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Biomedical subjects

L Heickendorff

Publications and source records attributed to L Heickendorff.

At least 55 records · Page 3Linked to original sources

The effect of human growth hormone on the carbohydrate units in arterial basement membrane-like material.

OBJECTIVE: The present study focuses on the pathogenesis of the large vessel disease in diabetes. The arterial wall from diabetic individuals displays characteristic alterations of the extracellular matrix. Other observations show that the metabolism is changed with increased levels of growth hormone in diabetes. DESIGN: The effects of growth hormone on the carbohydrate composition in the basement membrane around the arterial smooth muscle cells were investigated. METHODS: Basement membrane material was obtained from cultures of smooth muscle cells by sonication and differential centrifugation after labeling with either [(3)H]glucose or [(3)H]glucosamine. The proportions of galactose, glucose, mannose, xylose, fucose and glucosamine were evaluated after addition of 45.45pmol/l human growth hormone. Also, the proportion of glycopeptides generated from the basement membrane was analyzed after fractionation on a combination of a Concanavalin A and a Pea Sepharose column. RESULTS: The proportion of galactose and glucose was changed, and the incorporation of [(3)H]glucosamine was reduced. The proportion of glycopeptides containing high mannose moities was increased as well as that of triantinary glycopeptides with internal fucose residues. CONCLUSION: The current in vitro data indicates that growth hormone may change the carbohydrate composition of the arterial basement membrane.

Animals↗

[Natural history of abdominal aortic aneurysm with and without concomitant chronic obstructive pulmonary disease].

The relationship between abdominal aortic aneurysms (AAA) and chronical obstructive pulmonary disease (COPD), and in particular the suggested common elastin degradation caused by elastase and smoking was analysed by a cross sectional population mass screening study for AAA, and a prospective cohort study of small AAA. All previous computer-hospital-recorded diagnoses were received concerning 4,404 men invited to screening for AAA. One hundred and forty-one had AAA (4.2%). They were asked for an interview, a clinical examination, and a blood sample. Men with an AAA of 3-5 cm were offered annual control-scans to check for expansion. Of COPD-patients, 7.7% had AAA (crude OR = 2.05), however the adjusted OR was only 1.53 after adjusting for other co-existing diseases (p = 0.13). The mean annual expansion was 2.74 mm per year in COPD patients and 2.72 in non-COPD patients, and 4.7 mm in oral steroid-users compared to 2.6 in non-steroid-users (p < 0.05). S-elastin-peptides (SEP) and P-elastase-alpha1-antitrypsin-complexes (PEAC) were negatively correlated to FEV1 in COPD-patients. However, SEP, beta-agonist-treatment, and FEV1 was positively correlated to expansion by multivariate regression analysis, while PEAC and S-alpha1-antitrypsin did not influence expansion, suggesting elastase plays a major role in the pathogenesis of COPD but not in AAA. The high prevalence of AAA among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis.

Aortic Aneurysm, Abdominal↗

Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy.

Changes in bone remodeling and bone mineral density were observed during a period of 6 months after surgery in 24 patients with primary hyperparathyroidism (20 women and 4 men; age 54+/-12 years, range 26-69 years). All bone markers declined significantly within the 6 month follow-up period, but the time course for changes in renal N-terminal telopeptide of type 1 collagen (NTx) excretion differed from those of the other markers by a steep and significant reduction (p < 0.05) after less than 1 month. During the 6 month period, bone mineral density (BMD) increased significantly at all sites measured (p < 0.05) apart from the femoral neck and the proximal and midforearm. The greatest increase of 4.2% was observed in the trochanteric region (p < 0.001). The increase in BMD in spine, trochanteric, and intertrochanteric regions of the hip correlated inversely with baseline forearm BMD values (p < 0.05). Baseline bone markers (serum alkaline phosphatase [AP], serum bone AP, serum pyridinoline crosslinked telopeptide of type 1 collagen, urinary hydroxyproline, urinary osteocalcin), as well as baseline histomorphometric indices of bone turnover (eroded and labeled surface, bone formation rate, activation frequency, and cortical porosity) were positively correlated with changes in spinal BMD over 6 months (p < 0.05). It was concluded that, within 6 months after parathyroidectomy, patients with primary hyperparathyroidism obtain normalization of bone remodeling and a substantial increase in bone mineral density in regions rich in cancellous bone but no significant changes in regions with predominantly cortical bone.

