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Biomedical subjects

K Irjala

Publications and source records attributed to K Irjala.

At least 19 recordsLinked to original sources

Linking patient medication data with laboratory information system.

Dozens of new drugs are taken into clinical use each year. Even if the clinicians were able to learn the most important therapeutic effects of the drugs they prescribe, they would still be unable to remember all of their minor effects. After storing patient related medication data on computerized patient records it is possible to build decision support modules which automatically remind of possible drug influences on laboratory tests and cause alarms or alerts of drug interactions. Medication profiles coded using the Anatomical Therapeutic Chemical-code (ATC-code) constitutes a valuable part of an Electronic Patient Record (EPR). In this paper, we describe the benefits of our system. By building links to commercially available drug and laboratory databases we can automatically inform clinicians on clinically relevant drug influences on laboratory test results.

Clinical Laboratory Information Systems

Serum free testosterone in polycystic ovary syndrome measured with a new reference method.

OBJECTIVE: To quantify the actual serum free T with a specific new reference method in women with polycystic ovary syndrome (PCOS) and to analyze the effects of serum free T, total T, and the T:sex hormone-binding globulin (SHBG) ratio on the diagnosis of PCOS. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Forty-four oligomenorrheic women with PCOS and 26 weight-matched control women with regular menstrual cycles. MAIN OUTCOME MEASURES: The concentrations of free T, total T, androstenedione (A), LH, FSH, SHBG, and insulin in serum. RESULTS: The mean concentrations of free T, total T, A, and LH as well as the LH:FSH and T:SHBG ratios were higher, whereas the mean concentrations of FSH was lower in the women with PCOS than in healthy women. No differences were found in the free T, total T, or T:SHBG levels or in the body mass indexes (BMIs) between the hirsute (n=26) and nonhirsute (n = 18) women with PCOS. Both elevated free T concentrations and high T:SHBG ratios were associated with obesity, but serum total T was independent of BMI. The serum free T measurement discriminated PCOS women from controls to a similar extent as total T and T:SHBG ratio as judged by a receiver operating characteristics analysis. CONCLUSIONS: The present data indicate that determination of free T provides little additional information in the diagnosis of hirsutism or PCOS and does not have to be included to the basic evaluation of these patients. Only half of women with PCOS exhibited elevated serum free T concentrations.

Adolescent

Optimal use of hormone determinations in the biochemical diagnosis of the polycystic ovary syndrome.

OBJECTIVE: To investigate, using logistic regression analysis and receiver operator characteristic analysis, the biochemical diagnosis of polycystic ovary syndrome (PCOS) and if it could be improved by using an array of hormone measurements chosen to yield optimal and cost-effective discrimination between women with PCOS and healthy women. DESIGN: Retrospective clinical study. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Fifty-four oligomenorrheic women with PCOS diagnosed by ovarian ultrasonography, and 29 healthy regularly menstruating women with normal ovarian morphology. MAIN OUTCOME MEASURES: Concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin in serum. RESULTS: Luteinizing hormone, FSH and A, when used in combination, were the hormonal analytes of highest clinical utility. Diagnostic sensitivity, specificity, and overall concordance of 98%, 93%, and 96%, respectively, were attained. Each of the analytes used alone yielded lower degree of discrimination. CONCLUSIONS: Simultaneous use of the levels of LH, FSH, and A in serum can be used effectively for classification between women with PCOS and healthy women.

Adolescent

Normal serum uric acid concentrations in women with polycystic ovary syndrome.

Recently, an inverse correlation between serum uric acid concentrations and insulin sensitivity has been described in subjects with varying degrees of metabolic syndrome, suggesting that measurement of serum uric acid may provide a simple marker of insulin resistance. Several biochemical and clinical features of polycystic ovary syndrome (PCOS) resemble those of metabolic syndrome: women with PCOS are often obese; they are also at increased risk for the development of coronary artery disease, hypertension and diabetes mellitus. The objective of the present study was to analyse the usefulness of serum uric acid measurement in screening for the metabolic syndrome in women with PCOS. For that purpose serum concentrations of uric acid, insulin and triglycerides were measured in 38 women with PCOS and 20 weight-matched control women with regular menstrual cycles. No differences were found in the uric acid concentrations between the PCOS and control groups. The mean concentrations of triglycerides and fasting insulin were higher in the women with PCOS than in the healthy controls. Serum uric acid concentrations were inversely related to serum hormone-binding globulin (SHBG) concentrations, and positively with body mass index (BMI), insulin concentrations and testosterone:SHBG ratio in the PCOS group. Our results suggest that measurement of serum uric acid does not provide new means for identification of metabolic syndrome in patients with PCOS.

