Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 145 records · Page 8Linked to original sources

PubMed1999

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmö University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.

Adult↗

PubMed1999

Effects of an education programme to change clinical laboratory testing habits in primary care.

OBJECTIVE: The aim of this study was to investigate the use of clinical laboratory tests in primary care and to evaluate if it is possible to improve the cost-effectiveness of laboratory testing by a short-term education programme. Our main goal has been to lower the total costs of care. DESIGN: An education programme that was monitored by laboratory test ratios. SETTING: Primary health care. SUBJECTS: 63 primary care doctors at 19 primary care centres in the county of Uppsala, Sweden. MAIN OUTCOME MEASURES: The effects of the education programme were monitored by laboratory test ratios (e.g. ASAT/ALAT) of individual doctors before and after the education programme. RESULTS: The education programme resulted in significant changes for the majority of the ratios studied. The savings on direct laboratory costs were approximately SEK 400,000 for assays that were recommended to decrease. The increased cost for assays that were recommended to increase was approximately SEK 140,000 but was considered cost-effective. CONCLUSION: It is possible to achieve significant changes in clinical chemistry test ordering habits of primary care doctors with a 2 day education programme. It resulted in cost savings and a better use of clinical chemistry tests in primary care. The effects were sustained for at least 6 months.

Clinical Chemistry Tests↗

PubMed1999

Methods for estimating uptake and absorbed dose in tumours from 125I labelled monoclonal antibodies, based on scintigraphic imaging of mice.

Monoclonal antibodies for radioimmunotargeting are often tested in tumour bearing nude mice. In vivo determination of the uptake of the monoclonal antibody in the tumour requires quantitative scintigraphy, and this in turn requires an adequate method for subtraction of radiation from the normal tissue. For this reason, two different methods for background subtraction were evaluated, a contralateral background region of interest or an irregular one, surrounding the tumour. A pinhole collimator was used for the scintigraphy and the monoclonal antibodies were labelled with 125I. Furthermore, a method was developed for estimation of the mean absorbed dose in the tumour from these repeated quantitative scintigraphic measurements. This requires that the tumour mass can be accurately estimated in vivo. Finally, the results were compared with in vitro measurements of the uptake.

Absorption↗

PubMed1999

T(H)1 cytokines are produced in labial salivary glands in Sjögren's syndrome, but also in healthy individuals.

The aim of the present study was to assess the T cell cytokines IFN-gamma, IL-2, IL-4 and IL-5 in labial salivary glands (LSG) in Sjögren's syndrome (SS) and healthy controls using RT-PCR and immunohistochemistry. IFN-gamma is always or almost always produced in SS and in healthy controls. IL-2 was also found in some samples, but IL-4 and IL-5 were not. Less than 2% of all inflammatory mononuclear cells contained immuoreactive IFN-gamma or IL-2. Cytokine mRNA profile in LSGs in SS is skewed towards a T(H)1 pattern. The classical T(H)1 cytokines are also produced in normal glands, even in the absence of foci. T(H)1 type response may play an active role as part of the mucosal associated lymphoid tissue/responses, perhaps in prevention of reactivation of latent viruses. This may also make the exocrine glands a locus minoris resistentiae when the self tolerance is broken.

Antisense Elements (Genetics)↗

PubMed1999

Adult patients with "asymptomatic" and "compensated" hydrocephalus benefit from surgery.

OBJECTIVES: There exists no consensus regarding the appropriate treatment of the group of adult hydrocephalus patients often denoted as "arrested"/ "compensated", "asymptomatic" or "symptomatic congenital". Our case series describes the results of CSF diversion in these patients. MATERIAL AND METHODS: During the period of 1984 to 1994, 23 consecutive adult patients with "asymptomatic" (n = 10), "compensated" (n = 7) and "symptomatic congenital" (n = 6) hydrocephalus were prospectively evaluated. All patients showed signs of motor or psychometric impairment, had indications of an infantile or childhood debut, and had previously been ignored. In 15 patients the ventricular enlargement was a coincidental finding. Seventeen patients underwent shunt surgery or endoscopic third ventriculostomy. RESULTS: All but one operated upon improved. Six patients declined surgery, but have been followed with 1 showing deterioration, the remaining being unchanged. CONCLUSION: In addition to patients with "symptomatic congenital" most adult "asymptomatic" and "arrested"/"compensated" hydrocephalus patients can benefit from surgery despite a considerable duration of disease.