Aged↗

Primary hyperparathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year follow-up study.

Changes in skeletal remodeling (biochemical bone markers) and regional bone mineral density (spine, hip, and forearm bone mineral density [BMD]) were observed for 3 years in 20 patients (15 women and 5 men; age 54 +/- 11 years, range 29-69 years) after successful surgery for primary hyperparathyroidism (PHPT). Fifteen PHPT patients were compared with 15 normal controls who were exactly matched with respect to age, gender, and menopausal status (10 women and 5 men; age 53 +/- 12 years, range 29-65 years [PHPT] and 29-66 years [controls]). All bone markers (serum osteocalcin, bone alkaline phosphatase, and type I collagen telopeptide [ICTP], and urinary hydroxyproline and NTx/creatinine ratio) declined significantly and reached normal levels within 6 months. No major changes took place during the remaining 2.5 years, apart from urine hydroxyproline, which disclosed a small peak around 12 months with a further decline towards study end (p < 0.05). Bone mineral density increased significantly in all regions (p < 0.001). At all locations, except the intertrochanteric region of the hip, the increase continued from 6 months until study end (p < 0.05). The increase in BMD was unequally distributed among regions (p < 0.001). The increase at the proximal forearm was less than in the spine (p < 0.05), the trochanteric region of the hip (p < 0.05), and the distal forearm (p < 0.05). No difference in BMD increase was observed between men, and pre- and postmenopausal women. Compared with the matched control group, PHPT patients had significantly lower BMD at baseline in the proximal (p < 0.02) and distal (p < 0.05) forearm. Furthermore, during the 3-year follow-up period, the PHPT patients showed a significant increase in BMD compared with controls in the spine (p < 0.005), the trochanteric and intertrochanteric regions of the hip (p < 0.005 and p < 0.05, respectively), and the distal forearm (p < 0.005). In conclusion, bone remodeling is normalized within the first 6 months after successful parathyroid surgery, with no major changes during the following 2.5 years. Bone mineral density increases at both cancellous and cortical sites, but in predominantly cortical bone, the recovery in BMD is less than in cancellous bone-rich areas.

Adenoma↗

Primary hyperparathyroidism: whole-body bone mineral density in surgically treated Danish patients: a three-year follow-up study.

Whole-body bone mineral density (BMD) and body composition were measured before surgery in 25 patients (20 women and 5 men, aged 53 +/- 13 years, range 26-73 years) with mild to moderate primary hyperparathyroidism (PHPT) and compared with 25 controls exactly matched with respect to age, gender, and menopausal status. Fifteen pairs of matched patients and controls were reexamined 3 years later (5 men and 10 women, aged 53 +/- 12 years in both groups). In the untreated PHPT patients, whole-body BMD was 95.4% +/- 10.5% (SD) of control BMD (p < 0.05). Body weight and height, body mass index, whole-body fat mass, and lean body mass did not differ significantly between the groups. Relative to values in matched controls, whole-body bone mineral content (BMC) and BMD increased by 4.4% and 3.0%, respectively, in PHPT patients (p < 0.005) during the 3-year follow-up. Neither whole-body BMC nor BMD differed between patients and controls after the 3-year follow-up. A positive correlation was observed between initial serum calcium levels and the 3-year increase in whole-body BMD (r(s) = 0.645, p < 0.01). Baseline serum osteocalcin, serum pyridinoline crosslinked telopeptide of Type I collagen and several histomorphometric indices of trabecular bone turnover (eroded and labeled surfaces, bone formation rate, and activation frequency) also correlated positively with the subsequent increase in whole-body BMD. Six patients disclosed transient postoperative secondary hyperparathyroidism, probably due to hungry bones. Four of these patients completed 3 years of follow-up and had higher increases in whole-body BMD than the remaining normo-parathyroid patients (7.9% +/- 4.5%, range 4.3-14.3% versus 1.9% +/- 2.1%, p < 0.01). It is concluded that Danish patients with mild to moderate PHPT only reveal small reductions in whole-body mineral density. Furthermore, within 3 years after parathyroid surgery, most of the lost bone mineral is regained even in patients with initial high bone turnover. Finally, PHPT in these patients is not associated with substantial changes in body compositions.

