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Biomedical subjects

R Olsson

Publications and source records attributed to R Olsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Multistep solution-phase parallel synthesis of spiperone analogues.

A flexible, multistep parallel synthesis of spiperone analogues is described. A library of 4-substituted piperidines, assembled utilizing reductive amination and acylation protocols, was alkylated either homogeneously or heterogeneously, exploiting a product release only concept, to afford an oxa-series of spiperone analogues. Screening of the products at 5-HT2 and D2 receptors revealed 5-HT2A antagonists with improved selectivity compared to spiperone and AMI-193.

Antipsychotic Agents↗
PubMed2000

Local blood flow regulation in transplanted rat pancreatic islets: influence of adenosine, angiotensin II, and nitric oxide inhibition.

BACKGROUND: Transplanted islets lack endothelial cells immediately after implantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly formed islet graft microvessels are largely unknown. This study aimed to investigate the blood flow regulation of transplanted pancreatic islets. METHODS: Pancreatic islets were syngeneically transplanted beneath the renal capsule of control and streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks later using laser-Doppler flowmetry. Adenosine (0.6 mg x kg(-1) x min(-1), angiotensin II (AT II; 0.17 microg x kg(-1) x min(-1)) and the nitric oxide synthase inhibitor NG-nitro-L-arginine (25 mg/ kg) were given to each animal. RESULTS: An increased basal blood flow and basal vascular conductance in the islet grafts, but not in the renal cortex, were seen in diabetic rats compared with control rats. Adenosine increased, and AT II decreased, the vascular conductance of the islet grafts in both nondiabetic and diabetic animals. A more pronounced circulatory response to AT II was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft blood flow response between nondiabetic and diabetic animals. NG-Nitro-L-arginine decreased islet graft blood flow and vascular conductance in both nondiabetic and diabetic recipients, but the effect was more pronounced in the non-diabetic animals. CONCLUSIONS: Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were less dependent on nitric oxide to maintain a basal blood flow in the islet graft.

Adenosine↗
PubMed2000

Temporary in situ aluminum and zinc tethering in Diels-Alder reactions

[formula: see text] Temporary tethering using aluminum or zinc in Diels-Alder reactions made possible the use of otherwise "noncompatible" combinations of dienes and dienophiles, resulting in the one-step formation of substituted cyclohexene 1,2-bis-methanols. Excellent regioselectivity and also significant stereoselectivity were obtained.

Journal Article↗
PubMed2000

Dynamic phases and the peak effect in dirty type II superconductors

We study numerically and experimentally the dynamics of driven vortex matter. Our London-Langevin simulations find that the critical current exhibits a peak both across the Bragg glass to vortex glass transition and across the melting line. The peak is accompanied by a clear crossing of the I-V curves. We report transport measurements on untwinned YBCO crystals, in complete accordance with these findings. At higher drives disorder is averaged to reduced values, and in three dimensions the vortices reorder into a "moving solid." The effect of the disorder can be well represented with a "shaking temperature" which is inversely proportional to the velocity.

Journal Article↗
PubMed2000

The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium.

BACKGROUND: Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection. The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block. The secondary objective was to evaluate the effect of atracurium on pharyngeal function. METHODS: Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy. The initiation of the swallowing process, the pharyngeal coordination, and the bolus transit time were evaluated. Simultaneous manometry was used to document pressure changes at the tongue base, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, an intravenous infusion of atracurium was administered to obtain train-of-four ratios (T4/T1) of 0.60, 0.70, and 0.80, followed by recovery to a train-of-four ratio of more than 0.90. RESULTS: The incidence of pharyngeal dysfunction was 6% during the control recordings and increased (P < 0.05) to 28%, 17%, and 20% at train-of-four ratios 0.60, 0.70, and 0.80, respectively. After recovery to a train-of-four ratio of more than 0.90, the incidence was 13%. Pharyngeal dysfunction occurred in 74 of 444 swallows, the majority (80%) resulting in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis (P = 0.0081). The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 (P < 0.01). A marked reduction in the upper esophageal sphincter resting tone was found, as well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly. CONCLUSION: Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. The mechanism behind the pharyngeal dysfunction is a delayed initiation of the swallowing reflex, impaired pharyngeal muscle function, and impaired coordination. The majority of misdirected swallows resulted in penetration of bolus to the larynx.

Adult↗
PubMed2000

Eosinophilic hepatic necrosis in hypereosinophilic syndrome.

