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Biomedical subjects

M Helle

Publications and source records attributed to M Helle.

At least 19 recordsLinked to original sources

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Arthritis↗

Power Doppler ultrasonography and synovitis: correlating ultrasound imaging with histopathological findings and evaluating the performance of ultrasound equipments.

OBJECTIVES: To examine the validity of power Doppler ultrasound imaging to identify synovitis, using histopathology as gold standard, and to assess the performance of ultrasound equipments. METHODS: 44 synovial sites in small and large joints, bursae and tendon sheaths were depicted with ultrasound. A synovial biopsy was performed on the site depicted and a synovial sample was taken for histopathological evaluation. The performance of three ultrasound devices was tested using flow phantoms. RESULTS: A positive Doppler signal was detected in 29 of 35 (83%) of the patients with active histological inflammation. In eight additional samples, histological examination showed other pathological synovial findings and a Doppler signal was detected in five of them. No significant correlation was found between the amount of Doppler signal and histological synovitis score (r = 0.239, p = NS). The amount of subsynovial infiltration of polymorphonuclear leucocytes and surface fibrin correlated significantly with the amount of power Doppler signal: r = 0.397 (p<0.01) and 0.328 (p<0.05), respectively. The ultrasound devices differed in showing the smallest detectable flow. CONCLUSIONS: A negative Doppler signal does not exclude the possibility of synovitis. A positive Doppler signal in the synovium is an indicator of an active synovial inflammation in patients. A Doppler signal does not correlate with the extent of the inflammation and it can also be seen in other synovial reactions. It is important that the quality measurements of ultrasound devices are reported, because the results should be evaluated against the quality of the device used.

Adult↗

Feasibility of axillary ultrasound in the quality assessment of sentinel node biopsy in breast cancer surgery.

BACKGROUND AND AIMS: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound (AU) in detecting the rate of recurrence after a negative sentinel node (SN) biopsy in patients with breast cancer and without additional axillary dissection. MATERIALS AND METHODS: The operating oncologic surgeon performed 196 consequent sentinel node biopsies during surgery of breast cancer. The sentinel nodes were identified by using preoperative lymphoscintigraphy, intraoperative gamma probe and Patent Blue dye. A routine postoperative follow-up of the patients were performed every 3rd month including clinical examinations, blood chemistry and mammography. After 31 months (range 14-49 months), a high-resolution AU was performed for 107 patients with a negative sentinel node during surgery and without axillary dissection, to visualize any abnormal lymph nodes in the axilla. If necessary, large core biopsies were undertaken to obtain histology of abnormal axillary nodes. RESULTS: The SNs were visualized during preoperative lymphoscintigraphy in 167/196 (85%) and found during the surgery in 163/167 (98%) of patients. The mean number of removed SN were 1.7+/-0.8. The SN metastasis were found in 29% (56/196) of patients. During the follow-up, abnormal nodes were identified during AU in only 4/107 patients. Core biopsies confirmed benign histology in three patients and one case of lymphoma was detected. CONCLUSIONS: There were no axillary recurrences of breast cancer after a negative SN biopsy during the 2.6 year follow-up. Axillary ultrasound is a useful tool in the quality control of patients with negative SN biopsy and without diagnostic axillary dissection.

Axilla↗

Ultrasound guided synovial biopsy using portal and forceps.

OBJECTIVE: To describe a new method for taking a synovial biopsy specimen under ultrasound guidance using portal and forceps. METHODS: Percutaneous ultrasound guided biopsy was performed for 37 patients with mono- or polyarthritis as outpatients. A portal to a planned area was built using a needle, guiding wire, and dilators, through which forceps could be inserted and samples taken. Biopsy samples were taken from small and large joints, bursae, and tendon sheaths. RESULTS: Representative synovial tissue in adequate amounts for histopathological evaluation was obtained in 33/37 cases--a success rate of 89%. The biopsy procedures were well tolerated, but one complication of skin infection was encountered. CONCLUSION: The new method of synovium biopsy under ultrasound guidance using sheath introducer set and flexible forceps can be performed on most joints and even bursae and tendon sheaths. The method gives sufficient samples for clinical work in most cases, but further work is needed before accepting this promising technique for scientific purposes.