Adult↗

Natural history of abdominal aortic aneurysm with and without coexisting chronic obstructive pulmonary disease.

PURPOSE: To study the relation between abdominal aortic aneurysms and chronical obstructive pulmonary disease (COPD), in particular the suggested common elastin degradation caused by elastase and smoking. METHODS: A cross-sectional population study and a prospective cohort study of small abdominal aortic aneurysms was performed in a community setting. All previous diagnoses recorded in a hospital computer database were received for 4404 men 65 to 73 years of age who had been invited to a population screening for abdominal aortic aneurysm. One hundred forty-one men had AAA (4.2%). They were asked to participate in an interview, a clinical examination, and collection of blood sample. Men with an abdominal aortic aneurysm 3 to 5 cm in diameter were offered annual ultrasound scans to check for expansion. RESULTS: Among patients with COPD 7.7% had abdominal aortic aneurysms (crude odds ratio=2.05). The adjusted odds ratio, however, was only 1.59 after adjustment for coexisting diseases associated with abdominal aortic aneurysm (P=.13). The mean annual expansion was 2.74 mm per year among patients with COPD, 2.72 among patients without COPD, and 4.7 mm among patients who used oral steroids compared with 2.6 among patients who did not use steroids (P < .05). Concentration of serum elastin peptide and plasma elastase-alpha1-antitrypsin complexes correlated negatively with forced expiratory volume in the first second (FEV1) among patients with COPD. However, multivariate regression analysis showed that concentration of serum elastin peptide, therapy with beta-agonists, and FEV1 correlated positively with degree of expansion but that concentration of plasma elastase-alpha1-antitrypsin complexes and serum alpha1-antitrypsin did not influence expansion, suggesting that elastase plays an important role in the pathogenesis of COPD but not of abdominal aortic aneurysm. CONCLUSION: The high prevalence of abdominal aortic aneurysm among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis.

Aged↗

Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin.

In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from systemic sclerosis patients compared with healthy volunteers. ICAM-1 was localized to vessels and perivascular mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister fluid point towards activation of endothelial cells and T cells in both the transition zone and uninvolved skin of systemic sclerosis patients.

Adult↗

Long-term oral pamidronate treatment inhibits osteoclastic bone resorption and bone turnover without affecting osteoblastic function in multiple myeloma.

This study was performed as a cross-sectional substudy to the Danish-Swedish Pamidronate Study, a randomized placebo-controlled multicentre trial in multiple myeloma. The purpose was to evaluate the biological effects of long-term treatment with oral pamidronate 300 mg daily on bone metabolism by using histomorphometry and analysis of cytokines and biochemical markers of bone turnover. Sixteen patients were included after median 27.5 months of protocolized treatment; 10 patients received active treatment and 6 patients placebo. When compared with placebo, pamidronate treatment was associated with: (a) marked decreased osteoclastic resorption rate (0.86+/-0.59 microm/d vs. 5.7+/-5.0 microm/d, p=0.002), and diminished activation frequency (0.20+/-0.18 yr(-1) vs. 0.72+/-0.55 yr(-1), p=0.014); (b) compensatory reduced volume referent bone formation rate (0.17+/-0.21 yr(-1) vs. 0.71+/-0.54 yr(-1), p=0.007), but unaltered mineral appositional rate; (c) neutral (-0.66+/-5.6 mm) vs. negative (-2.15+/-2.2 microm, p=0.013) bone balance per remodelling cycle; (d) higher trabecular bone volume (21.0+/-6.2% vs. 13.0+/-3.7%, p=0.01); (e) suppressed urinary excretion and serum levels of some of the biochemical markers of bone metabolism; and (f) significant reduction of circulating soluble interleukin-6 receptor (IL-6sR) (25.9+/-4.1 ng/ml vs. 32.1+/-6.6 ng/ml, p=0.04), and (g) a uniform tendency of lower serum and marrow plasma levels of IL-6, IL-1beta, and TNFalpha. Thus oral pamidronate was absorbed in biologically active amounts, and reduced overall bone resorption and bone turnover without impairing osteoblastic bone formation. The observation that cytokine and cytokine receptor levels were reduced extends the possible and potential beneficial actions of bisphosphonates in multiple myeloma.

Administration, Oral↗

Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial ischemia.

