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Biomedical subjects

A Akesson

Publications and source records attributed to A Akesson.

70 records · Page 4Linked to original sources

Gastrointestinal function in patients with progressive systemic sclerosis.

In 24 patients with progressive systemic sclerosis (PSS) the pentagastrin-stimulated gastric acid secretion was determined to investigate if acid hypersecretion is associated with reflux-oesophagitis--the most common complication to oesophageal involvement in PSS. Gastro-oesophageal reflux was observed in 12, reflux-oesophagitis in 9 and oesophageal mycosis in 8 patients. Gastric acid secretion was increased in 13 (54%) patients and tended to be higher in patients with oesophagitis. Patients with reflux and increased acid secretion seemed to be free from oesophageal mycosis. Bacterial overgrowth and malabsorption are known complications to intestinal scleroderma and these items were investigated using non-invasive methods. Four patients had increased bile acid deconjugation, 3 had increased (14C)xylose degradation indicating bacterial overgrowth and 7 patients had decreased fat absorption in the triolein breath test. Nutritional status with respect to selenium, folate, cobalamin and fat-soluble vitamins was essentially normal.

Adult↗

Hepatotoxic effects of anti-rheumatic drugs in cultured rat hepatocytes.

Drug-induced liver injury has been suggested as a possible mechanism for the liver damage in rheumatic diseases. To evaluate the role of direct toxic action of drugs on hepatocytes, the effects of salicylate, chloroquine, prednisolone and indomethacin on LDH leakage from cultured rat hepatocytes were studied. Exposure for 24 h to the first two drugs induced liver damage, as reflected by LDH release, at concentrations 2-10 times as high as the therapeutic plasma levels in humans. Indomethacin and prednisolone at concentrations approx 50-100-fold higher than the therapeutic plasma levels, were not toxic to cultured hepatocytes. The data suggest that direct a toxic effect on hepatocytes is one possible mechanism of hepatotoxicity for salicylate and chloroquine, especially since the exposure time is much longer in humans than in the experimental model used here.

Animals↗

Prognosis in juvenile rheumatoid arthritis with systemic onset. A follow-up study.

Thirty-three patients with systemic onset JRA were followed up for 4 to 24 years (median 10 years). None had positive RF or ANA. Most patients developed polyarthritis. Cardiac involvement occurred in 14 patients (42%). Cardiac prognosis was good for pericarditis but seemed to be worse for myocarditis or perimyocarditis. Three patients contracted renal amyloidosis (9%). Severe growth retardation was observed in 39 per cent. Half of the patients had low activity or were in remission after in average 5.9 years' duration of the disease. Seventy per cent of the patients were in a good functional state. Patients with less than average radiological progression during the first 5 years of disease and those with onset of disease after the age of 5, seemed to have a better functional prognosis.

Amyloidosis↗

Liver function in some common rheumatic disorders.

Liver function was studied primarily by determination of serum gamma glutamyl transferase and alkaline phosphatase. In subsamples of patients the investigation was extended by determination of serum amino-transferases, isoenzyme analysis of alkaline phosphatase, 99mtechnetium scintigraphy, and liver biopsy. In 183 in-patients with rheumatoid arthritis, the serum gamma glutamyl transferase level was elevated in 47% and serum alkaline phosphatase (of liver origin) in 24%. A concomitant increase in serum aminotransferases was found in 15% of patients with elevated gamma glutamyl transferase level. A closely similar pattern was found in 45 patients with non-rheumatoid arthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and undefined arthritis), and in 5 patients with polymyalgia rheumatica. In 23 patients with non-rheumatic inflammation (pneumonia), liver dysfunction was common, though the pattern of serum enzyme changes was different. In rheumatoid arthritis, liver scanning showed irregular or low uptake, but biopsy only indicated reactive hepatitis. Hepatotoxicity could not be traced to any single drug or combination of drugs given. On the contrary, chloroquine appeared to reduce serum gamma glutamyl transferase, and corticosteroids had a similar effect on serum alkaline phosphatase. In patients not treated with corticosteroids, both serum gamma glutamyl transferase and alkaline phosphatase were weakly to moderately correlated with laboratory indices of disease activity (ESR and serum orosomucoid). The frequently occurring isolated increase of serum gamma glutamyl transferase and/or serum alkaline phosphatase in arthritis may be an unspecific reaction to inflammation.

Alanine Transaminase↗

Interactions between 1,2--propanediol (propylene glycol) and hexobarbital.