Adult↗

The demands of screening mammography on surgical inpatient services of breast cancer.

A nationwide mammographic screening of women ages 50 to 59 years commenced in Finland in January 1987. We studied the demands of screening on surgical inpatient services by comparing the treatment strategy, volume of breast biopsies, and hospital stay before and after implementation of mass screening of women age 50 to 59. Approximately 20 patients per 100,000 inhabitants were referred annually from mass screening for surgical biopsies, in half of which cancer was detected. In 1985 through 1986 (before screening) we operated on 134 patients suspected of having breast cancer. After the first (in 1990) and the second (in 1995) round of mammographic screening we operated on 161 patients in 2 years suspected of having breast cancer. Concurrently 25 of 92 cancers (27%) were found only because of the screening. Before the screening period clinical symptoms and palpable tumors were cause for referral to surgery in 84 per cent of the cases and abnormal mammography in only 16 per cent. During screening these ratios were 34 and 61 per cent, respectively. The number of T(is)-1 cancers (<2 cm) increased from 44 per cent before screening to 70 per cent during screening. In contrast the number of T2 cancers (2-4 cm) decreased from 40 to 20 per cent. The mammographic screening did not increase the hospital stay of patients. We conclude that the mammographic screening program of all women age 50 to 59 years increased the number of surgical biopsies in our hospital by only 30 per cent. Breast cancer was found at an earlier stage during screening. More than one-fourth of breast cancers are currently found through the mass screening program in Finland.

Biopsy↗

Transurethral resection with perioperative instilation on interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a prospective randomized multicenter study--Finnbladder III.

PURPOSE: We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary (not recurrent) superficial bladder cancer. MATERIALS AND METHODS: A total of 283 patients with stages Ta to T1 primary superficial, grades 1 to 3 bladder cancer was randomized into study groups 1-transurethral resection only, 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg. epirubicin. Eligible for final analysis were 200 patients, including 66 in group 1, 66 in group 2 and 68 in group 3. Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence. RESULTS: Group 3 had the most favorable outcome, since 45 of the 68 patients (66%) were without recurrence after 2 years compared to 24 of the 66 (37%) in group 2 and 26 of the 66 (40%) in group 1 (log rank test p <0.001). Side effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: A single 100 mg. dose of epirubicin given intravesically immediately after transurethral resection is safe, and significantly decreases the recurrence of primary superficial bladder cancer. A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose. The long-term effect of this treatment remains to be studied.

Administration, Intravesical↗

Immunoreactivity of bcl-2, p53 and EGFr is associated with tumor stage, grade and cell proliferation in superficial bladder cancer. Finnbladder III Group.

Immunoreactivity of bcl-2, p53, the epidermal growth factor (EGFr) and Ki-67 (MIB-1) proteins was assessed by immunohistochemistry in 185 patients with superficial bladder cancer (SBC) in order to evaluate their usefulness as indicators of tumor progression. Forty-one percent of the tumors were bcl-2 positive, 36% of them were positive for p53 (over 20% of nuclei), while 41% were positive for EGFr, and 30% of the tumors were MIB-1 positive (proliferation index > 15%). Immunoreactivity of all analyzed proteins was highly significantly related to tumor grade and stage. Tumors which were bcl-2, p53 or EGFr positive were also rapidly proliferative (MIB-1 score >15%). The obtained results suggest that all analyzed proteins may have prognostic significance in SBC. The prognostic value of the abnormal immunolabeling of the analyzed proteins will be established after an adequate follow-up period of this same cohort of patients.

Adult↗

Magnetoencephalographic cortical rhythms.

