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Eleven differently substituted 3,4-dihydro-2H-1,3-benzoxazine resorcarenes were studied by electrospray ionisation (ESI) and matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry, using Fourier transform ion cyclotron resonance (FT-ICR) and time-of-flight (TOF) mass spectrometers, respectively. Under ESI conditions it was possible to transfer the intact resorcarenes from solution to the gas phase, yielding [M + H]+ and [M + 2H]+ ions as the main ions observed. Energy increase of the ions induced ready decomposition through successive eliminations of four CH2NR groups. Ion-molecule reactions showed that the ionising proton was situated somewhere inside the molecule and could not be reached with neutral reagent gases. In the host-guest complexation experiments, the benzoxazine resorcarenes studied turned out to be poor hosts for alkali metal and ammonium ions. In MALDI experiments, 2,5-dihydroxybenzoic acid proved to be the best matrix for these compounds. However, the intensity of the [M + H]+ ions was low for all compounds, and extensive fragmentation with consecutive elimination of CH2NR groups was observed. Copyright © 2002 John Wiley & Sons, Ltd.

Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry was used to characterize the complexes formed between open-chain piperazine-containing ligands and transition metal salts (Cobalt, Copper, Zinc, and Cadmium as chlorides, nitrates, and acetates). Only single-charged complexes were observed, formed of one ligand (L) and mainly one metal ion (M). Since the net charge of the complexes was one, a counterion (X) was attached to some of the complexes, with formation of [L + M + X]+ complexes, and a proton was lost from others, as in [L − H + M]+ complexes. In most cases the composition of the complexes was more dependent on the ligand than the metal salt. Collision-induced dissociation measurements showed that complexes with related composition often differed in structure, or that interactions between the ligand and the metal ion were not alike. The metal ion influenced considerably the fragmentation pathways of the ligands, so that the fragmentation products could be used to deduce the binding sites of the metal. The variations observed in fragmentation behavior of complexes possessing the same ligand but different metal ions can mostly be explained by the ionic radius and electronic configuration of the metal ion. The results indicated a preference of the piperazine ring of the coordinated ligand for the boat conformation. Copyright © 2001 John Wiley & Sons, Ltd.

Ion−molecule reactions of protonated cavitands with neutral amines have been studied using electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. The cavitands studied are built by bridging a resorcin[4]arene skeleton with four aryl phosphate units. Each of the PO bonds can be directed toward the inside or the outside of the cavity leading to six stable diastereoisomers. ESI proved to be an effective ionization method for the cavitands, although the range of ionic species observed strongly depended on the orientation of the PO groups in the isomers and the solvent composition used. Five protonated diastereoisomers were studied in ion−molecule reactions with various types of neutral amines, and the corresponding reaction efficiencies were calculated. The data were compared with that observed for the complexes generated in solution. Collision-induced dissociation (CID) was used to study the structure and relative stability of the complexes formed from different di...

The size and severity of perfusion defects in acute cerebral ischaemia on single photon emission tomographic (SPET) images may provide useful information regarding long-term (> 3 month) stroke outcome. A decreased predictive value has been reported with delayed SPET more than 24 h after stroke onset. We examined 20 patients with acute middle cerebral artery (MCA) infarctions using serial 99Tcm-ECD or 99Tcm-HMPAO SPET (SPET 1 one day and SPET 2 three days after stroke onset). Neurological (NIH, SSS) and functional (Barthel, Rankin) scores were calculated simultaneously and 3 months poststroke. The two SPET scans correlated equally well with the severity of functional and neurological deficits evaluated 3 months after stroke onset. In comparison to clinical assessment, the prognostic value of SPET was relatively better on the first day than the third day. Crossed cerebellar diaschisis correlated with early SPET deficits, but did not predict functional outcome. Our results suggest that SPET, either with 99Tcm-ECD or 99Tcm-HMPAO, can be used to predict stroke outcome in acute MCA infarction up to 72 h poststroke without significant interference from luxury perfusion.

Five differently substituted 1-(2-benzothiazolyl)-3,5-diphenyl formazans were studied by laser desorption ionization (LDI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry. The best explanation of the results is that the formazan molecules are photoionized to molecular radical ions, which then further react by ion–molecule reactions. Supporting this proposal was the abundant formation of [M − H]+ ions under LDI. These ions are not observed at all under either electron or chemical ionization. Under MALDI, the extent of the oxidation process is clearly dependent on the ability of the matrix to act as a reducing agent. With transition metals the formazans formed singly charged 1:2 metal:formazan complexes. The most stable electronic configuration of the complex determined the oxidation state of the metal regardless of its initial oxidation state. In some cases, this process also demanded a gas-phase reduction of the formazan. The ionization efficiency and affinity for complex formation depended on the substituent at the 3-phenyl group; both were increased by an electron donating substituent. The formazans were also tested as potential matrices for MALDI. Reasonable results were observed for several groups of compounds; however, only the piperazine ligands produced higher quality spectra with formazans than with common commercial matrices.

