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Biomedical subjects

G Karlsson

Publications and source records attributed to G Karlsson.

At least 73 records · Page 4Linked to original sources

Mutant Met121Ala of Pseudomonas aeruginosa azurin and its azide derivative: crystal structures and spectral properties.

The crystal structures of the azurin mutant Met121Ala and its azide derivative Met121Ala-azide from Pseudomonas aeruginosa have been determined. The final crystallographic R values are 21.3 and 19.4% for the two structures, respectively. In the Met121Ala mutant, the distance between the copper ion and His117 increases by 0.34 A compared with the wild-type structure. The removal of the methionine in the apical position induces a shortening of the distance from the copper ion to the carbonyl O atom of Gly45 from 2.97 to 2.74 A. In the Met121Ala-azide structure, the azide anion occupies the cavity created by replacing the Met121 side chain with the smaller methyl group of Ala. The azide anion binds with a terminal N atom to the copper ion at a distance of about 2.04 A. In addition, the copper ion has moved out of the trigonal plane by about 0.26 A towards the azide anion. Thus, the copper site in this structure has a distorted tetrahedral arrangement. The spectroscopic characteristics show, in addition, that the copper sites in the two structures are distinctively different. The Met121Ala mutant still maintains the properties of an ordinary type 1 copper site while the Met121Ala-azide derivative has an absorption maximum at about 409 nm and the copper hyperfine coupling has increased to a value intermediate between those of type 2 copper and the wild-type azurin.

Journal Article↗

Identification of porin as a binding site for MAP2.

Porin or VDAC, the pore forming protein in the outer mitochondrial membrane, was identified as a binding site for microtubule-associated protein 2 (MAP2). By affinity chromatography using covalently bound MAP2, two proteins were selectively purified with molecular weights 63 and 70 KD. The 63 KD protein was identified to be the dimer of porin using affinity purified porin antibodies.

Animals↗

Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients.

In this study, patients with recurrent major depression were found to have significantly lower neuropeptide Y-like immunoreactivity (NPY-LI) in platelet-poor plasma (p < 0.01) and significantly higher NPY-LI in platelets (p < 0.001) compared to controls. Also, qualitative differences in the NPY-LI in platelet-poor plasma (PPP) and platelets were detected when the samples were analyzed by HPLC followed by RIA of the collected fractions.

Adult↗

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Administration, Intranasal↗

Nasal polyps: medical or surgical management?

Nasal polyposis is considered to be a non-IgE-mediated inflammatory condition of the nose and sinuses, often associated with chronic non-allergic rhinitis, aspirin intolerance and non-allergic asthma. The aetiology of nasal polyposis is unknown. The main symptoms are nasal obstruction and disturbance of the sense of smell. Occlusion of the nasal passage by a few large polyps could be treated by simple polypectomy to help the patient breathe through the nose. Polypectomy per se does not worsen asthma. Other surgical procedures can be performed, depending on the degree of the disease. The aim of surgery is to restore the physiological properties of the nose by making the nose as free from polyps as possible, and to allow drainage of infected sinuses. Complementary medical treatment of polyposis is always necessary, as surgery cannot treat the inflammatory component of the mucosal disease. In this respect, topical corticosteroids have long been the drugs of choice to reduce the size of polyps, to prevent recurrence after surgery, and are often the main treatment for the disease in many patients. Fluticasone propionate has now been shown to be at least as effective as beclomethasone dipropionate as a medical tool in the management of polyposis. Short-term treatment with systemic corticosteroids is an alternative method of inducing remission and controlling nasal polyps. However, in most patients with nasal polyps, treatment consists of both medical and surgical management.

Humans↗

Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.

Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HIV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HIV-1 group M (clades A to G), as well as an intersubtype recombinant (F/B) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay. This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env genes of primary HIV-1 isolates collected worldwide can vary considerably in their genetic, phylogenetic, and biological properties. The panel of env constructs described here should prove valuable for future structure-function studies of naturally occurring envelope glycoproteins as well as AIDS vaccine development efforts targeted against a broader spectrum of viruses.

Amino Acid Sequence↗

The decision rules of cost-effectiveness analysis.

It has become increasingly popular to carry out cost-effectiveness analyses in economic evaluations of healthcare programmes. Cost-effectiveness analysis is based on the maximisation of the health effects for a given amount of resources. However, many published studies fail to report the results of cost-effectiveness analysis in a way that is consistent with this underlying aim. The aim of this article is to demonstrate the decision rules of cost-effectiveness analysis in an easily accessible way for practitioners in the field. A hypothetical example is used to demonstrate the decision rules of cost-effectiveness analysis, and we also show how to estimate the appropriate incremental cost-effectiveness ratios and how to exclude dominated alternatives. It is then shown how fixed budgets or predetermined prices per effectiveness unit can be used as decision rules to maximise health effects and to determine which programmes to implement on the basis of incremental cost-effectiveness ratios. We hope that the article will contribute towards an increased understanding and application of the appropriate decision rules of cost-effectiveness analysis, so that the results of cost-effectiveness analyses can be interpreted meaningfully by decision makers.

