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Biomedical subjects

K Melby

Publications and source records attributed to K Melby.

At least 19 recordsLinked to original sources
PubMed2004

Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV-infected individuals. However, the emergence of long-term side-effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV-infected patients on HAART. MATERIALS AND METHODS: Ten HIV-infected patients on protease inhibitor-based HAART with hyperlipidaemia followed a cholesterol-lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol-lowering diet. RESULTS: Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild-type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and LDL-receptor expression. CONCLUSIONS: Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV-infected patients on HAART, potentially resulting in both hypolipidaemic and anti-inflammatory effects.

Adult↗
PubMed2000

Influence of mild hypothermia after hypoxia-ischemia on the pharmacokinetics of gentamicin in newborn pigs.

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39 degrees C) for 72 h (n = 8) or mild hypothermia (35 degrees C) for 24 h followed by normothermia (39 degrees C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39 degrees C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.

Animals↗
PubMed1999

[Listeria monocytogenes--the perfect parasite?].

The pathogen Listeria monocytogenes has an extraordinary intracellular life cycle, based on adaption to and exploitation of normal cellular mechanisms. Extracellular organisms induce their own phagocytosis, followed by destruction of the phagosomal membrane. Cytoplasmatic bacteria organize the intracellular protein actin into "comet tails", and thus gain motility. In contact with the plasma membrane, motile bacteria induce a pseudopodium, corresponding to an invagination of the plasma membrane of the neighbouring cell. Eventually, the pseudopodium is engulfed by the neighbouring cell, creating a double membrane vacuole. L. monocytogenes destroys the double membrane, and escapes into the cytoplasm. This article reviews the molecular biology of Listeria infection, and how research in this field has yielded increased insight into normal cellular processes. Finally, we propose that the neuroinvasive properties of L. monocytogenes is caused by actin-dependent transport within axons from the periphery to the central nervous system.

Actins↗
PubMed1996

Prediction of diagnosis in acute and subacute oligoarthritis of unknown origin.

A total of 146 consecutive patients between 18 and 60 yr of age with oligoarthritis of unknown origin (< or = 6 active joints, < or = 8 weeks duration) were examined by a variety of clinical, laboratory and microbiological investigations, and followed longitudinally for 24 weeks. Reactive arthritis was diagnosed in 46 patients (19 induced by Chlamydia trachomatis, 27 by enterobacteria), 62 had undifferentiated arthritis, eight other inflammatory arthritic diseases, 15 acute sarcoid arthritis and 15 non-inflammatory joint diseases. Group differences were found for many baseline variables, but with considerable overlap between the groups. A set of four clinical and laboratory variables (elevated CRP, genitourinary symptoms, metatarsophalangeal joint involvement. HLA B27) could predict reactive arthritis with a sensitivity of 69.2% and a specificity of 93.5%. A wide range of clinical and laboratory examinations are required to determine the final diagnosis in oligoarthritis, but individual and sets of clinical and laboratory measures may give helpful clues for the correct diagnosis.

Acute Disease↗
PubMed1996

The value of isotype determination of serum antibodies against Chlamydia for the diagnosis of Chlamydia reactive arthritis.

In clinical rheumatology, the diagnosis of Chlamydia reactive arthritis is difficult because an incomplete form of the disease can closely resemble an undifferentiated seronegative mono/oligoarthritis. We investigated whether measuring specific isotypes of anti-Chlamydia antibodies in serum can improve the diagnosis, by comparing such antibody concentrations in the serum of patients with well-defined disease, i.e. Chlamydia trachomatis sexually acquired reactive arthritis (CT-SARA), with other arthritides. Antibody levels were determined by enzyme-linked immunosorbent assay (ELISA). When considering two different isotypes and their combination, the best sensitivity (63%) was obtained for IgM and/or IgA results with a specificity of 81%. The patients with CT-SARA and SARA had the highest levels of antibodies of all isotypes tested. It is concluded that, in our experimental conditions, only very high values of specific isotypes could indicate a diagnosis of Chlamydia reactive arthritis.

Adolescent↗
PubMed1996

Synovial fluid and serum antibodies against Chlamydia in different forms of arthritis: intra-articular IgA production in Chlamydia sexually acquired reactive arthritis.

Since the presence of Chlamydia has been shown in synovial fluid (SF) from some patients with Chlamydia reactive arthritis, we investigated whether anti-Chlamydia antibodies present in the joint are derived from the circulation or are locally produced. We compared titres of IgG, IgM and IgA antibodies against Chlamydia, and against a control antigen (tetanus toxoid), by an enzyme-linked immunosorbent assay (ELISA), in paired samples of serum and SF from Chlamydia trachomatis sexually acquired reactive arthritis (CT-SARA) patients and from patients with other forms of arthritis. The ratio of serum/SF IgA anti-Chlamydia antibodies was significantly decreased in CT-SARA patients. It is concluded that, in our experimental conditions, we found evidence for intra-articular production of IgA anti-Chlamydia antibodies.

