Long-term changes in mood of an aged population: repeated Zung-tests during a 10-year follow-up

Associates and predictors of lowered mood were investigated in a 10-year prospective study of 411 random persons of three birth cohorts (aged 75, 80 and 85 years) in Helsinki, Finland. High Zung-score ( > 45 points = lowered mood) was found in 24% of subjects and clearly associated with age. Lowered mood was also associated with pessimistic attitudes towards life and impaired survival prognosis. The mean Zung-score fell drastically during the first follow-up (from 39.1 to 34.6 points, P < 0.001) and remained unchanged thereafter at 10-year examination of the survivors (33.9 points). Lowering mood (increase in Zung-score) was best predicted by low baseline Zung-score (r = -0.673, P < 0.001), high baseline MMSE-score (r = -159. P < 0.05) and simultaneous changes in MMSE-scores (r = 0.269, P < 0.01). The data show that lowered mood is associated with pessimistic attitudes towards life, cognitive impairment and impaired survival and that cognitive impairment exposes a patient to lowering mood. It is possible that a screening program improves the mood of aged population.     

Clinical study of biocompatibility between open and closed heparin-coated cardiopulmonary bypass circuits

The objective of this study was to investigate the difference between the closed circuit system and the open circuit system in clinical heparin-coated cardiopulmonary bypass (CPB) circuits with a centrifugal pump. We evaluated the coagulation, fibrinolysis, and inflammatory response in valvular heart surgery. Nineteen patients were assigned at random to a group for the closed circuit system or the open circuit system. This is the first report on the effect of a closed circuit in valvular surgery. We measured the platelet count, white blood cell count, plasma fibrinogen concentration, thrombin–antithrombin III complex, plasmin-2 plasmin inhibitor complex, D-dimer, interleukin-6, polymorphic neutrophil-elastase, and the plasma free hemoglobin. Blood samples were collected before the start of perfusion, 15 and 60min after the start of perfusion, 60min after the administration of protamine, and 1 day after the operation. During the perfusion, coagulation, fibrinolysis, and inflammatory responses were activated; however, no significant differences between the two groups were noted. In this clinical investigation with suction and the cell saving system, the closed circuit was not found to be superior to the open circuit with regard to biocompatibility.     

Quantitative determination,by real-time reverse transcription polymerase chain reaction,of aromatase mRNA in invasive ductal carcinoma of the breast

Background

Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-α. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited.

Methods

We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought.

Results

It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-α positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression.

Conclusion

These findings imply that ER-α and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression.

     

Transsphenoidale Frühdekompression bei indirekter traumatischer Optikusneuropathie

Zusammenfassung Hintergrund: Die indirekte traumatische Optikusneuropathie ist ein akut visusbedrohendes Krankheitsbild, dessen Therapie einer engen interdisziplin?ren Zusammenarbeit bedarf. Das therapeutische Vorgehen wird in der Literatur kontrovers diskutiert. Basierend auf Erfahrungen bei Rückenmarktraumata wird initial eine hochdosierte Steroidtherapie empfohlen, um sekund?re Traumafolgen zu minimieren. Der Wert einer zus?tzlichen chirurgischen Dekompression wurde zwar in mehreren Studien best?tigt, diese wird aber noch nicht grunds?tzlich empfohlen. In dieser Arbeit stellen wir unsere Ergebnisse der transsphenoidalen Optikusdekompression vor. Patienten und Methode: Bei 9 konsekutiven Patienten mit indirekter traumatischer Optikusneuropathie und hochgradigem Visusverlust (nulla lux, lux projectio falsa) wurde eine transsphenoidale Optikusdekompres-sion mit gleichzeitiger systemischer Mega-dosissteroidtherapie durchgeführt. Ergebnisse: Bei 5 Patienten zeigte sich postoperativ eine Visusverbesserung auf 1/35 bis 0,5. Bei 4 Patienten konnte kein Visusanstieg erreicht werden. Diskussion und Schlu?folgerung: Einige Autoren empfahlen, auf eine chirurgische Dekompression zu verzichten, wenn unmittelbar nach dem Unfall eine Erblindung vorliegt. Diese Situation lag bei 7 dieser Patienten vor. Der Visus von 4 Patienten blieb trotz chirurgischer Therapie bei nulla lux. Bei 3 der 7 Patienten konnte jedoch durch die Frühdekompression kombiniert mit Steroidtherapie ein Visusanstieg von Amaurose auf 1/35, 0,2 und 0,4 erreicht werden. Diese Erfahrung spricht zusammen mit den positiven Ergebnissen anderer Studien dafür, auch bei einer unmittelbar nach Trauma bestehenden Amaurose eine Dekompression des N. opticus durchzuführen. Eingegangen am 23. Juni 1997 Angenommen am 20. Oktober 1997     

Hypermethylation of the WT1 and calcitonin gene promoter regions at chromosome 11p in human colorectal cancer.