Adult

Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group.

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.

Acute-Phase Proteins

A method for measurement of free testosterone in premenopausal women involving equilibrium dialysis, chromatography, and radioimmunoassay.

A three-step procedure to evaluate the quantity of true free testosterone in female serum was established. Unbound and bound testosterone were first separated by equilibrium dialysis using undiluted serum. Testosterone in dialysate was extracted and separated from cross-reactive steroids by column chromatography and finally quantified with a sensitive radioimmunoassay. The detection limit of the radioimmunoassay was 2.7 pmol/L and the detection limit of the whole method was 6 pmol/L. The intra-assay coefficients of variation of the method were 20.6%, 16.8%, and 9.5% for free testosterone concentrations 12.0 pmol/L, 21.4 pmol/L, and 31.4 pmol/L, respectively. The interassay coefficients of variation were 26.3% and 14.8% for free testosterone concentrations 10.4 pmol/L and 21.3 pmol/L, respectively. Serum free testosterone concentrations were determined in 27 regularly menstruating control women. The mean concentration of actual free testosterone was 10.0 +/- 4.9 pmol/L (mean +/- SD, range from below 6 to 19 pmol/L, n = 27).

Adult

Total renin after gonadotropin stimulation in polycystic ovarian disease.

OBJECTIVE: To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. DESIGN: Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. SETTING: In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. PATIENTS: Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. MAIN OUTCOME MEASURES: The concentrations of total renin in plasma and FF, serum E2, and protein in FF. RESULTS: The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. CONCLUSIONS: In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Adult

Third generation time-resolved immunofluorometric TSH assay for automatic immunoassay system evaluated.

We evaluated a new, third generation assay for serum thyrotropin (TSH) based on time-resolved fluorescence (AutoDelfia hTSH Ultra) for the 1235 AutoDelfia automatic immunoassay system. The functional sensitivity of the TSH assay was 0.007 mIU l-1 (between-assay CV, 20%). The between-assay imprecision was CV 4.1-7.7%, between TSH concentrations of 0.026 and 23.8 mIU l-1. The within-assay imprecision was CV 1.2-1.5% between TSH concentrations of 0.5 and 12 mIU l-1. The degree of agreement between the AutoDelfia hTSH Ultra assay and a second generation TSH-IRMA was studied. The mean difference was -0.04 (SD 0.28) mIU l-1 at concentrations between 0.22 and 52 mIU l-1. Serum TSH concentrations of euthyroid subjects, hypothyroid and hyperthyroid patients as well as those of patients with non-thyroidal illness, and thyroid carcinoma patients with TSH suppressive thyroxine treatment were analysed. The AutoDelfia automatic immunoassay system offers many benefits in sensitivity, precision, speed, output rate, time and convenience. Overnight runs are possible, and the system is easy to operate.

Fluorescence Polarization Immunoassay

Nocturnal breathing abnormalities in acromegaly after adenomectomy.

OBJECTIVE: The incidence of sleep apnoea is increased in acromegaly. The aim of the study was to determine the occurrence of nocturnal breathing abnormalities and upper airway morphology in acromegalic patients some years after adenomectomy. DESIGN: A case-control study. PATIENTS: Eleven patients with treated acromegaly and two control groups: (1) sleep studies: 197 subjects randomly selected from the population, (2) cephalometry: 27 healthy subjects and 17 patients with obstructive sleep apnoea. MEASUREMENTS: Nocturnal breathing was monitored with a static charge-sensitive bed. The upper airway soft tissues and bone morphology were assessed by cephalometric X-ray photography. The upper airway collapsibility was investigated with dynamic nasopharyngoscopy. Endocrinological investigations were also performed. RESULTS: Nocturnal breathing abnormalities were present in all but one acromegalic patient (91%), which was far more frequent than in the general population (29.4%, P < 0.0001). Treated acromegaly was the most powerful predictor of breathing abnormalities, independent of the other significant predictors, age and body mass index. The predominant breathing abnormality was periodic breathing with symmetrically waxing and waning respiratory effort without a major body movement component. Episodes of complete obstruction with repetitive arousals were rare. Except for the longer soft palate, the cephalometric findings were similar to normal. In comparison to obstructive sleep apnoea, the treated acromegalic patients had rather prognathic than retrognathic mandibles. Fibreoptic endoscopy in the acromegalic patients revealed collapsible upper airways at the level of the soft palate, whereas at the base of the tongue little, if any, dynamic narrowing was observed. CONCLUSION: Our study confirms that nocturnal breathing abnormalities are common in treated acromegaly, and may persist years after the removal of the GH secreting tumour. The breathing abnormalities and the upper airway morphology in acromegalic patients after adenomectomy are different from those observed in primary obstructive sleep apnoea, suggesting a different pathophysiology of the airway obstruction.

