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Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 127 records · Page 7Linked to original sources

The role of second-look laparotomy in the long-term survival in ovarian cancer.

BACKGROUND: To elucidate the role of second-look laparotomy in the management of ovarian cancer patients, were retrospectively reviewed our experience with this procedure in epithelial ovarian cancer patients. PATIENTS AND METHODS: The hospital records of 617 patients with advanced ovarian cancer were reviewed. The 308 patients who underwent second-look laparotomy were followed from four to 18 years with a median follow-up of 12 years after start of primary chemotherapy. RESULTS: Patients who achieved pathological complete response (PCR), microscopic partial response (PPR mic.), macroscopic partial response (PPR mac.), stable disease (PSD), and progressive disease (PPD) at second-look laparotomy had a median survival time of 149, 39.5, 24, 14, and eight months, respectively. Secondary surgical cytoreduction could be performed only in 101 patients with macroscopic persistent disease. The group of all patients with secondary tumor debulking had no survival advantage compared with the group of patients with PPR mac., PSD, and PPD, unable to have secondary cytoreduction. Patients left with no tumor after second-look laparotomy did not survive as long as patients who achieved PCR and PPR mic. at second-look laparotomy. Factors prolonging survival after second-look laparotomy included younger age, good pre-treatment performance status, smaller primary residual tumor size, longer interval between start of chemotherapy and second-look laparotomy, and the pathologically proven CR or PR mic. CONCLUSION: Second-look laparotomy appears to have a minor role in the routine management of ovarian cancer patients, especially in the context of the limited effectiveness of second-line therapy. This procedure should be limited to clinical treatment protocols to determine effectiveness of new agents.

Adult↗

Serum and urinary markers of types I and III collagen turnover during short-term prednisolone treatment in healthy adults.

During recent years new sensitive serum and urinary makers have been introduced for assessment of collagen turnover. The aim of the present study was to assess whether short-term prednisolone treatment is associated with any adverse effects on serum levels of the type I collagen synthesis marker, the carboxy terminal propeptide of type I procollagen (PICP); on the type I collagen degradation marker in serum, the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); on a serum marker of type III collagen synthesis, the aminoterminal propeptide of type III procollagen (PIIINP), or on the type I collagen degradation markers urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations. We studied 12 men and 8 premenopausal women aged 19-45 years (mean 31). All subjects were healthy. The design was a randomized double-blind, placebo-controlled parallel group study with a 2-day run-in, a 3-day treatment period and a 4-day run-out. During run-in and run-out no medication was given. During the treatment period the subjects took either prednisolone, 40 mg per day, or placebo. Blood and urine were collected at the last day of each period. The intergroup comparisons of run-in treatment values showed that prednisolone suppressed PICP (p < 0.001) and PIIINP (p < 0.001). PICP levels remained suppressed during run-out, whereas PIIINP returned to pretreatment levels. NO prednisolone-induced effects on ICTP or on urinary PYD or DPD were detected by the intergroup comparisons. Short-term prednisolone treatment is associated with suppressive effects on type I and III collagen turnover. Whether serum PICP is more sensitive than urinary PYD and DPD for detection of short-term suppressive effects on type I collagen turnover remains to be further evaluated.

Adult↗

Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole-grain infant cereal.