Adult↗

PubMed1999

Evaluation of bone disease in multiple myeloma: a comparison between the resorption markers urinary deoxypyridinoline/creatinine (DPD) and serum ICTP, and an evaluation of the DPD/osteocalcin and ICTP/osteocalcin ratios.

Markers of bone metabolism were measured in 73 newly diagnosed myeloma patients and in age-matched controls. Correlations to bone disease on X-rays and survival were performed. In urine deoxypyridinoline/creatinine (DPD) and in serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), procollagen type I carboxy-terminal extension peptide (PICP) and osteocalcin were analyzed. The ratios DPD/osteocalcin and ICTP/osteocalcin were calculated. Skeletal X-ray findings were divided into no, limited and extensive bone involvement. DPD and ICTP levels were significantly elevated in patients compared to controls. Levels increased with advancing skeletal involvement. Serum osteocalcin was elevated in patients without visible bone disease. The level decreased with more advanced bone involvement. The finding of significantly elevated osteocalcin and ICTP levels in patients without bone involvement on X-rays indicates that bone markers might reflect bone disease better than X-rays in untreated myeloma patients. Ratios between bone resorption and bone formation markers added no further information on bone disease or survival. Only ICTP had prognostic value with an inverse correlation between serum levels and survival.

Aged↗

PubMed1999

Genotyping is a valuable diagnostic complement to neonatal screening for congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency.

To evaluate genotyping as a diagnostic complement to neonatal screening for congenital adrenal hyperplasia, 91 children who had been diagnosed with this condition between 1986 and 1997 were analyzed for mutations in the steroid 21-hydroxylase gene. Screening levels of 17-hydroxyprogesterone were compared in patients representing different genotypes. Genotyping was performed using allele-specific PCR, the patients were divided into four groups according to the severity of their mutations, and screening results were compared between these groups as well as with 141 values representing false positive samples. The screening levels of 17-hydroxyprogesterone were significantly different in the five groups of samples. Values above 500 nmol/L were clearly associated with the most severe genotypes, whereas conclusions concerning disease severity could not be drawn from individual samples representing lower levels. For example, values around 150-200 nmol/L could be seen in children with all degrees of disease severity and could also constitute false positive samples. We conclude that genotyping is a valuable diagnostic tool and a good complement to neonatal screening, especially in confirming or discarding the diagnosis in cases with slightly elevated 17-hydroxyprogesterone levels. An additional benefit is that it provides information on disease severity, which reduces the risk of overtreatment of mildly affected children.

Adrenal Hyperplasia, Congenital↗

PubMed1999

Cholecystokinin affects gastric emptying and stomach motility in the rainbow trout Oncorhynchus mykiss.

In this study, we describe new methods for recording gastric emptying and in vivo measurements of intragastric pressure in fish. Using these methods, we investigated the effects of the sulphated octapeptide of cholecystokinin (CCK8) on gastric emptying and on stomach motility in vivo and in vitro. Gastric emptying of 99Tcm-labelled food was measured in swimming fish by using a gamma camera, counting consecutive 2.5 min periods for 18-42 h. After 20 h, 55.3+/-4.0 % of the labelled food remained in the stomach of the control fish (mean s.e.m., N=9). Vascular infusion of CCK8 (25 pmol kg-1 h-1) delayed gastric emptying so that 70.4+/-4.8 % of the labelled food remained in the stomach after 20 h (N=8). Gastric pressure changes in vivo were measured using a balloon surgically fitted into the cardiac or pyloric part of the stomach. In the cardiac part, intra-arterial infusion of CCK8 at 0.1 nmol kg-1 h-1 resulted in a decrease in the frequency and amplitude of rhythmic contractions, while higher doses started/increased contractions. Atropine blocked much of the basal contractile activity, but did not influence the CCK8-induced inhibition of contractile activity. The pyloric part of the stomach was unaffected by intra-arterial infusion of CCK8 or atropine. In vitro perfusion of the stomach (with a balloon placed in the cardiac part to record motility) with CCK8 at high concentrations (10(-7 )mol l-1 and above) augmented the spontaneous contractions, while lower concentrations had inconsistent effects. In addition, CCK8 (10(-7) to 10(-6 )mol l-1) decreased the amplitude of spontaneous contractions in longitudinal strip preparations, usually in combination with an increase in the resting tension. The decrease in amplitude was not affected by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester hydrochloride (L-NAME; 10(-4 )mol l-1). Depending on the concentration and experimental arrangement, CCK8 had either inhibitory or excitatory effects on the cardiac stomach, suggesting the possible presence of different types of CCK receptor. We conclude that the predominant effect of CCK8 in vivo may be a slowing down of gastric emptying, presumably coinciding with a release of bile into the duodenum.