The interaction between 1,2--propanediol and hexobarbital was studied with an anaesthesia threshold method, where hexobarbital is infused intravenously. The dose needed to obtain a burst suppression of one second or more is determined and given as per cent of a pre-experimental value obtained in the same rat. The effect of varying the interval between the intraperitoneal injection of 1,2--propanediol (2.06 g/kg) and the threshold determination was investigated. In the intervals, 10--50 min., the hexobarbital threshold doses were significantly decreased by 13--27% (n = 7--18). Four different doses between 0.25 and 2.06 g/kg of 1,2--propanediol were then tested after a fixed interval of 30 min. As in the time interval study the thresholds after 2.06 g/kg were significantly decreased. No certain depressant effect was seen with 1.03 and 0.52 g/kg. With the lowest tested dose of 1,2-propanediol (0.25 g/kg) there was instead a significant increase in the threshold dose (13%). This might be an excitatory effect, which could correspond to the well-known effect, seen with low doses of other depressants for instance ethanol.

Animals↗

Ultrasound examination of skin thickness in patients with progressive systemic sclerosis (scleroderma).

A new ultrasound technique for measuring skin thickness in 40 patients with progressive systemic sclerosis (scleroderma) and in 10 healthy control subjects has been evaluated. High frequency (10 MHz) dynamic ultrasound examination was performed at the proximal and middle phalanges of both second fingers. Measurements of the control subjects on two separate occasions demonstrated a good reproducibility of the technique with a standard deviation of 0.06 mm. The skin was thicker in patients with scleroderma 3.3 +/- 0.7 mm (mean +/- SD) compared with control subjects 2.5 +/- 0.2 mm (p less than 0.001). No relation between skin thickness and duration of disease was observed. This method can be used to monitor changes in skin thickness over time.

Adult↗

Capillary density in patients with systemic sclerosis, as determined by microscopy counts and compared with computer-based analysis.

OBJECTIVE: To develop a method enabling capillary density to be determined rapidly and accurately in patients with systemic sclerosis. METHOD: Capillary density was determined in 11 controls and 22 patients: 5 with diffuse cutaneous systemic sclerosis (dSSc), 12 with limited cutaneous systemic sclerosis (lSSc), two with suspected systemic sclerosis (suspSSc), 2 with sclerodermatomyositis, and one with undifferentiated connective tissue disease. Using a microscope equipped with a graticule, nailfold capillaries were counted within a 3 mm length of the nailfold; these counts were made by 4 different observers. The results were compared with the corresponding values obtained by the computerbased analysis of photographs. RESULTS: The median capillary density according to the direct counts was 8.0 loops/mm (6.7-10.0) in the controls, 6.0 loops/mm (range 4.8-8.8) in the dSSc subgroup, 5.6 loops/mm (4.2-6.5) in the lSSc subgroup, and 7.2 loops/mm (6.2-8.2) in the suspSSc subgroup. In the series as a whole, there was no significant difference between the median values for the left hands and those for the right hands, nor between the median value for all digit IVs and the median value for all four digits analysed (II, III, IV, and V). Interobserver variation was small between the 4 different observers. Direct microscopy counts were slightly higher than the corresponding values obtained by computer-based analysis. CONCLUSION: Direct microscopy counting is a rapid, simple, and reliable means of determining capillary density for screening purposes.

Adult↗

The association between changes in skin echogenicity and the fibroblast production of biglycan and versican in systemic sclerosis.

OBJECTIVE: To investigate a possible association between the longitudinal changes in skin involvement and the fibroblast production of proteoglycans in vitro, among patients with early and untreated systemic sclerosis (SSc). METHODS: In 11 patients, 6 with diffuse cutaneous systemic sclerosis (dSSc) and 5 with limited cutaneous systemic sclerosis (ISSc), and in 6 controls skin thickness and skin echogenicity of the forearm was measured by high frequency (20 MHz) ultrasound. A skin biopsy was taken from the area of the ultrasound measurements, and from cultivated fibroblasts the production of the proteoglycans versican, perlecan, biglycan and decorin were measured. To investigate longitudinal changes in skin involvement, the ultrasound examination was repeated after 1-3 years. RESULTS: Compared to controls, SSc patients had increased skin thickness at the first evaluation. Patients with dSSc had lower skin echogenicity than both patients with lSSc and the controls. Patients with greater changes in skin thickness and skin echogenicity produced more versican, whereas the production of biglycan and decorin was higher only in patients with greater changes in skin echogenicity. There was a negative correlation between fibroblast production of biglycan and disease duration. CONCLUSION: High fibroblast synthesis of the proteoglycans versican and biglycan is associated with changes in skin echogenicity and may predict more progressive skin sclerosis in SSc.

Adult↗

Cineradiography identifies esophageal candidiasis in progressive systemic sclerosis.

Cineradiography of the esophagus showed signs of esophageal candidiasis in 11 out of 71 patients with progressive systemic sclerosis (PSS) - both in diffuse scleroderma and the CREST syndrome. Culture of esophageal brushings confirmed the presence of Candida albicans in eight of these 11 patients. Antimycotic treatment decreased the cineradiographic signs of candidiasis and the degree of dysphagia. Since impaired esophageal motility and treatment with immunosuppressive drugs may predispose to candida esophagitis, and since dysphagia will decrease after antimycotic treatment esophageal mycosis should always be sought in patients with PSS.