To evaluate apparent diffusion coefficient (ADC) in cerebellar subregions in patients with stroke.The total counts and ADCs were bilaterally measured on cerebellar white matter, gray matters of medial (G1), intermediate (G2), and lateral zones (G3) on SPECT and ADC maps from 20 patients with supratentorial ischemic stroke within the first 48 h and on day 8 after onset. ADCs were also obtained from 15 age-matched controls.Within 48 h, the ADCs were significantly increased bilaterally in the G3, and tended to be increased bilaterally in the white matter and G1, and contralateral G2 compared with controls. On day 8, the ADCs were significantly increased in all contralateral cerebellar subregions and in ipsilateral G1 and G2, and tended to be increased in ipsilateral G3. The ADC value was significantly higher in contralateral than in ipsilateral white matter on day 8. The interhemispheric asymmetry indices (AIs) of ADC and SPECT were significantly associated with each other in G2 and G3 within 48 h, but not on day 8. The AIs of ADC and SPECT were significantly related to each other in the G3 within 48 h and on day 8.Supratentorial ischemic stroke may cause mild cerebellar vasogenic edema.

99m Tc-labelled disodium cromoglycate particles and 111 In-labelled microspheres of disodium cromoglycate and polyacrylic acid were administered simultaneously to the nasal cavities of four healthy volunteers. The initial deposition patterns of the inhaled powder mixture as well as the drug removal due to the mucociliary clearance were monitored by a gamma camera. The double-labelling technique enabled in vivo comparison of simultaneously administered plain drug particles and polyacrylic acid microspheres of disodium cromoglycate. After administration, both the plain drug particles and the microspheres distributed equally effectively. On average, 27% of the 99m Tc-labelled plain drug particles and 50% of the 111 In-labelled microspheres were retained at the initial site of deposition 30 min after inhalation. Thus, the removal of microspheres from the nasal cavities was clearly impeded by polyacrylic acid.

Deposition of 99m Tc-labelled particles of disodium cromoglycate in the human respiratory tract after inhalation either from the conventional metered dose aerosol or from the new Ingelheim powder inhaler (FO II) was compared. Fractional deposition in the whole lung area, in the upper airways and in the device was measured using a gamma camera. Eight healthy informed volunteers participated in the inhalation test. The lung deposition of the inhaled drug was about 9% using the conventional aerosol actuator with the short plastic mouthpiece whereas, using the Ingelheim powder inhaler, on average 20% deposition in the whole lung area was achieved. In addition, with the Ingelheim inhaler drug particles seemed to be deposited in the more peripheral parts of the respiratory tract. The upper airway deposition was also reduced with the Ingelheim powder inhaler. On the other hand, a larger fraction of the drug dose was retained in the Ingelheim inhaler than in the aerosol actuator.

Bovine epithelial and urine antigen extracts were compared using enzyme-linked immunosorbent (ELISA) inhibition assay and sodium-dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with immunoblotting. According to ELISA inhibition results, the two extracts share about 2% of their antigenic components. Urine-derived antigens seem to be antigenically closer to serum proteins than epithelial antigens, as determined by rabbit immune sera. The IgG responses of allergic farmers against epithelial antigens were directed mainly against a protein of 20 kD, while non-allergic farmers had only very weak reactions. Generally, the IgG response against urinary antigens seemed to be more heterogeneous than against epithelial antigens. Almost all cow-allergic farmers reacted with a band at 20 kD in IgE immunoblotting against urinary and epithelial antigen while all non-allergic farmers showed negative results.

Objectives and methods - This study investigated the ease with which 52 Parkinson's disease patients already receiving adjunct entacapone to traditional levodopa were switched to Stalevo® (levodopa/carbidopa/ entacapone). Results - The switch to Stalevo was straightforward for most patients taking standard-release levodopa with 86% of these patients being able to replace their entire regimen without having to change the amount of levodopa taken. The majority of patients (54%, P = 0.162) preferred Stalevo; 31% preferred their prior treatment regimen; 15% had no preference. Patients found Stalevo more simple to dose (94%), more convenient to use (84%), easier to handle (84%), easier to remember (67%) and easier to swallow (59%), compared with their previous medication. Conclusions - Stalevo was well tolerated, with a low incidence of adverse events. The study shows that Stalevo is an effective, preferred and well-tolerated means of delivering levodopa/ carbidopa/entacapone in one easy-to-use tablet.

This paper is to analyze the characteristics of the spurious spectrum due to the RF bursting signals and its potential interaction with surrounding electronic equipment. The spurious spectra at different mode of transmissions in TDMA-based systems are discussed using FFT. The mechanism of the interaction is described on the base of the spectrum analysis. It is proved that that the level and feature of the interference would be basically determined by four factors: transmitter output power, RF carrier frequency, duty cycle, rise/fall time, repetition frequency of the RF pulses, modes of RF transmission, as well as the immunity of receptive equipment.

Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) methods were used to study open-chain piperazine-containing ligands (L) and their complexes formed with transition-metal salts. ESI and MALDI measurements were performed with a Fourier transform ion cyclotron resonance (FT-ICR) and a time-of-flight (TOF) mass spectrometer, respectively. Only singly charged complexes, between one ligand and one or several metal ions, were formed in the ESI measurements. Because the net charge was always one, one or several counterions were attached to the complex. Under ESI conditions, the complexes formed between the ligands and metal (Co, Ni, Cu, and Cd) salts were [L + M + X]+, [L + H + M + X2]+ and [L + M2 + X3]+ (M = metal ion, X = counterion). In collision induced dissociation reactions the [L + H + M + X2]+ complexes easily eliminated one proton and one counterion. Fragmentation pathways were more dependent on the metal ion than the ligand, and elimination of the second counterion occurred with one proton from copper and nickel complexes and with one proton and one hydrogen from cobalt complexes. Differences in the fragmentation of the complexes could be due to electronic configuration of the metal ion. In the MALDI measurements the ratio between the [L + H]+ and [L − H]+ ions varied with the matrix. Fragmentation of the ligands through elimination of 2-methylpyridine end groups occurred with the aromatic matrices containing carboxylic acid and hydroxyl substituents. Ionization of the complexes was not successful with MALDI as the matrix molecules were also attached to the complexes. Copyright © 2001 John Wiley & Sons, Ltd.

About one in every four cases of occupational rhinitis recorded in Finland is animal-induced. Bovine allergens are the most important in this respect and the largest patient group consists of dairy farmers. Allergen immunotherapy, if proven effective, safe and feasible, would be ideal for their treatment. The development of recombinant allergens has offered new potential therapeutic prospects. Fragments of recombinant Bos domesticus (Bos d 2) allergen could be suitable for this purpose because they are recognized by T cells but their IgE-binding capacity is attenuated.The aim of this study was to verify whether the potential of the two fragments of recombinant Bos d 2 (corresponding to amino acids 1-131 and 81-172) to induce immediate allergic reaction in a shock organ (nose) was decreased compared to the complete recombinant allergen, which would be an advantageous property for a preparation intended for allergen immunotherapy.The study group consisted of 10 dairy farmers with cow-induced allergic rhinitis. We used the IgE titres against native Bos d 2 measured by indirect IgE ELISA to characterize the level of sensitization and compared the IgE titres in the rhinitis patients with 12 cow-sensitized asthmatic farmers and 12 healthy students. In vitro reactivity against recombinant Bos d 2 and its two fragments was studied by indirect IgE ELISA and in vivo reactivity by nasal provocation tests.The IgE titres against native Bos d 2 of patients with rhinitis tended to be lower than the titres of asthmatics. The healthy students did not exhibit any detectable IgE reactivity to native Bos d 2. In the patients with rhinitis, there was no statistically significant difference between IgE responses against native and recombinant Bos d 2, whereas with both in vitro and in vivo, the reactivity to both fragments of recombinant Bos d 2 was lower than the reactivity to the complete recombinant allergen.Due to the decreased in vivo capacity to induce immediate allergic reactions, the fragments may be better tolerated in allergen immunotherapy than the complete allergen.

A population-based survey was conducted in 35 municipalities in Northern Finland to assess the incidence of lip cancer as well as the patient and tumour characteristics in cases diagnosed between 1983 and 1997. A total of 96 new patients emerged. The age-standardised incidence (per 100,000 years) of lip cancer in men decreased from 4.8 in 1983-1987 to 1.4 in 1993-1997. The incidences in women were 0.30 to 0.36, respectively. The median age of the patients increased from 66 to 73 years through the years. Overall, 90% of the patients had at least one of the known risk factors, namely rural domicile, outdoor occupation or smoking. The median duration of symptoms also remained the same, as did the median size and location of the tumour at diagnosis. In contrast, spread to regional lymph nodes became rare during the period.

Cumulative inactivation of tumor suppressor genes and/or amplification of oncogenes lead to progressively more malignant astrocytic tumors. We have analyzed the significance of tumor suppressor genes p53, p21, p16 and retinoblastoma protein (pRb) and proliferative activity for survival in 77 high grade astrocytic tumors. After operation, the patients--25 anaplastic astrocytomas (AA) and 52 glioblastomas (GBs)--were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohistochemically. p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower proliferation indices than p53 immunonegative tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive. Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB. In high grade astrocytic tumors p16 immunonegativity was an independent indicator of poor prognosis in addition to the previously established patient's age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (20%) in which the histopathological hallmarks of GB were lacking, but which had similarly dismal prognosis as GB.

