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M Blichert-Toft

Publications and source records attributed to M Blichert-Toft.

At least 55 records · Page 3Linked to original sources

The effects of interleukin-1beta (IL-1beta) on human thyrocyte functions are counteracted by the IL-1 receptor antagonist.

The cytokine interleukin-1beta (IL-1beta) is an important regulator of thyroid cell function. IL-1 receptors are present on normal thyrocytes, but the signaling pathway is not fully clarified. As the adenylate cyclase is presumably not activated, we have in the present study investigated whether the cGMP pathway was involved in the actions of IL-1beta, whether the effects of IL-1beta on cultured human thyrocytes were reversible, and whether the effects were counteracted by IL-1 receptor antagonist (IL-1ra), a naturally occurring, specific blocker of IL-1 receptors on many cells. TSH-stimulated cultured human thyroid cells exposed for 72 h to IL-1beta (0.0002-20 microg/liter = 1-105 IU/liter) exhibited a dose-dependent and reversible inhibition of thyroglobulin and cAMP release and a dose-dependent stimulation of cGMP and IL-6 release. These effects were counteracted by coincubation with 250 or 125 microg/liter, but not with 25 and 2.5 microg/liter, IL-1ra. IL-1ra by itself inhibited the release of cAMP, but did not modulate the release of thyroglobulin, cGMP, or IL-6 from the thyrocytes, and IL-1ra was not produced in the extracellular compartment. The nitric oxide generator, sodium nitroprusside, dose dependently generated a TSH-independent release of nitric oxide and cGMP from the thyrocytes. These results indicate that all of the studied effects of IL-1beta on cultured human thyrocytes were exerted through activation of the IL-1 receptor with a signaling pathway involving activation of cGMP and inhibition of cAMP.

Cells, Cultured↗

Experience in a specialist thyroid surgery unit: a demographic study, surgical complications, and outcome.

OBJECTIVE: To present a demographic study of thyroid diseases and thyroid surgical activity, to analyse the results of one department that has specialised in thyroid surgery during an 11-year period, and to try to define those groups of patients at increased risk of complications and untoward sequelae. DESIGN: Retrospective study. SETTING: Danish regional university hospital. SUBJECTS: The total series comprised 1099 consecutive patients who were operated on for benign goitre during an 11-year period. The demographic series comprised a subgroup of 933 patients with goitres from the defined catchment area composed of five municipalities. MAIN OUTCOME MEASURES: Annual number of operations for goitre, waiting time to operation, incidence of complications, and sequelae. RESULTS: In the demographic study the number of patients operated on for benign thyroid diseases declined from about 50 cases to about 25 cases/100000 inhabitants during the study period. At the same time the average waiting time between consultation and operation increased from 5-33 weeks. In the total series (n = 1099) 18 patients developed temporary unilateral vocal cord paralysis (2%), and 8 developed permanent paralysis (0.7%). There were no bilateral vocal cord paralyses, 7 patients developed temporary postoperative hypocalcaemia (0.6%), and an additional 8 patients (0.7%) developed permanent hypocalcaemia. 5 patients developed wound haematomas (0.5%), and 3 had wound infections (0.3%). A total of 16 patients (1.5%) had a permanent complication in the form of nerve injury or damage to the parathyroid glands. The rates of postoperative complications were significantly higher among patients who had two or more operations on the neck (p = 0.0004), intrathoracic goitres (p = 0.0002), large goitres (p = 0.0002), and those having emergency operations (p = 0.0091). CONCLUSION: The decline in the number of operations for benign goitre at Odense University Hospital parallels the increase it waiting time before operation. This can be explained by loss of operating room capacity rather than introduction of some alternative cure for goitre or change of criteria for operation. Certain groups of patients are at higher risk of complications than others.

Denmark↗

Plasminogen activator inhibitor type 1 in cytosolic tumor extracts predicts prognosis in low-risk breast cancer patients.