Candidiasis↗

Effect of long-term ketanserin treatment on 5-HT levels, platelet aggregation and peripheral circulation in patients with Raynaud's phenomenon. A double-blind, placebo-controlled cross-over study.

The long-term effects of the serotonergic (5-hydroxy-tryptamine, 5-HT) receptor antagonist, ketanserin, on 5-HT levels in whole blood, platelet aggregation and peripheral circulation were investigated in a double-blind placebo-controlled cross-over study. In 13 patients with Raynaud's phenomenon, 5-HT and catecholamine levels in whole blood were determined and platelet aggregation assayed after addition of ADP, collagen and 5-HT. Peripheral circulation was evaluated with fingertip temperatures and finger plethysmography before and after local cooling, with measurements repeated after indirect sympathetic blockade by body warming and after alcohol. Patients' symptoms were continuously registered in an individual diary. All measurements were performed 8 to 12 hours after the last drug intake. Five of seven scleroderma patients reported beneficial effects of ketanserin treatment and all six patients with primary Raynaud's phenomenon reported less severe and shorter cold-induced attacks. 5-HT levels in whole blood were significantly reduced after 5 weeks of ketanserin treatment (p less than 0.001) with a tendency for persistence of this reduction after halting of the medication (a "carry-over" effect). Platelet aggregation velocity induced by ADP, collagen and 5-HT was unaffected after ketanserin treatment. The diastolic blood pressure in these patients was decreased from 77.5 mmHg to 71.0 mmHg (p less than 0.001) after ketanserin, but the finger systolic blood pressure (FSBP) was unchanged. After sympathetic blockade by body warming, patients with ketanserin treatment had a paradoxical reduction in both FSBP and finger-tip temperatures, which makes a supposed alpha-receptor-blocking effect of ketanserin less likely. The reduced 5-HT levels in whole blood may explain the subjective favourable effect on patients with Raynaud's phenomenon.

Clinical Trials as Topic↗

Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment of skin involvement in systemic sclerosis (scleroderma).

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is a connective tissue disease characterized by microvascular changes and fibrosis of the skin and internal organs. Increased skin thickness proximal to the metacarpophalangeal joints is the single major diagnostic criterion. The aim of this study was to evaluate high frequency (20 MHz) ultrasound for the assessment of skin thickness in patients with SSc of different disease durations. METHODS: Skin thickness was measured with high frequency (20 MHz) ultrasound equipment (Dermascan) in 41 patients with SSc (23 women and 18 men) and in 41 controls. Twenty-five patients had limited cutaneous systemic sclerosis (ISSc), 12 had diffuse cutaneous systemic sclerosis (dSSc) and 4 had suspected SSc. RESULTS: Skin thickness of the forearm was inversely correlated to disease duration. Compared to controls, skin thickness was increased over the proximal phalanx of the right second finger and over the forearm in patients with a disease duration of 2 years or less. Assessments of skin thickness in 10 controls by 2 independent investigators showed an inter-observer variability of 1.0% for the proximal phalanx and 0.0016% for the forearm. Patients whose ultrasound showed increased skin thickness on the hand and forearm also had thickened skin by palpation. CONCLUSION: High frequency (20MHz) ultrasound is a feasible method for measuring skin thickness in SSc, and may be useful for diagnosis, long-term follow-up, and assessment in therapeutic studies.

Adult↗

Tissue concentrations of gastrointestinal regulatory peptides in the duodenal mucosa in systemic sclerosis.

OBJECTIVE: Esophageal hypomotility and abnormalities of intestinal function are important manifestations in systemic sclerosis (SSc), but their pathogenesis is not well understood. Since there is evidence that plasma concentrations of certain gastrointestinal regulatory peptides are increased in SSc, we were interested in examining the peptide concentrations and localization in biopsy specimens from the intestinal mucosa in SSc patients. We studied 12 patients with gastrointestinal disease. METHODS: Levels of corticotrophin-releasing hormone (CRH), motilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC), and the occurrence of motilin, PYY, somatostatin, and NPY were studied with immunohistochemistry. RESULTS: Except for the concentrations of CRH, which were increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased by approximately 50% among patients with esophageal and intestinal dysfunction (group B) compared to patients with impaired esophageal motility alone (group A). In addition, HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments among patients in groups A and B. In all patients duodenal motilin, PYY, and somatostatin were localized in the endocrine cells. The distribution and frequency of the cells did not differ among the patients. NPY was localized to neuronal elements; there was no overt difference among the patients with respect to the frequency of NPY-containing nerves. CONCLUSION: This study shows that patients with widespread gastrointestinal disease have lower tissue concentrations of regulatory peptides compared to patients with less widespread disease.

Adult↗