In acute ischemic stroke, the infarcted core is surrounded by a zone of tissue that has decreased perfusion. Some of this tissue may be salvaged by prompt, effective treatment. Diffusion-weighted MRI is sensitive in detecting the infarcted tissue, whereas SPECT also detects the hypoperfused tissue around the infarcted core. We studied the potential of combined diffusion-weighted MRI and SPECT to predict infarct growth and clinical outcome in patients not receiving thrombolytic treatment.Sixteen patients with acute stroke were examined consecutively with diffusion-weighted MRI and 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPECT within 24 h of the onset of symptoms. Follow-up diffusion-weighted MRI was performed on the second day and after 1 wk. The volumes of infarcted and hypoperfused brain tissue were measured from diffusion-weighted MRI and SPECT, respectively. The volume difference between the hypoperfused and infarcted tissue on the first day was compared with the possible increase in infarct volume during the follow-up. Each patient's neurologic status was assessed with the National Institutes of Health Stroke Scale (NIHSS).The volume of infarcted tissue increased from 48 +/- 54 cm3 (mean +/- SD) on the first day to 88 +/- 93 cm3 on the second day (P = 0.001) and to 110 +/- 121 cm3 at 1 wk (P = 0.001). The volume of hypoperfused tissue on the first day was significantly greater than the infarct volume (102 +/- 135 cm3; P = 0.001). The volume difference between the hypoperfused and infarcted tissue on the first day correlated significantly with the infarct growth between the first day and 1 wk (r = 0.71; P0.01). Between the first day and 1 wk, the increase of the infarct volume correlated significantly with the change in the NIHSS (r = 0.54; P0.05).A large hypoperfusion zone around the infarct core in the acute phase of ischemic stroke predicts the infarct growth during the first week, and this correlates significantly with the change in the neurologic status of the patient. Combined diffusion-weighted MRI and SPECT performed within 24 h after the onset of symptoms can be useful in the evaluation of acute stroke to predict infarct growth.

Knowledge of the dielectric properties of skin is important when electromagnetic (EM) fields are interacting with the human body or when EM fields are applied therapeutically or diagnostically. However, in published works the defmition of skin is often not given. Neither is the detailed description of the measurement system and the applied probes always well presented. This results in problems in interpreting the published dielectric data for the skin. We shall first summarize the structure of the skin from a dielectric point of view. Then, we describe methods, mainly related to radio frequencies, to measure the permittivity of skin

Head and neck cancer is very suitable for investigation with PET (positron emission tomography), usually owing to the locoregional spread at the time of diagnosis. Thus, the data collected enable any lesions present to be visualised. Evaluation of tumour metabolism with PET may simplify the diagnosis of metastases, and be of predictive value, enabling response to radiotherapy and cytostatic therapy to be predicted. It serves as a complement to CT (computed tomography) and MRI (magnetic resonance imaging) in the diagnosis of recurrence, and is thus useful in planning surgical intervention. Methods capable of distinguishing hypoxic or rapidly dividing cells can be useful in the choice of effective treatment methods such as hyperfractionated radiotherapy, drugs which enhance radiosensitivity, the degree of radical surgery, and the use of gene therapy.

An open-ended coaxial probe designed to measure layered biological media is analyzed with a new method. The probe is considered as an electrostatic circuit element whose capacitance is solved using a stationary functional. The fundamental transverse electric and magnetic field (TEM)-mode and the series of evanescent wavemodes in the coaxial cable are used as basis functions. The field outside the probe is solved using a Hankel transform. The capacitance is calculated for homogeneous materials and two-layer structures and the results are compared with values measured with a phantom model. The method can be easily extended for structures with an arbitrary number of layers. A practical approximation for two-layer cases, originally developed to take into account the effect of subcutaneous fat in skin measurements, is presented and its validity for different combinations of dielectric constants and the thickness of the first layer is demonstrated. The static approximation limits the frequency range, but it covers biological measurements up to 500 MHz. The developed method is accurate and easy to adopt in practice.