Animals↗

PubMed1999

Mutational scanning of PCR products by subtractive oligonucleotide hybridization analysis.

Here, we describe a new approach for mutational scanning of PCR products through hybridization analysis between complementary oligonucleotides. Sets of overlapping probe oligonucleotides complementary to wild-type (WT) sequence are hybridized to microbead-immobilized PCR products under solution-like conditions. Mismatch-hybridization situations between a mutant sample and probe oligonucleotides result in higher remaining concentrations in solution of involved probe oligonucleotides. Post-hybridization supernatants are subsequently analyzed for their probe oligonucleotide compositions using surface plasmon resonance-based biosensor technology. Relative remaining probe oligonucleotide concentrations are monitored in real-time through hybridization analysis between probe oligonucleotides and their corresponding sensor-chip immobilized complementary counterparts. This allows for the construction of composition diagrams revealing the existence and approximate location of a mutation within an investigated sample DNA sequence. Applied on PCR products derived from clinical samples of microdissected tumor biopsies, single mutations in exons 6 and 7 of the human p53 tumor-suppressor gene were successfully detected and approximately localized.

Biosensing Techniques↗

PubMed1999

An inhibitor of angiotensin converting enzyme (enalapril) augments endotoxin-induced hypotension in the pig.

Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalpril) [at a dose (0.5 mg x kg-1) that did not per se reduce mean arterial blood pressure (MAP); (n = 7)], or the corresponding volume of saline (n = 8). Another seven pigs were randomised for treatment with enalapril (0.5 mg x kg-1) + saline (n = 3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio-depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Chicken antibodies: a clinical chemistry perspective.

The chicken immune system has been studied for many years and these studies have contributed substantially to our understanding of the fundamental concepts of immunology and the development of different immunoglobulin classes. It is thus surprising that only a small fraction of the antibodies presently used in laboratories are of avian origin. A laying hen produces more yolk antibodies than a rabbit can produce during the same time period, and the animal care costs are lower for the chicken compared to the rabbit. Chicken antibodies offer many advantages to the traditional mammalian antibodies when used for the detection of mammalian antigen. Due to the evolutionary difference chicken IgY will react with more epitopes on a mammalian antigen, which will give an amplification of the signal. Chicken antibodies can also be used to avoid interference in immunological assays caused by the human complement system, rheumatoid factors, human anti-mouse IgG antibodies (HAMA) or human and bacterial Fc-receptors. The antibodies can be purified in large amounts from egg yolk, making laying hens highly efficient producers of polyclonal antibodies.

Animals↗

PubMed1999

Serum bone markers after intramedullary fixed tibial fractures.

Serum levels of bone markers were measured prospectively for 1 year in 30 adult patients with an intramedullary fixed tibial fracture. In a double blinded design, half of the patients received low intensity ultrasound. All fractures healed, although in seven of 30 the healing was delayed more than 6 months. There was no significant difference in radiologic healing time between the ultrasound group (median, 113 days) and the placebo group (median, 112 days). The marker for bone resorption, crosslinked telopeptide, peaked at 1 to 4 weeks, whereas markers for bone formation peaked at 10 to 16 weeks for bone specific alkaline phosphatase and osteocalcin. Crosslinked telopeptide was lower at 1 week in patients treated with ultrasound than in those receiving placebo. Patients with delayed healing did not differ in crosslinked telopeptide compared with patients with normal healing. There were no differences in bone formation markers between patients who received ultrasound or placebo. Patients with delayed healing had lower levels of bone specific alkaline phosphatase between 4 and 7 weeks than did patients with normal healing, although no such differences were seen for osteocalcin. The results indicate that low intensity ultrasound might slow bone resorption, although there is no visible effect on bone formation. Patients with delayed healing had adequate bone resorption but slower early bone formation than did patients with normal healing.

