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.     

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide). METHODS: During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.     

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.     

One-year sequential follow-up of venous emptying rate and leg temperature profiles after acute deep vein thrombosis

In order to study the natural course of venous flow and temperature reaction in the legs after symptomatic first episode of deep vein thrombosis (DVT), 65 patients (57 with proximal DVT) without further thromboembolic complications during the observation period were followed for 1 year by repeated plethysmography (PG) and thermography (TG). Regarding the non-invasive parameters substantial individual variations was observed during the observation period. After 1 year pathologic PG and TG were still demonstrated in 39% (I mu (95%) = /0.43 +/- 0.05/) and 65% (I mu (95%) = /1.18 +/- 0.11/), respectively, of the patients after proximal DVT. Only a minority of the patients were normalized permanently in both PG and TG during the first year. The high frequency of remaining venous obstruction and especially, persistent thermoactivity is notable and may be of clinical importance.     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

New type of spinocerebellar degeneration syndrome in a northern Swedish population

A follow-up investigation of 24 patients with hereditary spasticity in a geographically isolated northern Swedish population, first examined by Böök (1953), was performed. Fifteen of them were dead. During the period from 1950–1972 five new cases of spastic syndromes were diagnosed in this population. The patterns of clinical symptoms and the genetic associations between the new and 24 previously reported patients with spastic syndromes were analyzed. Three of the five new cases had a specific syndrome. This starts in the first years of life with ataxia, which is followed by dysarthria, spasticity and jerky intention tremor. Initially the patients are mentally normal, but there seems to be slight mental deterioration through the years. The disorder is a progressive spinocerebellar degeneration with autosomal recessive inheritance.     

Management of appendiceal masses.

OBJECTIVE: To evaluate the outcome of patients treated for appendiceal abscess, and managed either conservatively or surgically, and to describe the short and long-term outcome as well as incidence of interval appendicectomy in those treated conservatively. DESIGN: Retrospective study. SETTING: University hospital, Sweden. PATIENTS: Ninety-three patients with the diagnosis of appendiceal abscess, 50 treated conservatively and 43 who were operated on, with a mean age of 46 (14-93) years. Mean (range) follow-up for patients operated on was 65 (11-135) and for those treated conservatively 66 (6-136) months. MAIN OUTCOME MEASURES: Course of acute disease, recorded complications, recurrence of appendicitis and incidence of interval appendicectomy during follow-up. RESULTS: The duration of pain before admission was 4 (0.5-82) days for those operated on and 7 (2-60) days for those treated conservatively. A palpable mass was more common in the conservatively managed group. Complications were common among patients who were operated on. No interval appendicectomies were done during the second half of the study period. 4 of the patients treated conservatively (8%) had an underlying tumour diagnosed at follow-up. CONCLUSIONS: Operative management of patients with appendiceal masses seems to be associated with a high risk of postoperative complications and the risk of a more extensive surgical procedure. If possible, a conservative approach should be advocated. Because of inaccurate radiological imaging during the acute phase and the risk of an underlying malignancy, routine follow-up is necessary. Routine interval appendicectomy cannot be recommended.     

MRI of transplanted pancreatic islets.

A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing beta-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine.