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Biomedical subjects

M Eriksson

Publications and source records attributed to M Eriksson.

At least 37 records · Page 2Linked to original sources

No influence of simvastatin treatment on platelet function in vivo in patients with hypercholesterolemia.

Hypercholesterolemia is associated with platelet activation. Reduction of plasma cholesterol levels by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin has been found to improve certain aspects of platelet function in vitro and in vivo, but controlled trials are largely lacking. The present randomized, double-blind, crossover study was performed to evaluate whether 10- to 12-week treatment with simvastatin or placebo affects platelet function in vivo in 23 hypercholesterolemic men. Measurements were performed at rest and during mental stress. Simvastatin treatment reduced plasma total cholesterol levels by 18 +/- 2% and low density lipoprotein cholesterol levels by 26 +/- 2% (P < .001 for both), whereas high density lipoprotein cholesterol levels increased slightly (6 +/- 2%, P < .05). Platelet aggregability as assessed by filtragometry ex vivo was unaffected by simvastatin treatment both at rest and during mental stress. Plasma beta-thromboglobulin levels, which reflect platelet secretion, were also unaltered by simvastatin treatment both at rest (antilog of the mean: 20.2 versus 20.0 ng/mL during placebo) and during mental stress. Moreover, nocturnal excretion of 11-dehydrothromboxane B2 in urine did not differ between placebo and active treatment: 218 versus 216 ng/mmol creatinine, respectively. The corresponding values for urinary excretion of high-molecular-weight beta-thromboglobulin were 1.78 versus 1.92 ng/mmol creatinine. Thus, simvastatin treatment had no clear-cut effect on platelet function, as assessed by four different in vivo related platelet function variables, in hypercholesterolemic men.

Blood Platelets

Is a speculum examination sufficient for excluding the diagnosis of ruptured fetal membranes?

OBJECTIVE: To determine the false negative rate of a sterile speculum examination for the diagnosis of rupture of the membranes in women not in labor and without visible amniotic fluid at speculum examination. Furthermore, possible risks to the mother and the baby after suspected rupture of the membranes were analyzed. STUDY DESIGN: In women not in labor with suspected rupture of the membranes between gestational weeks 34 and 42, a sterile speculum examination was performed. If no amniotic fluid was visible, a test for Diamine oxidase was carried out. The results of tests were not known to the obstetricians or the women. The women were allowed to return home with no further controls if no amniotic fluid was visible at the speculum examination. Neonatal and obstetric outcome was recorded prospectively. RESULTS: Of 27,502 deliveries, 2,099 women not in labor attended the delivery ward for suspected rupture of the membranes after week 34. Amniotic fluid was visualized in 1,580 women. In 519 women in whom no amniotic fluid was seen at the speculum examination, the Diamine oxidase test was negative in 456 and positive in 63. Antibiotics were given to eleven children (2.4%) in the group with a negative Diamine oxidase and to one infant (1.6%) in the positive Diamine oxidase group (p>0.05). No differences in obstetric outcome were recorded. CONCLUSIONS: The false negative rate of a speculum examination for the diagnosis of rupture of the membranes in women without amniotic fluid visible at a speculum examination was 12% when Diamine oxidase was used as the standard for the diagnosis of rupture of the membranes. This study did not show any disadvantages for mothers and infants if the women were sent home after a false negative speculum examination. The value of biochemical methods in the management of women not in labor with rupture of the membranes after thirty-four weeks of gestation could be questioned.

Amine Oxidase (Copper-Containing)

Practice variation in Swedish primary care.

OBJECTIVE: To study individual practice patterns of physicians working in primary health care for standardized simulated cases on their first visit, and relate them to resource consumption for diagnostic tests, drugs and sick leave from a combined perspective of the health care and social security systems. DESIGN: Postal questionnaire presenting six hypothetical working-age cases with symptoms of ailments common in primary care asking physicians to order diagnostic tests and procedures, drugs, follow-up appointments and sick pay. SETTING: Swedish primary health care centres. SUBJECTS: Two hundred randomly selected physicians. MAIN OUTCOME MEASURES: Activities taken by the physician-diagnostic and laboratory tests ordered, drugs prescribed, length of sick leave and the cost of these actions. RESULTS: Practice patterns varied considerably, corresponding to a six-fold difference in total cost between the "cheapest" and "most expensive" physician. The largest share was loss of production as estimated by the cost of prescribed sick leave. Physicians who practised further away from hospitals and those who had worked more years tended to prescribe more measures. However, this only explained a small portion of the observed variation, which may be due to different physician attitudes to taking risks. CONCLUSION: "Paper" cases of common medical ailments presented to primary care physicians revealed considerable differences in practice style, resulting in six-fold differences in cost of measures prescribed at first visits.

Adult

A prospective follow-up study of acute deep venous thrombosis using colour duplex ultrasound, phlebography and venous occlusion plethysmography.

OBJECTIVE: To study the extent of deep venous thrombosis (DVT) and thrombus regression over time and to compare the results obtained with different diagnostic techniques. EXPERIMENTAL DESIGN: A prospective follow-up study with repeated examinations during a 6-month period. SETTING: Patients studied at clinical vascular laboratories. PATIENTS: Forty patients hospitalised for acute DVT. Thirty-six of these completed the follow-up period. MEASURES: The diagnosis of DVT was confirmed with phlebographic and/or ultrasonographic techniques. The patient were then re-examined with colour duplex ultrasound and venous occlusion plethysmography after one week, 3 months and 6 months and with phlebography after 1 week and 6 months. The extent of DVT and number of occluded segments were determined with phlebographic and ultrasonographic techniques. Venous occlusion plethysmography was used to evaluate the functional degree of outflow obstruction. RESULTS: Colour duplex scanning at 3 months' and 6 months' follow-up showed that 55% and 74% of initially occlusive thrombi, respectively, were recanalized, with thrombus resolution occurring faster and more completely in those initially limited to popliteal and/or calf level. Discrepancies between phlebography and duplex scanning were found in 6% (26/441) of venous segments investigated by both methods, primarily concerning flow in the veins below the knee. CONCLUSIONS: In comparison with phlebography, colour duplex scanning is an accurate method for evaluation and follow-up of patients with DVT. The non-invasive nature of colour duplex scanning makes this method extremely suitable for repeated studies and thus a potentially very valuable tool for both clinical and research studies of circulatory changes involved in acute and chronic DVT.

Adult

Comorbidity of personality disorders and major depression in patients with somatoform pain disorders or medical illnesses with long-standing work disability.

The comorbidity between major depression and personality disorders in patients with long-standing work disability at a rehabilitation clinic was investigated. Sixty patients with a somatoform pain disorder and 66 patients with different medical illnesses were assessed by means of a self rating scale for major depression, and the SCID screen personality disorder questionnaire. In the total series, 27% of the patients had a diagnosis of major depression and 34.9% had at least one personality disorder. Personality disorders were significantly more common in patients with medical illness than in patients with a somatoform pain disorder. There was a high frequency of comorbidity between major depression and personality disorders, especially borderline and avoidant personality disorders. If this is due to a common pathogenetic mechanism, it could explain why SSRIs are effective in both depression and some personality disorders.

Adult

Discovery of an algal mitochondrial carbonic anhydrase: molecular cloning and characterization of a low-CO2-induced polypeptide in Chlamydomonas reinhardtii.

In green unicellular algae, several polypeptides are induced upon exposure to limiting CO2. We report here on the localization and characterization of one of these, a 22-kDa polypeptide in Chlamydomonas reinhardtii. This nuclear-encoded polypeptide is induced in the mitochondria by a lowering of the partial pressure of CO2 in the growth medium from 5% to air CO2 levels. Sequencing of two different cDNA clones coding for the polypeptide identified it as a 20.7-kDa beta-type carbonic anhydrase (CA; carbonate dehydratase, carbonate hydro-lyase, EC 4.2.1.1). The two clones differ in their nucleotide sequences but code for identical proteins, showing that this CA is encoded by at least two genes. Northern blot hybridization reveals that mRNA transcripts are only present in cells transferred to air CO2 levels. A comparison of the deduced amino acid sequence with those of other beta-CAs shows the largest degree of similarity with CA from the cyanobacterium Synechocystis (50% identity and 66% similarity). To our knowledge, this is the first identification and characterization of a mitochondrial CA from a photosynthetic organism.

Amino Acid Sequence

Two conserved tyrosine residues in protein R1 participate in an intermolecular electron transfer in ribonucleotide reductase.