We have characterized the magnetic 10- and 20-Hz rhythms recorded with a whole-scalp neuromagnetometer during different conditions. Sources of the posterior 10-Hz (alpha) rhythm clustered mainly around the parieto-occipital sulcus and, to a lesser extent, around the calcarine sulci, with several generators. Temporal Spectral Evolution (TSE) analysis, used to follow event-related changes in the different frequency bands, showed strong dampening of the alpha within 200 ms after the appearance of a visual stimulus and also during visual imagery. Suppression was often followed by a rebound above the baseline level. The rolandic mu rhythm consisted of 10- and 20-Hz components with different reactivity and source locations. The 10-Hz component seems to be mainly somatosensory in origin whereas the 20-Hz signal also receives contributions from the motor cortex, and even shows 'motorotopy' in its reactivity: the source locations depend in a somatotopical manner on the site of the moving body part. The frequency composition of the posterior spontaneous activity was disturbed in patients with small infarcts of the medial thalamus. It is shown with simulations that a surprisingly small number of synchronized cortical neurons could generate the major part of the recorded oscillatory signal. Finally, some clarifications are suggested to the terminology of brain rhythms.

Animals↗

Expression of MIB-1, mitotic index and S-phase fraction as indicators of cell proliferation in superficial bladder cancer. Finnbladder Group.

Cell proliferation of transitional cell bladder cancer (TCC) was determined by MIB-1 immunolabeling, volume-corrected mitotic index (M/V index) and S-phase fraction measurement in 207 patients with superficial (Ta-T1) bladder cancer. The results were compared to T category, WHO grade and DNA-ploidy. The MIB-1 score was related to T category (P < 0.001), WHO grade (P < 0.001), DNA ploidy (P < 0,0001), M/V index (P < 0.0001) and fraction of cells in S phase (P < 0.0001). The mean MIB-1 score was 6.37% for G1, 14.59% for G2 and 28.59% for G3 carcinomas (P < 0.001). The MIB-1 score for Ta tumors was 9.24% and for T1 tumors 25.34% (P < 0.001). The M/V index was 3.9 for G1, 11.5 for G2 and 25.9 for G3 tumors (P < 0.0001). The M/V index for Ta tumors was 6.4 and 25.3 for T1 tumors (P < 0.0001). WHO grade 1 tumors had 7.7%, grade 2 tumors 13.8% and grade 3 tumors 21.8% of cells in S phase (P < 0.001). Of grade 1 tumors, 97% were diploid and 3% aneuploid, and 78% of grade 2 tumors were diploid and 22% aneuploid. Of grade 3 tumors, 30% were diploid and 70% aneuploid (P < 0.001). Of Ta tumors, 92% were diploid and 8% aneuploid, respectively, whereas 40% of T1 tumors were diploid and 60% aneuploid (P < 0.0001). The results show that quantitative cell proliferation indices are associated with T category and WHO grade in superficial bladder cancer. The prognostic value of the S-phase fraction and mitotic index has been demonstrated in several previous analyses of prognostic factors while the value of MIB-1 score on bladder cancer prognosis remains to be established in further follow-up studies.

Adult↗

The expression of CEA, CA 19-9 and HMFG antigens in ovarian clear-cell and endometrioid carcinomas.

The tumour antigen expression of ovarian and endometrial endometrioid carcinomas, ovarian clear-cell carcinomas as well as endometrial and cervical clear-cell carcinomas were immunohistochemically compared. Of special interest were potential differences between the endometrioid and clear-cell carcinomas of the ovary. The expression of CEA and CA 19-9 tumour antigens in all these tumour types was heterogeneous, with 10-20% of the cases being positive for CEA and 40-75% being positive for CA 19-9. In contrast, HMFG IIIC 12, a monoclonal antibody originally directed against human milk fat globule (HMFG) membrane antigens, invariably detected a corresponding antigen on every case of these tumour types. Another HMFG antibody, SM IF 3, on the other hand, detected antigenic material on all clear-cell tumour types, but only rarely on endometrioid tumours of the ovary or endometrium. While HMFG IIIC 12 detects an antigen present on all ovarian, endometrial and mammary carcinomas, antibody SM IF 3 thus appears to be more restricted in its staining patterns. Our results with both of these antibodies indicate that ovarian clear-cell carcinomas and ovarian endometrioid carcinomas have antigenic differences, which provides further evidence that they belong to different tumour entities.

Adenocarcinoma↗

Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera.

