Search PubMed⌕ Search

Biomedical subjects

M Juhola

Publications and source records attributed to M Juhola.

At least 19 recordsLinked to original sources

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.

Adolescent↗

Gene expression signatures for colorectal cancer microsatellite status and HNPCC.

The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours (10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.

Adenocarcinoma↗

Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma.

BACKGROUND AND AIMS: Preoperative radiotherapy (PRT) for rectal carcinoma has been shown to cause tumour regression and increase local control and patient survival. The aim of this study was to examine the usefulness of tumour regression grading (TRG) in quantifying the effect of PRT. METHODS: Depending on the tumour stage (uT), as defined by preoperative endorectal ultrasound (ERUS), fixity and distance from the anal verge, 126 patients with rectal cancer underwent either surgery alone, or received short-course 25-Gy radiotherapy or long-course 50-Gy radiotherapy combined with 5-fluorouracil (5-FU) before surgery. TRG in each group was assessed and compared with the downstaging, defined as a change in preoperative uT stage and pathologic stage (pT). RESULTS: Complete response (no residual tumour, TRG 1) was seen in 7% of the patients (3/44) and total or major regression (TRG 1-3) in 73% of the patients (32/44) treated with 50-Gy chemoradiation. Of those treated with 25-Gy PRT, 21% (9/42) showed major tumour regression. Of the patients who underwent ERUS and PRT, 32% (26/83) were downstaged when comparing uT with pT, but 53% (14/26) of the downstaged tumours showed no response by TRG. In comparison, 50% (28/57) of the tumours with no downstaging showed a marked response by TRG (p=0.05). CONCLUSIONS: Tumour regression grading offers detailed information of the effect of PRT and shows that tumour regression is more marked after long-term chemoradiation than after short-course radiotherapy (p=0.02). In contrast, T-stage downstaging was similar in both groups and did not correlate with the TRG results (p=0.05).

Adenocarcinoma↗

Is it possible to reduce endoscopy workload using age, alarm symptoms and H. pylori as predictors of peptic ulcer and oesophagogastric cancers?

OBJECTIVES: We examined referrals to oesophagogastroduodenoscopy and the impact of demographic and clinical variables to predict major findings (peptic ulcer, cancer) on oesophagogastroduodenoscopy. METHODS: We collected data on 3669 consecutive patients referred for oesophagogastroduodenoscopy. RESULTS: Dyspeptic and reflux symptoms constituted 80% of oesophagogastroduodenoscopy referrals. A major finding was observed in 419 patients (11.4%). The mean age of cancer patients was 72.7 years (95% confidence interval (CI) 70.0-76.5 years) and that of peptic ulcer patients 62.0 years (95% CI 60.5-63.5 years). Independent risk factors for a major finding were age >50 years (odds ratio (OR) 1.62, 95% CI 1.24-2.10), male sex (OR 1.38, 95% CI 1.11-1.72), ulcer-type pain (OR 2.33, 95% CI 1.80-3.02), weight loss (OR 1.70, 95% CI 1.14-2.53), anaemia (OR 1.82, 95% CI 1.38-2.40), bleeding symptoms (OR 3.27, 95% CI 2.26-4.75) and Helicobacter pylori (OR 2.49, 95% CI 2.00-3.11), whereas reflux symptoms were protective (OR 0.73, 95% CI 0.53-1.00). The area under receiver operating characteristic curve of age over 50 years with alarm symptoms to predict major finding was 0.68 (95% CI 0.65-0.71), which positive H. pylori status increased to 0.71 (95% CI 0.69-0.74). Of the major findings, 87.2% were detected in patients with risk factors. Major findings were detected in 15.1% patients with and 8.1% (p < 0.001) without alarm symptoms. CONCLUSIONS: Dyspeptic and reflux symptoms constitute the majority of oesophagogastroduodenoscopy workload. Discriminative power of alarm symptoms even with positive H. pylori status to detect peptic ulcer or cancer was low. Because of their low cancer risk, reflux and dyspeptic patients younger than 50 years can be treated without oesophagogastroduodenoscopy.

Age Factors↗

Gastric metaplasia and chronic inflammation at the duodenal bulb mucosa.

