OBJECTIVES:To find out how patients perceive their health-related quality of life after they have been treated in an intensive care unit and whether preexisting disease influenced their perception. DESIGN:: Follow-up, quantitative, dual-site study. SETTING:Combined medical and surgical intensive care units of one university and one general hospital in Sweden. PATIENTS:Among the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the intensive care unit, and age >18 yrs). The effect of preexisting disease was assessed by use of a large reference group, a random sample (n = 10,000) of the main intake area of the hospitals. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:During 2000-2002, data were collected from the intensive care unit register and from a questionnaire mailed to the patients 6 months after their discharge from hospital. Subjects in the reference group were sent postal questionnaires during 1999. Of the patients in the intensive care unit group, 74% had preexisting diseases compared with 51% in the reference group. Six months after discharge, health-related quality of life was significantly lower among patients than in the reference group. When comparisons were restricted to the previously healthy people in both groups, the observed differences were about halved, and when we compared the patients in the intensive care unit who had preexisting diseases with subjects in the reference group who had similar diseases, we found little difference in perceived health-related quality of life. In some dimensions of health-related quality of life, we found no differences between patients in the intensive care unit and the subjects in the reference population. CONCLUSIONS:Preexisting diseases significantly affect the extent of the decline of health-related quality of life after critical care, and this effect may have been underestimated in the past. As most patients who are admitted to an intensive care unit have at least one preexisting disease, it is important to account for these effects when examining outcome.

In view of unsolved issues regarding cellular events underlying the adaptation of insulin secretion to insulin resistance, together with the observation that insulin secretion induced by the gastrointestinal hormone and neuropeptide cholecystokinin (CCK) is not solely explained by phospholipase C-protein kinase C (PLC-PKC) pathway activation, this study aimed at delineate mechanisms responsible for the hyperinsulinemia in insulin resistance, with particular attention paid to the action of glucose vs. non-glucose secretagogues, such as CCK. In glucose-intolerant and insulin-resistant high-fat diet-fed C57BL/6J mice, glucose-stimulated insulin secretion was impaired both in vivo and in vitro, whereas non-glucose-stimulated insulin secretion, by CCK or carbachol, was potentiated, revealing an important role of non-glucose secretagogues in islet adaptation to insulin resistance. Furthermore, in isolated rat islets, CCK induced activation of phospholipase A2 (PLA2), both in the presence and absence of extracellular Ca2+, indicating that CCK activates both the Ca2+-dependent and the Ca2+-independent forms of PLA2. This ability differed from that of the cholinergic agonist carbachol, which was unable to stimulate PLA2 in the absence of Ca2+. Moreover, the PLA2-activating capacity of CCK was partially dependent on PKC, whereas it was independent of the cyclooxygenase and lipoxygenase pathways. In addition, the CCK-stimulated PLA2 stimulation was decreased by activation of the cyclic AMP-protein kinase A (cAMP-PKA) pathway, which also reduced an expected CCK-induced potentiation of insulin secretion. Finally, in islets from high-fat diet-fed C57BL/6J mice, CCK-induced activation of PLA2 was exaggerated. Thus, in conclusion, these studies suggest that (i) insulin resistance increases the islet sensitivity to non-glucose stimuli. such as CCK, (ii) that the islet PLA2 signalling pathway is involved in the insulinotropic action of CCK, and (iii) that insulin resistance causes an enhanced CCK-induced activation of islet PLA2 signalling.

With the purpose of searching for chemical bases for the transfer of differentiation information through metaphase, efforts have been made cytochemically to identify chemical and physiochemical differences between different parts of metaphase chromatin in Vicia.

Fluorescent DNA-reagents with different modes of binding have been used for the purpose of identifying chemical differences along metaphase chromosomes. The DNA-distribution pattern along the chromosomes, determined with very high resolution procedures, has been used as reference when studying the differential uptake of different chromosome regions of the compounds. For quantitative measurements of the fluorescence of very small objects a special system has been developed. Several types of plant material and also Chinese hamster have been investigated. Great and reproducible differences in the uptake of the fluorescent reagents by different chromosome regions were observed. In Trillium a good correlation was found between regions reacting with several different fluorescent compounds and heterochromatin as defined by cold treatment. The looseness of the several presently used definitions of heterochromatin is stressed.

The karyotype provides valuable information about the chromosomal complement of an individual. To perform a karyotype cell culture metaphasic chromosomes (standard karyotype) or prometaphasic chromosomes (high-resolution karyotype) are required. After cell culture different banding techniques can be applied by staining whole chromosomes or specific regions of the chromosomes enabling the recognition of chromosomes and identification of specific segments of each chromosome. Karyotyping provides a chromosomal formula that summarizes a detailed description of an individual’s karyotype. Chromosomal anomalies, chromosomopathies, as numerical and structural rearrangements, are responsible for gestational losses, implantation failures, and congenital malformations, therefore karyotyping has been recommended for infertile couples.

From five normal individuals the DNA content and the DNA arm ratios of the 24 metaphase chromosomes were determined by means of scanning densitometry of photographic negatives of Feulgen-stained metaphase preparations. The results showed high reproducibility of the measuring procedure. The obtained DNA values for the 24 chromosomes showed general correspondence between the individuals. No differences between males and females were found. The DNA arm ratios showed somewhat higher inter-individual variability, especially for the acrocentric chromosomes. Our data are in agreement with other data published so far, which were obtained with somewhat different techniques, indicating that the DNA content of the individual human chromosomes in general is highly constant. Attempts were made to distinguish chromosomes by their DNA content and DNA ratio. It appears that classification of chromosomes using these parameters cannot compete with classification according to the banding patterns. Determination of the total DNA content and DNA distribution along the metaphase chromosomes may, however, provide a frame of reference for cytochemical methods directed towards the localization and quantification of molecular properties of the chromosome.