A monoclonal antibody and an affinity purified polyclonal antibody, both raised against recombinant human IL-6, have been employed in an ELISA procedure to quantitate human IL-6. Both antibodies were very potent in neutralizing the biological activity of recombinant as well as natural human IL-6. The monoclonal antibody was used as the capture antibody whilst the polyclonal antibody, in biotinylated form, was used as the detecting antibody in combination with a streptavidin horseradish peroxidase conjugate and a signal amplification system. The detection limit for natural as well as recombinant IL-6 was 1 pg/ml. A good correlation was found between the ELISA and the B9 biological assay when IL-6 was measured in crude culture supernatants, in synovial fluids of rheumatoid arthritis patients and in the sera of patients with diverse diseases. Immunoprecipitation of IL-6, produced by different cell types, such as monocytes, endothelial cells and smooth muscle cells or derived from biological fluids, such as the serum of a patient with septic shock or the synovial fluid of a rheumatoid arthritis patient, revealed in every case only molecules in the molecular weight range of 21,000-26,000.

Animals↗

Differential induction of interleukin-6 production by monocytes, endothelial cells and smooth muscle cells.

Studying the production of IL-6 by monocytes, endothelial cells and smooth muscle cells we observed that cytokine inducers like IL-1, TNF alpha, LPS, SAC and PMA could be divided roughly into two categories. One, that consisted of LPS and SAC, which had a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells. The other category, consisting of IL-1, TNF alpha and PMA, induced IL-6 production in endothelial- and smooth muscle cells and of which IL-1 also induced IL-6 in monocytes. Only IL-1 induced IL-6 production in monocytes as well as in endothelial cells and smooth muscle cells. Besides IL-6, also IL-1 and TNF alpha were produced by monocytes however with different kinetics. None of the stimuli had any inhibitory effect on IL-6 production with the exception of PMA. Whereas PMA induced IL-6 production in endothelial cells and it potentiated the induction of IL-6 by IL-1 in these cells, it inhibited LPS-stimulated IL-6 production in monocytes. In line with the effects of PMA, staurosporin induced IL-6 production in monocytes and it inhibited IL-1 driven IL-6 production by endothelial cells.

Antibodies, Monoclonal↗

Analysis of interleukin-6 in endotoxin-induced uveitis.

The mechanisms underlying the induction of intraocular inflammation in the rat model of endotoxin-induced uveitis (EIU) and the subsequent development of tolerance after repeated endotoxin injections are poorly understood. Interleukin-6 (IL-6) was measured in the aqueous humor and serum of Lewis rats after single and repeated injections of endotoxin into the footpad. After a single injection, a rise in serum and aqueous-humor levels of IL-6 was seen after 2 and 16 hr, respectively. The highest aqueous-humor level of IL-6 was seen 20 hr postinjection and was tenfold that seen in the serum sample taken at the same time, suggesting intraocular synthesis of this cytokine. Four hours later the most active uveitis and the highest total aqueous-humor protein level were observed. Repeated injection of endotoxin still resulted in a moderate but significant systemic release of IL-6 but no detectable IL-6 in the aqueous humor and the absence of uveitis. Intravitreal injection of endotoxin-free human recombinant IL-6 (10-10(5) U) in rats resulted in uveitis, resembling the ocular response to endotoxin. There appeared to be a prozone effect regarding the total aqueous-humor protein concentration. The largest amount of aqueous-humor protein was seen in the eyes injected with 10(2) U of IL-6, but increasing concentrations of intravitreal IL-6 showed a corresponding decrease in protein levels. In the fellow saline-injected eyes, a clear consensual response was observed with regard to the extravasation of protein, although the uveitic grade in these eyes was low or zero. Repeated intravitreal injection of IL-6 resulted in ocular unresponsiveness in nine of 11 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interleukin-6 and its relation to the humoral immune response and clinical parameters in burned patients.

