The Impact of Exacerbations on the Asthmatic Patient's Preference Scores

The purpose of this study was to examine the effect of exacerbations on mild to moderate asthmatic patients' preference-based, health-related, quality of life scores and also to describe the effect of these exacerbations on daily life. In a survey, 100 mild to moderate asthmatic patients in the United Kingdom were asked to rate three different health marker states on a scale between 0 (death) and 100 (perfect health), defined as: your asthma of today, a mild exacerbation, and a severe exacerbation of asthma. They were also asked to describe their symptoms and what they did when experiencing an exacerbation. During exacerbations the vast majority of asthmatic patients have significant symptoms and consume a considerable amount of health care resources, which often overlap. The health marker state “your asthma of today” was given a mean score of 81.0, a mild exacerbation a score of 62.1, and a severe exacerbation a score of 25.6, indicating a large impact on patients' daily life and their health-related quality of life. In conclusion, asthmatic patients are severely affected in their health and daily living by mild and severe exacerbations. Considerable effort should be made to reduce the number and severity of exacerbations.     

Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.     

Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy

Objective: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. Methods: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. Results: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml ·  min⁻¹ at week 26 to 180 ml · min⁻¹ at week 36. In 7 of 25 women, CL/F increased >20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol · l⁻¹. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. Conclusion: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml · min⁻¹ (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml · min⁻¹ in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas. Received: 3 July 1996 / Accepted in revised form: 5 November 1996     

Tick-borne Borrelia-meningitis in children. An outbreak in the Kalmar area during the summer of 1984

Nine children, aged 5 to 11 years, with subacute or chronic meningitis were studied. Symptoms started during the summer season in all patients and in eight of the patients the disease began with a localized erythematous lesion (ECM), mostly in the face. In one patient only there was a history of an insect bite at the site of the erythema. The neurological abnormalities included aseptic meningitis, peripheral facial nerve palsy (5/9) and oculomotor nerve palsy (1/9). Most children complained of headache, fatigue, loss of appetite and had a low grade fever. High antibody titers to Borrelia spirochetes in serum and/or cerebrospinal fluid (CSF) were demonstrated by ELISA in eight of the nine patients and by indirect immunofluorescence assay (IFA) in three patients. All patients had a dramatic improvement in their general condition and became afebrile within three days of institution of i.v. penicillin G treatment (i.v. cefuroxime in one patient).     

Validity of repeated dietary measurements in a dietary intervention study.

The aim of the study was to evaluate the compliance in a dietary intervention study. When drawing conclusions about the relationship between dietary intake and disease occurrence/disease-related variables it is important to obtain valid dietary data. 20 healthy, non-smoking normal-weight omnivores changed from a mixed to a lactovegetarian diet. Dietary surveys (four 24 h recalls per person and time-period), urinary and faecal sample collections were performed before and 3, 6 and 12 months after the dietary shift. The validation of energy, protein, sodium and potassium yielded approximately the same ratio of dietary intake to biological marker at 0 and 3 months. This ratio decreased towards 6 months and continued to decrease towards 12 months. The fibre intake was compared to the total faecal weight directly and indirectly by calculating the fibre intake from the stool weight, the water content in faeces and the excretion of short-chain fatty acids (SCFAs). These four methods of fibre validation showed that the ratio of dietary intake to biological marker was always highest at 12 months, indicating an overestimation of the fibre intake at the end of the study. This is the first time these methods of validating fibre intake have been used in an epidemiological study. The ratio of dietary calcium intake to urinary and faecal calcium excretion did not show any statistical difference between the period before and 3 months after the dietary shift. To conclude, almost all investigated dietary data show approximately the same validity before and 3 months after the dietary shift, and show the least validity 12 months after the dietary shift. Thus, this study demonstrates that it is difficult to obtain valid dietary data 1 year after a drastic dietary change, indicating a decreased compliance to the new dietary regimen at the end of the 1 year study period. This represents important information when attempting to relate biological effects to dietary intake, and illustrates the importance of using biological markers for food intake in dietary surveys.     

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.     

Structural and functional aspects of platelet-derived growth factor and its role in the pathogenesis of glioblastoma

The platelet-derived growth factor (PDGF) family consists of three different dimeric forms, AA, BB, and AB, of the two consitituent polypeptide chains, A and B. These interact with two different cell surface receptors that, in part, mediate different cellular functions. The various forms of PDGF, as well as the receptors, are expressed at high frequency in glioblastoma multiforme, and it has been suggested that the growth of this tumor might be affected by autocrine loops involving PDGF and its receptors. The present paper focuses on recent discoveries regarding the family of PDGF ligands and receptors, as well as reviews results concerning PDGF-dependent autocrine growth in experimental and spontaneous glioblastoma.