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Martin Bak

Publications and source records attributed to Martin Bak.

8 recordsLinked to original sources

Prediction of metastasis from low-malignant breast cancer by gene expression profiling.

Promising results for prediction of outcome in breast cancer have been obtained by genome wide gene expression profiling. Some studies have suggested that an extensive overtreatment of breast cancer patients might be reduced by risk assessment with gene expression profiling. A patient group hardly examined in these studies is the low-risk patients for whom outcome is very difficult to predict with currently used methods. These patients do not receive adjuvant treatment according to the guidelines of the Danish Breast Cancer Cooperative Group (DBCG). In this study, 26 tumors from low-risk patients were examined with gene expression profiling. An intermediate risk group of 34 low-malignant T2 tumors that fulfilled all other low-risk criteria than tumor size was included to increase statistical power. A 32-gene classifier, HUMAC32, was identified and it predicted metastases with 80% sensitivity and 77% specificity. The classifier was also validated in an independent group of high-risk tumors resulting in comparable performance of HUMAC32 and a 70-gene classifier developed for this group. Furthermore, the 70-gene signature was tested in our low- and intermediate-risk samples. The results demonstrated high cross-platform consistency of the classifiers. Higher performance of HUMAC32 was demonstrated among the low-malignant cancers compared with the 70-gene classifier. This suggests that although the metastatic potential to some extend is determined by the same genes in groups of tumors with different characteristics and risk, expression-based classification specifically developed in low-risk patients have higher predictive power in this group.

Biomarkers, Tumor↗

Effects of the adenosine A1 receptor inhibitor FK 838 on proximal tubular fluid output in rats.

BACKGROUND: Adenosine A(1) receptor blockade has been suggested as a treatment in conditions with sodium and fluid retention because it increases urinary Na(+) excretion and increases proximal tubular fluid output. In the present study, we examine the time course for the renal responses to adenosine A(1) receptor blockade in order to investigate whether the effects may be prolonged and not just temporary. METHODS: The acute effects of the adenosine A(1) receptor inhibitor FK 838 on segmental tubular Na(+) handling were examined by a renal clearance technique in conscious chronically instrumented rats. Lithium clearance (C(Li)) was used as a clearance marker of proximal tubular fluid output. RESULTS: Acute adenosine A(1) receptor inhibition did not affect the glomerular filtration rate (GFR) significantly. In contrast, the inhibition led to significant increases in C(Li) (from 290+/-28 to 431+/-28 microl/min/100 g), fractional Li(+) excretion (FE(Li)) (from 33+/-2 to 47+/-3%) and fractional Na(+) excretion (FE(Na)) (from 0.44+/-0.07 to 2.03+/-0.42%). Sodium excretion, expressed as a fraction of proximal tubular fluid output (C(Na)/C(Li)), rose from 1.3+/-0.2 to 4.2+/-0.4%, suggesting that the natriuretic effect was supported by inhibition of distal nephron Na(+) reabsorption. All values returned to baseline values during the clearance study and thereby indicated that neither proximal tubular fluid output nor urinary sodium excretion remained elevated for a prolonged time. CONCLUSION: It is concluded that in conscious unstressed rats, acute adenosine A(1) receptor inhibition by FK 838 led to a significant natriuresis that was caused by inhibition of proximal tubular Na(+) reabsorption, possibly with a contribution from inhibition of distal nephron Na(+) reabsorption. The increased proximal tubular fluid output and the increased urinary Na(+) excretion returned to baseline values during the clearance study, indicating that none of these effects of adenosine A(1) blockade were long lasting.

Adenosine A1 Receptor Antagonists↗

[Fibroadenoma of the breast--modern strategy of treatment].

Fibroadenoma is the third most frequent palpable phenomenon in the breast in women and is most often seen around the age of 30. The size varies but is in average between one and three centimeters. Fibroadenomas originate from a breast lobule and can be situated anywhere in the breast. The ethiology is uncertain but it seems as if hormonal factors play a role. Investigations have shown that many of the fibroadenomas decrease in size and even more regress. The traditional treatment of fibroadenomas is excision but a conservative treatment seems to be reasonable. We conclude that fibroadenomas in adolescents can safely be treated conservatively after having been examined by an experienced breast surgeon. In adult women a benign triple test is a prerequisite for conservative treatment.

Adolescent↗

A model for intracortical visual prosthesis research.

In the field of visual prosthesis research, it has generally been held that animal models are limited to testing the safety of implantable hardware due to the inability of the animal to provide a linguistic report of perceptions. In contrast, vision scientists make extensive use of trained animal models to investigate the links between visual stimuli, neural activities, and perception. We describe an animal model for cortical visual prosthesis research in which novel animal psychophysical testing has been employed to compensate for the lack of a linguistic report. One hundred and fifty-two intracortical microelectrodes were chronically implanted in area V1 of a male macaque. Receptive field mapping was combined with eye-tracking to develop a reward-based training procedure. The animal was trained to use electrically induced point-flash percepts, called phosphenes, in performing a memory saccade task. It is our long-term goal to use this animal model to investigate stimulation strategies in developing a multichannel sensory cortical interface.