The enzyme ribonucleotide reductase consists of two nonidentical proteins, R1 and R2, which are each inactive alone. R1 contains the active site and R2 contains a stable tyrosyl radical essential for catalysis. The reduction of ribonucleotides is radical-based, and a long range electron transfer chain between the active site in R1 and the radical in R2 has been suggested. To find evidence for such an electron transfer chain in Escherichia coli ribonucleotide reductase, we converted two conserved tyrosines in R1 into phenylalanines by site-directed mutagenesis. The mutant proteins were shown to be enzymatically inactive. In addition, the mechanism-based inhibitor 2'-azido-2'-deoxy-CDP was incapable of scavenging the R2 radical, and no azido-CDP-derived radical intermediate was formed. We also show that the loss of enzymatic activity was not due to impaired R1-R2 complex formation or substrate binding. Based on these results, we predict that the two tyrosines, Tyr-730 and Tyr-731, are part of a hydrogen-bonded network that constitutes an electron transfer pathway in ribonucleotide reductase. It is demonstrated that there is no electron delocalization over these tyrosines in the resting wild-type complex.

Base Sequence

Distribution and origin of peptide-containing nerve fibres in the rat and human mammary gland.

The structures in the mammary gland involved in milk ejection have been investigated with regard to their relation to different types of peptidergic nerve fibres and their origin. Lactating rats were studied with immunohistochemistry focusing on the nipple, the parenchyma, the mammary blood vessels and the mammary nerve. The human mammary gland was also analysed. In the mammary gland from rat and human, nerve endings in the subepidermis, around smooth muscle cells in the nipple, in the connective tissue surrounding lactiferous ducts and alveoli in the nipple and in the parenchyma of the mammary gland showed immunoreactivity for calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide, peptide histidine isoleucine, neuropeptide Y, galanin and tyrosine hydroxylase, whereas dynorphin-positive nerve fibres could not be detected. The mammary nerve contained calcitonin gene-related peptide, vasoactive intestinal polypeptide, neuropeptide Y and tyrosine hydroxylase immunoreactivities; the adventitia of the mammary artery contained nerve fibres immunoreactive for neuropeptide Y and tyrosine hydroxylase, while vasoactive intestinal polypeptide-, peptide histidine isoleucine-, calcitonin gene-related peptide- and substance P-positive fibres were found in the tissue surrounding the artery. The wall of the mammary vein had nerve terminals immunoreactive for neuropeptide Y, tyrosine hydroxylase, calcitonin gene-related peptide and substance P. With the help of retrograde tracing using wheat germ agglutinin in combination with immunohistochemistry, projections of calcitonin gene-related peptide-immunoreactive cells in the dorsal root ganglia to the nipple were established. Neurons in the sympathetic stellate ganglion containing neuropeptide Y and tyrosine hydroxylase also projected to the mammary gland. Moreover retrogradely-labelled cells were found in the nodose ganglion, and they were vasoactive intestinal polypeptide-immunoreactive. These results demonstrate a rich distribution of different types of nerve fibres in structures of the mammary gland related to milk ejection. These nerve fibres and their peptides may be involved in the local control of milk ejection.

Animals

The long-term outcome of proximal vein thrombosis during pregnancy is not improved by the addition of surgical thrombectomy to anticoagulant treatment.

OBJECTIVES: To compare the long-term outcome for pregnant/puerperal women with iliofemoral venous thrombosis treated either with thrombectomy and additional anticoagulants or with anticoagulants alone. DESIGN: Retrospective study of two treatment methods. MATERIALS: Thirty women with iliofemoral venous thrombosis during pregnancy or puerperium were treated with thrombectomy and additional anticoagulants. Twenty-five women, with the same condition, treated with anticoagulants only were obtained from a registry. The mean follow-up time for both groups was 9 years. The patients of the two groups were well matched, had the same risk factor score and were comparable except for duration of symptoms before treatment. METHODS: The follow-up comprised history and clinical examination, colour Duplex ultrasound and venous strain-gauge plethysmography. RESULTS: Patency of iliac veins, symptoms of chronic venous disease, venous emptying and venous reflux did not differ between the groups. A significant reduction of outflow was found in 20% of the surgically treated patients and 16% of the controls. Impaired muscle pump function was seen in less than half of the patients in both groups. CONCLUSIONS: Surgical thrombectomy does not offer any advantage over anticoagulation treatment alone in the long-term outcome for patients with iliofemoral venous thrombosis during pregnancy or puerperium.