Adult↗

PubMed1998

Autoradiographic discrimination of melanocortin receptors indicates that the MC3 subtype dominates in the medial rat brain.

In the present study, we developed an autoradiographic method to visualize the distribution of melanocortin (MC) receptors 3 and 4 in sagittal sections of the rat brain. The method takes advantage of the MC3 and MC4 receptor selective compounds, gamma1-MSH and HS014. First, we characterized the binding of gamma1-MSH, HS014 and the radioligand [125I]NDP-MSH to the rat MC3 and MC4 receptors expressed in COS cells. [125I]NDP-MSH was found to be non-selective, whereas gamma1-MSH showed a 40-fold preference for the rat MC3 receptor, and HS014 an over 300-fold preference to the rat MC4 receptor. Second, to discriminate between the MC3 and MC4 receptors in rat brain sections, the sections were incubated with [125I]NDP-MSH in the presence of graded concentrations of the MC3 selective ligand, gamma1-MSH, or the MC4 selective ligand, HS014. From the autoradiograms thus made, competition curves of gamma1-MSH and HS014 could be constructed for different regions of the rat brain. Our results indicate that in the nucleus accumbens shell, the medial preoptic area, and the ventromedial nucleus of the hypothalamus, there is a clear dominance of the MC3 receptor, whereas in the lateral septum and the olfactory tubercle, there seem to be present both MC3 and MC4 receptors, although the MC3 receptor may still be the dominating subtype. In the optic layer of the superior colliculus, our data indicate a more abundant expression of the MC4 receptor. In the ventral tegmental area, there might be an additional MSH-peptide binding site of unknown origin.

Animals↗

PubMed1998

Patients with genetic defects in the gamma-glutamyl cycle.

In the gamma-glutamyl cycle, hereditary defects have been described in four of the six enzymes namely: gamma-GC synthetase; GSH synthetase; gamma-glutamyl transpeptidase and 5-oxoprolinase. Mutants are still to be found in gamma-glutamyl cyclotransferase and in the dipeptidase. Deficiency of GSH synthatase or gamma-GC synthetases results in low levels of GSH. In gamma-GC synthetase deficiency hemolytic anemia is the most prominent symptom, with or without hepatosplenomegaly. In generalized GSH synthetase deficiency 5-oxoproline is overproduced due to lack of feedback inhibition of gamma-GC synthetase. These patients have metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and about 50% of them also have progressive neurological symptoms. Treatment includes acidosis correction, high doses of vitamin E and C and avoidance of drugs precipitating hemolytic crises in G6PD deficiency. Therapeutic trials with GSH analogues, N-acetylcysteine and GSH esters have been carried out. Glutathione synthetase deficiency restricted to erythrocytes results in hemolytic anemia but no 5-oxoprolinuria. gamma-Glutamyl transpeptidase deficiency is associated with GSH-emia and GSH-uria whereas 5-oxoprolinase deficiency is associated with 5-oxoprolinuria. In diagnostic work it must be emphasized that erythrocytes contain an incomplete gamma-glutamyl cycle; they lack both gamma-glutamyl transpeptidase and 5-oxoprolinase and these enzyme activities must therefore be analyzed in other types of cells such as leukocytes and fibroblasts. It is also important to investigate other patients with inherited defects in the gamma-glutamyl cycle to learn more about the biological role of GSH in man.

Erythrocytes↗

PubMed1998

Drug absorption from nifedipine hydrophilic matrix extended-release (ER) tablet-comparison with an osmotic pump tablet and effect of food.

