MDR1 gene expression and drug resistance of AML cells

We investigated the cellular drug resistance to aclarubicin (Acla), cytosine arabinoside (Ara-C), daunorubicin (Dau), doxorubicin (Dox), etoposide (Etop) and mitoxantrone (Mitox) using the MTT assay at time of disease presentation in 93 cases of acute myeloid leukaemia (AML). In 31 cases we concomitantly investigated MDR1 (multiple drug resistance 1 gene) expression (semi-quantitative competitive RT-PCR) of the leukaemic cells. Drug resistance towards Dau, Dox and Etop was correlated to the MDR1 expression of the AML cells ( P  < 0.05) with high MDR1 expression being associated with high drug resistance towards these drugs. Although the data did not allow firm conclusions to be drawn on the correlation between MDR1 expression and drug resistance towards Ara-C and Mitox, the drug resistance towards Acla clearly was not correlated to, or dependent on, the MDR1 expression level of the AML blast cells. In addition, when examining the cross-activities among the six drugs distinct patterns emerged. Thus, high to very high degrees of cross-activity were found to exist between Dau, Dox, Etop and Mitox, whereas Ara-C had moderate cross-activity with the other drugs except Acla, which showed absent to moderate cross-activity with the other drugs. We conclude that MDR1 gene expression is of significance for cellular drug resistance towards specific (MDR1-related) drugs in AML, whereas it is not of significance regarding drug resistance towards other drugs, which is the case with the anthracycline Acla. We suggest that in the place of other more or less complicated ways to circumvent MDR1-mediated drug resistance, Acla may be used to replace Dau, Dox and other MDR1-related drugs if proven as potent as the drug it is to substitute.     

Long-term outcome after ruptured lateral ankle ligaments: A prospective study of three different treatments in 79 patients with 11-year follow-up

In a prospective study of 79 patients with arthro-graphicalfy verified acute ruptured lateral ankle ligaments we have evaluated the long-term results of 3 different treatments: operation and walking-cast tor 5 weeks, walking-cast alone, and elastic bandage. The follow-up period was 11 (9-13) years. Residual disabilities and late complications, such as instability, pain on activity, and the number of ligament reconstructions and talocrural arthroses were equally low in all 3 groups.

We conclude that noooperative treatment seems adequate.     

Skin burned by contact with flagstones made of cement.

Chemical burns account for few admissions to burns units. A well-known but rare cause is wet cement. We present a case where a man had a full-thickness skin burn after contact with flagstones made of cement.     

Patient-reported outcomes after breast reconstruction with deep inferior epigastric perforator flaps.

We assessed patient-reported outcomes in 34 women who had had their breasts reconstructed with a deep inferior epigastric perforator (DIEP) flap, and compared them with those of 24 patients who were waiting for breast reconstruction. Both groups completed the Short Form 36 (SF-36) questionnaire. The DIEP flap group also assessed their preoperative conditions retrospectively and completed a study-specific questionnaire. The DIEP group reported higher SF-36 mental health scores after the operation than before, but no difference on other SF-36 scales. There was no difference on any SF-36 scale between patients who had had DIEP flaps and those waiting for reconstruction. Most of the DIEP group was satisfied with their bodies, the appearance of their breasts after reconstruction, and would have chosen operation again. In conclusion, there was little improvement in generic health-related quality of life after reconstruction with a DIEP flap. However, patients' satisfaction was high after the procedure.     

Skin viability and wound strength in single and multiple based perforator flaps in an experimental rat model.

Our aim was to evaluate the effect of single and multiple based perforator flaps on the skin viability and wound strength in rats. We used 17 Wistar rats in which two symmetrical abdominal flaps were raised around the midline. On one side all major perforators to the flap were left intact, and on the other side only one perforator was retained. After dissection, the flaps were sutured back in their original position. After seven days each rat was killed and the skin viability and wound strength were measured. The multiple based perforator flap had a mean skin viability of 98% compared with 95% in the single based perforator flap (p =0.08). The mean (SD) wound strength was 3.8 (0.9) N in the multiple based perforator flap compared with 3.0 (1.1) N in the single based perforator flap (p =0.02). We conclude that there is significantly greater wound strength at day 7 with the multiple based perforator flap than with the single one.     

Associations between maternal socioeconomic position and psoriasis: a cohort study among the offspring of the Danish National Birth Cohort

Psoriasis is a common skin disease that is often characterized by well-defined red or scaly patches on the skin. The disease affects approximately 0.4 percent of children in Denmark, with similar rates in other western countries. Psoriasis occurring in childhood may be referred to as paediatric-onset psoriasis. In this Danish study, the authors aimed to find out whether children with a lower socioeconomic position (from families with lower education, income and employment) were more likely to suffer from paediatric-onset psoriasis compared to those with a higher socioeconomic position. The authors used data from a study in which mothers and their children participated from pregnancy and the children's birth until the children were 11 years old. At the 11-year follow-up of children, mothers were asked whether their child had psoriasis. Information on socioeconomic position was gathered by using data from official databases on the mothers’ income, education and work. The authors investigated whether these factors affected the chances of their child developing paediatric-onset psoriasis and found that they were strongly related. Children whose mothers had a lower education or income were more likely to have paediatric-onset psoriasis than children whose mothers had a higher education or income. Social and economic circumstances at birth and in childhood appear to play a role in the risk of getting paediatric-onset psoriasis.     