The reliable interpretation of the nasal provocation test in allergy diagnosis requires objective and measurable monitoring parameters for clinical practice. The clinical usefulness of the nasal provocation test has been limited by scanty knowledge of the specificity and sensitivity of the test and a lack of reference values.To test and compare three objective monitoring parameters of a nasal provocation test in occupational allergic rhinitis. To evaluate the magnitude of the nasonasal effects in a unilateral allergen challenge.The monitoring parameters of the nasal reaction were derived from the minimum cross-sectional area on acoustic rhinometry, the nasal resistance on active anterior rhinomanometry and the amount of nasal secretion measured at 15 min intervals for 60 min. Twenty-three bovine-allergic dairy and beef cattle farmers and 19 exposed, non-allergic control subjects were challenged first with a control solution and then with the cow allergen.All the three monitoring parameters showed high specificity and sensitivity in finding allergic and non-allergic subjects. The secretion parameter was found to be slightly superior to the acoustic rhinometry and rhinomanometry parameters. The side difference in the nasal response between the allergen-challenged and the contralateral diluent-challenged cavity was significant for all the parameters among the allergic subjects. The contralateral secretion amount was 1/3 of the ipsilateral secretion, indicating the magnitude of the contralateral nasonasal reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The coefficient of variation was significantly lower for the acoustic rhinometry than for the rhinomanometry (P=0.0001). The optimal threshold values for a positive test were a secretion amount of 100 mg, a 15% decrease in the minimum cross-sectional area and a 50% increase in the resistance for the observation period of 30 min and correspondingly 210 mg, 30% and 100% for 60 min.The low-pressure aspiration of the nasal secretion from the anterior part of the nasal cavity was found to be a reliable and practical monitoring parameter to be used together with acoustic rhinometry or rhinomanometry in the nasal provocation test for clinical purposes. Although significant nasonasal effects took place in the unilateral allergen challenge, the response was more prominent in the allergen-challenged than in the contralateral diluent-challenged nasal cavity in most allergic subjects.

Acute acalculous cholecystitis is a well recognized complication of many acute illnesses. Ischaemia of the gallbladder seems to have an important role in its pathogenesis.Microangiography was performed in 15 gallbladders immediately after cholecystectomy by infusing 10 per cent barium sulphate into the specimen. Five patients had symptomatic gallstone disease, five had acute gallstone-associated cholecystitis and five had acalculous cholecystitis. Sections for histological examination were taken from adjacent sides of the microangiography section. Filling of the vessels by contrast medium was compared with histological findings.Microangiography of the gallbladder in acute gallstone-associated cholecystitis showed strongly dilated arterioles and regular filling of the capillary network, whereas in acalculous cholecystitis the capillary filling was poor and irregular.Disturbed microcirculation may play an important role in the pathogenesis of acute acalculous cholecystitis.

The optimal thickness of gold coating of cilia for scanning electron microscopy was studied using respiratory mucosa obtained from pigs. We tested 8 different coating times, from 10 seconds to 4 minutes, which resulted in gold layer thicknesses varying from 16 +/- 1 nm to 100 +/- 3 nm. The thickness of the gold layer with a coating time of 60 seconds and voltage of 2.5 kV was 43 +/- 5 nm. This thickness of gold layer gave good image quality without causing any electric charging. With thinner gold films, the amount of electric charging increased. When the coating time was longer, the gold layer was thicker but image quality did not improve. The thicknesses of the gold layers were measured using transmission electron microscopy (TEM).

A randomized prospective study was performed to compare the recovery in 41 patients undergoing uvulopalatopharyngoplasty (UPPP) with either propofol-nitrous oxide-fentanyl or thiopentone-isoflurane-nitrous oxide-fentanyl anaesthesia. The patients were referred to UPPP after examination including polysomnography and otorhinolaryngological examination. The propofol group received propofol 2 mg.kg-1 for induction followed by an infusion of 10 mg.kg-1.h-1 after intubation. The thiopentone-isoflurane group received 5 mg.kg-1 of thiopentone for induction followed by isoflurane (0.5-2%) after intubation. Other medication was similar in both groups. In the propofol group the patients had a significantly better oxygen saturation during the first postoperative hour (P < 0.05), and a higher rate of breathing (P < 0.05), indicating a more rapid recovery of the physiologic control of breathing. Pain as measured by visual analogue score was lower (P < 0.05) during the second postoperative hour compared with the isoflurane group. Apneic episodes occurred with similar frequency in both groups, and they were related to the severity of obstructive sleep apnea (OSA). We conclude that propofol is preferable to thiopentone-isoflurane in UPPP operations, because physiologic respiratory control recovers faster and postoperative pain is less intense.

Fluorine content in bone samples taken from the middle ears of otosclerotic patients was determined. Otosclerotic stapes footplate was found to have a significantly higher content of fluorine than skeletal bone from the meatus. Fluorine contents in footplate and meatal wall samples of otosclerotic patients drinking fluoridated water were slightly higher than those of patients drinking low-fluoride water. In the clinical part of the study, hearing levels of 280 patients with otosclerosis living in an area with low-fluoride water were assessed. In 344 operated ears, the preoperative and long-term postoperative air conduction and bone conduction thresholds of patients drinking fluoridated water did not differ significantly from those of patients drinking low-fluoride water. After a mean follow-up period of 9.6 years, air conduction thresholds of non-operated ears in patients drinking fluoride-poor water were found to be significantly worse than those of patients drinking fluoridated tap water, likewise there were significant differences in bone conduction thresholds at 2 and 4 kHz. Thus, fluoridation of drinking water has a beneficial effect on non-operated otosclerotic ears but has no significant effect on hearing levels of operated ears.

