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Biomedical subjects

A M Pedersen

Publications and source records attributed to A M Pedersen.

At least 19 recordsLinked to original sources
PubMed2003

Oral lichen planus and intake of drugs metabolized by polymorphic cytochrome P450 enzymes.

OBJECTIVE: To study if patients with oral lichen planus (OLP) had a medication profile different from that of a control group without oral mucosal lesions. It was hypothesized that OLP lesions might result from poor drug metabolism (PM) because of genetic variation of the major cytochrome P450-enzymes (CYPs with a PM-risk). SUBJECTS AND METHODS: Dental records of 172 OLP patients were reviewed in this cross-sectional study and 152 sex- and age-matched subjects served as controls. The measures for the drug profiles were medicine type (ATC-code), mono- and polypharmacy, CYP-enzyme metabolism pattern, and medicine with a potential to induce lichenoid drug eruptions. RESULTS: Fifty per cent of the OLP patients consumed daily medications as compared with 59% of the controls. The OLP patients more frequently consumed medicines metabolized by CYPs with a PM-risk (P = 0.03). Furthermore, they consumed more medicine with an inhibitory effect on one or more CYPs than the controls (P = 0.01). CONCLUSION: Confounders like sex, age, systemic diseases, drug distribution into the therapeutic classes, and polypharmacy were similar in the two groups; but the OLP patients consumed more drugs metabolized by CYPs with a PM-risk. The results argue for further investigation of associations between OLP, medication intake and the CYP-enzyme metabolic pathways.

Adult↗
PubMed2002

Oral findings in patients with primary Sjögren's syndrome and oral lichen planus--a preliminary study on the effects of bovine colostrum-containing oral hygiene products.

Bovine colostrum is rich in antimicrobial substances and growth factors. The purpose of this open study was to examine and compare the interventory effects of daily use of bovine colostrum-containing oral hygiene products (CHP) on oral symptoms and findings in 20 patients with primary Sjogren's syndrome (pSS) and 20 age-matched patients with oral lichen planus (OLP). Objective oral measures and self-assessment of oral symptoms and general health were conducted before and after 90 days' use of CHP. The pSS patients had more systemic diseases, medication intake, oral dryness, poorer general health and lower salivary secretion than the OLP patients, who had the highest plaque index (PI) and the most mucosal soreness. Oral dryness and soreness were correlated to general health. In both patient groups. unstimulated whole saliva flow rate (UWS) had increased, PI and periodontal pocket depth (PPD) were reduced, and general health and oral dryness and soreness had improved after using CHP. A decrease in hyphae was found in candida smears from both groups and in blastospores in OLP smears. A reduction in the extension of the mucosal lesions was observed in 15 OLP patients. Results suggested beneficial effects of intervention with CHP on oral symptoms, general health, UWS, PI, PPD and candidal load in two patient groups--pSS and OLP--representing different oral symptomatology.

Adult↗
PubMed2002

Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion.

Saliva has multiple essential functions in relation to the digestive process taking place in the upper parts of the gastrointestinal (GI) tract. This paper reviews the role of human saliva and its compositional elements in relation to the GI functions of taste, mastication, bolus formation, enzymatic digestion, and swallowing. The indirect function of saliva in the digestive process that includes maintenance of an intact dentition and mucosa is also reviewed. Finally, pathophysiological considerations of salivary dysfunction in relation to some GI functions are considered.

Deglutition↗
PubMed2001

A dependent-rates model and an MCMC-based methodology for the maximum-likelihood analysis of sequences with overlapping reading frames.

We present a model and methodology for the maximum-likelihood analysis of pairwise alignments of DNA sequences in which two genes are encoded in overlapping reading frames. In the model for the substitution process, the instantaneous rates of substitution are allowed to depend on the nucleotides occupying the sites in a neighborhood of the site subject to substitution at the instant of the substitution. By defining the neighborhood of a site to extend over all sites in the codons in both reading frames to which a site belongs, constraints imposed by the genetic code in both reading frames can be taken into account. Due to the dependency of the instantaneous rates of substitution on the states at neighboring sites, the transition probability between sequences does not factorize and therefore cannot be obtained directly. We present a Markov chain Monte Carlo procedure for obtaining the ratio of two transition probabilities between two sequences under the model considered, and we describe how maximum-likelihood parameter estimation and likelihood ratio tests can be performed using the procedure. We describe how the expected numbers of different types of substitutions in the shared history of two sequences can be calculated, and we use the described model and methodology in an analysis of a pairwise alignment of two hepatitis B sequences in which two genes are encoded in overlapping frames. Finally, we present an extended model, together with a simpler approximate estimation procedure, and use this to test the adequacy of the former model.