Adolescent↗
PubMed1996

DNA fingerprinting and serotyping of Campylobacter jejuni isolates from epidemic outbreaks.

The aim of the present investigation was to compare DNA fingerprinting and serotyping (heat-stabile and heat-labile antigens) of isolates from epidemic outbreaks as well as of solitary isolates. Campylobacter jejuni isolates from two epidemic outbreaks in Sweden, one milkborne (35 isolates) and one waterborne (17 isolates), and one waterborne outbreak in Norway (11 isolates), as well as 30 solitary isolates from Swedish patients with gastroenteritis, were analyzed. A total of 93 isolates were analyzed. In the waterborne outbreak in Norway, only one serotype with one DNA pattern was found. In the milkborne outbreak in Sweden, two serotypes (HS2:HL4 and HSNT:HL4) with two different DNA patterns were found. The isolates from the waterborne outbreak in Sweden were different serotypes. For two isolates of the same serotype, different DNA patterns were seen. This was also recorded for isolates from solitary cases. It was concluded that serotyping is a useful tool in most epidemiological situations but sometimes lacks sufficient discriminatory power. DNA fingerprinting can add valuable epidemiological information to that supplied by serotyping and can in some situations provide sufficient epidemiological information when used alone.

Animals↗
PubMed1996

Risk of toxoplasmic encephalitis in AIDS patients: indications for prophylaxis.

To establish the indications for primary prophylaxis against toxoplasmic encephalitis in the Norwegian HIV-positive population, we estimated the incidence of toxoplasmic encephalitis, and related the degree of immunodeficiency and the presence of IgG antibodies against Toxoplasma gondii (T. gondii) to the development of toxoplasmic encephalitis. This retrospective study includes all HIV-positive patients at our hospital from April 1983 to October 1994 (n = 705). A total of 238 patients had AIDS, which represents almost 90% of all AIDS patients in Oslo. Autopsy was done in over 70% of the patients who died during this period; 19 patients developed toxoplasmic encephalitis (8.0%). The median CD4 cell count was 75 x 10(6) cell/I (range 0-280) at the time of diagnosis of toxoplasmic encephalitis. T. gondii serology was studied in 698 (99.0%) of the patients, and was found positive for 17.8%. Of the patients with toxoplasmic encephalitis 18/19 had IgG antibodies against T. gondii and of the 40 AIDS patients who had anti-T. gondii IgG, 18 (45%) developed toxoplasmic encephalitis. We conclude that there is indication for prophylactic treatment of HIV positive patients who have IgG antibodies against T. gondii and who have fewer than 200 x 10(6) CD4 cells/I.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Proper use of antibiotics--what is that?].

Antibiotics are one of the cornerstones of modern medicine. During the last 20 years there has been an alarming world-wide spread of multiple-resistant bacteria. One of the main reasons is the overuse of all types of antibiotics, especially broad-spectrum drugs. This paper gives general advice on antibiotic therapy in Norway. We adovcate the use of drugs with little ecological impact, such as the penicillins. Whenever possible, empiric treatment with macrolides, tetracyclines cefalosporines, imipenem and fluoroquinolones should be avoided.

Anti-Bacterial Agents↗
PubMed1995

[The end of antibiotics? Increasing bacterial resistance in global and Norwegian perspective].

During the last 20 years there has emerged a growing world-wide problem with regard to multidrug-resistant microbes. The most serious examples so far are vancomycin-resistant strains of Enterococcus faecium, totally resistant isolates of Mycobacterium tuberculosis and multiple-resistant Staphylococcus aureus and Streptococcus pneumoniae. With the exception of some few strains of methicillin-resistant S. aureus and vancomycin-resistant enterococci, such bacteria have not been found in Norway. In this article we discuss possible ways of preventing further selection and spread of multiple-resistant microbes. We stress the importance of infection control programmes and restrictive use of antibiotics.

Communicable Disease Control↗
PubMed1995

[Diagnostic evaluation of suspected reactive arthritis].

On the basis of an epidemiological study on recently onset, possible reactive arthritides in Oslo we propose a programme for diagnostic evaluation. Disease symptoms and signs provided little help for an ethiological diagnosis. Therefore a variety of diagnostic tests and examinations are recommended in order to obtain a correct diagnosis; such as clinical examination, chemical and serological blood tests, bacteriological examinations from throat, of stools and of specimens from urethra-cervix, examination of synovial fluid and synovial tissue and X-ray examination of affected joints, sacroiliacal joints and lungs. About one third of the recently onset arthritides in the Oslo study were diagnosed as reactive arthritis, one third as possible reactive arthritis and another third as inflammatory arthritides.

Arthritis, Reactive↗
PubMed1995

Amplification of plasmid and chromosome Chlamydia DNA in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies.

