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Biomedical subjects

P Koivunen

Publications and source records attributed to P Koivunen.

At least 19 recordsLinked to original sources
PubMed2007

Nasopharyngeal dimensions in magnetic resonance imaging and the risk of acute otitis media.

BACKGROUND: We have previously found by lateral cephalometry an association between nasopharyngeal anatomy and the risk of acute otitis media (AOM). We evaluate here the association of nasopharyngeal dimensions in magnetic resonance imaging (MRI) with the occurrence of AOM in otherwise healthy children. METHODS: Sixty-one healthy children (mean age 5.7 years, range 3.9-6.9) were recruited from child care centres. The parents filled in a questionnaire on the child's history of ear infections and adenoidectomy. MRI was performed with a 4 mm slice thickness during an upper respiratory infection. Five dimensions and two angles expressing the structure of the bony nasopharynx were measured in sagittal images. RESULTS: The dimension from the caudal edge of the septum to the midpoint of the sella, reflecting the height of the nasopharynx, was on average 2.2 mm smaller in the children who had had AOM attacks during the last 12 months than those without attacks (95% confidence interval (CI) 0.9 to 3.4, p=0.001) and the nasal base angle was on average 2.1 degrees smaller (95% CI 0.7 to 3.5, p=0.004). These differences remained significant after adjustment for age, sex and previous adenoidectomy in the logistic modelling. A history of adenoidectomy did not have any effect on the dimensions. CONCLUSIONS: The nasopharynx was smaller in the children with AOM attacks during the last year. The value of this finding for predicting susceptibility to recurrent AOM and directing preventive procedures should be evaluated.

Acute Disease↗
PubMed2005

Impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal carcinoma.

OBJECTIVES: To evaluate the impact of patient and professional diagnostic delays on the risk of recurrence in laryngeal squamocellular carcinoma (LSCC). DESIGN: Retrospective study using primary health care records completed before the diagnosis of malignancy. SETTING: One primary health care district (onset of symptoms), one tertiary centre (final diagnosis). PARTICIPANTS: A population-based sample of 99 patients, of which 66 fulfilled the entry criteria, with LSCC diagnosed in northern Finland in 1990-1995. MAIN OUTCOME MEASURES: Impact of patient delay (interval between the onset of symptoms and the first visit to a physician) and professional delay (interval between the first medical visit and histologically verified diagnosis) on the risk of local, neck and distant recurrence in LSCC. RESULTS: Professional delay of 1 year or longer was an independent predictor of both local [adjusted relative hazard (HR) 4.62, P = 0.02] and neck (HR 9.5, P = 0.015) recurrence. Longer professional delay was associated with the risk of recurrence particularly among patients with early stage (stages I-II) disease. Professional delay was almost exclusively because of a delay in referring patients from primary care to an ENT centre. CONCLUSIONS: Lengthened professional diagnostic delay is an independent predictor of an increased risk of local and neck recurrence in early stage LSCC. These patients could benefit from more aggressive primary treatment or more meticulous follow-up.

Adult↗
PubMed2003

Cross-sectional survey of paranasal sinus magnetic resonance imaging findings in schoolchildren.

AIM: Sinus image abnormalities are common among children examined for indications other than sinus disease. The purpose of this study was to determine the frequency of sinus abnormalities among otherwise healthy children attending school. METHODS: Magnetic resonance imaging (MRI) was performed on 24 children aged 8-9 y, 18 of whom were re-examined after 6-7 mo. RESULTS: Sinus abnormalities were common. An abnormality was seen in 12 of the children [50%, 95% confidence interval (95% CI) 29-71%], and 9 (38%, 95% CI 19-59%) had abnormalities in the maxillary sinuses. As many as 8 (42%, 95% CI 20-67%) of the asymptomatic children (lacking clinical symptoms or findings) had abnormalities in the maxillary or ethmoidal sinuses. The follow-up examination showed that about half of the abnormal sinus MRI findings had resolved or improved without any intervention. CONCLUSION: Abnormal sinus MRI findings are common both among otherwise healthy children attending school and in totally asymptomatic children. As incidental findings, these should be interpreted as normal and do not indicate any need for treatment in children imaged for purposes other than sinus disease.

Adolescent↗
PubMed2001

The impact of patient and professional diagnostic delays on survival in pharyngeal cancer.