Hypereosinophilic syndrome has been reported to be associated with liver disease, predominantly in men, in the form of acute and chronic active hepatitis with an inflammatory infiltrate that is mainly composed of eosinophils. We describe a female patient with peripheral blood and bone marrow eosinophilia, in whom liver biopsy displayed areas of necrosis with eosinophilic inflammation, with other regions showing features of chronic hepatitis. The patient also had antimitochondrial antibodies in serum. She responded favorably to immunosuppressive therapy.

Aged↗
PubMed2000

Identification of Helicobacter pylori and other Helicobacter species by PCR, hybridization, and partial DNA sequencing in human liver samples from patients with primary sclerosing cholangitis or primary biliary cirrhosis.

Helicobacter pylori was identified in human liver tissue by PCR, hybridization, and partial DNA sequencing. Liver biopsies were obtained from patients with primary sclerosing cholangitis (n = 12), primary biliary cirrhosis (n = 12), and noncholestatic liver cirrhosis (n = 13) and (as controls) normal livers (n = 10). PCR analyses were carried out using primers for the Helicobacter genus, Helicobacter pylori (the gene encoding a species-specific 26-kDa protein and the 16S rRNA), Helicobacter bilis, Helicobacter pullorum, and Helicobacter hepaticus. Samples from patients with primary biliary cirrhosis and primary sclerosing cholangitis (11 and 9 samples, respectively) were positive by PCR with Helicobacter genus-specific primers. Of these 20 samples, 8 were positive with the 16S rRNA primer and 9 were positive with the 26-kDa protein primer of H. pylori. These nine latter samples were also positive by Southern blot hybridization for the amplified 26-kDa fragment, and four of those were verified to be H. pylori by partial 16S rDNA sequencing. None of the samples reacted with primers for H. bilis, H. pullorum, or H. hepaticus. None of the normal livers had positive results in the Helicobacter genus PCR assay, and only one patient in the noncholestatic liver cirrhosis group, a young boy who at reexamination showed histological features suggesting primary sclerosing cholangitis, had a positive result in the same assay. Helicobacter positivity was thus significantly more common in patients with cholestatic diseases (20 of 24) than in patients with noncholestatic diseases and normal controls (1 of 23) (P = <0.00001). Patients positive for Helicobacter genus had significantly higher values of alkaline phosphatases and prothrombin complex than Helicobacter-negative patients (P = 0.0001 and P = 0.0003, respectively). Among primary sclerosing cholangitis patients, Helicobacter genus PCR positivity was weakly associated with ulcerative colitis (P = 0.05). Significant differences related to blood group or HLA status were not found.

Alkaline Phosphatase↗
PubMed2000

Inverse relationship between protein intake and plasma free amino acids in healthy men at physical exercise.

The effect of a "normal" (n = 8) and "high" (n = 6) protein intake (1 and 2.5 g x kg(-1) x day(-1), respectively) and of exercise on plasma amino acid (AA) concentrations, insulin, and glucagon concentrations was followed throughout a continuous 24-h period in adult male subjects at energy balance after six days on a standardized diet and exercise program. Subjects were fasting from 2100 on day 6 to 1200 on day 7 and then fed 10 identical meals hourly until 2100. Physical exercise was performed (46% maximal oxygen uptake) between 0830 and 1000 (fasting) and in a fed state (1600-1730) on each day. The normal-protein group showed fasting plasma AA concentrations that were higher (P < 0.05) than those for the high-protein group, except for leucine, methionine, and tyrosine. Glutamine, glycine, alanine, taurine, and threonine concentrations were distinctly higher ( approximately 30% or greater) throughout the 24-h period in subjects consuming the normal- vs. the high-protein diets. Exercise appeared to increase, although not profoundly, the plasma concentrations of amino acids except for glutamate, histidine, ornithine, and tryptophan. The profound diet-related differences in plasma AA concentrations are only partially explained by differences in the renal clearance of the amino acids. We speculate on the possible metabolic basis for these findings.

Adult↗
PubMed2000

Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men.

Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.

Adult↗
PubMed2000

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

Administration, Intravesical↗
PubMed2000

Engraftment and growth of transplanted pancreatic islets.

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.

Animals↗
PubMed1999

Videomanometric analysis of supraglottic swallow, effortful swallow, and chin tuck in healthy volunteers.

Simultaneous videoradiography and solid-state manometry (videomanometry) was applied in eight healthy volunteers (four women, four men; age range 25-64 years, mean age 41 years) without swallowing problems. Three different swallowing techniques were tested; supraglottic swallow, effortful swallow, and chin tuck. Seven videoradiographic variables and six manometric variables were analyzed. The supraglottic swallowing technique did not differ significantly from that of the control swallows. The effortful swallow had a significantly (p = 0.0001) reduced hyoid-mandibular distance preswallow due to an elevation of the hyoid and the larynx, which caused a significantly (p = 0.007) reduced maximal hyoid movement and a significantly (p = 0.009) reduced laryngeal elevation during swallow. The chin tuck swallow had a significantly (p = 0. 001) reduced laryngohyoid distance and also a significantly (p = 0. 004) reduced hyoid-mandibular distance. The chin tuck swallow also displayed significantly (p = 0.003) weaker pharyngeal contractions. Videomanometry allows for analysis of bolus transport, movement of anatomical structures, and measurement of intraluminal pressures. These variables are important when evaluating swallowing techniques. In the present study, we made a few observations that never have been reported before. When healthy volunteers performed supraglottic swallow, they performed the technique somewhat differently. Therefore, we assume dysphagic patients would need a substantial period of training to perform a technique efficiently. Chin tuck could impair protection of the airways in dysphagic patients with weak pharyngeal constrictor muscles.

Adult↗
PubMed1999

A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis.

BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing cholangiocarcinoma (CC), which is notoriously difficult to diagnose since these patients may have increased levels of bilirubin due to benign strictures. To evaluate the validity of different tumor markers as an aid to diagnosing CC, we have carried out serial serum tumor marker analyses in patients with PSC who have been followed for several years. METHODS: Seventy-five patients with PSC, without any clinical signs of CC were included in the study. They were investigated every 6th months for 3 years, with extensive liver function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The patients were then followed for 5 years to exclude the possibility that CC remained unrecognized. RESULTS: Of the 75 patients, two (3%) developed CC during the 3-year period. One of these had normal levels, and one had significantly increased levels of the tumor markers. In the follow-up part of the study two further patients died from CC and one from hepatocellular carcinoma, 3 and 4 years after the 3-year study, respectively. Twenty-one patients had an increase of one of the markers on at least one occasion. Five patients had a transient increase of more than double the upper normal limit of the tumor markers on more than one occasion. There was a good correlation between CA 19-9, CA 50 and CA 242, but not with CEA. Fourteen of the 75 patients had periods of increased bilirubin levels, but none of these showed increased tumor markers. CONCLUSIONS: The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for the detection of CC in patients with PSC because of low specificity. However, we found no falsely increased values in patients with hyperbilirubinemia.

Adult↗
PubMed1999

Follow-up after liver transplantation for primary sclerosing cholangitis: effects on survival, quality of life, and colitis.

BACKGROUND: Except for primary biliary cirrhosis, primary sclerosing cholangitis (PSC) is now the commonest indication for liver transplantation in Sweden. There are several specific problems related to post-transplantation life in these patients. METHODS: We analyzed a 10-year cohort of 47 patients transplanted at our center. RESULTS: Incidental biliary carcinoma was diagnosed in 13%,, with a 2-year survival of only 17%, compared with 70% in the other patients. The 2-year survival has improved considerably (to 82%) in recent years. Quality of life was much or slightly improved in 80%. The colitis was much or slightly improved in 65%, with some deterioration in only 6%. No patient developed colonic carcinoma. Previous biliary tract surgery was identified as a risk factor for a worse 1-year mortality. CONCLUSIONS: Liver transplantation for PSC is now associated with a high survival rate and an improvement in the quality of life and course of ulcerative colitis. Previous biliary tract surgery is a risk factor for non-survival.

Adolescent↗
PubMed1999

Estrogen-progestogen therapy for low bone mineral density in primary biliary cirrhosis.

AIMS/BACKGROUND: Patients with primary biliary cirrhosis (PBC) often have osteoporosis of the high-turnover type, suggesting that estrogen could have a beneficial effect. However, the cholestatic potential of estrogen could imply a risk of increased cholestasis in a disease characterized by cholestasis. The aim of the present study was to test whether hormone replacement therapy (HRT) could be used to increase bone mineral density (BMD) in PBC patients with osteoporosis, without causing deterioration of the liver function. METHODS: Nine female PBC patients with osteoporosis and one with osteopenia were offered HRT for two years. The change in BMD was compared to the change in ten age-matched female PBC patients who had less severe or no osteopenia and who did not receive HRT. Liver function tests were checked at six-month intervals. RESULTS: HRT patients showed a statistically significant increase in lumbar spine BMD and total body BMD whereas control patients showed a significant decrease in lumbar and total body BMD. In contrast to the controls, HRT patients also showed a decrease in truncal fat (-3.8%). Neither of the groups showed any statistically significant changes in the liver function tests. CONCLUSIONS: HRT is safe and effective in female PBC patients with osteoporosis.

Absorptiometry, Photon↗