OBJECTIVE: To investigate the hypothesis that whole bacteria might be found in the joints of patients with Chlamydia-associated reactive arthritis. METHODS: The presence of 2 plasmid- and 2 chromosome-specific sequences of Chlamydia DNA was investigated by amplification with the polymerase chain reaction, in synovial fluid (SF) samples from 71 patients with various arthropathies. RESULTS: Chlamydia DNA was found in SF samples from 22 patients. CONCLUSION: Whole chlamydiae are likely present in the SF of patients with Chlamydia-associated reactive arthritis.

Adolescent↗
PubMed1995

Abnormal intestinal motor patterns explain enteric colonization with gram-negative bacilli in late radiation enteropathy.

BACKGROUND & AIMS: Bacterial overgrowth and intestinal pseudo-obstruction may succeed abdominal radiotherapy, and absence of intestinal migrating motor complex (MMC) has been reported in bacterial overgrowth. The aims of this study were to address the relationship between intestinal patterns of motility and gastrointestinal microflora and to elucidate the pathogenesis of late radiation enteropathy. METHODS: Forty-one consecutive female patients with symptoms of late radiation enteropathy were examined by prolonged ambulatory manometry, culture of gastric and duodenal samples with quantification of gram-negative bacilli (GNB) by the glucose gas test, the [14C]D-xylose breath test, and determination of pH and short-chain fatty acids in gastric juice. RESULTS: The intensity of MMC explained 61% (P < 0.001) and 71% (P < 0.001) of the variability of GNB in the stomach and duodenum, respectively, corresponding to the severity of disease. Abnormal MMC index and presence of irregular bursts were the best predictors of GNB (86%; P < 0.001, multiple regression). Fasting gastric pH explained gastric bacterial counts (63%; P < 0.001) but did not predict GNB. CONCLUSIONS: Impaired motility emerges as a causal factor for gastrointestinal colonization with GNB, whereas hypochlorhydria facilitates unspecific gastric colonization. Abnormal motility and GNB in the proximal small intestine are essential factors in the pathogenesis of severe late radiation enteropathy.

Adult↗
PubMed1995

Acute sarcoid arthritis: occurrence, seasonal onset, clinical features and outcome.

In a 2-yr prospective follow-up study of patients presenting clinically with possible reactive arthritis (ReA), 17 (9%) of the patients turned out to have acute sarcoid arthritis (SA). The number of new cases of SA per year was 2.9/100,000 persons in the city of Oslo between 18 and 60 yr of age. The onset of SA clustered in the spring. All the SA patients presented with bilateral ankle joint involvement and bilateral hilar lymphadenopathy, and ten (59%) presented with the triad of erythema nodosum, arthritis and lung involvement. A prospective follow-up after 104 weeks showed complete remission of arthritis in all 17 cases of SA. The total duration of arthritis [median (range)] was 11 (2-107) weeks. Erythema nodosum was mild and transient in all cases. At week 104, the lung and hilar manifestations had resolved. We conclude that the outcome of SA appeared favourable. Bilateral ankle joint involvement, erythema nodosum and bilateral hilar lymphadenopathy found at the routine chest X-ray examination are important clues for the diagnosis of SA.

Adult↗
PubMed1994

[Diagnosis and treatment of infections of the digestive system in HIV-infected patients].

Patients with HIV infection often suffer from opportunistic and bacterial infections of the digestive tract. The most common agents are Candida albicans, Herpes simplex and Cytomegalovirus, Mycobacterium avium intracellulare, Cryptosporidium parvum, and enteropathogenic bacteria such as Salmonella, Shigella and Campylobacter. The diagnosis is established by means of microbiological examination of blood and faeces, often supplemented by gastrointestinal endoscopy, with mucosal biopsies for culture and histology. Most patients respond well to specific treatment, but the infections tend to relapse after withdrawal of drugs.

AIDS-Related Opportunistic Infections↗
PubMed1994

Calcitonin elevation in small cell lung cancer without ectopic production.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

Adult↗
PubMed1994

Reactive arthritis: a favorable 2 year course and outcome, independent of triggering agent and HLA-B27.

OBJECTIVE: To study the 2 year course and clinical and radiological outcome of reactive arthritis and to identify possible outcome predictors. METHODS: Patients with chlamydia induced arthritis (n = 25) and arthritis induced by enterobacteria (n = 27), all derived from a 2-year epidemiological study on reactive arthritis (ReA) and possible ReA, were followed prospectively with clinical, laboratory and radiographic examinations. RESULTS: After one year, 40% of patients with chlamydia induced arthritis and 20% of those with enteroarthritis still had clinical signs of arthritis. After 2 years, 100 and 95%, respectively, had recovered. At that time, one patient with enteroarthritis had developed radiographic abnormalities exceeding grade I in peripheral joints. None developed bilateral sacroiliitis during the course. The duration of ReA was found to be independent of the triggering agent, sex, age, duration of arthritis prior to entry, pain, index of active joints, CRP and the presence of HLA-B27. CONCLUSION: Early recognition and elimination of the triggering microbe seems important for the arthritis outcome in ReA. The results do not support the hypothesis that the presence of HLA-B27 heralds a more serious disease course or less favorable outcome, nor that the type of triggering agent predicts the outcome.

Adolescent↗