Characterization of Aerosols of Human Recombinant Deoxyribonuclease I (rhDNase) Generated by Jet Nebulizers

Recombinant human deoxyribonuclease I (rhDNase) is a new therapeutic agent developed to improve clearance of purulent sputum from the human airways. It is delivered by inhalation. Four jet nebulizers, T Up-Draft II (Hudson), Customized Respirgard II (Marquest), Acorn II (Marquest), and Airlife Misty (Baxter), were evaluated in vitro for their ability to deliver aerosols of rhDNase. The aerosols were generated from 2.5-mL aqueous solutions of rhDNase, at concentrations of either 1 or 4 mg/mL. In all experiments, the Pulmo-Aide Compressor (De Vilbiss) was used to supply the air to the nebulizers. Between 20 and 28% of the rhDNase dose initially placed in the nebulizers was delivered to the mouthpiece in the respirable range (1-6 µm). Evaluation of the rhDNase following nebulization in all four devices indicated that there was no loss in enzymatic activity and no increase in aggregation. Circular dichroism spectrophotometry indicated there was no change in either the secondary or the tertiary structure in rhDNase following nebulization. These results show that all four nebulizers are essentially equivalent in their ability to deliver respirable doses of rhDNase in an intact, fully active form. Changing the concentration of the solution in the nebulizer from 4 to 1 mg/mL rhDNase leads to a proportional reduction in the respirable dose delivered to the mouthpiece.     

Effect of hydrophobic coating on the behavior of a hygroscopic aerosol powder in an environment of controlled temperature and relative humidity

Powders of uncoated disodium fluorescein (DF) and DF coated with various amounts of lauric or capric acids were generated as aerosols in an environment of controlled temperature and relative humidity. The particle size and distribution of these powders were characterized using a cascade impactor and a computerized data inversion method of analysis. Disodium fluorescein exhibited a hygroscopic growth ratio of 1.5 at a relative humidity of 97%. This growth was reduced to 1.3 by coating with 0.15 g of lauric acid or 0.8 g of capric acid per gram of DF, and was eliminated with 0.2 g of lauric acid or 0.18 g of capric acid per gram of DF. The reduction in hygroscopic growth probably reflects an inhibition of the growth rate. In the time following generation and prior to deposition in the collection device, approximately 40 s, the coated aerosol powders do not seem to reach their equilibrium droplet diameter. These studies indicate that these combinations of DF and fatty acid would result in larger equilibrium droplet diameters than that of the dye alone.     

A case of bronchocentric granulomatosis presenting as a tumorous shadow on chest X-ray film]

A 57-year-old woman was admitted to our hospital with cough, sputum and abnormal chest X-ray. In summer, 1989, she developed cough which gradually worsened in autumn. In November, the chest X-ray revealed a tumorous shadow in the left suprahilar region. On admission, there were no symptoms of bronchial asthma. Chest X-ray revealed a subpleural tumorous shadow in the left upper lung field. X-ray findings suggested that the tumorous shadow in the suprahilar region moved to the left peripheral upper lung field. Left B1+2 orifice obstruction with necrotic tissue was seen on fiberoptic bronchoscopy. Transbronchial biopsies failed to yield specific diagnostic findings, except for bronchitis with exudate containing eosinophils. In February, 1990, she developed hemosputum and left chest pain. Chest X-ray showed consolidation in the left apical lung field. Left upper lobectomy was performed. Histological examination disclosed many granulomas with central necrosis around the bronchi, and aspergillus hyphae were seen. These findings are compatible with bronchocentric granulomatosis without asthma.     

Association analysis of 5-HTTLPR variants, 5-HT2a receptor gene 102T/C polymorphism and migraine

It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. There is evidence to suggest that serotonin-related genes participate in the pathogenesis of migraine. Previous studies have shown that gender differences influence the serotonergic neurotransmission and, in addition, the migraine prevalence is higher in females than males. Therefore, we investigated the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the 102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female population. These genes were analysed in 126 migraine sufferers (with or without aura)and 101 unrelated healthy controls using case control design. A borderline association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12) between 5-HTTLPR short (S) allele and migraine was found. No significant difference between migraine sufferers and controls was observed for the 102T/C polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In conclusion, our results support that the genetic susceptibility of migraine may be associated with a locus at or near the 5-HT transporter gene.     

Activation of secondary cytotoxic lymphocytes by cell-free factors from I-region-primed and D-region-primed lymphocytes.

Cell co-operation in the generation of secondary cytotoxic responses was studied by selectively sensitizing lymphocytes in mixed lymphocyte culture (MLC) across I or D region difference and by combining the primed lymphocytes in the secondary MLC. Secondary cytotoxic responses were induced in D-region-primed lymphocytes by restimulation with the original priming D-region antigens, by co-culturing with the I-region-primed lymphocytes in the presence of the priming I-region antigens, or by cell-free supernatants obtained 24 h after the restimulation of D-region-primed lymphocytes and I-region-primed lymphocytes, The active MLC supernatants produced by both I-region-primed and D-region-primed cells also induced accelerated proliferative responses in D-region-primed lymphocytes. Heat-treatment or ultraviolet irradiation of the stimulator cells eliminated the capacity of the cells to induce the production of CTL-helper factor in I-region-primed and D-region-primed lymphocytes. It was concluded that both I-region-primed and D-region-primed lymphocytes produce a cell-free factor which induces proliferation and secondary cytotoxicity in D-region-primed lymphocytes. The possible participation of D-region reactive helper T cells and D-region reactive cytotoxic T cells in the cytotoxic responses to D-region antigens in the absence of I-region difference is discussed.     

Ganglioneuroma of the adrenal gland]

149 patients with adrenal incidentalomas were examined. Sixty-eight cases were histologically confirmed, five of them had ganglioneuromas. On the basis of these patients history current knowledge of this benign tumour was summarized. Histological and pathological characteristics of one tumour suggest that ganglioneuromas may develop by maturing of malignant neuroblastic tumours. The clinical symptoms (abdominal pain, meteorism) were local. In 2 of 5 cases mildly elevated levels of urinary vanillylmandelic acid and catecholamine could be measured. One patient had persisting hypertension after surgery. In an other patient previous diarrhoea stopped after the removal of tumour. On the basis of ultrasound and computertomographic features, the size and origin of a tumour and its relation to the surrounding organs can be well characterized. One patient was inoperable because of an infiltratively spreading tumour, but during five years of follow-up no tumour progression could be observed with computertomography. After surgery we could follow only 2 of 4 patients. Until now no recurrence of tumour were detected.