Results of 404 primary myringoplasty operations were critically analyzed. Patients who underwent tympanic membrane repair as the only procedure were included. In all cases, temporal muscle fascia was used as graft material. Mean follow-up period was 5.5 years. Overall success rate was found to be 88 percent. Welding injuries did not heal as well as other traumatic perforations or perforations caused by otitis media. Age of the patient, size or site of perforation, or surgical technique (underlay or overlay) did not affect success rate. Twenty-five percent of the failures were considered to be attributable to eustachian tube insufficiency. One percent (5 cases) failed as a result of chronic mastoiditis overlooked by the surgeon. Postoperative cholesteatoma developed in three ears (0.7%). Postoperative air-bone gap within 10 dB was achieved in 61 percent and within 20 dB in 87 percent of patients. In 11 of the audiologic failures, the cause of persistent conductive hearing loss was found to be fixation or erosion of the ossicles overlooked by the surgeon. The most decisive factor influencing results appeared to be the surgeon's experience.

Impaired mucociliary function is a common finding in patients with recurrent respiratory infections, sinusitis and otitis media. One main component of mucociliary transport, ciliary beating activity, is sensitive to environmental hydrogen ion concentration (pH). The pH of secretion in 103 specimens from acute or chronic sinusitis and in 98 specimens from acute or secretory otitis media were measured. There were no differences between acute and chronic sinusitis (mean of pH 7.5 +/- 0.5 and 7.4 +/- 0.6) or between mucous and purulent secretions. In acute otitis media, secretion was significantly more acidic than in secretory otitis media (mean of pH 7.7 +/- 0.5 versus 8.2 +/- 0.4). The pH was less than 7.0 in 16 (15.5%) patients with chronic sinusitis and in two (8%) patients with acute otitis. The study shows that pH of sinusal or tympanal secretion is, in the majority of patients, within limits that do not cause ciliostasis.

Nineteen dairy farmers with nasal symptoms associated with working in cowhouses participated in the study. Nasal challenge with bovine epithelial antigen (BEA) and bovine urinary antigen (BUA) was made before and after the indoor feeding season. Nasal challenge made before the indoor feeding season with BEA was positive in five patients and three of them showed positive reaction in nasal challenge also with BUA. After the indoor feeding season the results in nasal challenge with BEA were approximately equal to BEA and four of them showed positive response in nasal challenge to BUA. However, we did not find any significant increase in sensitivity in nasal challenge to BEA or BUA after the indoor feeding season. In addition to these patients, two patients who were excluded from nasal challenge before the indoor feeding season showed positive results in nasal challenge after the indoor feeding season with both BEA and BUA. Our results suggest that BUA in addition to BEA may have significance to nasal symptoms.

Adenosine triphosphate (ATP) has been shown to revitalize the disturbed nasal mucociliary function in man. We investigated the effects of ATP on the ciliary beat frequency (CBF) in animals by immersing tracheal explants from rats in various concentrations of ATP, and by infusing ATP intravenously to guinea pigs. CBF was measured with a photodetector technique from the surface of the explants or from the incised trachea. ATP (from 0.01 to 1 mg/ml) in vitro increased CBF in rat tracheal explants up to 10.5% (p less than 0.05). In vivo ATP (1 mg/kg) increased the CBF by 29% (p less than 0.01) in the guinea pig trachea. As the CBF was increased by ATP, both in vitro and in vivo, it can be suggested that the improvement in mucociliary transport by exogenous ATP as shown in previous studies is caused by the ciliostimulatory effect of ATP.

Codeine, the basic antitussive drug, has generally been thought to impair mucociliary function. Using the photodetection method the effect of codeine on mucociliary function was studied in rat after local and systemic administration and in guinea pig after systemic administration. In vitro rat tracheal ciliary beat frequency (CBF) was measured up to 40 min. There was 24.6 +/- 2.5% and 26.6 +/- 1.6% decrease in CBF after 1 mg/ml and after 10 mg/ml codeine solutions, respectively. In vivo codeine was administered in single i.v. doses of 10 and 15 mg/kg. No statistically significant differences were found in CBF responses, although there was a CBF decreasing tendency after the 15 mg/kg dose. The total follow-up time was 120 min. In guinea pig, 10 days s.c. codeine administration in daily doses of 3, 10 and 30 mg/kg had no effect on CBF. Although codeine was used in much higher concentrations than tissues concentrations after therapeutic doses of codeine, the effects on CBF were minimal. So it can be concluded that the generally accepted ciliostatic effect of codeine is overestimated.

A 55-year-old woman was operated because of bilateral parotid tumours which appeared with an interval of three years. Histopathologically, both of the tumours had characteristics typical of acinic cell tumour, so-called clear cell type. Both tumours were regarded to be multifocal. In the case of bilateral parotid tumours, acinic cell tumour should also be kept in mind and total parotidectomy is the treatment of choice.