Budgets↗

Economic evaluation in gastrointestinal disease.

Safety and efficacy are not the only parameters of interest in the choice of medical technology--costs are playing an increasingly important role. There is growing interest in 'value for money', which can be assessed economically by comparing the costs and consequences of alternative courses of action. A number of different economic evaluation methods may be used: cost-minimization (only costs examined with no consideration given to consequences); cost-effectiveness (in which a unidimensional clinical outcome is assessed, for example, life-years gained); cost-utility (multidimensional outcomes measured, for example quantity and quality of life); and cost-benefit (where outcome is considered in monetary terms). Ulcer disease offers several examples of how economic evaluation can be used to address issues related to efficiency and value for money in healthcare. In a study of reflux oesophagitis, omeprazole was shown to be more cost-effective than ranitidine in a 12-week treatment study. With omeprazole the costs were lower and the effectiveness better than with the H2-receptor antagonist. In a later study the cost-effectiveness of omeprazole and ranitidine are compared for both intermittent and maintenance treatment in reflux oesophagitis. Using a Markov chain approach, Swedish cost data and studying a time period of 12 months, it found that omeprazole is both more effective in providing healthy days and less costly than ranitidine for both treatment strategies. The comparison between intermittent treatment and maintenance treatment with omeprazole shows that the latter is more effective but also more costly. It is concluded that the relative cost-effectiveness of omeprazole maintenance treatment increases with the risk of relapse when off treatment, the severity of symptoms following relapse, and the value of healthy days, i.e. days free from reflux oesophagitis. A model analysis comparing Helicobacter pylori eradication with conventional treatments in patients with duodenal ulcer disease has shown H. pylori eradication to be cost-effective when compared with either episodic therapy using omeprazole or maintenance therapy with ranitidine. The study used a Markov chain approach, and included the cost of treatment, in Swedish crowns, in a Swedish primary care setting over a period of 5 years. In the analysis, patients receiving conventional therapy were initially healed with omeprazole, 20-40 mg once daily. Following healing patients were either treated with further courses of omeprazole upon relapse or were given maintenance treatment with ranitidine, 150 mg once daily. The patients who were assigned to the H. pylori eradication therapy group were initially given an H. pylori test. Those patients who proved positive for the bacterium received omeprazole, 20 mg twice daily, plus amoxicillin, 2000 mg daily in divided doses, for 2 weeks, followed by omeprazole, 20 mg once daily, for a further 2 weeks to ensure healing. Patients who were H. pylori-negative were assigned to receive either episodic or maintenance therapy as described above. The model assumption applied in the H. pylori eradication group was that, following successful healing and H. pylori eradication, virtually all patients were cured and experienced no relapse during the following 5 years. by contrast, almost all the patients assigned to episodic therapy relapsed, and during maintenance therapy with H2-receptor antagonists, most patients experienced at least one relapse. Although H. pylori eradication resulted in initial higher costs than the alternative strategies, it reduced the risk of recurrence and for most patients there were no future costs. The investment therefore paid off within a relatively short period of time. Even when unfavourable assumptions were made, such as an H. pylori eradication rate of only 50%, the H. pylori eradication strategy had a pay-off period of less than 1.3 years compared with maintenance treatment, and 3 years compared with episodic

Anti-Inflammatory Agents, Non-Steroidal↗

Improved nasal clearance among pulp-mill workers after the reduction of lime dust.

OBJECTIVES: The purpose of this study was to investigate nasal symptoms and function among workers exposed to lime dust and to determine if a reconstruction of the workplace improved the worker's nasal health. METHODS: In 1992, pulp-mill workers (N = 15) exposed to lime dust and an equal number of matched unexposed referents were examined by questionnaires, nasal peak expiratory flow, the saccharin test, nasal lavage, and a clinical examination of the upper airways. The study was repeated one year later, after the pulp mill had been rebuilt. Dust levels were measured on both occasions with stationary and personal samplings. RESULTS: In 1992 the total dust level was 1.2 mg.m-3. The saccharin test showed a significantly increased nasal transit time for the exposed workers in comparison with that of the unexposed referents (difference 3.5 min, 95% confidence interval 0.1-6.9 min). One year later the dust levels had decreased to 0.1 mg. m-3, and the difference in nasal transit time had decreased (difference- 0.8 min, 95% confidence interval -4.8-3.3 min). CONCLUSIONS: Workers exposed to lime dust have an impaired mucociliary function. This impairment is probably due to the alkalinity of the lime. When dust levels are reduced, mucociliary function improves; therefore renovating a workplace to reduce dust levels has a positive effect.

Air Pollutants, Occupational↗

Cost-effectiveness of fracture prevention in established osteoporosis.

