Biomedical subjects

L Lundberg

Publications and source records attributed to L Lundberg.

At least 19 recordsLinked to original sources

PubMed2000

Heroin impurity profiling. A harmonization study for retrospective comparisons.

Three laboratories present a harmonised system for the retrospective comparison of south west Asian heroin. It consists of an improved gas chromatographic (GC) profiling method and a computerised data retrieval. The investigations of the GC were necessary with a view to improve the reproducibility of the system. The necessity of a strict quality control is emphasized. The peaks of the GC profile were investigated for abundance, intensity, GC behaviour (reproducibility) and correlations; 16 of them were selected for describing the heroin profile in the database. The results from intra-lab profile comparisons are reported. The reproducibility of the analysis was good and the variation between the samples was large, thus, allowing conclusions with a high degree of certainty. The criteria of similarity were defined. The system is successfully running in all three labs. In connection with inter-laboratory comparison, the aspects of method harmonisation and standardisation are discussed. It appeared that the GC method is a very subtile one, urging for a strict standardisation between the three labs. Despite a long cooperation between three well-equipped and experienced labs, a more or less serious loss of reproducibility was noticed in the inter-lab results in comparison with the intra-lab results. The loss could for the greater part be attributed to the (limits of the) GC technique; a number of compounds, necessary for making the discrimination between samples, showed difficult chromatographic behaviour, leading to insufficient inter-lab reproducibility. Using the actual variables, improvements in performance can hardly be expected in the near future. The loss of reproducibilty implies that the number of false positive matches in a database search increases. This may strongly reduce the value of a relatively large, international database. The study shows that so far, the best option for international comparison is the analysis in a central laboratory. The idea of local determination at a large number of national labs and the use of a common database is not a realistic aim for this type of analysis.

Chromatography, Gas↗

PubMed1999

A note on validating Wagstaff and van Doorslaer's health measure in the analysis of inequalities in health.

The aim of this note is to validate Wagstaff and van Doorslaer's approach of constructing a continuous health measure to be used in the analysis of inequalities in health. We calculate health concentration indices for Uppsala County in Sweden based on three different health status measures: health measured according to the WvD approach based on a self-assessed categorical health measure, health measured by the rating scale method, and health measured by the time trade-off method. The concentration index does not differ significantly for the three health status measures, and our results thus support the validity of the WvD method.

Developed Countries↗

PubMed1999

Quality of life, health-state utilities and willingness to pay in patients with psoriasis and atopic eczema.

Skin diseases have been shown to have a significant adverse impact on the health-related quality of life of patients that may be underestimated by objective assessments of clinical severity. The main aim of this study was to measure the health-state utilities on a scale between 0 (dead) and 1 (full health) of patients with psoriasis and atopic eczema, and to measure the willingness to pay for a cure for psoriasis and atopic eczema. A second aim was to analyse how these measures are related to different dimensions of health-related quality of life, as measured by general and disease-specific quality of life instruments and a subjective measure of disability activity. This study was based on data from a questionnaire administered to, and interviews conducted with, 366 patients with psoriasis and atopic eczema aged 17-73 years, attending the dermatology outpatient clinic in Uppsala, Sweden from November 1996 to December 1997. The survey included: a rating scale question, a time trade-off question, a standard gamble question, a dichotomous choice willingness to pay question, a bidding-game willingness to pay question, a generic quality of life instrument (SF-36), a disease-specific quality of life instrument (the Dermatology Life Quality Index) and a subjective measure of disease activity (on a visual analogue scale). The mean health-state utility was 0.69 (rating scale), 0.88 (time trade-off) and 0.97 (standard gamble) for patients with psoriasis. The corresponding health-state utilities for patients with atopic eczema were 0.73, 0.93 and 0.98. On average, patients were willing to pay between 1253 and 1956 Swedish crowns (SEK) per month for a psoriasis cure and between SEK 960 and 1083 per month for an atopic eczema cure ($1 = SEK 8.25 and pound1 = SEK 13.23). The health-state utilities were related to SF-36, the Dermatology Life Quality Index and disease activity in the expected direction and the correlations were strongest for rating scale and weakest for standard gamble. The willingness to pay was correlated with the Dermatology Life Quality Index and disease activity, but not with SF-36. The study indicates that it is feasible to measure health-state utilities and willingness to pay in this patient population, and the sizeable willingness to pay suggests that skin diseases are associated with substantial reductions in quality of life.

Adolescent↗

PubMed1999

The impact of over-the-counter availability of nasal sprays on sales, prescribing, and physician visits.