BACKGROUND: Casein phosphopeptides (CPP) are phosphorus-rich peptide fragments of casein, assumed to contribute to the high bioavailability of calcium from milk. METHODS: The effect of casein phosphopeptides on calcium and zinc absorption from infant foods was investigated. Twenty-two men and women were given single test meals extrinsically labeled with Ca and Zn. Absorption was calculated from measurements on whole-body retention of the radioisotopes. Each subject was given either rice-based cereal (n = 11) or whole-grain cereal (n = 11) on three occasions together with 250 ml water and added 0, 1, and 2 g CPP in random order. One serving of rice-based cereal contained 481 mg Ca and 1.29 mg Zn; whole-grain cereal contained 541 mg Ca and 1.77 mg Zn. One and 2 g of CPP contributed with additional 69 and 138 mg Ca, respectively. RESULTS: From rice-based cereal, fractional calcium absorption was not affected by CPP addition (mean +/- SD): 16.0 +/- 4.0% (no CPP), 17.6 +/- 4.5% (1 g CPP), and 15.8 +/- 4.3% (2 g CPP), while the total quantity of calcium absorbed was significantly improved: 7 +/- 19 mg, 97 +/- 25 mg, and 98 +/- 26 mg, respectively (p = 0.0004). Fractional zinc absorption as well as total quantity of zinc absorbed were increased with addition of CPP: 19.4 +/- 9.0% (0.25 +/- 0.12 mg), 25.2 +/- 7.5% (0.33 +/- 0.10 mg) and 23.9 +/- 5.4% (0.31 +/- 0.07 mg) at the three CPP levels (p = 0.04). From whole-grain cereal, CPP had no effect on the percentage or actual quantity of calcium absorbed: 17.0 +/- 3.2% (92 +/- 18 mg), 17.2 +/- 4.5% (105 +/- 27 mg), and 15.0 +/- 4.6% (102 +/- 31 mg), respectively. Zinc absorption was also not influenced by CPP: 16.0 +/- 5.1% (0.28 +/- 0.09 mg), 15.3 +/- 3.1% (0.27 +/- 0.06 mg) and 18.1 +/- 4.4% (0.32 +/- 0.08 mg), respectively. CONCLUSIONS: CPP addition improved calcium and zinc absorption from rice-based cereal, while no effect was seen from whole-grain cereal.

Adult↗

Synostotic frontal plagiocephaly: anthropometric comparison of three techniques for surgical correction.

Surgical correction of synostotic frontal plagiocephaly ("unilateral coronal synostosis") focuses on distortions of the forehead and orbits. Technical variations include unilateral versus bilateral fronto-orbital positioning. Surgical alignment of the deviated nasal root was introduced in our unit. Anthropometry was used to assess anatomic outcome, and results were compared in 22 children with synostotic frontal plagiocephaly who had either (1) unilateral fronto-orbital advancement ("canthal advancement") (n = 8), (2) bilateral fronto-orbital advancement/ modeling without nasal straightening (n = 7), or (3) bilateral fronto-orbital advancement/modeling with closing wedge nasal osteotomy (n = 7). Postoperative fronto-orbital asymmetry was most marked in the group I patients wherein the ipsilateral supraorbital rim was retruded 3.9 mm and elevated 2.6 mm, on average relative to the corneal apex, compared with the normal side. Group II children averaged 2-mm orbital retrusion and 2.2-mm elevation. Group III patients averaged 1.4-mm orbital retrusion and 2.9-mm elevation. These differences in orbital rim measurements among the three groups were not statistically significant. Postoperative nasal root angulation of 4 degrees or more was found in more than 50 percent of children who had either a unilateral or a bilateral procedure, without nasal correction. In contrast, primary nasal osteotomy resulted in a nasal cant of 3 degrees or less in all children. This difference in nasal angulation among the three groups was statistically significant (p = 0.035). Group III had a straighter nasal angle than groups II and I (in that order). Measurement of the distances from nasion to inner and to outer canthi also reflected persistent deviation of the nasal root. Group III children had a more central radix than either group I or II (p = 0.05). The data in this study support an operative strategy of bilateral (parallelogrammic) positioning of the forehead/ superior orbits with primary correction of nasal root angulation.

Cephalometry↗

Two pathways for induction of apoptosis by ultraviolet radiation in cultured human keratinocytes.

Loss of attachment may induce apoptosis in epithelial cells, but it is unclear whether substrate adhesion modulates apoptosis triggered by genotoxic agents such as ultraviolet radiation (UV). To investigate this issue, we plated neonatal human keratinocytes on different substrates and irradiated them with UVB. DNA strand breaks were nick-labeled to identify apoptotic nuclei. Keratinocytes grown in monolayers were less susceptible to UV-induced apoptosis than were cells freshly seeded on glass (ED50 2130 +/- 96 J per m2, mean +/- SD, versus 131 +/- 96 J per m2, mean +/- SD, respectively). This phenomenon depended on differences in integrin-mediated adhesion, because blocking of integrin beta1 with a monoclonal antibody increased sensitivity of keratinocyte monolayers to UV and an increase in beta1 integrin receptor occupancy by plating on fibronectin, type IV collagen, or keratinocyte-derived extracellular matrix diminished the UV-dependent apoptosis. Down-regulation of p53 with an anti-sense oligonucleotide did not affect apoptosis in glass-plated keratinocytes but effectively suppressed apoptosis in keratinocytes adhering via beta1 integrin. Thus, in addition to the known p53-dependent pathway, UV was able to induce a p53-independent apoptosis that could be blocked by integrin-mediated cell attachment (the integrin-sensitive pathway). The susceptibility to the p53-dependent apoptosis, but not to the integrin-sensitive process, varied among keratinocytes of different clonogenic potential: transit amplifying cells > stem cells > terminally differentiated cells. The p53-independent integrin-sensitive apoptotic pathway may provide an additional mechanism counteracting UV carcinogenesis in the skin.