BACKGROUND: Chronic inflammation and gastric metaplasia are often observed in biopsy specimens from the duodenal bulb of Heliobacter pylori positive patients with duodenal ulcer disease (DU). AIMS: We set out to investigate the prevalence of these lesions and their associations with other gastric and duodenal histopathological lesions. PATIENTS: A total of 1255 consecutive patients who underwent upper gastrointestinal endoscopy were recruited into the present study. METHODS: Two biopsy specimens were obtained from each of the following sites: duodenal bulb, gastric antrum, gastric body, and distal to the superior duodenal angle. These specimens were stained with hematoxylin-eosin, alcian blue periodic acid Schiff (pH 2.5) and modified Giemsa (Heliobacter pylori infection was determined only by histology). RESULTS: The mean age of the study population was 57 years, and male:female ratio 1:1.6. Overall, 235 (19%) had gastric metaplasia and/or chronic inflammation in the duodenal bulb mucosa, and H. pylori organisms could be found in 17 (1%). In univariate analyses, gastric metaplasia and/or chronic duodenal bulb inflammation positively associated with male sex (p = 0.046), Heliobacter pylori-positive chronic gastritis (p = 0.033), villous atrophy of distal duodenal mucosa, i.e., coeliac disease (p < 0.001), duodenal ulcer (p < 0.001), and duodenal bulb deformity and scarring in endoscopy (p < 0.001), but not with age (p = 0.7) nor use of nonsteroidal anti-inflammatory drugs (p = 0.055). Multivariate analysis revealed that independent risk factors for gastric metaplasia and chronic inflammation in duodenal bulb were duodenal Heliobacter pylori infection (odds ratio 1.6, 95% confidence interval CI 1.1-2.1), and villous atrophy of the distal duodenal mucosa (odds ratio 12.7, 95% CI 4.4-36.5), while chronic atrophic gastritis was protective against them (odds ratio 0.5, 95% CI 0.3-0.8). CONCLUSIONS: In addition to Heliobacter pylori infection, duodenal bulb gastric metaplasia and chronic inflammation may result from predisposition to toxic dietary components in gluten-sensitive subjects.

Chronic Disease↗

Impact of clinical symptoms and referral volume on endoscopy for detecting peptic ulcer and gastric neoplasms.

BACKGROUND: We investigated the volume of dyspeptic patients referred by general practitioners (GPs) to upper gastrointestinal endoscopy and the impact on endoscopic findings. We also examined the correlation between clinical symptoms and endoscopic findings. METHODS: We collected data on patients sent for upper gastrointestinal endoscopy by GPs of 30 healthcare centres in 1996 in our hospital referral area of 260,000 inhabitants. In addition, national and local cancer registries were used to enumerate the gastric cancer cases detected in 1996. RESULTS: The study population consisted of 3378 patients, mean age 58 years (interquartile range 25 years, male:female 1:1.3). Among the 30 healthcare centres, referral volumes for upper gastrointestinal endoscopy varied from 0.6 to 9.2 per 1000 inhabitants per year (median 3.3/1000/year). In healthcare units with 'high' (> or = 3.3/1000/year, 15 healthcare units, 1297 patients) and 'low' (<3.3/1000/year, 15 healthcare units, 2065 patients) referral volumes, the detection rates were as follows: duodenal ulcer (DU) 3.5% (n = 46) versus 4.0% (n = 83, P = 0.5), gastric ulcer (GU) 4.9% (n = 64) versus 5.3% (n = 110, P = 0.6), gastropathy 43.8% (n = 568) versus 35.6% (n = 736, P < 0.001), gastric cancer 0.5% (n = 6) versus 0.5% (n = 11, P = 0.8), gastric polyps 2.4% (n = 31) versus 1.5% (n = 30, P < 0.05). Independent risk factors for gastric cancer were age (OR 6.5 per decade, 95% CI 2.4-17.9), male sex (OR 5.5, 95% CI 1.8-17.1) and alarming symptoms and/or signs (OR 3.6, 95% CI 1.2-10.7); for GU, Helicobacter pylori (OR 2.6, 95% CI 1.9-3.5) and alarming symptoms (OR 2.0, 95% CI 1.4-2.7); for DU, male sex (OR 1.6, 95% CI 1.1-2.2) and H. pylori (OR 3.9, 95% CI 2.7-5.5); and for gastric polyp(s), age (OR 2.0 per decade, 95% CI 1.1-3.5) and high referral volume (OR 1.7, 95% CI 1.0-2.0). A high referral volume did not associate positively either with the number of peptic ulcers or gastric cancer. CONCLUSIONS: Alarm symptoms associate strongly with significant gastric lesions such as GU and cancer. Increased referral volume results in an increased number of gastropathy and gastric polyp(s), but not of peptic ulcer or cancer.

Dyspepsia↗

Immunohistochemical study of neuroendocrine cells at the gastric cardia mucosa.