Animals↗

Mammography screening in the county of Fyn. November 1993-December 1999.

This report covers the outcome of the first three invitation rounds of the organised mammography screening programme in the county of Fyn. The programme started in November 1993, and the third invitation round ended on 31 December 1999. The screening takes place either at a special clinic located at University Hospital Odense or in a mobile unit. Women living in and around the city of Odense are examined at the clinic (about 55%), while the rest are examined in the mobile unit. Two-view mammography is used at the first screening. Women with dense breast tissue will continue to have two-view mammography (about 60%), whereas the rest will have singleview mammography at the subsequent screens. All screening images are exposed at the mammography-screening clinic and evaluated with double reading in the clinic. The programme targets women aged 50-69, except those undergoing treatment for breast cancer or going for regular check-ups following breast cancer. Based on the updated population register, the IT-Centre of the county of Fyn issues the invitations. Invited are all women aged 50-69 and living in the county of Fyn when their general practitioners' patients are invited. During the first 3 invitation rounds, 136,079 screening tests were made. Of these, 129,375 tests were made in the women aged 50-69 targeted by the programme. In addition, 6682 screening tests were made in women aged 70 and above, and 22 screening tests were made in women below the age of 50. As a consequence of the mammography screening 2657 assessments were made, 1145 women had surgery, 782 women were diagnosed with invasive breast cancer, and 109 women were diagnosed with ductal carcinoma in situ. A participation rate for the first invitation round was calculated immediately after the end of the round based on the number of participants divided by the number of women invited. This percentage was 88%. Invitation data are, however, not stored. It is therefore not possible now to calculate the participation rates in previous invitation rounds based on the same method. We have therefore chosen to calculate the participation rate as the coverage, i.e. the number of participants divided by the average number of women in the county of Fyn during a given invitation round. Calculated in this way, 84% participated in the first round, 84% in the second round, and 82% in the third round. It should be remembered that these figures do not take into account that some women are not invited because they 1) were undergoing current treatment for breast cancer or going for regular check-ups following breast cancer, or 2) did not participate in the previous round (and never actively informed the programme that they wanted an invitation to the next invitation round), relevant only for the second and third invitation round. For the second and third invitation rounds, the programme only invited women who participated in the previous invitation round, asked the clinic for an invitation, or entered the target population since the last invitation round. Therefore the participation rate in the second invitation round among actually invited women will be close to 94%, as 94% of those participating in the first round came for the second round. For the third invitation round, the participation rate among actually invited women will be close to 96%, as 96% of those participating in the first and second rounds came for the third round. One per cent of the participants in the first invitation round were diagnosed with invasive breast cancer or ductal carcinoma in situ. The detection rate was 0.5% in both the second and third invitation rounds. Ductal carcinoma in situ cases constituted 14% of the detected cases in the first and second rounds, and 10% in the third round. The percentage of invasive breast cancer 10 mm of less was 38%, 31%, and 32%, respectively, and 68%, 74%, and 73%, respectively, were node-negative. The screening programme of the county of Fyn fulfilled all the quality assessment parameters specified by the European guidelines on breast cancer screening, except two. The proportionate interval cancer rate was higher than specified in the guidelines, probably mainly due to the fact that the Fyn programme operates without early recalls. The proportion of stage II+ cancers was higher than specified in the guidelines, which seems, however, to be due to inconsistency between some of the performance indicators in the European guidelines. This analysis of the outcome from the first three invitation rounds of the mammography screening programme in the county of Fyn thus showed that it is a programme of high quality with a favourable profile of the prognostic indicators. The screening programme is hopefully well on its way to reducing breast cancer mortality in the county of Fyn.

Aged↗

Renal enlargement precedes renal hyperfiltration in early experimental diabetes in rats.

The order of appearance between renal hypertrophy and hyperfunction in early experimental diabetes is still disputed. The reason for previous discrepant results is believed to be methodologic problems, as most previous studies of renal function have been performed in anesthetized animals. In the present study in nondiabetic and streptozotocin-diabetic animals, renal volume was measured by a noninvasive magnetic resonance imaging technique, while renal function parameters were measured in conscious, chronically catheterized animals. To avoid artifacts caused by the procedures associated with induction of streptozotocin-diabetes (fasting, brief anesthesia, and transient hypoglycemia) on renal growth and function, diabetic animals were injected with insulin to obtain euglycemia for 4 d before study start. At day 0, insulin administration was withdrawn and all animals developed hyperglycemia within 12 h. Renal volume and kidney function were measured on days 0, 1, 2, 3, 5, and 7. Renal enlargement was detectable at day 1 (20%) and reached an increase of 40% at day 7. No changes were seen in effective renal plasma flow or effective renal vascular resistance within the first 7 d after development of hyperglycemia. GFR tended to rise on day 5 and was increased by 16% at day 7. The absolute proximal reabsorption showed a pronounced rise (30%) at day 7, whereas no change was seen in the proximal tubular fluid output. It is concluded that renal enlargement precedes renal hyperfunction in the early phase after onset of experimental diabetes.

Absorption↗