Adhesins, Bacterial↗

Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer.

PURPOSE: To investigate the antiemetic effect and tolerability of the 5-hydroxytryptamine3(5-HT3) antagonist ondansetron plus the dopamine D2 antagonist metopimazine versus ondansetron alone in patients receiving platinum-based chemotherapy. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients who were scheduled to receive two consecutive courses of platinum-based chemotherapy were randomized between ondansetron 8 mg intravenously (IV) followed by 8 mg orally twice a day plus metopimazine 35 mg/m2 as a 24-hour continuous infusion followed by 30 mg orally four times a day for 4 days, or ondansetron plus placebo. The study used a double-blind, crossover, placebo-controlled design. RESULTS: Ninety-four patients completed the crossover. Complete response (CR; no emetic episodes) was obtained on day 1 in 77.7% of the patients who received the combination versus 50.0% of those who received ondansetron alone (P = .00002), and in 51.7% versus 31.0% on days 2 to 6 (P = .0009). The overall CR (days 1 to 6) was 48.9% versus 25.3% (P = .0002). Additionally, significantly less nausea was observed with the combination on day 1 (P = .0002), days 2 to 6 (P = .0001), and days 1 to 6 (P = .00004). Patient preference was 63.6% for the combination and 13.6% for ondansetron alone; 22.7% expressed no treatment preference (P < .0001; therapeutic gain 50.0%; 95% confidence interval [CI], 31.6% to 68.4%). Adverse reactions were mild and without significant differences between the two treatments. CONCLUSION: Metopimazine plus ondansetron was significantly superior to ondansetron alone, concerning all efficacy parameters assessed, in patients who received platinum-based chemotherapy.

Adult↗

Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids.

Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and 800 micrograms/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002, and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x 10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800 micrograms, caused suppression of PICP compared with fluticasone propionate, 200 micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.

Administration, Inhalation↗

1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in keratinocytes: involvement of protein kinase C.

Signaling via intercellular junctions plays an important role in the regulation of growth and differentiation of epithelial cells. Loss of cell-cell contacts has been implicated in carcinogenesis, tumor progression, and metastasis. Here, we investigated whether 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was able to stimulate the assembly of adherens junctions and/or desmosomes in cultured human keratinocytes. After 4-day incubation, 1,25-(OH)2D3 caused assembly of adherens junctions, but not desmosomes. The adherens junctions were identified upon known ultrastructural criteria and evidence of the translocation of specific junctional proteins (E-cadherin, P-cadherin, alpha-catenin, and vinculin) to the cell-cell borders. The presence of alpha-catenin and vinculin at cell-cell borders indicated that the adherens junctions were functional. This was further supported by showing that anti E-cadherin antibody inhibited the 1,25-(OH)2D3-induced keratinocyte stratification. A relation between protein kinase C and adherens junction regulation was noticed. 1,25-(OH)2D3-dependent formation of junctions was blocked by the inhibitors of protein kinase C, bisindolylmaleimide and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), and treatment of keratinocytes with 1,25-(OH)2D3 caused a rapid activation of protein kinase C and its translocation to the membranes. Formation of intercellular contacts may be an important mechanism of 1,25-(OH)2D3 action in hyperproliferative and neoplastic diseases.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Effect of chronic ethanol on reproductive and growth hormones in the peripubertal male rat.