We have reported previously that both urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) are statistically significant prognostic variables in patients with high-risk breast cancer (Grondahl-Hansen et al., Cancer Res., 53:2513-2521, 1993), and we recently described that the uPA receptor (uPAR) is a prognostic marker in postmenopausal, node-positive breast cancer patients (Grondahl-Hansen et al., Clin. Cancer Res., 1:1079-1087, 1995). The present retrospective study describes the prognostic impact of uPA, its receptor uPAR, and PAI-1 in breast cancer cytosol from 111 low-risk premenopausal patients and 184 low-risk postmenopausal patients with a median follow-up of 6.0 years (range, 3.8-14.9) and 7.4 (range, 3.7-14.0) years, respectively. uPA, uPAR, and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays, and data were dichotomized using the median value as the cutoff for calculation of recurrence-free survival and overall survival. A correlation was found between the levels of each of the three molecules. In univariate analysis, high PAI-1 was significantly associated with short overall survival in postmenopausal patients [relative risk (RR), 2.3; 95% confidence interval (CI), 1.3-4.3; P = 0.005] and shorter recurrence-free survival in both premenopausal (RR, 2.5; 95% CI, 1.3-4.7; P = 0.004) and postmenopausal (RR, 1.8; 95% CI, 1.1-2.9; P = 0.02) patients. Neither uPA nor uPAR reached statistical significance in the univariate analyses. The prognostic value of uPA, uPAR, and PAI-1 was then compared with that of other established prognostic variables by multivariate analysis. PAI-1 was an independent prognostic variable for recurrence-free survival in premenopausal patients, with a RR of 2.6 (95% CI, 1.3-5.0). For recurrence-free survival (RR, 1.9; 95% CI, 1.1-3.5) and overall survival (RR, 2.6; 95% CI, 1.2-5.7) in postmenopausal patients, PAI-1 was the only independent variable left in this group of patients. Neither uPA nor uPAR reached significance in the multivariate analysis. These data, together with previously published data on the prognostic significance of components of the urokinase plasminogen activation system in breast cancer cytosols, strongly indicate that PAI-1 is a statistically significant and independent prognostic marker in both low- and high-risk breast cancer patients.

Adult↗

[Preoperative scintigraphic localization of hyperfunctioning parathyroid glands].

Preoperative identification of hyperfunctioning parathyroid glands was performed by 99m-Tc-sestamibi scintigrams in 29 patients with hyperparathyroidism. Out of 30 histopathologically proven diseased parathyroid glands 21 were identified by scintigraphy. The diagnostic specificity (PVpos) was 88%. All diseased glands weighing more than 1200 mg were identified by scintigraphy including four glands in the mediastinum. 99m-Tc-sestamibi scintigraphy can identify the larger hyperfunctioning parathyroid glands with high reliability. The method was of great value in situations with ectopic abnormal parathyroid glands.

Adult↗

[Mammographic screening in the municipality of Copenhagen. Results of the first screening round].

The aim of the study was to evaluate the results from the prevalence round of the mammography screening programme in the Municipality of Copenhagen. All women who by 1 April 1991 were 50-69 years old, and who lived in the Municipality of Copenhagen, were during the period 1 April 1991-24 April 1993 offered a mammography. Those with suspect findings were recalled for further examination and possible biopsy. Women with breast cancer were offered treatment according to the standard national protocols (DBCCG). The participation rate was 71% (30,416/43,087). Among these 2043 (6.7%) were re-examined and 592 (1.9%) underwent surgical biopsy. Breast cancer was revealed in 359 (1.2%) women, of whom 88% had an invasive breast cancer. Prevalence of breast cancer increased significantly with increasing age. The positive predictive value for breast cancer among those re-examined was 18% and for those who had a surgical biopsy 61%. Among women with an invasive breast cancer 41% had a tumour of 10 mm or less, 80% had negative lymph node status and 56% had breast conserving surgery. During the following 12 months 14 women with a normal mammogram at the screening round developed breast cancer giving a sensitivity of 96%. It is concluded that the first mammography screening in Denmark showed the highest breast cancer prevalence published so far. A possible explanation could be a high sensitivity of the screening method, indicated by a relatively high frequency of small cancers. The screening programme was fully comparable with international standards.

Aged↗

[Treatment of primary breast cancer. Consequences of mammographic screening in the municipality of Copenhagen].