Acromegaly

Effects of a long acting somatostatin analog on pituitary, adrenal, and testicular function during rest and acute exercise: unexpected stimulation of testosterone secretion.

The purpose of this study was to delineate the possible endocrine effects of exercise-induced GH secretion. Twelve healthy adult males were studied during short (20 min) and subsequent prolonged (2 h) physical exercise and recovery period (2 h), both after injection of a long acting somatostatin analog [Sandostatin (ST); 0.1 or 0.05 mg, sc] and after a control saline injection. Additional subjects were studied during rest with similar injections of ST (0.1 mg) and saline (n = 7) or using a lower ST dose (0.01 mg; n = 6). Several venous blood samples were taken during the trials and analyzed for selected hormones, monitoring pituitary, testicular, and adrenal functions. ST injection blocked the serum GH response to short term maximal bicycle ergometer exercise, but not to the following prolonged bicycle exercise. No relationship of the exercise-associated GH increase to the concomitant endocrine responses of the adrenals and testes was observed. Unexpectedly, the higher ST doses (0.1 and 0.05 mg) increased the mean levels of serum testosterone by 18-25% in both exercise (P = 0.0017) and rest trials (P < 0.0001), respectively. ST did not affect the levels of LH, FSH, or cortisol. ST slightly increased serum sex hormone-binding globulin (3%; P = 0.021) and albumin (4%; P = 0.017) concentrations, but not that of free testosterone. Because the testosterone response to somatostatin was fast and without a simultaneous increase in LH, it was consistent with a direct testicular response. The explanation for this novel ST effect remains obscure, but it may be due to modulation of some paracrine mechanisms inhibiting testicular steroidogenesis.

Adrenal Glands

Using computerized individual medication data to detect drug effects on clinical laboratory tests.

In clinical practice, thousands of drugs are used daily. Clinicians know the therapeutic effects of drugs but other minor drug effects are often ignored either because of inadequate knowledge of these effects or simply because of the limited memory capacity of a human being. This problem can be solved by using a computerized information system, which includes medication data of individual patients as well as information about non-therapeutic drug-effects. One of these non-therapeutic confusing drug effects is the influence of drugs on laboratory tests; a problem that should be taken into account in clinical practice and diagnostics. Other complicating drug effects include drug interactions and patient related adverse drug reactions. In a computerized information system, it is possible to build decision support modules that automatically give alarms or alerts of important drug effects other than therapeutic effects. If these warnings concern laboratory tests they are checked by a laboratory physician and only those with clinical significance are sent to clinicians. Warnings of drug interactions and adverse drug reactions are immediately evaluated by the physician responsible for the treatment. By means of the computerized information system, it is also possible to get better information of current medication practice which in turn gives better chances to agree on common guidelines and enables better quality assurance.

Adverse Drug Reaction Reporting Systems

Using data preprocessing and single layer perceptron to analyze laboratory data.

During daily work in hospitals a large amount of clinical data is produced each day. Totally computerized patient records are not yet widely used but a large part of essential information is already stored on computer files. These include laboratory test results, diagnoses, codes for operations, codes of histopathological diagnoses and maybe even the patient's medication. Accordingly, these databases include much clinical knowledge that would be useful for clinicians. Laboratories try to support clinicians by producing reference values for laboratory tests. It is, of course, necessary information but, however, it does not give very much information about the weight of evidence that an abnormal laboratory test will give in special clinical settings. We have developed a software package - DiagaiD - in order to build a smart link between patient databases and clinicians. It utilizes neural network-based machine learning techniques and can produce decision support which meets the special needs of clinicians. From example cases it can learn clinically relevant transformations from original numeric values to logical values. By using data transformation together with a single layer perceptron it is possible to build nonlinear models from a set of preclassified example cases. In this paper, we use two small datasets to show how this scheme works in the diagnosis of acute appendicitis and in the diagnosis of myocardial infarction. Results are compared with those obtained using logistic regression or backpropagation neural networks. The performance of our neuro-fuzzy tool seemed to be slightly better in these two materials but the differences did not reach statistical significance.

Appendicitis

Free thyroid hormones and a third-generation TSH assay in the detection of hyperthyroidism during long-term thyroxine treatment in thyroid carcinoma patients.