The cytokine interleukin-6, which has been shown to be increased in patients with burn injuries, is produced by activated monocytes and endothelial cells and has many in vitro activities, including stimulation of acute-phase protein synthesis in hepatocytes, immunoglobulin synthesis in B lymphocytes, and stimulation of growth of megakaryocytes. In 13 patients with a mean of 31% full-thickness burns, we studied the relation of serum interleukin-6 to clinical parameters and parameters of the acute-phase response and immunoglobulin production. Interleukin-6 was already elevated within hours after the injury was sustained, and it remained elevated for several weeks. All components of the acute-phase response were observed: fever, tachycardia, leukocytosis with an associated left shift, elevation of C-reactive protein and alpha 1-antitrypsin, and a decrease in albumin levels. In the second week after burn injury, immunoglobulin M levels peaked, followed by a prolonged elevation of immunoglobulin G levels. Thrombocyte counts initially decreased and rebounded to supranormal levels after 2 weeks. Interleukin-6 levels were positively correlated with acute-phase responses. We believe that the production of interleukin-6 induces the synthesis of acute-phase proteins. High interleukin-6 levels may also be an etiologic factor in the marked immunoglobulin response observed. Likewise, the relation between the megakaryocyte-promoting activity of interleukin-6 and the rebound thrombocytosis requires further investigation.

Adult↗

Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage.

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin-6 (IL-6) in culture. However, IL-1 induced massive production of IL-6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose-dependent manner (in some cases, a peak value was reached). The levels of induced IL-6 were similar to those found in rheumatoid arthritis synovial fluid. At IL-1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL-6 production could still be increased considerably. Exogenous IL-6 inhibited PG synthesis by up to 25%. IL-1-induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL-6. These results suggest that IL-6 is required for the IL-1-induced inhibition of PG synthesis.

Adult↗

Steroid receptors and Ki-67 reactivity in ovarian cancer and in normal ovary: correlation with DNA flow cytometry, biochemical receptor assay, and patient survival.

Steroid hormone receptors and reactivity for Ki-67 proliferation antigen were studied immunohistochemically in non-neoplastic post-menopausal human ovary and in 29 ovarian cancers. In the normal ovary, oestrogen (OR) and progesterone receptors (PR) were found in the surface epithelium and PR also in the ovarian stroma. Of the ovarian carcinomas 38 per cent (11/29) contained OR and 69 per cent (20/29) PR. Oestrogen receptor expression was confined to malignant cells, whereas PR was present occasionally also in the tumour stroma. In most cases, ORs and PRs were found only in a small population of cancer cells. The growth fractions assessed by the percentage of Ki-67-positive cells ranged from 1 to 59 per cent (mean 19.7 per cent) with a significant correlation (r = 0.74, P less than 0.0001) to S-phase values (mean 12.9 per cent, range 1.2-25.9 per cent) determined by DNA flow cytometry. High Ki-67 (greater than or equal to 15 per cent) and S-phase levels (greater than or equal to 7.5 per cent) correlated with advanced disease stage and patient survival but not with OR or PR status, suggesting that hormone-receptor pathways and proliferative activity are not related in ovarian cancer. Positive OR status, however, identified patients with a better prognosis (P = 0.02), suggesting a correlation with tumour differentiation. The independent prognostic value of oestrogen receptor status and Ki-67 remains to be determined, but the prognostic impact of Ki-67 was comparable to that of S-phase values.

Adult↗

The relation among stress, adrenalin, interleukin 6 and acute phase proteins in the rat.

Stress reactions exist in many conditions in which plasma interleukin 6 (IL-6) is elevated. Examples are burns and sepsis. In these situations fever is often present. These stress situations are always accompanied with high levels of adrenalin and corticosteroids. These hormones, especially when given together, elicit a definite response of acute phase proteins in normal rats. In two stress models, (i) laparotomy and (ii) fever induced by administration of PGE2 in the lateral intracerebral ventricle, we observed a rise of adrenalin and corticosteron followed by an elevated level of plasma IL-6. Therefore, we studied the effect of adrenalin and corticosteron on the plasma level of IL-6. Adrenalin evokes high levels of IL-6, and this effect can be blocked by propranolol. When IL-6 release is blocked in this way, the response of alpha 2 macroglobulin and the cysteine protease inhibitor, both fast-reacting acute phase proteins in rat, is strongly depressed. Isoprenalin, an adreno beta 2 agonist, also causes very high levels of IL-6, indicating that the release of IL-6 can be mediated by an adreno beta 2 receptor whose presence has been demonstrated in monocytic cells. The results suggest a relation between stress situations and IL-6 and may be another factor besides the presence of endotoxins, virus, etc. explaining the high levels of IL-6 observed in many serious clinical situations.

Acute-Phase Proteins↗