In order to analyse changes in the pattern of primary treatment of breast cancer after introduction of mammography screening in the Copenhagen municipal area every second year, retrospective analyses of data from the Danish Breast Cancer Cooperative Group were performed. Newly diagnosed patients with breast cancer of the age of 50-69 years from the Copenhagen municipal area (1040 patients) were compared to a similar group of patients from the rest of Denmark (7353 patients). Parameters such as tumour size, lymph node status, grade of anaplasia, frequency of breast preserving surgery and adjuvant treatment were analysed. Introduction of mammography screening resulted in almost a doubling of newly diagnosed patients with invasive breast cancer during the prevalence phase, and a significant increase in the number of patients with tumour size < or = 1 cm without metastases to the axillary nodes. The frequency of breast preserving surgery increased from 5 to 45% in the municipality of Copenhagen compared to 6 to 19% in the rest of the country. Ratio between low-risk versus high-risk patients increased from 1.0 before screening to 2.7 in the following prevalence phase and 2.5 in the first year of the subsequent incidence phase, while the ratio in the rest of Denmark was the same throughout the whole study period. It can be concluded that the introduction of mammography screening resulted in significant changes in the treatment pattern of patients with primary breast cancer.

Aged↗

Comparison of the surgical procedures for breast conserving treatment of early breast cancer in seven EORTC centres.

The aim of this study was to develop a standardised surgical report for breast-conserving procedures, supporting the systematic documentation of the different aspects of the surgery. The surgical procedure for tumourectomy and axillary clearance was translated into a series of steps that could be quantitatively documented. This description was submitted twice to a group of surgeons from different departments to ensure that all steps that are considered to have relevance for outcome were included and that no superfluous data were collected. After two corrective phases, a first test format was developed. Between February 1993 and May 1994, seven surgical departments, participating in EORTC trials, completed this questionnaire for a number of their patients. The data collected related to general information on the department, the tumour excision itself, the axillary dissection and, in a later phase, on pathology. 269 questionnaires (264 tumour excisions, 259 axillary dissections and 189 pathology reports) were collected and analysed. Even though the participating departments were involved in a single trial on breast-conserving surgery and had previously developed regular contacts about the practical aspects of treatment, many differences were detected. In general, variations were found in the waiting time between treatment prescription and execution, experience of the surgeon, duration of the procedure, and the use of prophylactic antibiotics. Also, in the practical execution of the procedure, major variations in the type of incision, width of tumour excision, closure of the breast tissue and skin, the use of frozen sections and the extent of the axillary dissection were found. The most relevant differences and their possible consequences are discussed. It has been proven possible and feasible to document quantitatively a surgical procedure. The fact that within a group of surgeons participating in the same clinical trials, many differences in the surgical techniques are observed, stresses the need to reach a consensus on a stricter set of guidelines for breast-conserving procedures and their documentation, especially when conducting clinical trials.

Axilla↗

Breast cancer.

Explore the source record for details and available documents.

Breast Neoplasms↗

[Significance for prognosis of delayed diagnosis and treatment of breast cancer].

In a study of 7608 patients with primary breast cancer the effect of patient's and doctor's delay on survival was examined. The delay was arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The delay had significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was better for patients with a long doctor's delay compared to that of a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a short one, and by 13% for a short doctor's delay compared to a long one. This suggests that all causes of delay should be kept at a minimum.

Adult↗

[Indication for thyrotoxine therapy after surgery of non-endemic non-toxic goiter].

Levo-thyroxine has for many years been used after operation for non-toxic goitre to prevent recurrence and postoperative thyroid hypofunction. The philosophy behind prevention was to suppress production of the thyroid stimulating hormone (TSH), which was assumed to be the main growth factor for the thyroid gland. Suppression of the serum-TSH concentration by thyroxine therefore seemed logical. No scientific documentation verifying this assumption has been found in non-endemic goitre areas. Treatment with levo-thyroxine subsequent to goitre surgery is thus only indicated in situations with risk of hypofunction, viz. when only a small thyroid remnant is left.

Goiter↗

[Primary breast reconstruction after mastectomy for breast cancer].

Primary breast reconstruction in connection with mastectomy is a well-established procedure. The reconstruction may be carried out by the submuscular implantation of a prosthesis, in some cases preceded by tissue expansion. In situations where there is insufficient skin--or muscle-coverage, a musculocutaneous transposition flap may be used. The aim of breast reconstruction is to prevent the psychosocial sequelae of mastectomy. From experiences with secondary reconstruction, it seems that the reconstruction especially helps correct loss of feminine identity and negative body-image. Certain investigations indicate that primary reconstruction results in a clearly reduced postoperative psychological stress, whereas the extent of social and sexual sequelae seems not to vary when compared to results of secondary reconstruction. Conditions for adjuvant treatment as well as for follow-up concerning loco-regional tumour reappearance do not seem to be affected by the reconstruction. In studies published to date, consisting of relatively small patient groups and short observation periods, numbers without relapse and overall survival are found to be equivalent to that following mastectomy without reconstruction.