Ethanol (EtOH) has previously been shown to have profound effects on various endocrine systems. The present study further investigates the action of EtOH on testosterone and on the GH-IGF-I axis. Since these hormones are particularly important in male rats progressing through puberty, we examined the effect of 10 days of EtOH treatment at three different ages (35, 50 and 65 days old) as male rats progressed through puberty into adulthood. After 10 days of feeding a 6% EtOH liquid diet, serum testosterone levels were markedly decreased in all three ages (P < 0.02 at 35 days, P < 0.01 at 50 days and P < 0.03 at 65 days). IGF-I was assessed and was differentially affected at each age. At 35 days IGF-I levels were suppressed by EtOH (P < 0.0002), at 50 days no change was apparent, and at 65 days levels were significantly higher in EtOH-treated (P < 0.01) compared with liquid-fed controls. The levels of IGF-I in the EtOH-treated animals paralleled pituitary GH mRNA levels with a significant fall in the expression of GH mRNA levels noted at 35 days (P < 0.04), no change at 50 days and a significant rise observed at 65 days (P < 0.03). At the hypothalamic level, GH-releasing hormone (GRF) mRNA was significantly reduced in the two younger EtOH-treated age groups compared with controls (P < 0.04 at 35 days; P < 0.02 at 50 days). At 65 days of age, EtOH did not alter GRF mRNA levels. No EtOH-induced changes were seen in GRF content at any age. These observations indicate definite age-related alterations in hormonal gene expression and circulating serum hormone levels and emphasize the importance of studying these critical peripubertal ages after chronic EtOH exposure.

Animals↗

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis.

The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but the combinations are expected to be equally effective. A disadvantage of the cisplatin-based regimen is that patients need to be admitted to the hospital. The carboplatin regimen can be administered to outpatients. We tested both combinations administered every 3 weeks in a randomized phase III study in patients with previously untreated epithelial ovarian cancer. An interim analysis for toxicity was performed in 145 patients shortly after study closure. We observed a difference in the incidence of nausea, vomiting, and neurotoxicity favoring the women treated with the carboplatin regimen, but this regimen caused more myelotoxicity. Maturation of the study is awaited before survival data can be analyzed and final conclusions can be drawn.

Adult↗

[Blunt thoracic trauma--therapeutic relevance of results of roentgen image, ultrasound and computerized tomography].

In 60 patients with severe thoracic trauma the diagnostic procedures--X-ray of the chest, sonography and thoracic computed tomography (CT)--were reviewed for their incidence of finding all injuries. X-ray of the chest often failed to detect lung contusion and injuries in the mediastinal space. Four of five ruptures of the diaphragm were incidental findings on the occasion of laparotomy because of intraabdominal bleeding.

APACHE↗

[Headache, fatigue and edema of the lower limbs during the third trimester of normal pregnancy].

A series of 180 pregnant women with normal pregnancies participated in the study. A questionnaire concerning the presence of headache, fatigue and oedema of the lower limbs was filled out daily from the 30th gestational week to delivery. After the study period 120 questionnaires, of whom eight were excluded, were available for analysis. The weekly prevalences of headache and fatigue during the observation-period were nearly constant with values of 20% and 50%, respectively. The weekly prevalence of oedema increased significantly from 20% in the 31st week to 60% in the 42nd gestational week. Thirty-five percent had not suffered from headache, 22% did not report fatigue, and 42% did not describe oedema at all during the third trimester. The prevalence of headache and fatigue correlated significantly to increasing parity whereas headache was significantly correlated to decreasing age. Headache, fatigue, and oedema are common symptoms in the third trimester of normal pregnancy, and as such their presence alone should not usually give cause for suspicion of disease.

Edema↗

SV40-like sequences in human bone tumors.

Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by polymerase chain reaction (PCR) with primers that amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Southern blot hybridization, and sequence analysis revealed that these samples also contained sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein. These results indicate that SV40-like sequences are present in human bone tumors.

Base Sequence↗

Treacher Collins syndrome: phenotypic variability in a family including an infant with arhinia and uveal colobomas.

We report extreme expression of Treacher Collins syndrome in an infant with arhinia, anotia, absent zygomatic bones, hypoplastic mandibular rami, and bilateral coloboma of iris, choroid plexus, and optic nerves. The Treacher Collins phenotype was mildly expressed in the mother and moderately in the sister. The father had no signs and was not ruled out as the father by DNA fingerprinting, thus making homozygosity by descent in the severely affected son very unlikely.

Adult↗