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Biomedical subjects

J Nuutinen

Publications and source records attributed to J Nuutinen.

At least 19 recordsLinked to original sources

Influence of azelastine and some selected drugs on mucociliary clearance.

The effect of azelastine and some selected compounds on ciliary beating frequency (CBF) was investigated in vitro using human mucosal samples and in vivo using anesthetized guinea pigs. Further influence of azelastine on mucus secretion was evaluated in mice and on mucociliary clearance in anesthetized rabbits. Azelastine influenced the ciliary beating frequency neither in vitro nor in vivo. Azelastine, similarly to salbutamol, ambroxol, and bromhexine, increased mucus secretion measured by the tracheal output of phenol red. Azelastine dose-dependently enhanced mucociliary clearance measured by elimination of 99mTc-labeled erythrocytes in rabbits. The activity of azelastine proved to be about 10 times stronger than that of bromhexine. Since the ciliary activity remained unchanged under the influence of azelastine, it is likely that azelastine increases the mucociliary clearance by enhancing bronchial secretion. It is possible that the observed increase in mucociliary clearance may contribute to the beneficial effect of azelastine in the treatment of respiratory diseases.

Animals

Long-term hearing results of one-stage tympanoplasty for chronic otitis media.

A study of 277 ears with chronic otitis media undergoing one-stage tympanoplasty has been carried out. The mean follow-up period was 6.4 years. Ears with intact ossicular chains were excluded. Ossiculoplasty was performed using autologous ossicles or cortical bone. Mean hearing gain was 10.8 dB. Closure of the postoperative air-bone gap to within 20 dB was achieved in 51% of cases. The best results were obtained in ears with intact stapes, while cholesteatomatous ears showed poorer results than other chronic ears. The present findings show that autologous ossicle and cortical bone are still suitable for ossicular reconstruction in chronic ears, especially when one-stage surgery is preferred.

Auditory Threshold

Long-term results of surgery for childhood cholesteatoma.

The study includes 54 cholesteatomatous ears in 50 children aged 16 years or less. The mean follow-up period after surgery was 7.1 years. In 26% of the ears the cholesteatoma was 'huge' involving the middle ear and the attic and filling the entire mastoid air cell system. A patient had lateral sinus thrombophlebitis. Patients with large cholesteatomas underwent canal wall down mastoidectomy with simultaneous tympanoplasty and, in most cases, cavity obliteration. Limited cholesteatomas were removed using either intact canal wall mastoidectomy or tympanotomy approach. Recurrence rate (including both residual and recurrent cholesteatomas) for the total series was 15% and 12% for the 50 cases undergoing one-stage surgery. Serviceable hearing (< or = 30 dB) was achieved in 57% of the ears. A reoperation was necessary in 26% and a third operation in 2%. At last follow-up examination, 94% of the ears had intact tympanic membranes but 4 patients (8%) suffered from cavity-related problems. Possible reasons for the disappointing results of surgical treatment for childhood cholesteatoma are discussed.

Adolescent

Long-term results of revision stapes surgery.

Results of 45 re-operations for persistent or recurrent conductive deafness after primary stapes surgery were studied. The mean follow-up period after the revision surgery was 7.6 years. Long-term hearing results were found to be disappointing, air-bone gap to within 10 dB was achieved in only 46 per cent of the patients. Mean hearing levels improved by 11 dB or more in 73 per cent. Outcome of surgery was dependent on the surgical pathology, the best hearing results were obtained in cases with re-fixation after stapes mobilization operation. Sensorineural hearing loss as a result of surgical trauma to the inner ear occurred in revision surgery more frequently than in primary operations, cases with regrowth of otosclerotic bone to the oval window after stapedectomy having the greatest risk of labyrinthine trauma.

Adult

Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium.