BACKGROUND: Cancers of the head and neck still are detected mostly at an advanced stage, especially pharyngeal cancers. METHODS: To study the impact of patient and professional delay on survival, the authors collected the data from 84 patients with pharyngeal cancer. In addition to clinical data from the tertiary care center, the authors evaluated the data from the first medical visit in primary care before the diagnosis of malignancy had been made. RESULTS: The patients who had a patient delay of 2 months or more had a significantly higher relative hazard of death (HR; HR, 2.5; 95% confidence interval (CI), 1.39-4.38) compared with the patients with less than 2 months of patient delay. This risk was significant among the patients with oropharyngeal (P = 0.008) and nasopharyngeal cancer (P = 0.03), but not in those with hypopharyngeal cancer (P = 0.56). In contrast, there was no relation between professional diagnostic delay and prognosis. Advanced stage (International Union Against Cancer [UICC] TNM; Stage IV vs. Stage I-III; HR, 3.19; CI, 1.61-6.35) and age (> or = 65 vs. < 65 years; HR, 2.47; CI, 1.32-4.62) also were associated with an impaired prognosis. CONCLUSIONS: Shortening of patient delay would substantially improve survival in pharyngeal cancer, but this goal seems difficult to attain because symptoms emerge late in pharyngeal cancer, and no specific symptoms or patient characteristics were related to a long patient delay. Professional delay does not have an impact on survival in pharyngeal cancer.

Adult↗
PubMed2001

Decreasing incidence and improved survival of laryngeal cancer in Finland.

The decreasing incidence rate and improvement in survival of laryngeal cancer patients in Finland are exceptions among western countries. A descriptive study of these trends was conducted including both nationwide population-based cancer registry data with 5 766 patients diagnosed in 1956-1995 and regional hospital-based data from Northern Finland, allowing classification into supraglottic and glottic cancers, with 353 patients diagnosed in 1976-1995. In Finland, the age-adjusted incidence rate among males decreased from 6.5 per 100 000 in 1956-1965 to 3.5 in 1986-1995, while in females the rate remained around 0.3 per 100 000. The rates in Northern Finland were slightly higher and the supraglottic to glottic incidence ratio diminished from 1.4:1 in 1976-1985 to 0.5:1 in 1986-1995. The 5-year relative survival rate improved in both Northern Finland and the whole country, most noticeably among males and the elderly. In the data from Northern Finland, the survival rate was more favourable in glottic (80%) than in supraglottic cancer (64%). Considering the marked decrease in the incidence of the less favourable supraglottic disease, the observed improvement in survival was small.

Adolescent↗
PubMed2001

Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual serous von Ebner's glands.

Salivary carbonic anhydrase VI (CA VI) appears to contribute to taste function by protecting taste receptor cells (TRCs) from apoptosis. The serous von Ebner's glands locating in the posterior tongue deliver their saliva into the bottom of the trenches surrounding the TRC-rich circumvallate and foliate papillae. Because these glands deliver their saliva directly into the immediate vicinity of TRCs, we investigated whether CA VI is secreted by the von Ebner's glands, using immunochemical techniques. The immunohistochemical results showed that CA VI is present in the serous acinar cells, ductal cells, and ductal content of von Ebner's glands and in the demilune and ductal cells plus ductal content of rat lingual mucous glands. More importantly, CA VI was also detected in taste buds and in the taste pores. Western blotting of saliva collected from the orifices of human von Ebner's glands and CAs purified from rat von Ebner's glands confirmed that CA VI is expressed in these glands and secreted to the bottom of the trenches surrounding the circumvallate and foliate papillae. These findings are consistent with the hypothesis that locally secreted CA VI is implicated in the paracrine modulation of taste function and TRC apoptosis. (J Histochem Cytochem 49:657-662, 2001)

Animals↗
PubMed2000

Domains b' and a' of protein disulfide isomerase fulfill the minimum requirement for function as a subunit of prolyl 4-hydroxylase. The N-terminal domains a and b enhances this function and can be substituted in part by those of ERp57.