Disodium cromoglycate particles were labelled with 99mTc by spray-drying technique. The in vitro dissolution profile as well as the leakage of radioactivity from the drug particles were determined using a through-flow cell method. The radioactive drug particles were mixed with a lactose carrier and inhaled from a dry powder device by five healthy volunteers. The removal of the inhaled drug particles from the lungs was evaluated by a gamma camera. A close relationship between the dissolution of the drug as such and the leakage of radioactivity was noted. Gamma scintigraphy indicated a biphasic exponential removal of radioactivity from the lung region. The slow component with the halftime of about 55 min was mainly due to the dissolution of drug particles in the lungs. The halftime of the fast component describing mucociliary clearance was less than 10 min. This process was the dominating one for the removal of the drug from the lungs. The experiment thus showed that the main fraction of the inhaled dose was deposited in the tracheobronchial region. Accordingly, only a small portion of the dose initially deposited in the lung can be absorbed and induce a therapeutic effect.

The effect of adenosine triphosphate (ATP) on the airway ciliary beating frequency (CBF) of mucosal explants excised from human maxillary sinuses was studied by measuring CBF photoelectrically before and after immersion of the explants in a solution containing ATP. In samples from 64 patients with chronic sinusitis the CBF was not significantly different from the CBF in mucosal specimens from healthy tissue of 22 patients without infection. During 15 min immersion, ATP (1 mg/ml) slightly (by 5%, p less than 0.05 in healthy tissue; by 2.7%, p less than 0.01, in tissue from sinusitis patients) increased the CBF. The effect of 10 mg/ml concentration was more pronounced (19.6%). It is concluded that the impairment in ciliary function caused by chronic sinusitis is reversible when the mucosal endothelium is cleansed of the infected mucus, and that the ciliostimulatory action of ATP seen in animals is also present in human respiratory mucosa.

The deposition patterns of 99mtechnetium labelled disodium cromoglycate particles administered either from a metered dose aerosol with a conventional nasal adaptor or from a dry powder nasal inhaler were studied using gamma camera. Disodium cromoglycate particles were firstly labelled with 99mTc using the spray drying technique. Both the metered dose aerosol and the dry powder dosage form were formulated using these radioactive drug particles. Seven healthy volunteers inhaled either three aerosol doses or one dry powder dose unit into one nostril. The drug dose reaching nasal cavity after administration from these two dosage forms was about the same. The deposition patterns as well as the changes in distribution due to the mucociliary transport were monitored by a gamma camera equipped with a low energy all purpose collimator. Initially drug doses deposited in a wider area of the nasal cavity when disodium cromoglycate particles were administered as a dry powder dosage form. In addition, retention index (%) which illustrates the movements of drug particles by mucociliary transport from the initial area of application seemed to be slightly higher for a metered dose aerosol than for a dry powder dosage form. At the end of the 30 minutes measuring period the area of the mucosal layer covered by radioactive drug particles was clearly wider for the dry powder dosage form than for the metered dose aerosol. Thus it is well possible to administer drug particles effectively into the nasal cavity as a dry powder dosage form.

A modified cascade impaction method as well as a radiotracer technique has been used to assess the effects of the 700 ml collapsible holding chamber (InspirEase) on the in vitro and in vivo deposition of inhaled metered dose aerosols. The in vitro deposition of beclomethasone dipropionate 250 micrograms/dose aerosol administered either through the conventional aerosol actuator with the short plastic mouthpiece or through the InspirEase-device was evaluated with the modified cascade impactor which method imitated the human respiratory tract. For the in vivo study the disodium cromoglycate particles were labelled with pure gamma-radiator 99mTc using a coprecipitation technique based on spray drying. The deposition of the inhaled disodium cromoglycate particles in the human respiratory tract after administration of the drug doses from the devices tested was determined by means of gamma camera. InspirEase increased both in the in vitro and in vivo tests the fraction of the drug dose deposited into the therapeutically significant regions of the respiratory tract. In addition, the therapeutically insignificant fraction deposited in the upper passages and mouth clearly decreased. Thus using the InspirEase holding chamber not only a better lung penetration of the inhaled drug particles can be achieved but also the local side effects would be decreased.

The effect of the new spacer-device on the in vitro and in vivo deposition of inhaled drug particles was studied. The in vitro deposition of beclomethasone dipropionate 250 micrograms/dose aerosol administered either through the conventional aerosol actuator with the short plastic mouthpiece or through the new pear-shaped spacer-device was evaluated with the modified cascade impactor method. For the in vivo study the disodium cromoglycate particles were labelled with a pure gamma-radiator 99mTc using a coprecipitation technique based on spray drying. The deposition of the inhaled disodium cromoglycate particles in the human respiratory tract after administration of the drug doses from the devices tested was determined by means of a gamma camera. The new spacer-device increased both in the in vitro and in vivo tests the fraction of the drug dose deposited into the therapeutically significant regions of the respiratory tract. In addition, the therapeutically insignificant fraction deposited in the upper airways and mouth clearly decreased. Thus using the new spacer-device evaluated in this study the local side effects would be decreased.