Changes in the ultrastructure of human respiratory cilia caused by the common cold were studied in 12 patients. The nasal mucosa was studied three times: on the first or second day after the beginning of symptoms, and 1 week and 3 weeks after the first biopsy. The damage was most severe at 1 week. The most remarkable finding was the loss of cilia and ciliated cells. However, the ultrastructure was usually normal, without any increase in tubular anomalies, as compared with the normal material of the previous reports. Three weeks after the beginning of the disease the number of cilia and ciliated cells had increased to nearly normal. However, as a sign of regeneration, immature short cilia (0.7 to 2.5 microns in length) were often seen. The ciliary orientation was uniform, dynein arms were normal, and there was no increase in the number of tubular anomalies. The results suggest that the impaired mucociliary function during viral infections is due to the loss of cilia and ciliated cells, rather than to ultrastructural anomalies in the cilia. The development of tubular anomalies and random ciliary orientation may require more extensive exposure to factors affecting ciliary function.

Biopsy

Nasal sensitization of dairy farmers to bovine epithelial and urinary antigens.

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.

Adult

Head and neck manifestations of Wegener's granulomatosis.

Sixteen of 17 patients with Wegener's granulomatosis were found to have head and neck involvement. Rhinitis and/or nasal obstruction were the most common presenting symptoms. On initial clinical examination, paranasal sinus involvement was observed in 11 patients, ear involvement in 7 and subglottic stenosis in 2 patients. One patient presented with a large and rapidly widening ulcer on the lateral pharyngeal wall. Diagnosis was often difficult and severe delay in diagnosis occurred in 7 patients. In recent years tests for ANCA appeared to be extremely useful.

Adolescent

ATP induces respiratory ciliostimulation in rat and guinea pig in vitro and in vivo.

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.

Adenosine Triphosphate

Short nasal respiratory cilia and impaired mucociliary function.

A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities.

Cilia

Perilymph fistula--a diagnostic dilemma.

A retrospective series is presented of 51 cases operated on for suspected perilymph fistula. In 26 ears a fistula was identified at surgery. A positive fistula test was found to strongly indicate a perilymph fistula but was more often negative than positive in surgically demonstrated fistula ears. Other vestibular tests were found to be of little value in the pre-operative diagnosis. Ears with a surgically demonstrated fistula and sensorineural hearing loss had either flat or downward-sloping audiograms. Difficulties in diagnosing a perilymph fistula at tympanotomy are discussed. At follow-up, vestibular symptoms were found to be eliminated or improved in 96 per cent of cases with surgically demonstrated fistulae and in 68 per cent of cases in which no fistula was detected at tympanotomy but hearing improved significantly in only one ear (4 per cent) of the former group and in five ears (20 per cent) of the latter group.

Adolescent

View from beneath: pathology in focus bilateral acinic cell tumours of the parotid gland.

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.

Female

Occupational exposure of forest workers to glyphosate during brush saw spraying work.

The purpose of this study was to measure forest workers' exposure to the herbicide glyphosate during silvicultural clearing work done with brush saws equipped with pressurized herbicide sprayers. Both the exposed (study) group and the nonexposed (control) group contained five persons who were medically examined before and after their 1-week working period (including laboratory tests) for possible health effects. In addition, exposure to glyphosate was measured in the study group from samples taken from the workers' breathing zone and from urine samples collected during the afternoons of the workweek. The laboratory tests and urinary glyphosate analyses were repeated for the exposed group 3 weeks later, when the men had entirely stopped their work with the herbicide. Exposure to glyphosate through the workers' breathing zone was low. The highest value found was 15.7 micrograms/m3. In this study, a biological monitoring method was also developed to monitor the workers' exposure to glyphosate. Urine concentrations were under the gas chromatographic detection level of less than 0.1 ng/microL (less than 1.0 mumol/L). No major differences were noted, either in medical examinations or in the laboratory tests performed, between the exposed and control groups before and after the work period.

Adult

Removal of inhaled 99mTc-labelled particles of disodium cromoglycate from the lungs.

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.

Aerosols

Effect of codeine on rat and guinea pig tracheal ciliary beat frequency.

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.

Animals

Effects of inspirease holding chamber on the deposition of metered dose inhalation aerosols.

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.

Administration, Inhalation

Nasal distribution of radioactive drug administered using two dosage forms.

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.

Administration, Inhalation

The effect of ATP on the ciliary activity of normal and pathological human respiratory mucosa in vitro.

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.

Adenosine Triphosphate