Base Sequence↗
PubMed2001

Primary Sjögren's syndrome: oral aspects on pathogenesis, diagnostic criteria, clinical features and approaches for therapy.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory systemic autoimmune disease affecting the exocrine glands and predominantly the salivary and lacrimal glands. The impaired gland function is assumed to be a result of progressive lymphocyte-mediated destruction of the exocrine gland tissue leading to the cardinal manifestations, hyposalivation and keratoconjunctivitis sicca (KCS), as well as devastating symptoms of oral and ocular dryness. Although primarily characterised as an exocrine dysfunction, non-exocrine organs may also be affected. The onset and course of pSS is usually insidious but may develop into a disabling disease, which profoundly affects the patient's general well being and quality of life. Moreover, pSS may even evolve into a lymphoid malignancy. The aetiology of pSS remains unknown but the pathogenesis of exocrine cell damage is apparently multi-factorial, including immunological, genetic, hormonal and viral components. Recent research also includes neurogenic aspects of exocrine gland dysfunction, including the interference of immune mediators with glandular response to neurotransmitters released from nerve fibres. pSS usually affects middle-aged women and the female:male ratio is 9:1. The prevalence varies from 0.29-4.8%, depending on the population sampled and the diagnostic criteria used. At present, there are no specific diagnostic tests for pSS and no universally accepted diagnostic criteria. The current therapy is primarily symptomatic. This review focuses on the current oral clinical, diagnostic, pathogenic and therapeutic aspects of pSS.

Animals↗
PubMed2000

Innervation pattern and Ca2+ signalling in labial salivary glands of healthy individuals and patients with primary Sjögren's syndrome (pSS).

We have characterised the innervation pattern and intracellular Ca2+-signalling in labial salivary glands (LSG) of 16 patients with primary Sjögren's syndrome (pSS) and 27 healthy controls. Numerous immunoreactive nerve fibers (IRF) containing vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) were found around acini, ducts and blood vessels. Substance P (SP)-, neuropeptide Y-, tyrosine hydroxylase- and nitric oxide synthase-IRF were mainly surrounding ducts and blood vessels. The majority of pSS patients had inflamed LSG and the presence of focal lymphocytic infiltrates (FI) were more frequent and pronounced as compared with healthy controls. In areas with normal or diffusely inflamed LSG tissue, pSS patients demonstrated the same distribution of IRF as healthy controls with similar histology. However, IRF were absent in central areas of FI both in pSS and age-matched healthy controls. Although all pSS patients had hyposalivation, stimulation with acetylcholine, norepinephrine, phenylephrine, isoproterenol, VIP, PACAP, SP, adenosine 5'-triphosphate and uridine 5'-triphosphate induced the same increase in the intracellular free Ca2+ concentration in LSG acini from both pSS patients and healthy controls, indicating the presence of functional receptor systems in vitro.

Adult↗
PubMed2000

Codon-substitution models for heterogeneous selection pressure at amino acid sites.

Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega < 1 purifying selection, and omega > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is <1, but in which some sites are clearly under diversifying selection with omega > 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.

Amino Acid Substitution↗
PubMed2000

Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells.

We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis and [Ca2+]i. It was found that a simple correlation between the rise in [Ca2+]i and the rate of NO production following NE stimulation does not exist, and studies in which [Ca2+]i was elevated by means of the Ca2+ ionophore, ionomycin, further established that even a very large rise in [Ca2+]i did not cause significant NO synthesis. We furthermore found that activating adrenoceptors with NE causes synthesis of cGMP by activating a guanylyl cyclase, and that an enhanced [cGMP] evoked by use of caged cGMP causes Ca2+ release from internal stores. Thus, upon sympathetic stimulation, salivary gland acini synthesize NO that, in addition to playing a role in controlling intracellular [Ca2+]i, also might play a role in retrograde signaling processes to the surrounding tissue.

Acetylcholine↗
PubMed1999

[The effect of giving a copy of the discharge letter to parents].

The purpose of this study was to evaluate the effect of giving parents a copy of the discharge letter (DL) concerning the hospitalization of their child. Questionnaires were sent to parents, general practitioners (GP) and health visitors (HV). Sixty-one per cent of the parents and 64% of the GPs and HVs returned the questionnaires. Seventy-seven per cent of the responding parents had received the discharge letter within a week after the discharge, and 64% of the parents understood the DL without difficulties. The majority regarded it as an improvement of the service to the families.

Adult↗
PubMed1999

Percutaneous endoscopic gastrostomy in children with cancer.

