An exploration of patient-reported symptoms in systemic lupus erythematosus and the relationship to health-related quality of life.

OBJECTIVE: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics, and disease characteristics (duration, activity, organ damage). METHODS: In a cross-sectional study, patients with SLE (n = 324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analysed for patient demographics, disease duration, and results from the following questionnaires: the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the Systemic Lupus Activity Measure (SLAM), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Twenty-three symptom categories were identified. Fatigue (51%), pain (50%), and musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting fatigue showed a statistically significant impact on both mental and physical components of HRQoL. Patients with no present symptoms (10%) had higher HRQoL (p < 0.001) and lower levels of depression (p < 0.001), anxiety (p < 0.01), and disease activity (SLAM) (p < 0.001). CONCLUSION: Fatigue, pain, or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue.

Hand eczema and quality of life: a population-based study.

BACKGROUND: Hand eczema is a common disease in the population and is of interest from a public health perspective. Health-related quality of life (HRQoL) is increasingly being measured in dermatology. OBJECTIVES: To investigate HRQoL in relation to hand eczema in the general population. METHODS: In the Public Health Survey of Stockholm County Council 2006, a questionnaire was sent to 57 009 randomly selected individuals aged 18-84 years. The response rate among persons of working age (18-64 years) was 58%. The questionnaire included a validated question concerning hand eczema and a generic instrument for measurement of HRQoL, the EQ-5D. RESULTS: The proportion of individuals reporting problems was significantly larger among those with than without hand eczema in all five dimensions of the EQ-5D. Gender differences were found in some age subgroups. The EQ-5D index was lower for individuals with hand eczema than for those without, and on the same level as for psoriasis and asthma. Beta regression showed that the strongest confounding factors were low back pain, depression and hay fever/asthma. CONCLUSIONS: HRQoL was negatively affected in individuals with hand eczema irrespective of age. With the EQ-5D instrument it is also possible to detect certain gender differences. The EQ-5D index for hand eczema was of the same size as for psoriasis and asthma, all common diseases with an impact on public health. It is of importance to acknowledge the influence of hand eczema on daily life, in order to give the patients good care.

Remembering childhood atopic dermatitis as an adult: factors that influence recollection.

BACKGROUND: Atopic dermatitis (AD) is common in the population, and studies have shown that the disease is on the increase. Studies based on hospital records reflect selected populations and may miss less severe cases of AD, and the use of self-reported questionnaires has the drawback of recall bias. OBJECTIVES: To investigate some possible factors influencing recall bias when questionnaires are used to establish the prevalence of childhood eczema in an adult population. METHODS: A questionnaire regarding past and present eczema was sent to 557 cases (with signs suggesting the diagnosis AD) and 554 matched controls (subjects lacking signs of AD) born during 1960-1969 and identified in school health medical records. Cases and controls were aged 31-42 years at the time of the study and 70.5% returned the questionnaire. RESULTS: Of 403 cases, 29% did not report childhood eczema in the questionnaire. There was a difference between those who did recall their childhood AD (remembering group, RG), and those who did not (forgetful group, FG) in who had documented the diagnostic signs in the school health records. In the RG the signs were reported by both parents and school health personnel in 51% of cases, and in the FG this was true of only 16%. The RG had a higher prevalence of eczema after 15 years of age and of hand eczema. The RG also reported more visits to physicians after the age of 15 years and more time taken as sick leave due to eczema. CONCLUSIONS: Several factors influence how well people remember their AD in childhood. These factors include disease activity in adult life, disease severity, and who noticed the eczema in childhood.

Patterned self-assembled beads in silicon channels.

A novel technique enabling selective bead trapping in microfluidic devices without the use of physical barriers is presented in this paper. It is a fast, convenient and simple method, involving microcontact printing and self-assembly, that can be applied to silicon, quartz or plastic substrates. In the first step, channels are etched in the substrate. The surface chemistry of the internal walls of the channels is then modified by microcontact printing. The chip is submerged in a bead slurry where beads self-assemble based on surface chemistry and immobilize on the internal walls of the channels. Silicon channels (100 microm wide and 50 microm deep) have been covered with monolayers of streptavidin-, amino- and hydroxy-functionalized microspheres and resulted in good surface coverage of beads on the channel walls. A high-resolution pattern of lines of self-assembled streptavidin beads, as narrow as 5 microm, has also been generated on the bottom of a 500 microm wide and 50 microm deep channel. Flow tests were performed in sealed channels with the different immobilized beads to confirm that the immobilized beads could withstand the forces generated by water flowing in the channels. The presented results indicate that single beads can be precisely positioned within microfluidic devices based on self-assembly which is useful as screening and analysis tools within the field of biochemistry and organic chemistry.

Synthesis and application of chiral P,N-ligands with pseudo-meso and pseudo-C(2) symmetry.