Deposition of 99mTc-labelled particles of disodium cromoglycate in the respiratory tract was evaluated after inhalation from two dry powder inhalers. The inhalers tested were a new multiple dose powder device (Chiesi Farmaceutici) and the Rotahaler powder device (Glaxo). Fractional deposition in the whole lung area, the upper respiratory passages and the stomach, as well as in the inhaler, was measured using a gamma camera. Ten healthy volunteers participated in the inhalation test. The mean, whole lung deposition of the inhaled disodium cromoglycate particles was about 9 per cent of the dose for the both devices. The deposition patterns of the inhaled drug doses in the lung area given by the devices were, however, clearly different. The Chiesi powder inhaler was more efficient in dispersing the drug particles into the therapeutically important alveolar regions of the lungs. The fraction of the dose retained in the inhaler was significantly higher for the Rotahaler than for the Chiesi powder device. On the other hand, the deposition in the upper passages was somewhat larger for the Chiesi device than for the Rotahaler. According to the deposition results of this study, a new multiple dose powder inhaler can be useful in inhalation therapy.

Results of diagnostic procedures are presented on 259 successive patients with bronchial cancer at Päivärinne Chest Hospital during the period 1967-73. The most common tumours were epidermoid (56%), 'small cell' (20.5%) and adenocarcinoma (9.5%). In 106 patients (41%) chest radiography suggested a tumour, though bronchoscopy was normal, and in 22 cases (8.5%) the radiograph was normal but bronchoscopy revealed a tumour. In 10 (4%) both the radiological and the bronchoscopic findings were normal. A definite histopathological diagnosis was reached by bronchoscopy in 144 patients (44%), by mediastinoscopy in 14 (5%), by fine needle biopsy in 28 (11%) and operatively in 103 (40%). Using all methods of treatment prognosis was significantly better in the group that had been diagnosed by mass miniature radiography, or accidentally (29% alive) as compared with those who had symptoms of the disease (6%).

Disodium cromoglycate particles were labelled with pure γ-radiator, 99m Tc, using the co-precipitation technique based on spray drying. Radioactive drug particles were mixed with lactose carrier and filled into hard gelatin capsules. Seven healthy volunteers inhaled drug doses using Spinhaler I.S.F., Berotec, and Rotahaler dry powder devices. The fractional deposition of drug particles in the upper airways and lung region were monitored using a gamma camera. The fraction of the dose retained in the powder inhaler was the smallest for I.S.F. and especially for Berotec inhalers. These devices have narrower air channel constructions with a smaller wall surface area than the Spinhaler and Rotahaler devices. Thus the sticking of the drug particles onto the plastic walls was less probable for the first-mentioned devices. The drug particles from all the dry powder inhalers seemed to be more able to follow the inspired air stream without depositing in the upper airways than previously documented for pressurized metered dose aerosols. I.S.F. and Berotec inhalers with narrow air channels gave the greatest lung deposition of the inhaled drug particles. Thus the design of the dry powder inhaler was noticed to have a remarkable effect both on the emptying of the capsules as well as on the redispersion of the powder mixture.

Disodium cromoglycate particles were labelled with a pure ζ-radiator 99mTc using a novel co-precipitation technique based on spray drying. Metered dose aerosols as well as a dry powder dosage form were prepared using these labelled drug particles. Fractional deposition of the drug particles was determined in vivo by means of gamma camera. Inhalation patterns of seven healthy volunteers were compared to deposition patterns evaluated in vitro using a modified cascade impactor. On average only 9 per cent of the aerosol dose deposited in a whole lung area and about 81 per cent in the upper airways of the volunteers. The in vitro results showed clearly greater deposition of the drug particles into the imitated bronchial and alveolar stages. The physiological factors of the human respiratory tract as well as the individual differences in the inhalation techniques seemed to have a significant influence to the deposition and aerodynamic behaviour of the inhaled drug particles. The in vitro results indicat...

214 patients with chronic bronchitis were subjected to bronchial studied at Paivarinne Chest Hospital during the period 1967-1973. Bronchoscopy alone gave a frequency of 30% for bronchiectases while the information from bronchography increased this figure to 44%. In addition, 24% of the patients showed bronchographic changes in the form of naked filling or mucus obstrcution. Sputum specimens were less reliable indicators of infection than bronichial aspirates in patients with chronic bronchitis. Tracheobroncho-malacia was found in 50 patients and greatly increased the gravity of the disease.