We reviewed the clinical course of 32 children with cancer who received nutrition through a feeding tube placed percutaneously during gastroscopy (PEG). Their median age was 5.1 y (75%, range: 1.8-13.7 y, min: 3.5 mo) when the PEG was done 0.7-23 mo after diagnosis (median: 1.8 mo, 75%; range: 0.9-8 mo). Five of the children underwent bone marrow transplantation with the gastrostomy in place. There was a significant (p = 0.0001) decrease in the median weight-for-age SDS of 0.55 (75%, range: -1.18-0.28) from the time of diagnosis to placement of the gastrostomy. Twenty-two percent of the children had neutrophils < 0.5 x 10(9)l at the time of placement. There were no major postoperative complications. Seventy-two percent of the patients experienced a total of 55 minor and transient complications including leakage of gastric juice (n = 29), superficial wound infections (n = 23), mechanical problems (n = 2), or bleeding (n = 1). There were no documented cases of bacteraemia. Twelve of the wound infections (52%) arose during neutropenic episodes. Two tubes were replaced due to mechanical problems. There was a median increase in weight SDS of 0.3 (75%, range: -0.6-1.1) from the time of placing the gastrostomy to the end of follow-up (p = 0.054). Nutrition via gastrostomy in children with cancer has several advantages. It is rarely associated with more than minor complications, it is cosmetically more acceptable than the nasogastric tube and it improves nutrition at far lower cost than parenteral nutrition. In selected cases in which bone marrow transplantation or intensive treatment protocols are planned, we suggest that a gastrostomy should be considered before malnutrition develops.

Adolescent↗
PubMed1999

Primary Sjögren's syndrome (pSS): subjective symptoms and salivary findings.

We studied the relationship between dry mouth, general health and objective findings in 16 patients having primary Sjögren's syndrome (pSS) according to the 1993 European classification criteria as well as in healthy controls. Serum autoantibody to SSA/SSB (AB) was correlated to unstimulated whole saliva flow (UWS) and labial salivary gland focus score (FS). All patients had dry mouth symptoms and UWS < or = 0.10 ml/min, but patients with UWS < 0.05 ml/min and AB had more complaints of oral and ocular dryness. These patients also tended to have more exocrine and non-exocrine manifestations, and oral dryness had a greater impact on their self-reported general health than in patients with UWS > or = 0.05 ml/min. Accordingly, we consider rating of oral dryness by visual analogue scales or categorised questionnaires to be valuable for the evaluation of oral involvement in pSS.

Adult↗
PubMed1999

Primary Sjögren's syndrome: salivary gland function and clinical oral findings.

OBJECTIVE: To evaluate salivary gland function, saliva composition and oral findings in patients with primary Sjögren's syndrome (pSS) subdivided into patients with and without focus score > or = 1 (FS) and/or antibodies to SSA/SSB (AB) as well as in healthy controls. SUBJECTS AND METHODS: Unstimulated (UWS) and chewing stimulated (SWS) whole saliva, and stimulated parotid saliva (SPS) were collected in 16 patients fulfilling the European classification criteria for pSS subdivided into those with FS and/or AB (n = 8) and those without FS and AB (n = 8), and in age-matched (n = 14) and young healthy controls (n = 13). UWS and SWS were analysed for Na+ and K+. SPS was analysed for Na+, K+, statherin, and proline-rich proteins (PRPs). Sicca symptoms, DMFT/DMFS, plaque (PI) and gingival (GI) scores, periodontal pocket depth (PPD), and mucosal status were recorded. RESULTS: The young healthy controls had lower UWS as compared to the aged controls (P = 0.03). However, the aged controls had higher DMFT/DMFS (P < 0.001) and PI, GI and PPD (P < 0.01). Patients with FS and/or AB generally had lower saliva secretory rates than patients without FS and/or AB (P = 0.01 for UWS and SPS) and age-matched healthy controls (P = 0.001). There was no significant difference in the content of Na+ and K+, statherin and PRPs between groups. Patients with FS and/or AB had the highest frequency of oral mucosal changes and higher DMFT/DMFS than patients without FS and/or AB and healthy controls (P < 0.01). However, PI, GI, and PPD did not differ significantly. CONCLUSION: Patients with FS and/or AB had lower salivary secretory rates, higher DMFT/DMFS, and more oral mucosal changes than patients without FS and/or AB. Additionally, data suggest that salivary gland function in healthy individuals do not decrease with age.

Adult↗
PubMed1998

[Self management of peroral anticoagulant therapy in patients with artificial heart valves].

Twenty-one heart valve operated patients (age 19-70 years) were trained in self-managed oral anticoagulant therapy using a home coagulometer (CoaguChek). Twenty patients accomplished between eight and 29 (median 24) months of self management and were fully capable of self management after 30 weeks of training. No patients experienced major bleeds or thrombo-embolic events. A control group of 20 patients from our department was matched, retrospectively, to the study group. The self-managing patients were within the therapeutic INR range 78% of the study period compared to 54% for the control patients. All self-managing patients had their median INR-value within the therapeutic range, versus only 14 in the control group. Self-management of oral anticoagulant therapy seems feasible for selected patients.