We evaluated the value of serum-free thyroid hormone and thyrotropin (TSH) concentrations in the detection of peripheral hyperthyroidism during thyroxine suppression therapy. A total of 57 patients on a stable thyroxine dose and 70 controls participated in the study. Serum-free thyroxine (FT4), free triiodothyronine (FT3) and TSH were measured by immunoassays based on time-resolved fluorescence (Delfia). The assay for TSH was a modification of a third generation Delfia hTSH Ultra method. The patients were classified into euthyroid and hyperthyroid subgroups based on clinical signs and symptoms (Wayne index). Systolic time intervals (STI) were measured. The Wayne indices were higher among patients than controls (p < 0.0001). The STI results were similar in patients and controls. Only FT4 had the discriminatory power for classifying euthyroid and hyperthyroid patients according to discriminant analyses. The diagnostic value of FT4 was further assessed by calculating the area under the relative operating characteristic (ROC) curve. The area was 0.707 (SE 0.0918), which was significantly different from an area of 0.5, i.e. the area of a test of no value (p = 0.032). In conclusion, a high serum FT4 concentration indicates hyperthyroidism during long-term thyroxine treatment among thyroid carcinoma patients. Although the degree of TSH suppression can now be exactly monitored with new third generation TSH assays, hyperthyroidism cannot be defined using TSH concentration in thyroid carcinoma patients. Therefore, additional serum FT4 concentration assays are needed in the assessment of hyperthyroidism associated with TSH suppression therapy in thyroid carcinoma patients.

Adult

Health-based reference intervals for ALAT, ASAT and GT in serum, measured according to the recommendations of the European Committee for Clinical Laboratory Standards (ECCLS).

The reference intervals for the activities of L-alanine aminotransferase (EC 2.6.1.2, ALAT), L-aspartate aminotransferase (EC 2.6.1.1, ASAT) and gamma-glutamyltransferase (EC 2.3.2.2, GT) in serum were determined according to the recommendations of the European Committee for Clinical Laboratory Standards (ECCLS). Serum specimens from 954 subjects were analysed for ALAT and ASAT and from 794 subjects for GT. The subjects, aged 27-67 years, were participants in general health surveys. The reference population was formed by excluding subjects with any disease, or on any medication, affecting the liver, and also those consuming excessive amounts of alcohol. The 95% inner reference intervals for ALAT and ASAT were 9-50 (n = 189) and 15-36 U l-1 (n = 192) in men and 8-38 (n = 270) and 13-33 U l-1 (n = 270) in women. For GT the reference interval was 11-58 in men (n = 165) and 8-42 U l-1 in women (n = 220). Serum GT levels correlated clearly with alcohol consumption. Serum ALAT and ASAT were only slightly associated with alcohol consumption at levels less than 280 g per week in men and 190 g per week in women. There were modest positive associations between the three enzyme levels and body mass index. None of the enzymes correlated significantly with age.

Adult

Serum total renin is elevated in women with polycystic ovarian syndrome.

OBJECTIVE: To examine the serum total renin in women with polycystic ovarian syndrome (PCOS) and in controls. SETTING: Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS: Forty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0 kg/m2) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5 kg/m2). MAIN OUTCOME MEASURES: The concentrations of total renin, LH, FSH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum. RESULTS: The concentration of total renin in serum was higher in PCOS women than in healthy women independently of BMI, age, or serum insulin. The serum total renin measurement discriminated PCOS patients and control women to a similar extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as judged by receiver-operating characteristic analysis. Positive correlations were found between the serum total renin level and LH concentration, LH:FSH ratio, T and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients during oligomenorrhea and after menstruation did not reveal any significant changes. CONCLUSIONS: The elevated concentration of serum total renin suggests an enhanced activity of ovarian renin-angiotensin system in PCOS. The determination of serum total renin may provide a novel tool in the diagnostics of PCOS, because its serum level is elevated in PCOS women independently of BMI and serum insulin.

Adult

Coding drug effects on laboratory tests for health care information systems.

Drugs interfere with laboratory diagnostics. This interference is not only confusing for clinicians but may lead to wrong diagnoses or treatments as well as unnecessary further tests. However, at the moment the drug-laboratory interferences are usually ignored in patient care because clinicians do not know or remember these properties of drugs. In Turku University Central Hospital we are now able to bring this information automatically available for clinicians by using a computerized system for linking individual patient medication data with laboratory information system. For this purpose, we are building a rule base containing the effects of drugs on laboratory tests. In order that the rule base would give the maximum benefit for all users, even other hospitals, the data included have to be classified and coded properly taking into account the various requirements and needs of all users. In this paper we introduce a coding scheme for classification and coding of drug effects on laboratory tests.

Classification