Adolescent

A non-random deletion in the p53 gene in oral squamous cell carcinoma.

In a retrospective study of the mutational spectrum of the p53 gene in oral squamous cell carcinoma, 80 primary tumours diagnosed in 1980-90 were included. Using polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis 47 mutations were found distributed in 39 of the tumours (49%). Unexpectedly, the majority of the mutations (29/47; 62%) were found in exon 8, and at sequencing 17 of them showed a 14 bp deletion in codons 287-292, causing formation of a stop codon and accordingly a truncated protein lacking the C-terminal. The majority of the patients with the 14 bp deletion were women (13/17), and it seemed as though certain potential risk factors for carcinoma of the head and neck were less common in this group.

Age Factors

Studies on cutaneous blood flow in the mammary gland of lactating rats.

The mechanisms that regulate mammary blood flow during lactation are not fully understood. In the present study laser Doppler flowmetry (LDF) was used to measure blood flow in the cutaneous microvessels of the mammary gland of lactating rats. The effects of suckling on blood flow were examined, as were those of local injection of oxytocin (0.5-5 mU) and the vasoactive peptides calcitonin gene-related peptide (CGRP; 0.1-10 pmol), vasoactive intestinal polypeptide (VIP; 0.4-20 pmol) and neuropeptide Y (NPY; 1-40 pmol). Blood flow responses to suckling varied depending on how much time had lapsed since the previous suckling. In rats with milk in the gland, suckling caused an initial increase in blood flow. In connection with milk let-down, the blood flow decreased, but was followed by a second increase. In recently suckled rats with no milk in the gland the increase in blood flow corresponded to the number of pups suckling. Oxytocin injections also had varying effects on mammary blood flow depending on how recently suckling had taken place. In non-suckled rats with milk in the gland, oxytocin injections caused a rise in blood flow that was interrupted by a fall during milk ejection. In recently suckled rats, all doses of oxytocin caused an increase in blood flow of similar magnitude. However, the effect of the higher doses had a longer duration. CGRP and VIP injections caused a dose-dependent increase in mammary blood flow regardless of when suckling last occurred. NPY injections caused a dose-dependent decrease in blood flow.

Animals

Changes in biliary lipid output after interruption of pravastatin treatment in humans.

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (e.g. pravastatin) has gradually increased in the treatment of hypercholesterolaemia. By inhibiting HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) activity, cholesterol synthesis in the liver is reduced and the plasma level of cholesterol, especially low-density lipoprotein (LDL)-cholesterol, is substantially lowered. Simultaneously, inhibition of HMG CoA reductase activity is associated with increased synthesis and accumulation of larger amounts of HMG CoA reductase enzyme protein. The main purpose of this study was to determine if the cessation of pravastatin treatment causes a rapid increase in the synthesis and biliary secretion of cholesterol, a condition which might lead to a temporarily increased cholesterol saturation of bile. Nine patients undergoing surgery for stones in the common bile duct were fitted with T-tubes in the common bile duct peroperatively; the side arm of the T-tube was left open postoperatively, creating a biliary fistula. All patients were given 6 days' treatment with pravastatin (20 mg b.i.d.) following the operation. Bile was collected from the T-tube, in 12-h fractions during this period and for another 3 days after termination of the treatment. Plasma levels of lipoproteins and lathosterol--reflecting cholesterol synthesis--were determined on several occasions. After cessation of pravastatin treatment, the plasma levels of total cholesterol and LDL-cholesterol increased by 21% and 33% respectively. High-density lipoprotein (HDL)-cholesterol did not change. The plasma level of lathosterol was increased two- to fourfold. Outputs of bile acids and phospholipids were significantly increased (23% and 10% respectively) after termination of treatment, whereas the output of cholesterol was not significantly changed. Cholesterol saturation was reduced by 20%, from 175 +/- 37% to 140 +/- 19%, but this change was not significant. The results indicate that, with the present experimental model (biliary diversion), the synthesis and biliary secretion of bile acids seem to be largely dependent on the de novo synthesis of cholesterol in the liver, whereas the biliary output of cholesterol is not.

Acyl Coenzyme A