Protein disulfide isomerase (PDI) is a modular polypeptide consisting of four domains, a, b, b', and a', plus an acidic C-terminal extension, c. PDI carries out multiple functions, acting as the beta subunit in the animal prolyl 4-hydroxylases and in the microsomal triglyceride transfer protein and independently acting as a protein folding catalyst. We report here that the minimum sequence requirement for the assembly of an active prolyl 4-hydroxylase alpha(2)beta(2) tetramer in insect cell coexpression experiments is fulfilled by the PDI domain construct b'a' but that the sequential addition of the b and a domains greatly increases the level of enzyme activity obtained. In the assembly of active prolyl 4-hydroxylase tetramers, the a and b domains of PDI, but not b' and a', can in part be substituted by the corresponding domains of ERp57, a PDI isoform that functions naturally in association with the lectins calnexin and calreticulin. The a' domain of PDI could not be substituted by the PDI a domain, suggesting that both b' and a' domains contain regions critical for prolyl 4-hydroxylase assembly. All PDI domain constructs and PDI/ERp57 hybrids that contain the b' domain can bind the 14-amino acid peptide Delta-somatostatin, as measured by cross-linking; however, binding of the misfolded protein "scrambled" RNase required the addition of domains ab or a' of PDI. The human prolyl 4-hydroxylase alpha subunit has at least two isoforms, alpha(I) and alpha(II), which form with the PDI polypeptide the (alpha(I))(2)beta(2) and (alpha(II))(2)beta(2) tetramers. We report here that all the PDI domain constructs and PDI/ERp57 hybrid polypeptides tested were more effectively associated with the alpha(II) subunit than the alpha(I) subunit.

Animals↗
PubMed2000

Mutations that destabilize the a' domain of human protein-disulfide isomerase indirectly affect peptide binding.

Protein-disulfide isomerase (PDI) is a catalyst of folding of disulfide-bonded proteins and also a multifunctional polypeptide that acts as the beta-subunit in the prolyl 4-hydroxylase alpha(2)beta(2)-tetramer (P4H) and the microsomal triglyceride transfer protein alphabeta-dimer. The principal peptide-binding site of PDI is located in the b' domain, but all domains contribute to the binding of misfolded proteins. Mutations in the C-terminal part of the a' domain have significant effects on the assembly of the P4H tetramer and other functions of PDI. In this study we have addressed the question of whether these mutations in the C-terminal part of the a' domain, which affect P4H assembly, also affect peptide binding to PDI. We observed a strong correlation between P4H assembly competence and peptide binding; mutants of PDI that failed to form a functional P4H tetramer were also inactive in peptide binding. However, there was also a correlation between inactivity in these assays and indicators of conformational disruption, such as protease sensitivity. Peptide binding activity could be restored in inactive, protease-sensitive mutants by selective proteolytic removal of the mutated a' domain. Hence we propose that structural changes in the a' domain indirectly affect peptide binding to the b' domain.

Amino Acid Sequence↗
PubMed2000

Otoacoustic emissions and tympanometry in children with otitis media.

OBJECTIVE: To examine otoacoustic emission and tympanometric findings in children with surgically confirmed middle ear effusion (MEE). DESIGN: A total of 102 children aged 0.7 to 11.4 yr undergoing surgery because of otitis media were included in the study. A tympanometric examination and transient evoked otoacoustic emission (TEOAE) measurement were performed on each ear before myringotomy. MEE was aspirated, weighed and classified as mucoid or nonmucoid. TEOAE measurements were compared with the quantity and quality of MEE and to the tympanometric findings. RESULTS: Fifty (72%) ears out of the 65 ears containing effusion showed reduced TEOAE. The quantity of effusion was associated significantly (p < 0.001) with the TEOAE responses, and mucoid effusion reduced the emissions more than nonmucoid. The sensitivity of tympanometry in identifying the ears without recordable TEOAE was 73% and the specificity 81%. CONCLUSION: MEE results in a significant reduction in TEOAEs even when the effusion is nonmucoid. This suggests that transmission of acoustic energy to and from the middle ear is altered in children experiencing any form of otitis media with effusion.

Acoustic Impedance Tests↗
PubMed1999

Cloning of the alpha subunit of prolyl 4-hydroxylase from Drosophila and expression and characterization of the corresponding enzyme tetramer with some unique properties.

Prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline in collagens. The vertebrate enzymes are alpha2beta2 tetramers, whereas the Caenorhabditis elegans enzyme is an alphabeta dimer, the beta subunit being identical to protein-disulfide isomerase (PDI). We report here that the processed Drosophila melanogaster alpha subunit is 516 amino acid residues in length and shows 34 and 35% sequence identities to the two types of human alpha subunit and 31% identity to the C. elegans alpha subunit. Its coexpression in insect cells with the Drosophila PDI polypeptide produced an active enzyme tetramer, and small amounts of a hybrid tetramer were also obtained upon coexpression with human PDI. Four of the five recently identified critical residues at the catalytic site were conserved, but a histidine that probably helps the binding of 2-oxoglutarate to the Fe2+ and its decarboxylation was replaced by arginine 490. The enzyme had a higher Km for 2-oxoglutarate, a lower reaction velocity, and a higher percentage of uncoupled decarboxylation than the human enzymes. The mutation R490H reduced the percentage of uncoupled decarboxylation, whereas R490S increased the Km for 2-oxoglutarate, reduced the reaction velocity, and increased the percentage of uncoupled decarboxylation. The recently identified peptide-binding domain showed a relatively low identity to those from other species, and the Km of the Drosophila enzyme for (Pro-Pro-Gly)10 was higher than that of any other animal prolyl 4-hydroxylase studied. A 1. 9-kilobase mRNA coding for this alpha subunit was present in Drosophila larvae.

Amino Acid Sequence↗
PubMed1999

The acidic C-terminal domain of protein disulfide isomerase is not critical for the enzyme subunit function or for the chaperone or disulfide isomerase activities of the polypeptide.

Protein disulfide isomerase (PDI) is a multifunctional polypeptide that acts as a subunit in the animal prolyl 4-hydroxylases and the microsomal triglyceride transfer protein, and as a chaperone that binds various peptides and assists their folding. We report here that deletion of PDI sequences corresponding to the entire C-terminal domain c, previously thought to be critical for chaperone activity, had no inhibitory effect on the assembly of recombinant prolyl 4-hydroxylase in insect cells or on the in vitro chaperone activity or disulfide isomerase activity of purified PDI. However, partially overlapping critical regions for all these functions were identified at the C-terminal end of the preceding thioredoxin-like domain a'. Point mutations introduced into this region identified several residues as critical for prolyl 4-hydroxylase assembly. Circular dichroism spectra of three mutants suggested that two of these mutations may have caused only local alterations, whereas one of them may have led to more extensive structural changes. The critical region identified here corresponds to the C-terminal alpha helix of domain a', but this is not the only critical region for any of these functions.

Amino Acid Sequence↗
PubMed1999

Changing trends in the occurrence and subsite distribution of laryngeal cancer in Finland.

Cancer of the larynx represents worldwide approximately 1-2% of all cancers and generally occurs predominantly in males. Based upon many reports, the age-adjusted incidence of laryngeal cancer has been rising in recent years, especially among women. Squamous cell carcinomas arising in the glottic region are the most common of all laryngeal cancers and more prevalent than the supraglottic ones. Subglottic disease is still rare. The Finnish Head and Neck Oncology Group evaluated the present occurrence of laryngeal cancer by site and gender in Finland. The annual age-standardized incidence of laryngeal cancer is 3.2 per 100,000 for men and 0.3 per 100,000 for women. The proportion of females in the five university centers reviewed was 5%. During the 30-year time period from the early 1960s to the 1990s there has been a significant decrease in the laryngeal cancer incidence rates for males, but no change for females. Finland thus seems to be the only Western country with clearly declining occurrence rates in recent decades. In the same time period a clear decrease in the incidence of bronchial cancer has occurred in males and an increase in females. The results also show that in all five university hospital districts glottic cancer became more common (50-68%) in the late 1980s and 1990s, which is opposite to the situation in the 1960s when supraglottic localizations (65%) dominated in Finland.

Adult↗
PubMed1999

Acute epiglottitis in northern Finland today--still a potential emergency situation.

To examine patient characteristics related to airway intervention in acute epiglottitis and how the intervention affected the further course of the disease, 46 pediatric and 49 adult cases were retrospectively evaluated. All three airway management approaches, namely observation, nasotracheal intubation and tracheotomy were needed in both the children and adults. Five out of every six children needed an artificial airway, while observation was sufficient in three out of every five adults. H influenzae type b bacteremia in children, a short duration of the symptoms in adults and most important, respiratory distress in both were the best predictors of the need for an artificial airway. Nasotracheal intubation may be a successful means of implementing an artificial airway, but it is a technically demanding procedure and complications are frequent. Despite the recent changes in the occurrence of acute epiglottitis it remains a potential emergency situation both in children and adults.

Acute Disease↗