Adult↗
PubMed1996

Nortriptyline-induced hepatic failure.

We report a case of hepatic injury after treatment with nortriptyline in a therapeutic dose. There were symptoms of hepatitis and increased prothrombin time, serum alanine aminotransferase and alkaline phosphatases. The patient recovered after discontinuation of the drug.

Alanine Transaminase↗
PubMed1996

Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation.

We present reference intervals for total homocysteine and methylmalonic acid in plasma based on samples from 126 women (ages 20-85 years, median 49 years) and 109 men (ages 20-84 years, median 50 years). The central 0.95 interval for methylmalonic acid was 0.08-0.28 micromol/L. Supplementation with cyanocobalamin caused a nonsignificant decrease in methylmalonic acid. Supplementation with folic acid caused a decrease in homocysteine concentrations, with data analysis identifying two significantly different clusters: 182 subjects with the lowest initial concentrations (7.76 +/- 1.54 micromol/L, mean +/- SD) and the smallest decrease (1.26 +/- 0.96 micromol/L), and 53 subjects with the highest initial concentrations (12.33 +/- 2.04 micromol/L) and greatest decrease (4.14 +/- 1.32 micromol/L). We argue in favor of the age- and gender-specific central 0.95 intervals obtained for the 182 subjects before being supplemented with folic acid: 4.6-8.1 micromol/L for subjects at <30 years; 4.5-7.9 micromol/L for women, ages 30-59 years; 6.3-11.2 micromol/L for men, ages 30-59 years; and 5.8-11.9 micromol/L for subjects at >60 years.

Adult↗
PubMed1995

Tumor necrosis factor-alpha affects in vitro hormone production by JEG-3 choriocarcinoma cell cultures.

Steroid hormones, produced by the placenta, appear to be critically important in maintaining the pregnancy of experimental animals and possibly humans. Previous studies in our laboratory have shown that macrophage-conditioned media, which are known to contain several cytokines including tumor necrosis factor-alpha (TNF-alpha), decreased the in vitro synthesis of progesterone (P) and increased the synthesis of estradiol (E2) by placental fragments. The present study was designed to further our understanding of the effect of cytokines on the synthesis of placental trophoblast hormones. The current study shows that TNF-alpha (1-20 ng/ml) decreases the in vitro synthesis of P and increases the synthesis of both E2 and human chorionic gonadotropin (hCG) by JEG-3 choriocarcinoma cells (a model for trophoblast hormone synthesis). The effects of TNF-alpha are independent of changes in formation of adenosine 3':5' cyclic-monophosphate, guanosine 3':5' cyclic-monophosphate, prostaglandin E2, and prostaglandin F2 alpha. However, the effect of TNF-alpha on P formation is blocked by cycloheximide (1 microgram/ml). These observations suggest TNF-alpha could have effects on placental hormone synthesis which might be important in the pathogenesis of both normal and preterm labor. At least some of these effects appear mediated through new protein synthesis.

Choriocarcinoma↗
PubMed1992

Studies of fluoride retention by oral soft tissues after the application of home-use topical fluorides.

Previous studies have focused on enamel and plaque as the primary sites of fluoride (F) retention in the mouth. The present study was undertaken to evaluate the role of oral soft tissue as a site of F retention by comparing an edentulous subject panel (n = 9) with a fully dentate panel (n = 10). Unstimulated whole saliva samples were collected by having subjects pool saliva for two min. Samples were collected over a 24-hour period after application of a placebo dentifrice (PD; 0.4 ppm F), fluoride dentifrice (FD; 1100 ppm F), fluoride rinse (FR; 226 ppm F), or fluoride gel (FG; 5000 ppm F) delivered in custom trays. There was no statistically significant difference in salivary flow rate between the two panels for any of the treatments. The edentulous panel had higher salivary F levels than the dentate panel, which reached statistical significance (p less than 0.05) for the FD and FG treatments. In a separate study involving the same treatments, F levels at specific soft-tissue sites were measured over a one-hour period by use of absorbent discs placed in different soft-tissue areas of the mouth. The tongue and lower posterior vestibule retained the highest F levels, followed by the upper posterior buccal vestibule and upper anterior labial vestibule, with the lowest F levels retained in the lower anterior vestibule and the floor of the mouth. There was a strong-to-moderate correlation between whole saliva F concentration and F levels at specific soft-tissue sites. This study establishes the importance of oral soft tissue as the major site of F retention in the mouth.

Analysis of Variance↗