OBJECTIVE: The aim was to study changes in sales and prescribing of nasal decongestants containing oxymetazoline or xylometazoline, changes in number of physician visits for rhinitis and sinusitis, and changes in public expenditures for physician visits due to the switch of these drugs from prescription to over-the-counter status in Sweden in 1989. DESIGN: Retrospective registry study using the local sales statistics on medicines in the municipality of Tierp from The National Corporation of Swedish Pharmacies and the individual-based computerised registry in Tierp based on health care utilisation and drug use from the Centre for Primary Care. Analyses were carried out during the time period 1988-1995. SETTING: The Swedish community of Tierp with about 20,000 inhabitants. SUBJECTS: The population of Tierp. MAIN OUTCOME MEASURE: Sales of nasal decongestants and dispensed prescriptions of nasal decongestants, physician visits for rhinitis and sinusitis, and public expenditures for these. RESULTS: Sales of nasal sprays increased, while sales of nasal drops decreased. The number of dispensed prescriptions as well as physician visits decreased. The public expenditures estimated for physician visits decreased as well. CONCLUSION: This study shows an increase in sales of nasal decongestants and a significant decrease in prescribing of nasal decongestants and the number of physician visits for rhinitis and sinusitis as well as the public expenditures estimated for these, after the switch from prescription to over-the counter status of nasal sprays in 1989.

Adolescent↗

PubMed1998

Effects of user charges on the use of prescription medicines in different socio-economic groups.

This study examined the sensitivity towards increases in user charges for different types of drugs and among different socio-economic groups. It was based on responses by 2008 consumers of prescription drugs to a self-administered postal questionnaire sent to a random sample of 8000 inhabitants in Uppsala County in Sweden. The questionnaire included a question about whether the respondents would use fewer prescription drugs if the user charges increased by a specific amount. The increase in user charges was varied between 9 and 150% in five different subsamples. Logistic regression analysis was used to estimate the probability that a respondent would reduce consumption of prescription drugs as a function of the size of the user charges increase, socio-economic characteristics and the type of drug used. Results showed that the price sensitivity decreased with increasing age, income, education and self-rated health status. Price sensitivity was highest for antitussives and lowest for climacteric drugs. If the user charges doubled, 40% of antitussives users would reduce their consumption whereas only 11% of climacteric drugs users would reduce their consumption. It is concluded that sensitivity to increases in user charges varied greatly between different types of drugs and between socio-economic groups. The young, those with poor health status, low education and low income are most likely to decrease consumption of prescription drugs when user charges increase.

Attitude to Health↗

PubMed1997

Naturally occurring variants of human milk bile salt-stimulated lipase.

Analysis of milk samples from a number of lactating women revealed molecular variants of bile salt-stimulated lipase (BSSL) of both lower and higher molecular mass than that commonly occurring. In contrast to previous observations, we report on individuals having only a variant of lower mass, both one of lower and one of common mass, or both one of lower and one of higher mass of the lipase. From two individuals we purified the lower molecular mass BSSL variant and characterized it. The amount of lipase in the milk of these two individuals was considerably less than average (mean of 10 women with BSSL of the most common molecular mass). The BSSL variant of lower mass showed the same bile salt activation, pH dependency, temperature stability as those most commonly occurring. We could localize the difference in mass to the large O-glycosylated repeat sequence close to the C-terminus of the protein. With respect to all characteristics studied, the BSSL variant of higher mass was also similar to that most commonly ocurring. Again, the difference in mass could be localized to the repeat region of the protein. Hence, it appears as if the repeat region, normally carrying 16 repeats of 11 amino acids each, varies in size between individuals.

Amino Acids↗

PubMed1997

Subunit G of the vacuolar proton pump. Molecular characterization and functional expression.

The vacuolar type proton pump of clathrin-coated vesicles has a multisubunit ATP hydrolytic center that is peripheral to the membrane. Polypeptides present in this domain include the well characterized subunits A, B, C, D, E, and F; SFD, a dimer composed of 50- and 57-kDa polypeptides; and polypeptides termed G and H. Of these, subunits A, B, C, and E have been shown to be necessary but not sufficient for significant ATPase activity; in addition, either polypeptide G or H is also required for ATP hydrolysis (Xie, X.-S. (1996) J. Biol. Chem. 271, 30980-30985). In this study, the polypeptides G and H were purified and directly sequenced. Subsequent molecular analysis has revealed that these proteins are isoforms, which we designate G1 and G2. The cDNAs encoding the rat and bovine brain and chicken osteoclast forms of G1 have been cloned. The open reading frames of the rat and bovine clones encode hydrophilic proteins of 118 amino acids that differ at only five residues; bovine G1 has 36% identity with VMA10, a component of the proton channel of yeast. Northern blot analysis revealed a 1. 0-kilobase pair transcript encoding G1 in bovine brain, kidney, heart, and spleen. The cDNA encoding bovine polypeptide H was cloned and sequenced, revealing this protein to be 64% identical to G1, constituting isoform G2. In Northern blot analysis, a single 1. 7-kilobase pair transcript hybridized with a probe to G2 in brain, but not in heart, kidney, or spleen. An antibody against a bovine G1-specific domain reacts with V pump from bovine brain, kidney, and chromaffin granule, whereas an anti-G2 antibody reacts only with proton pump from brain. The bovine forms of G1 and G2 were subsequently expressed in Escherichia coli and Sf9 cells, respectively, and purified to homogeneity. Reconstitution of ATP hydrolysis was achieved by combination of recombinant subunits A, B, C, and E with either recombinant G1 or G2, demonstrating the role of these isoforms in pump function.