The aim of the present study was to compare the bioavailability of nifedipine when administered as a hydrophilic matrix tablet (ER) and a push-pull osmotic pump tablet (XL) administrated after fasting, and to evaluate the effect of food for the hydrophilic matrix tablet. For this purpose, three separate studies were performed on healthy volunteers (n = 58) including gammascintigraphic monitoring of tablet erosion and localisation in the gastrointestinal tract for ER in one study. Both ER and XL provided almost constant drug delivery over 24 h, after administration under fasting conditions, and bioequivalence was obtained according to 90% confidence intervals of the difference between formulations within 80-125% for Cmax and AUC. Food significantly increased AUC for ER but no significant difference was obtained between ER and XL with food with respect to extent of bioavailability. The rate of absorption was increased to a higher degree for ER than for XL, as indicated by a Cmax which was almost twice as high for ER compared with XL. This finding was shown to be related to an increased tablet-erosion rate for ER, leading to more rapid drug release.

Adult↗

PubMed1998

In vitro and in vivo erosion of two different hydrophilic gel matrix tablets.

The aim of the present work was to establish in vivo predictive in vitro tests for the tablet erosion of two different compositions (A and B) of hydrophilic matrix tablets based on hydroxypropyl methylcellulose. The tablet erosion was studied in a modified USP II apparatus at different agitation intensities and ionic strengths according to 2(2) factorial design. The in vivo tablet erosion was studied in 8 healthy human volunteers by gamma scintigraphy after administration of the tablets together with breakfast. In vitro agitation intensity increased the erosion rate for both tablets whereas increased ionic strength caused a slower rate for tablet A and a faster rate for tablet B. The choice of in vitro testing conditions proved to be critical for the attainment of in vivo predictive results. The best in vitro/in vivo correlation for the two formulations was obtained at a paddle stirring rate of 140 rpm and a ionic strength of 0.14 obtained by addition of sodium chloride.

Adult↗

PubMed1998

Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjögren's syndrome.

Type IV collagenases/gelatinases (matrix metalloproteinases MMP-2 and MMP-9) in labial salivary glands (LSG) and saliva in Sjögren's syndrome (SS) and healthy controls were studied. Zymograms and Western blots disclosed that SS saliva contained 92/82 kD MMP-9/type IV collagenase duplex. Specific activity measurement disclosed 53.1+/-9.8 U/mg protein MMP-9 in SS compared to 16.5+/-2.6 U/mg in healthy controls (p=0.01). MMP-2 did not differ between SS and controls. In SS salivary glands, MMP-2 and MMP-9 were also expressed, in addition to stromal fibroblasts and occasional infiltrating neutrophils, respectively, in acinar end piece cells. In addition, an effective proMMP-9 activator, human trypsin-2 (also known as tumor-associated trypsin-2 or TAT-2), was found in acinar end piece cells and in saliva. Interestingly, proteolytically processed MMP-9 was found in saliva (vide supra), and in vivo activated MMP-9 was significantly higher in SS than in controls (p=0.002). LSGs, particularly in SS, were characterized ultrastructurally by areas containing small cytoplasmic vesicles in the basal parts of the epithelial cells associated with areas of disordered and thickened basal lamina. Based on our results, we conclude here that SS saliva contains increased concentrations of MMP-9, which is of glandular origin in part. Pro MMP-9 is to a large extent proteolytically activated. This is probably mediated by the most potent pro MMP-9 activator found in vivo thus far, namely trypsin-2. Therefore, the MMP 9/trypsin-2 cascade may be responsible for the increased remodelling and/or structural destruction of the basement membrane scaffolding in salivary glands in SS. Due to the role of basal lamina as an important molecular sieve and extracellular matrix-cell signal, these pathological changes may contribute to the pathogenesis of the syndrome.

Blotting, Western↗

PubMed1998

Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer.

Serum p53 antibody levels were analysed using an enzyme-linked immunosorbent assay in serum samples obtained before surgery from 184 consecutive patients with primary colorectal cancer. Possible associations with tumour stage and tumour differentiation and the relation to patient survival time after a median follow-up of 6 years were studied. Analysis of serum p53 antibodies in the entire material demonstrated prognostic value in univariate analysis (P = 0.02); a finding that did not remain (P = 0.07) when the Dukes' stage was included in a multivariate analysis model. When the survival analysis was restricted to the potentially cured patients in Dukes' stages A-C, the serum p53 antibody levels retained independent prognostic value (P = 0.03). No clear association with tumour differentiation was found. We conclude that analysis of serum p53 antibodies may be of value for the identification of patients with different prognoses. This may be of relevance for selection of patients for adjuvant treatment.

Adult↗