The short arm of the chromosome 11, known to harbour a number of putative and established tumour-suppressor genes, is frequently hypermethylated in various human neoplasms. We subjected the promoter regions of two genes residing at 11p, namely the tumour-suppressor gene WT1 (Wilms'' tumour gene) (11p13) and the calcitonin gene (11p15.5), to methylation analysis in human sporadic colorectal cancer using genomic sequencing. Both genes showed significant hypermethylation of CpG sites within their promoter regions in adenomas and carcinomas compared with normal colonic mucosa. Although the WT1 promoter region was significantly hypermethylated, two CpG sites located in Sp1 motifs were unmethylated in the majority of cases (68-74% of carcinomas). The expression of WT1 gene, as revealed by in situ hybridization, showed no differences between normal colonic mucosa and malignant carcinoma. Together with earlier observations, our present results support the view that the short arm of human chromosome 11 is subjected to widespread regional hypermethylation in various human malignancies.     

Selective enhancement of spatial learning under chronic psychosocial stress

The hippocampus has long been proved to be implicated in several learning and memory processes. Being integrated into the limbic-hypothalamus-pituitary-adrenal axis, the hippocampus also plays an active role in the regulation of the stress response. Long lasting elevated levels of glucocorticoids resulting from a prolonged stress exposure affect hippocampal functions and structure, inducing learning and memory alterations and suppressing cell proliferation in the adult dentate gyrus. Here, adult male tree shrews (Tupaia belangeri) exposed to chronic psychosocial stress were tested repeatedly on a holeboard apparatus using two different learning tasks devised to evaluate hippocampal-dependent and hippocampal-independent cognitive function. We show that chronic stress enhanced learning in animals performing the hippocampal-dependent task, whereas no stress-induced effect was found in the hippocampal-independent task. Additionally, after five weeks of stress, cell proliferation was reduced in the hippocampal dentate gyrus. These results indicate that specific memory processes not only may remain intact, but indeed are facilitated by chronic stress, despite elevated cortisol levels and suppressed hippocampal cell proliferation.     

The antiproliferative action of a melphalan hexapeptide with collagenase-cleavable site

Purpose: The objective of the present study was to examine the relevance of collagenase in the antitumor action of a melphalan peptide (MHP) with a collagenase-cleavable sequence. The question was addressed as to whether collagenase may act as an activator or a target in the antiproliferative mechanism of MHP. Methods: Melphalan was inserted into peptides representing the sequence Pro-Gln-Gly-Ile-Ala.Gly of the collagenase-cleavable site in collagens. Changes in growth and collagenase IV activities of HT-1080, HT-29, HT-168, and MCF-7 cell cultures were investigated. Results: The present investigations provide data indicating that Pro-Gln-Gly-Ile-Mel-Gly (melphalan hexapeptide, MHP) is a substrate for both bacterial and 72-kDa type IV collagenases and that in this way it can generate Ile-Mel-Gly (melphalan tripeptide, MTP) of higher cytotoxic potency. Indeed, the formation of MTP was detected in the conditioned medium of HT-1080, a collagenase IV-producing human fibrosarcoma. In a comparison of equimolar concentrations of melphalan and its two peptide derivatives (MHP and MTP), superior antiproliferative action of MTP was seen in HT-29, HT-1080, and HT-168 tumor cell cultures. However, the relatively modest cytostatic actions of MHP were increased when bacterial collagenase was added to the cell cultures. After melphalan treatment, reduced levels of both 92 and 72-kDa type IV collagenases were seen in the HT-1080 cell cultures. However, the reduction of collagenase activity and the cell counts did not run parallel in the MTP- or MHP-treated cultures; indeed, collagenase activity related to cell numbers showed an elevated level. Conclusions: As the conversion of MHP to the more toxic MTP was detected in the presence of collagenases, it is possible that collagenase-directed activation of prodrugs may be a promising approach for the development of more selective cytostatic drugs against malignant tumors with high collagenase activities. Received: 6 October 1996 / Accepted: 22 July 1997