Adenosine Triphosphate↗

PubMed1996

Recombinant human bile salt-stimulated lipase: an example of defective O-glycosylation of a protein produced in milk of transgenic mice.

The expression of recombinant human bile salt-stimulated lipase (bssl) was targeted to the lactating mammary gland of transgenic mice. Expression of recombinant genes comprising bsslcDNA, or alternatively genomic bssl DNA, under control of regulatory elements derived from the murine whey acidic protein (wap) gene was achieved and evaluated. Constructs containing genomic bssl sequences mediated high levels (0.5-1 mg ml-1) of recombinant human BSSL in the milk. The recombinant BSSL produced was purified, biochemically characterized and compared to native BSSL and recombinant BSSL produced in mouse C127 and hamster CHO cells. Recombinant BSSL derived from transgenic mice showed a different migration and distribution after SDS-PAGE electrophoresis, lower apparent molecular mass on size-exclusion chromatography and no detectable interactions with a panel of lectins. These results indicate a significantly lower degree of O-glycosylation of recombinant BSSL in milk from transgenic mice than was found for the native enzyme or recombinant CHO- or C127 cell-produced BSSL. Despite these differences, mouse-milk-derived recombinant BSSL exhibited similar lipase activity, the same stability to low pH and similar sensitivity to elevated temperatures as the native enzyme. The observation that mouse-C127-cell-produced recombinant BSSL is heavily O-glycosylated makes species-related restrictions less attractive as an explanation for the reduced O-glycosylation.

Animals↗

PubMed1996

Long-term experience of self-injection therapy with prostaglandin E1 for erectile dysfunction.

A total of 42 evaluable patients 36-80 years old were treated with intracavernous injection of prostaglandin E1 for erectile dysfunction. They reported retrospectively via a questionnaire their long-term experience of this method. Twenty-four patients (57%) were after 46.9 months still using the technique, while 18 patients (43%) had abandoned the method after 21.4 months of use. No major complications were observed or reported.

Adult↗

PubMed1996

PD treatment for severe congestive heart failure.

Our objective was to evaluate if peritoneal dialysis (PD) could improve survival of patients with progressive severe congestive heart failure resistant to drug therapy. The patients were selected by the cardiologist in cooperation with a nephrologist, including patients not responding to conventional medication with an expected fatal outcome within the next months. The study included 16 consecutive patients with a chronic progressive severe refractory heart failure (sHF) of NYHA class III (n = 6) or IV (n = 10) who did not respond to diuretics and angiotension converting enzyme (ACE) inhibitors. They had a mean age of 60 years (+/- 14, range 30-75, median 62 years). Nine of the patients had sHF as the only reason for initiating PD (all NYHA IV), while 7 also needed dialysis due to uremia. Five of 7 had been on hemodialysis but switched to PD due to a progressive congestive sHF. In 2 patients, PD was decided already at start of dialysis therapy due to the severity of their heart failure. The reason for sHF was: valvular dysfunction (n = 5) with defect prosthesis (n = 3); in the course of a myocardial infarction (n = 4); and cardiomyopathy (n = 4). Tenckhoff catheters were inserted under local anesthesia and ultrafiltration was started and maintained until discharge. The survival time and change in heart size by x-ray was used for analyses. All patients improved their stage of congestive heart failure by NYHA classification already during the first month. Six patients died during the follow-up period due to cardiac reasons (sudden death, relapse of sHF) after a mean of 10.7 months (+/- 3.7, range 1-24 months). Ten were alive after a median observation period of 10 months (+/- 12.5, range 1-36 months). Heart size was reduced in 15 of the patients. Three of the patients with sHF but without uremia could stop the PD. The results showed that ultrafiltration by PD was easy to perform despite low initial blood pressure. The sHF was reduced and life span was prolonged with improved quality of life.

