderly hospitalised patients in Slovakia

Objective The aims of the present study were to: analyse the prevalence of polypharmacy in a group of older patients; evaluate the influence of hospital stay on the number of drugs taken; assess the most frequently prescribed pharmacological classes; identify risk factors that predisposed the patient to polypharmacy. Setting The study was carried out in the Department of Internal Medicine of a non-university general hospital. Method In the retrospective study, 600 patients aged 65 years or more were enrolled. They were hospitalised in the period from 1st December 2003 to 31st March 2005. Each person taking six or more medications per day was considered to be a patient with polypharmacy. Particular sociodemographic and clinical characteristics, as well as comorbid conditions, were evaluated as factors potentially influencing the prevalence of polypharmacy. Main outcome measure The number and type of medications taken at the time of hospital admission and discharge were recorded and compared for each patient. Results Polypharmacy on admission and at discharge was observed in 362 (60.3%) and 374 (62.3%) patients, respectively. Hospitalisation led to a significant increase in the number of medications. The spectrum of medications used corresponded to the proportions of diagnoses in the evaluated group, in which cardiovascular diseases were most prevalent. According to the multivariate analysis using a logistic regression model, diabetes mellitus (odds ratio (OR) 2.40; 95% confidence interval (CI): 1.64–3.50), heart failure (OR 2.14; 95% CI: 1.46–3.14), dementia (OR 2.12; 95% CI: 1.26–3.57), living alone (OR 2.00; 95% CI: 1.28–3.10), arterial hypertension (OR 1.63; 95% CI: 1.08–2.44) and cerebrovascular disease (OR 1.58; 95% CI: 1.03–2.44) significantly increased the risk of the presence of polypharmacy. Conclusion Our study confirmed a relatively high prevalence of polypharmacy in Slovak elderly patients. Polypharmacy risk rose especially with the increased prevalence of diseases of advancing age (diabetes mellitus, heart failure, arterial hypertension, dementia and cerebrovascular diseases). The increasing numbers of medications in inpatients indicate the need for the careful re-evaluation of pharmacotherapy during the stay in hospital.     

T3 replacement does not prevent excitotoxic cell death but reduces developmental neuronal apoptosis in newborn mice.

BACKGROUND: Periventricular leukomalacia (PVL) is a major cause of neurological handicap in pre-term infants. At present, there are no effective or causal therapies available. Thyroid hormones play an essential role in brain development and are reported to be decreased in pre-terms and following brain injury in adults. HYPOTHESIS: Excitotoxic brain damage of newborn mice decreases thyroid hormone concentrations. Exogenous T3 administration restores thyroid hormone levels and reduces perinatal brain damage in an animal model of PVL. DESIGN AND METHOD: To create white and gray matter (WM/GM) lesion mimicking several key aspects of PVL, we injected ibotenic acid (Ibo), a glutamate analog, into the right hemisphere (intracranially (i.c.)) of 5-day-old mice. T3 (10 microg/kg body weight (bw)) was injected intraperitoneally (i.p.) 1 h or repeatedly 1/24/48/72/96 h post-insult. We determined lesion size, number of apoptotic cells in WM/GM and serum T3/T4 concentration at 24 and 120 h after injury. Serum T3/T4 concentration was also determined before and 1 and 2h after T3 administration. RESULTS: Excitotoxic brain damage did not alter serum T3/T4 concentrations within 120 h of injury. Serum T3 levels were distinctly elevated within 1 h of T3 injection; however, this elevation was relatively short-lived (half-life estimated to be less than 12 h). Neither single nor repetitive T3 treatment regimen reduced excitotoxic lesion size, but it did reduce apoptosis. CONCLUSIONS: T3 replacement does not prevent excitotoxic cell death, but it does reduce developmental neuronal apoptosis, which could participate to the beneficial neuropsychological effects of hormone therapy. Further study is therefore warranted.     

Removal of thrombus associated with ablation of atrial fibrillation -- the role of intracardiac echocardiography

Lef atrial thrombus formation during ablation of atrial fibrillation carries the risk of thrombo-embolic complications. We describe a case of a 55 year old male in whom thrombus formation was detected by intracardiac echocardiography. Thrombus was safely removed by aspiration into transseptal sheath.     

Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival

Cardiac stem cells and early committed cells (CSCs-ECCs) express c-Met and insulin-like growth factor-1 (IGF-1) receptors and synthesize and secrete the corresponding ligands, hepatocyte growth factor (HGF) and IGF-1. HGF mobilizes CSCs-ECCs and IGF-1 promotes their survival and proliferation. Therefore, HGF and IGF-1 were injected in the hearts of infarcted mice to favor, respectively, the translocation of CSCs-ECCs from the surrounding myocardium to the dead tissue and the viability and growth of these cells within the damaged area. To facilitate migration and homing of CSCs-ECCs to the infarct, a growth factor gradient was introduced between the site of storage of primitive cells in the atria and the region bordering the infarct. The newly-formed myocardium contained arterioles, capillaries, and functionally competent myocytes that with time increased in size, improving ventricular performance at healing and long thereafter. The volume of regenerated myocytes was 2200 microm3 at 16 days after treatment and reached 5100 microm3 at 4 months. In this interval, nearly 20% of myocytes reached the adult phenotype, varying in size from 10,000 to 20,000 microm3. Moreover, there were 43+/-13 arterioles and 155+/-48 capillaries/mm2 myocardium at 16 days, and 31+/-6 arterioles and 390+/-56 capillaries at 4 months. Myocardial regeneration induced increased survival and rescued animals with infarcts that were up to 86% of the ventricle, which are commonly fatal. In conclusion, the heart has an endogenous reserve of CSCs-ECCs that can be activated to reconstitute dead myocardium and recover cardiac function.