[structure: see text] Two diastereoisomeric P,N-ligands, (S,S)-1 and (R,S)-1, were synthesized and assessed in palladium-catalyzed allylic alkylations. With rac-1,3-diphenylpropenyl acetate as substrate, ligand (S,S)-1, with "pseudo-C(2)" symmetry, exhibited higher reactivity and higher enantioselectivity than the "pseudo-meso" ligand (R,S)-1, whereas reversal reactivity and selectivity were observed with rac-3-cyclohexenyl acetate.

A high frequency of sequence alterations is due to formalin fixation of archival specimens.

Genomic analysis of archival tissues fixed in formalin is of fundamental importance in biomedical research, and numerous studies have used such material. Although the possibility of polymerase chain reaction (PCR)-introduced artifacts is known, the use of direct sequencing has been thought to overcome such problems. Here we report the results from a controlled study, performed in parallel on frozen and formalin-fixed material, where a high frequency of nonreproducible sequence alterations was detected with the use of formalin-fixed tissues. Defined numbers of well-characterized tumor cells were amplified and analyzed by direct DNA sequencing. No nonreproducible sequence alterations were found in frozen tissues. In formalin-fixed material up to one mutation artifact per 500 bases was recorded. The chance of such artificial mutations in formalin-fixed material was inversely correlated with the number of cells used in the PCR-the fewer cells, the more artifacts. A total of 28 artificial mutations were recorded, of which 27 were C-T or G-A transitions. Through confirmational sequencing of independent amplification products artifacts can be distinguished from true mutations. However, because this problem was not acknowledged earlier, the presence of artifacts may have profoundly influenced previously reported mutations in formalin-fixed material, including those inserted into mutation databases.

Anisomycin and verapamil influence the action of progesterone on regulation of term human myometrial contractile activity.

OBJECTIVE: Progesterone has been shown to have both stimulatory and inhibitory effects on term human myometrial contractile activity. The mechanisms involved in this action of progesterone are still poorly understood. DESIGN: Myometrial tissues were obtained from the lower uterine segment at elective Caesarean section of 30 term pregnant women. The contractile activity of muscle strips was measured by a superfusion technique and protein synthesis evaluated by [3H]-leucine incorporation. RESULTS: [3H]-leucine incorporation into term myometrial strips was not affected by progesterone (10 mumol/l), but was markedly reduced by the protein synthesis inhibitor anisomycin (P < 0.05). However, progesterone increased frequency and tonus of contractions and reduced the activity-area of contractions (P < 0.01). Anisomycin (100 mumol/l) did not change these effects or the spontaneous contractile activity. Removal or extracellular Ca2+ or addition of the L-type calcium channel blocker verapamil prevented the spontaneous as well as the progesterone-induced contractions, but had less pronounced effects on contractions initiated by oxytocin. CONCLUSION: The results indicate that the actions of progesterone on term myometrial contractile activity occur without protein synthesis and that increased Ca2+ influx or decreased outward transport of Ca2+ may play a possible role)

Effects of estradiol and interaction with progesterone or oxytocin on term human myometrial contractile activity.

BACKGROUND: To investigate the effects of estradiol (E2) alone and in combination with progesterone or oxytocin on contractile activity of term human myometrium in vitro. METHODS: Myometrial specimens were obtained from 24 term pregnant women not in labor who underwent elective cesarean. Biopsies were kept in ice-cold and oxygenated Hepes buffer and buffer containing different hormonal solutions. The biopsies were dissected and mounted in tissue baths at 37 degrees C and isometric tension was recorded. RESULTS: (1) Estradiol at 0.1 and 1 microgram/mL increased the contractile frequency (p < 0.01 for each), decreased the tonus (p < 0.05 and p < 0.01) and suppressed the activity area of contractions (p < 0.05 and p < 0.01) as compared to control. (2) No significant differences in frequency and activity area of contractions between strips superfused with E2 plus progesterone and progesterone alone were recorded. Myometrial tonus was decreased by 0.1 microgram/mL or 1 microgram/mL E2 plus progesterone as compared to progesterone alone (p < 0.05 and p < 0.01). (3) There were no significant differences in frequency between strips superfused with E2 plus oxytocin and oxytocin alone. Myometrial tonus was decreased by 0.1 microgram/mL or 1 micrograms/mL E2 plus oxytocin as compared with oxytocin alone (p < 0.05 and p < 0.01). Estradiol at 0.1 microgram/mL or 1 micrograms/mL plus oxytocin reduced the activity area of contractions compared to oxytocin (p < 0.05 and p < 0.01). CONCLUSIONS: These data suggest that E2 had both stimulatory and inhibitory effects on term human myometrial contractility and that E2 altered the myometrial response to progesterone and oxytocin mainly by decreasing tonus.

Zanvil Alexander Cohn 1926-1993.

Zanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of this Journal, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn's collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease.(ABSTRACT TRUNCATED AT 400 WORDS)