Adult↗

PubMed1995

Molecular cloning and characterization of the mouse carboxyl ester lipase gene and evidence for expression in the lactating mammary gland.

DNA hybridization was used to isolate a 2.04-kb cDNA encoding carboxyl ester lipase (CEL) from a mouse lactating mammary gland, lambda gt10 cDNA library. The cDNA sequence translated into a protein of 599 amino acids, including 20 amino acids of a putative signal peptide. Comparison of the deduced amino acid sequence of the mouse CEL with CEL from five other species revealed that there is a high degree of homology between the different species. The mouse CEL gene was also isolated and found to span approximately 7.2 kb and to include 11 exons. This organization is similar to those of the recently reported human and rat CEL genes. We have also analyzed expression of the CEL gene in the mammary glands from other species by performing a Northern blot analysis with RNA from goat and cow. The results show that the gene is expressed in both species.

Amino Acid Sequence↗

PubMed1995

Recombinant human-milk bile-salt-stimulated lipase. Functional properties are retained in the absence of glycosylation and the unique proline-rich repeats.

Human milk bile-salt-stimulated lipase ensures efficient utilization of milk lipid in breast-fed infants. The N-terminal two-thirds of the peptide chain is highly conserved and shows striking similarities to typical esterases. In contrast, the remaining C-terminal part consists of a unique sequence of 16 proline-rich O-glycosylated repeats of 11 residues each. Recently we could show, using recombinant lipase variants, that neither these repeats nor the single N-linked sugar chain are essential for catalytic efficiency. In the present study, we report on the lack of importance of glycosylation and the unique repeats for other important functional properties, i.e. bile-salt activation, heparin binding, heat stability, stability at low pH and resistance to proteolytic inactivation. Compared to native enzyme, recombinant full-length lipase produced in two mammalian cell lines differed slightly in glycosylation pattern with no effects on the functional properties. Moreover, a variant lacking all repeats and the C-terminal tail following the last repeat exhibited the same functional characteristics as purified native milk enzyme. Thus, the structural basis for all the typical and functionally important properties reside in the N-terminal conserved part, in spite of the fact that none of these properties are shared by typical esterases. We could however, demonstrate that the C-terminal repeats are responsible for the unusual behaviour of the enzyme in size-exclusion chromatography, resulting in a considerably higher than expected apparent molecular mass.

Animals↗

PubMed1994

Complement activation is influenced by the membrane material, design of the dialyser, sterilizing method, and type of dialysate.

The complement system becomes activated during blood-membrane contact in the dialyser. This study was designed to evaluate to what extent the dialyser design, the sterilization method, and the type of dialysate influence complement as measured by C3d. Twelve patients were dialysed three times on each of four different dialysers. Two hollow-fibre dialysers made of cuprophane (Hf-CuE ethylene-oxide-sterilized, Hf-CuS steam-sterilized) were compared with two plate dialysers made of cuprophane (P-Cu) or polycarbonate (P-Pc). Five patients were dialysed with acetate and seven with bicarbonate. Differences in C3d between at start of dialysis and after 180 min were calculated. C3d was increased more by P-Cu than by the other dialysers (P < 0.012, n = 12). In the bicarbonate group, C3d was increased more by P-Cu than by Hf-CuS or P-Pc (P < 0.022, n = 7) and more by Hf-CuE than Hf-CuS (P = 0.013). In the acetate group, C3d was increased more by Hf-CuS and P-Cu than by P-Pc (P < 0.006, n = 5). In conclusion, complement activation during dialysis varied due to membrane material, membrane design, sterilization method, and dialysate composition.

Adult↗

PubMed1994

The prevalence of circulating anti-tubular basement membrane-antibody in renal diseases, and clinical observations.

Anti-tubular basement membrane antibodies were determined by ELISA in 217 patients with different renal diseases. The assay for antibodies in serum was based on a 58 kD bovine tubular basement membrane antigen. Sera were studied from 69 patients with different forms of interstitial nephritis; 15 patients (10 women, 5 men) had anti-tubular basement membrane titers above the normal (compared with a reference group of healthy blood donors). Three patients are presented in greater detail. Thirty-four patients with pyelonephritis (confirmed by intravenous urogram) were investigated; one serum was positive. Sera from 114 patients with renal glomerular and/or vascular disease were studied; 12 had positive titers for tubular basement membrane and glomerular basement membrane or other kidney disease antibodies. This study supports the opinion that damage in the renal medulla can be caused by an autoimmune process. Circulating anti-TBM antibodies may be of value in the investigation of patients with tubulo-interstitial diseases but the cause and prognosis of this condition is, however, not known.