Breast Implants↗

[Intrathoracic goiter. Diagnostic aspects, surgical complications and permanent sequelae].

During the course of 1151 thyroidectomies performed during an 11-year period, 195 patients were found to have intrathoracic goitre. Centre experience of operating this disease and the usefulness of applied diagnostic methods are analysed. The sensitivity of physical examination (palpation), technetium scintigraphy and chest roentgenogram is respectively 52%, 33% and 65%, while specificity is respectively 99%, 98% and 95%. These three methods together ensure the diagnosis in 82% of the patients. Positive predictive values are respectively 95%, 78%, and 72%, while negative predictive values are found to be 91%, 89%, and 93%. Frequency of permanent unilateral vocal cord paresis is 2.5%, no cases of bilateral recurrent nerve damage occurred. The frequency of unilateral vocal cord paresis is found to be 1.4%, if nerves of risk are considered. The incidence of hypocalcemia requiring permanent treatment reaches 2%. Intrathoracic goitre can be treated surgically with an only slightly elevated risk for surgical complications and permanent sequelae, especially when performed in the elective phase and within the frame of centre facilities. Intrathoracic components can nearly always (97%) be reached through cervical incision.

Adult↗

[Surgical treatment of benign recurrent goiter. Technique, complications and permanent sequelae].

Centre experience of reoperation for recurrent goitre in 82 patients during an 11-year period is analysed. The lateralposterior approach is used as a standard surgical technique. Postoperative complications are prevalent only among patients previously operated on the thyroid gland twice or more, among patients with recurrent intrathoracic goitre, and among patients with large goitre relapse. Frequency of permanent unilateral vocal cord paresis amounts to 3.6%. There were no cases of bilateral recurrent nerve damage. The incidence of hypocalcemia requiring permanent treatment reaches 1.2%. Centre experience tends to reduce surgical complications rates with increasing specialized training. The surgical treatment for recurrent goitre ought to be radical to avoid further relapses. We recommend lobectomy in cases of unilateral recurrence and lobectomy of the dominant lobe with contralateral resection in case of bilateral relapse.

Adult↗

Patient's and doctor's delay in primary breast cancer. Prognostic implications.

In a study of 7,608 patients with primary breast cancer patient's and doctor's delay were examined in relation to age, tumour size, grade of anaplasia, and number of positive lymph nodes. The delays were arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The well-established patient and tumour characteristics were shown to have prognostic significance. Similarly the delays showed significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was superior for patients with a long doctor's delay compared to those with a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a shorter and by 13% for a short doctor's delay compared to a longer. This indicates that doctors are capable of distinguishing between more and less aggressive malignancies. The study also suggests that all sources of delays should be kept at a minimum.

Adult↗

Primary hyperparathyroidism: incidence and clinical and biochemical characteristics. A demographic study.

OBJECTIVE: To give a demographic description of primary hyperparathyroidism (pHPT) in a region in which the incidence of operative treatment was low (2/100,000 inhabitants/year) and to describe the association between histology, biochemistry, and morbidity among the patients. DESIGN: Retrospective study. PATIENTS: 107 consecutive patients who were operated on for pHPT referred for surgery during an 11 year period in a population comprising one million people. RESULTS: The median weight of adenomas was 1,300 mg (range 200-13,500), weight o hyperplastic tissue removed was median 1,500 mg (range 100-23,800). Weight of abnormal parathyroid tissue correlated significantly with preoperative serum calcium concentration (r = 0.50, p < 0.001). Preoperatively serum immunoreactive parathyroid hormone concentration was correlated with serum calcium concentration (r = 0.39, p < 0.001) and with serum creatinine concentration (r = 0.52 p < 0.001). In a quarter of the patients the serum calcium concentration fell below 2.0 mmol/l after operation. In this subgroup the weight of pathological parathyroid tissue was significantly higher than among those who did not develop hypocalcaemia. Preoperative serum calcium concentration was unrelated to postoperative hypocalcaemia. CONCLUSION: Patients from an area in which few operations are done for pHPT had biochemically and clinically advanced disease compared with patients from comparable areas in which more operations are performed. There is a good correlation between biochemistry, organ involvement, and histology. The serum concentration of calcium preoperatively seems to underestimate the presence of advanced disease in patients in whom the bones are affected.

Adenoma↗