This study presents the results of a computer simulation model for calculating the cost-effectiveness and cost-utility of treating patients with established osteoporosis in order to reduce the risk of fractures. The results are based on Swedish data for risk of fracture and costs. The treatment intervention modelled is based on treatment of a 62-year-old woman with established osteoporosis. The cost per hip fracture avoided is 350,000 SEK, assuming a 50% reduction in the risk of fracture due to 5 years of treatment. A sensitivity analysis for changes in the cost and effectiveness of treatment, the risk of fracture and the discount rate is performed. The cost per life-year gained and the cost per quality-adjusted life-year (QALY) gained is presented to enable comparison of the cost-effectiveness of treating osteoporosis with that of other health care interventions. A comparison between treating the same woman for osteoporosis and mild hypertension shows a cost per life-year gained of 220,000 SEK and 128,000 SEK respectively. Cost per QALY gained is very similar for the two interventions: 105,000 SEK and 103,000 SEK respectively. This model provides a tool to enable clinicians, administrators and health policy makers to analyze and understand the economic aspects of a major health policy issue.

Computer Simulation↗

Complexes between cationic liposomes and DNA visualized by cryo-TEM.

The association structures formed by cationic liposomes and DNA-plasmids have been successfully employed as gene carriers in transfection assays. In the present study such complexes was studied by cryo-TEM (cryo-transmission electron microscopy). Cationic liposomes made up by DOPE (dioleoylphosphatidylethanolamine) and various amounts of three different cationic surfactants were investigated. The cryo-TEM analysis suggests that an excess of lipid in terms of charge, leads to entrapment of the DNA molecules between the lamellas in clusters of aggregated multilamellar structures. With increasing amounts of DNA free or loosely bound plasmids were found in the vicinity of the complexes. The importance of the choice of surfactant, as reported from many transfection assays, was not reflected in changes of the type of DNA-vesicle association. A tendency towards polymorphism of the lipid mixtures is reported and its possible implications are discussed.

Cations↗

Structure of metal site in azurin, Met121 mutants of azurin, and stellacyanin investigated by 111mCd perturbed angular correlation (PAC).

The geometries of the metal sites in cadmium-substituted azurins have been investigated by 111mCd perturbed angular correlation (PAC). The study includes wild type azurin as well as Met121 mutants of azurin, where methionine has been substituted by Ala, Asn, Asp, Gln, Glu, and Leu. The nuclear quadrupole interaction of wild type azurin analyzed in the angular overlap model is well described as coordination of His46, His117, and Cys112 and cannot be described by coordination of Met121 and/or Gly45. For most of the mutants, there exist two coordination geometries of the cadmium ion. With the exception of the Glu and Asp mutants, one of the conformations is similar to the wild type conformation. The other coordination geometries are either best described by a coordinating water molecule close to the original methionine position or by coordination by the substituting amino acid. These experiments show that even though the methionine does not coordinate it plays an important role for the geometry of the metal site. The nuclear quadrupole interaction of stellacyanin was also measured. The value resembles the most prominent nuclear quadrupole interaction of the Met121-->Gln mutant of Alcaligenes denitrificans azurin, indicating that the structures of the two metal sites are similar.

Azurin↗

Cost-utility analysis of group living in dementia care.

A cost-utility analysis (CUA) was applied to group living for dementia patients. A Markov-model of an expected life-length of 8 years was used. Forty-six patients in group living were compared to 39 patients living at home by inclusion and 23 institutionalized patients. When the cost per gained quality-adjusted life-year (QALY) was calculated, the group living alternative was the most favorable for the patients, giving a cost per paired QALY of US dollars < 0. In the extensive sensitivity analysis the main result was consistent but methodological problems were indicated.

Aged↗

Costs of periodontal and prosthodontic treatment and evaluation of oral health in patients after treatment of advanced periodontal disease.

Retrospective estimations of dental care costs of periodontal and prosthodontic treatment and evaluation of oral health in 37 patients with advanced periodontal disease were carried out. Measures of their subjective evaluation of oral health 7-10 yr after the treatment are presented as a health profile and as indices in single numbers. The relations between oral health as an index and the dimensions in the health profile are analyzed. Dental care costs for treatment in the mandible was SEK 35 550, for the maxilla SEK 45 380 and for both jaws SEK 74 230. After the treatment oral health as well as general health were in excess of 75 on a 0 to 100 scale. Chewing ability, comfort and aesthetics were the variables found to significantly affect the subjective oral health. Oral health in terms of periodontal and prosthodontic conditions was maintained over the observation period.

Adult↗

[Care of patients with dementia--a ticking cost bomb?].

Owing to the increasing number of elderly people, the prevalence of dementia will also increase. In 1990, there were about 101,000 people with moderate to severe dementia in Sweden, or 6.4 percent of the population over 65 years of age (65+ pop.). The figure will increase to about 121,000 by the year 2000 (7.7 percent of the 65+ pop.), and to 156,000 by 2025 (7.5 percent of the 65+ pop.). The corresponding health care costs, which were SEK 30 billion in 1991, are estimated to reach SEK 35 billion by 2000, and SEK 46 billion by 2025. Assuming comparable increases in the prevalence of dementia in the other Nordic countries, the overall number of dementia patients will increase from 247,000 in 1991 to 371,000 by 2025, and the respective costs from SEK 74 billion to SEK 110 billion.

Aged↗