BACKGROUND/AIMS: The gastric cardia mucosa is a narrow band of tissue between the oesophagus and the stomach. The physiological role of this tissue is unknown. This study examined the presence and characteristics of neuroendocrine cells at this site. METHODS: Biopsy samples were obtained from across normal appearing squamocolumnar junctions. The cardiac mucosa was defined as the presence of special type mucosa composed of mucous secreting glands in the immediate vicinity of oesophageal squamous epithelium. Biopsy specimens were stained with haematoxylin and eosin, alcian blue (pH 2.5) periodic acid Schiff, and modified Giemsa. The chromogranin A and Fontana-Masson stains were used to identify neuroendocrine cells, which were also stained immunohistochemically for gastrin, serotonin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal peptide. RESULTS: Chromogranin positive cells were seen in 18 cases with adequate biopsy specimens from the gastric cardia mucosa. These cells were all serotonin positive, but stains for other peptide hormones remained negative. Serotonin positive cells were detected only at the base of foveolae at the periphery of mucous secreting cardiac glands, giving a microscopic appearance resembling that of endocrine cells at the gastric antrum. The presence and numbers of serotonin positive cells did not correlate with chronic inflammation or intestinal metaplasia of the cardiac mucosa. These cells were seen both in Helicobacter pylori positive and negative patients. CONCLUSIONS: Serotonin positive cells appear to be the sole neuroendocrine cell type at the gastric cardia mucosa. These cells may have a role in regulating the physiology of the gastric cardia mucosa and the lower oesophageal sphincter.

Adolescent↗

Foveolar hyperplasia at the gastric cardia: prevalence and associations.

AIMS: In the gastric antrum and body, foveolar hyperplasia is a feature of reactive gastritis resulting from--for example, duodenogastric bile reflux and the use of non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to examine the occurrence and clinical relevance of gastric cardiac foveolar hyperplasia. METHODS: The study population was drawn from a consecutive series of 1698 patients sent for upper gastrointestinal endoscopy. Only cases without chronic gastritis or Barrett's oesophagus were included. The final study population consisted of 307 patients. RESULTS: Foveolar hyperplasia was seen in the gastric cardiac mucosa in 31 (10%) patients with histologically normal stomach mucosa, but none had endoscopically noticeable hyperplastic polyps. Compared with patients without gastric cardiac hyperplasia, those with hyperplasia more often had chronic inflammation and complete intestinal metaplasia in the junctional biopsies (48% v 77% and 9% v 26%, respectively). Logistic regression analysis revealed that chronic cardiac inflammation (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3 to 7.8) and intestinal metaplasia of the complete type (OR, 2.8; 95% CI, 1.1 to 7.1) were independent risk factors for cardiac foveolar hyperplasia. In univariate analysis, endoscopic erosive oesophagitis (endoscopy positive gastro-oesophageal reflux disease) and the use of NSAIDs were not related to the presence of foveolar hyperplasia. CONCLUSIONS: Foveolar hyperplasia in the gastric cardiac mucosa occurs in patients with histologically normal non-gastritic stomachs and may develop as a consequence of chronic inflammation limited to the gastro-oesophageal junction ("junctitis"). It is not associated directly with endoscopy positive gastro-oesophageal reflux disease or the use of NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

Analysis of the imputed female urinary incontinence data for the evaluation of expert system parameters.

We evaluated parameters for an expert system which will be designed to aid the differential diagnosis of female urinary incontinence by using knowledge discovered from data. To allow the statistical analysis, we applied means, regression and Expectation-Maximization (EM) imputation methods to fill in missing values. In addition, complete-case analysis was performed. Logistic regression results from the imputed data were reasonable. The significant parameters were mostly those that are important in the diagnostic work-up. Moreover, directions of relations between the parameters and the stress, mixed and sensory urge diagnoses were as expected. Analysis with the complete reduced data set gave clearly insufficient results. Imputed values had a moderate agreement, but odds ratios and classification accuracies of logistic regression equations were similar. Results suggest that with these data, simpler methods may be used to allow multivariate analysis and knowledge discovery, when better methods, such as EM imputation, are unavailable. Cluster analysis detected clusters corresponding to the small normal class, but was unable to clearly separate the larger incontinence classes.

Adult↗

On preprocessing of protein sequences for neural network prediction of polyproline type II secondary structures.

Polyproline type II stretches are somewhat rare on proteins. The backbone of this secondary structural element folds to a triangular form instead of the normal alpha-helix with 3.6 residues per turn. It is a very challenging task to try to detect them computationally from protein sequence. Here, we have studied the preprocessing phase in particular, which is important for any machine learning method. Preprocessing included selection of relevant data from the Protein Data Bank and investigation of learnability properties. These properties show whether the material is suitable for neural network computing. The complexity of algorithms in connection with preprocessing was briefly considered. We found that feedforward perceptron neural networks were appropriate for the prediction of polyproline type II and also relatively efficient in this task. The problem is very difficult because of the great similarity of the two classes present in the classification. Nevertheless, neural networks were able to recognize and predict about 75% of secondary structures.