Social inequality and incidence of and survival from male genital cancer in a population-based study in Denmark, 1994-2003

We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from prostate and testicular cancer diagnosed 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on data on 8279 men with prostate cancer and 1770 with testicular cancer in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. We found that men with higher education and the highest disposable income had the highest incidence of prostate cancer. The 1-year and 5-year relative survival after prostate cancer were best amongst men of the highest socioeconomic position. We found no substantial social gradients in the incidence of or survival from testicular cancer.     

The Effect of a-Trinositol on Cholera Toxin-Induced Hypersecretion and Morphological Changes in Pig Jejunum

Abstract: α-Trinositol (D-myo-inositol 1,2,6-trisphosphatc, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenous α-trinositol on basal and acute fluid transport and morphological changes following cholera toxin administration in pig jejunum in vivo. Using isolated jejunal tied-off loops, the fluid hypersecretory (accumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4 , 8, 16 and 32 mg×kg^-1×hr^-1) of α-trinositol. Levels of α-trinositol, as well as stereomicroscopical, light microscopical and scanning electron microscopical morphological studies were performed. Cholera toxin evoked a dose-dependent fluid hypersecretion. Treatment with α-trinositol caused a dose-dependent inhibition of the cholera toxin-induced fluid hypersecretion and did not affect basal fluid absorption. The 16 mg×kg^-1xhr^-1 α-trinositol dose gave a maximal inhibition of 36%. Morphological studies showed only minor changes following 6 hr of exposure to 20 μg×loop^-1 cholera toxin. These changes consisted of dilation of the villus capillaries, an increase of apical membrane blebbing and a reduction of the intercellular space. Treatment with 16 mg×kg^-1+hr^-1 a-trinositol alone did not induce any morphological changes, and did not alter the morphological changes induced by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, a-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering basal fluid absorption, basal morphology, or cholera toxin-induced morphological changes in pig jejunum in vivo.     

Epimerization and stability of two new cis-benzo[a]pyrene tetrols by the use of liquid chromatography-fluorescence and mass spectrometry

Quantitative determination of the hydrolysis products from proteins and DNA gives valuable information regarding the reactive metabolite that forms the protein and DNA adduct. Quantification of protein-benzo[a]pyrene (BP) adducts represents a more sensitive method than quantification of BP-DNA adducts. The aim of the present study was to identify two hydrolysis products from BP-derived protein adducts found in vitro and in vivo in a previous study. Male Wistar rats were injected i.p. with BP, and serum albumin was isolated and subjected to acid hydrolysis at 70 degrees C for 3 h. The hydrolysate was subjected to LC separation, and fractions of the two unknown compounds were collected. The molecular masses of the two unknown compounds were in accordance with being tetrols as judged by LC electrospray mass spectrometry. The fragmentation patterns were characteristic of tetrols with formation of the molecular ion and the loss of water molecules. In addition, the compounds were subjected to acid hydrolysis at 70 degrees C with 0.1 M HCl for 3 h. We observed that two of the known tetrols epimerized to the two unknown tetrols and vice versa. This is probably a characteristic epimerization involving not only position C(10)-OH but also another site like position C(7)-OH. The in vivo findings of the two unknown adducts are probably the result of the formation of BPDE III in the metabolism of BP. These two tetrols must then have the C(7)-OH and C(8)-OH groups in a cis position.     

Microcirculation in single and multiple-based perforator flaps in an experimental model of rats.

Our aim was to evaluate the effect of single and multiple-based perforator flaps on the microcirculation in rats. Two symmetrical abdominal flaps were raised around the midline in 17 rats, and sutured into their original positions after dissection. All major perforators in the flap were left intact on one side, and on the opposite side only one perforator was retained. The microcirculation in the flaps was measured with laser Doppler perfusion imaging at different time intervals. Before dissection of the flap the mean (SD) microcirculation was 5.5 (1.6) units in the multiple-based perforator flap and 5.5 (1.4) in the single-based perforator flap. Within the first two hours after the flap had been raised the highest microcirculation was found after 30 minutes with 7.3 (1.3) units in the multiple-based perforator flap compared with 6.5 (1.4) units in the single-based perforator flap (p = 0.002). We conclude that the microcirculation in the single-based perforator flap was not reduced after dissection. However, a reactive hyperaemic response was found only in the multiple-based perforator flap.