Adult↗

PubMed1994

Backdiffusion or bicarbonate may stimulate complement activation during haemodialysis with low-flux membranes.

Backdiffusion of dialysate during haemodialysis with low-flux membranes and the use of bicarbonate dialysatebase, may increase the risk for contamination. The influence on the complement system was studied by altering the flux of acetate or bicarbonate dialysate base across the membrane. Eight patients were dialysed with a transmembrane pressure of 100 mm Hg (group I) during the first 60 min to standardize the ultrafiltration (UF) and acetate as dialysate. In eight other patients (group II) the UF was "set at zero" ml during the first 60 min using an FCM 10-1 monitor (Gambro) and bicarbonate as base. The groups were dialysed three times on two hollow-fiber membranes made of Hemophan and cellulose acetate (CA). Blood samples were taken at 0, 15, 60 and 180 min, and analysed for plasma protein, haematocrit and complement C3d. In group II there was a reduction in plasma protein concentration at 15 and 60 min (p < 0.002) for Hemophan and at 60 min (p < 0.01) using CA. C3d was increased at 15 min for both filters (p < 0.03). The reduction of protein in group II was followed by changes in the haematocrit, indicating a backdiffusion of dialysate, which may contribute to the concomittant increase in C3d.

Adult↗

PubMed1993

Recombinant human milk bile salt-stimulated lipase. Catalytic activity is retained in the absence of glycosylation and the unique proline-rich repeats.

Human milk bile salt-stimulated lipase ensures efficient utilization of triacylglycerol by breast-fed infants. Cloning and sequencing of cDNA have revealed that the peptide chain consists of 722 amino acid residues showing only little homology to typical lipases. The sequence is identical to that of pancreatic carboxylic-ester hydrolase. The COOH-terminal part contains 16 proline-rich repeats of 11 residues with O-linked carbohydrate. The only N-linked sugar chain is situated close to the active-site serine. Using C127 cells and a bovine papilloma virus vector, high and stable expression of full-length lipase and of several variants, obtained by site-directed mutagenesis, was achieved. The produced proteins were purified and further characterized. Variants lacking all, or all but two, repeats were active with similar specific activity and the same bile salt dependence as the native milk enzyme. Changing the asparagine necessary for N-glycosylation gave the same principal results. Active recombinant full-length lipase was also produced in a bacterial system. We conclude that neither glycosylation (N- or O-linked) nor the proline-rich repeats are essential for catalytic activity or bile salt activation of human milk bile salt-stimulated lipase.

Amino Acid Sequence↗

PubMed1992

Immunologically induced purulent anterior segment inflammation of the guinea pig eye.

A single conjunctival application of ovalbumin to inbred guinea pigs (IMM/S 209) immunized with the same antigen in Freund's complete adjuvant provoked an acute purulent inflammation of the anterior segment of the eyes with a duration of up to 1 week. Intense conjunctival injection and chemosis were followed by a purulent discharge. A corneal haze was observed regularly, and a considerable proportion of the animals developed a pronounced pannus and corneal ulcers. Tear fluid cytology revealed a rapid increase in cell concentration, from the normal level (less than 10(8)/l) to greater than 10(11)/l. Seventy to 95% of the cells were polymorphonuclear leukocytes. Histological examination revealed an acute inflammatory reaction which radiated from the conjunctival fornices to the entire anterior segments of the eyes. The process was characterized by an intense oedema, vasodilation and perivascular aggregations of polymorphonuclear leukocytes, and to a lesser extent eosinophilic granulocytes which characteristically infiltrated and penetrated the epithelial layers. Neovascularization could be observed early after challenge in the stroma of all parts of the outer eye. Ulcerations of the conjunctival and corneal epithelia were observed frequently. After a number of reiterations of the antigenic challenge, a marked infiltration with lymphocytes and basophils/mast cells was observed, and significant scarring of the conjunctival mucosa developed. In several animals, a slight, but significant co-reaction of the contra-lateral, non-challenged eye was observed.

Acute Disease↗

PubMed1992

Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity. 2. A genetic study of spontaneous and immunization-induced eosinophilia.

In 4 inbred strains of guinea pig the tendency to develop peripheral high-eosinophilia was shown to be genetically controlled. The development of eosinophilia with age and following immunization was examined in high- and low-eosinophilic parental strains, in F1-hybrids and in backcross offspring. The results show that probably only one or a very few segregating genes control eosinophilia, and they also indicate that different genes are involved in the determination of spontaneous (age-related) and immunization-induced eosinophilia.

Animals↗