The costs of atopy and asthma in children: Assessment of direct costs and their determinants in a birth cohort

The aim of this study was to estimate costs accrued by the health care of children with asthma in comparison to children with atopic eczema and seasonal rhinitis and to investigate cost determinants. From the multicenter cohort study (MAS-90), we selected children with an asthma, atopic eczema and/or seasonal rhinitis diagnosis during the first 8 years of life, and overall 8-year health care utilization was estimated retrospectively by reviewing medical records. Asthma treatment (n = 76) incurs an average cost of US$ 627 per year, 44% due to hospital stays. Atopic eczema treatment (n = 91) cost on average US$ 219 and seasonal rhinitis (n = 69) US$ 57 per year. In asthma and atopic eczema, costs increase significantly with disease severity. Allergy diagnostics use accounts for only 1% of total costs. Costs for asthma and atopic eczema treatment are highest in those years when topical steroids are used for the first time, but decrease with every further year of steroid use. A remarkable 25% of asthmatic children with severe symptoms were not treated according to national guidelines, so that most steroid treatment was initiated during the first hospital stay. In the case of asthma, total direct costs increased until the 3rd year of the disease, and then decreased with further years of diagnosis, while steroid use continued to increase. These results indicate a 'learning effect' in the treatment of asthma and atopic eczema for each patient as well as considerable cost-saving potential by preventing severe asthma. Moreover, the importance of considering cost-driving factors and using cohort or longitudinal designs in cost-of-illness approaches is emphasized.     

Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course of a cervicothoracic astrocytoma WHO grade II

CASE REPORT: The reported female patient underwent sub-total resection of an intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at the age of 18 months and received local irradiation. In 1989, a local recurrence was diagnosed and a partial resection was performed. Sixteen years later, a small recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve roots and the left cerebellar cortex was apparent on MRI. The patient was implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing papilloedema, which eventually lead to amaurosis. After an extended biopsy, the invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months later, the patient died after rapid progression of the caudal cranial nerve dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination of spinal astrocytomas even two decades after initial diagnosis and treatment are rare. Therapies and diagnostic follow-up strategies are discussed.     

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines,XXX: Absorption,Organ Distribution,and Excretion of the Oligoamine (+)-(S,S)-1,4-Bis-[4-(3-iodo-4-methoxyphenyl)-butylamino]-butane-2,3-diol and its Metabolites

The pharmacokinetic behaviour of the 131-iodine-labelled title compound 3 * and its metabolites in mice was investigated. A two phase, 1st order elimination profile was observed. The second phase is very slow leaving about 35% of radioactivity in the mice even 100h after i.v. injection, because of high affinity to liver and spleen, caused by strong binding of oligoamines to phospholipids of liver and blood cell membranes. The blood-brain-barrier is not passed. No deep compartments were observed. The doses necessary for antithrombotic effects in vivo were calculated from the blood levels to be 20.5–39.7 μmol/kg for a time interval of 1–6 h after administration.     

Metabolism of the benzodiazepine antagonist 11C-Ro 15-1788 after intravenous administration in man

The metabolic fate of the benzodiazepine antagonist RO 15-1788 labelled with ¹¹C was studied in plasma from human subjects after intravenous administration in connection with positron emission tomography. Ro 15–1788 and its metabolites were separated by thin-layer chromatography and the radioactivity in the different compounds was determined. ¹¹C-Ro 15–1788 was extensively and rapidly metabolised to the corresponding free acid. At 36 minutes after administration only 50% of the radioactivity in plasma represented unchanged compound.     

Enhanced Intestinal Absorption of Oxytocin Peptide Analogues in the Absence of Pancreatic Juice in Pigs

Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸]-oxytocin (F314), [Mpa¹, D-Tyr(Ethyl)², Val⁴, D-Arg⁸]-oxytocin (CAT), and [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸, desGly⁹, carba⁶]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

In vitro evaluation of ablation parameters of normal and fibrous aorta using smooth excimer laser coronary angioplasty

A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm² in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc.     

Application of the Minnesota Code in evaluating electrocardiographic features of ischemic heart disease in patients exposed to carbon disulphide

Summary We examined 81 men exposed for a long time to carbon disulphide (CS₂) and tested the possible electrocardiographic (ECG) changes of ischemic heart disease (I.H.D.). The subjects were examined twice in two years. In order to make the ECG evaluation more objective, the Minnesota Code was applied. Two obligatory ECG examinations and only one submaximal effort test were carried out. For comparative evaluation, the control group was examined once. We proved that, in spite of the accepted opinion concerning the atheromatous action of CS₂, this compound does not cause ECG symptoms of I.H.D. in a higher percentage of exposed persons. It also does not cause any significant increase in I.H.D. symptoms in dynamic ECG observations.