Algorithms↗

Evaluating training data suitability for decision tree induction.

Decision tree induction, as well as other inductive learning methods, requires training data of high quality to be able to generate accurate and reliable classification models. Example cases should form a representative sample from the application area, and the attributes used to describe example cases should be relevant and adequate for the classification task to be solved. In this paper, measures of the strength of association and an entropy-based approach have been used to assess the quality of the training data. Studied classification tasks related to three otological data sets: a conscript data set, a vertigo data set, and a postoperative nausea and vomiting data set. The paper suggests that the studied approaches give some guidelines about the quality of the training data, but other approaches are also needed to guide training data building.

Adolescent↗

Classification of patients on the basis of otoneurological data by using Kohonen networks.

Machine learning methods such as neural networks, decision trees and genetic algorithms can be useful to aid in the classification of patients. We tested Kohonen artificial neural networks, which are known to be effective for classification tasks. Our sample included patients with six different diseases. The Kohonen network algorithm recognized the four largest groups reliably, but the two smallest groups were too small for the method. Neural networks seem to be promising for the computer-aided classification of otoneurological patients provided that the number of patients used is sufficiently large.

Algorithms↗

Impact of non-steroidal anti-inflammatory drug and aspirin use on the prevalence of dyspepsia and uncomplicated peptic ulcer disease.

BACKGROUND: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. METHODS: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. RESULTS: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). CONCLUSIONS: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.

Aged↗

Experiences of otoneurological expert system for vertigo.

We have developed an OtoNeurological Expert system (ONE) to aid the diagnostics of vertigo, to assist teaching and to implement the database for research. The database contains detailed information on the patient history, signs and test results necessary for the diagnostic work with vertiginous patients. The pattern recognition method was used in the reasoning process. Questions regarding symptoms, signs and test results are weighted and scored for each disease, and the most likely disease is recognized from the defined disease profiles. Uncertainties in reasoning, caused by missing information, were solved with a method resembling fuzzy logic. We have also applied adaptive computer applications, such as genetic algorithms and decision trees, in the reasoning process. In the validation the expert system ONE proved to be a sound decision maker, by solving 65% of the cases correctly, while the physicians' mean was 69%. To improve the expert system ONE further, a follow-up should be implemented for the patients, to ease the diagnostic work of some difficult diseases. The six diseases were detected with high accuracy also with adaptive learning methods and discriminant analysis. An expert system is a practical tool in otoneurology. We aim to construct a hybrid program for the reasoning, where the best reasoning method for each disease is used.

Decision Making↗

Application of artificial intelligence in audiology.

In this paper, machine learning methods based on artificial intelligence theory are applied to the computer-aided decision making of some otoneurological diseases, for example Ménière's disease. Three methods explored are decision trees, genetic algorithms and neural networks. By using such a machine learning method, the decision-making program is trained with a representative training set of cases and tested with another set. The machine learning methods are useful also for our otoneurological expert system, One, which is based on a pattern recognition approach. The methods are able to differentiate most of the cases tested between the six diseases included, provided that a sufficiently large training set is available.

Algorithms↗

A novel machine learning program applied to discover otological diagnoses.

A novel machine learning system, Galactica, has been developed for knowledge discovery from databases. This system was applied to discover diagnostic rules from a patient database containing 564 cases with vestibular schwannoma, bening paroxysmal positional vertigo, Ménière's disease, sudden deafness, traumatic vertigo and vestibular neuritis diagnoses. The rules were evaluated using an independent testing set. The accuracy of rules for these diagnoses were 91%, 96%, 81%, 95%, 92% and 98%, respectively. Besides being accurate, the rules contained the five most important diagnostic questions identified in the earlier research. The knowledge presented with rules can be easily comprehended and verified.

Ear Diseases↗

Using decision tree induction to model oculomotor data.

Decision tree induction is a machine learning method used to generate classification models from data sets. Numerous decision trees were constructed to examine relationships between oculomotor test parameters and lesion sites in a data set containing cases with operated cerebello-pontine angle tumour, operated hemangioblastoma, infarction of cerebello-brainstem and Ménière's disease, and control subjects. The aim was to find useful parameter combinations with discriminatory power. Decision trees constructed using both pursuit eye movements and saccadic eye movements yielded the best classification results. This is reasonable: oculomotor test results vary according to the site of the lesion and so the performance ability of subjects has to be taken into account in the classification. The decision tree program was able to generate classification models from the oculomotor data set. Generated decision trees were intelligible and can be utilized in physicians' research work.

Decision Making↗