BACKGROUND: Studies have demonstrated that troponin T is a strong independent indicator of a poor prognosis in patients with unstable coronary artery disease. Up to the present, no study has compared the prognostic value of troponin T with that of troponin I in the same cohort of patients. METHODS AND RESULTS: Patients (n=516) suspected of having unstable coronary artery disease were investigated. Follow-up was done after 30 days, and the occurrences of cardiac death, acute myocardial infarction, refractory angina pectoris, and recurrent angina pectoris were registered. Elevated levels of troponin T (> or = 0.10 microg/L) were associated with an increased risk of cardiac death at 30 days compared with patients with normal levels, 3.2% versus 0.4% (P=.014). Troponin I values above the chosen cutoff (2.0 microg/L) were similarly found to be an indicator of increased risk of cardiac death, 3.2% versus 0.7% (P=.026). With regard to the composite end point of cardiac death/acute myocardial infarction, the troponins were strong independent indicators of adverse outcome. CONCLUSIONS: In patients suspected of having unstable coronary artery disease, both troponin T and troponin I provide independent prognostic information with regard to cardiac death and acute myocardial infarction.

Adult↗

Ischemia and reperfusion of the porcine myocardium: effect on collagen.

We studied the effect of acute myocardial infarction and late reperfusion on myocardial collagen in a closed chest porcine model, to investigate if any collagen degradation could be detected in blood samples and myocardium. Sixteen 60-80 kg pigs were used with six animals serving as controls and 10 submitted to ischemia-reperfusion. In the ischemia-reperfusion group the left anterior descending coronary artery was occluded for 6 h by inflation of a percutaneous transluminal coronary angioplasty balloon followed by reperfusion for 3 h. Blood samples were taken from the aorta and the coronary sinus and analyzed for creatine kinase and collagen degradation products, i.e. the N-terminal propeptide of procollagen type III (PIIINP) and C-terminal pyridinoline cross-linked telopeptide of collagen type I (ICTP). Myocardial tissue samples were analyzed for content of hydroxyproline, collagen volume fraction and amount of extractable PIIINP/dry weight. Transmission electron microscopy of biopsies was performed to evaluate myocytes and collagen structure outside and within the infarct zone. Creatine kinase showed a statistically significant increase during ischemia and reperfusion but we found no evidence of release of collagen degradation products either during ischemia or reperfusion compared with control. Myocardial content of hydroxyproline, collagen volume fraction and extractable PIIINP/dry weight did not differ between groups. Transmission electron microscopy of biopsies from the infarct zone showed myocyte damage but no visible evidence of collagen degradation when photos were evaluated blindly. In this porcine model of acute myocardial infarction and late reperfusion no release of collagen degradation products from the myocardium or any decrease in or damage to myocardial collagen was detected.

Analysis of Variance↗

Serum-elastin-peptides as a predictor of expansion of small abdominal aortic aneurysms.

OBJECTIVE: To optimise the indication and time for operation for abdominal aortic aneurysm (AAA), we analysed whether or not serum-elastin-peptides (SEP) could be a potential predictor for expansion. MATERIALS AND METHODS: Four thousand, four hundred and four 65-73-year-old males were invited for screening to detect an AAA. Three thousand, three hundred and thirty-four attended (76%). One hundred and forty-one had AAA, and 19 > 5 cm in diameter were referred for immediate operation. The remaining 122 AAA were offered an annual follow-up. Ninety-nine were later asked for a blood-sample, 83 attended. SEP was determined using an ELISA-technique. The observer was blinded to the SEP result. RESULTS: The average expansion was 2.6 mm/year, and 10 (8.1) were referred for operation because of a diameter of > 5 cm. SEP were positively correlated to expansion (R = 0.4, F = 14.65). In multiple regression analyses, AAA size, SEP, beta-agonist-treatment, and FEV1, but not beta-blockers, were predictors of expansion. SEP remained a relatively strong predictor (F = 13.13). CONCLUSIONS: Serum-elastin-peptides seem to predict expansion, but a larger, longer study is needed to establish clinical recommendations.

Aged↗

Bone marrow fibrosis and disease activity in multiple myeloma monitored by the aminoterminal propeptide of procollagen III in serum.

Simple bone marrow fibrosis is seen in 10-30% of multiple myeloma (MM) patients. We investigated the incidence and characteristics of the bone marrow stromal alterations, in order to characterize the collagens involved by immunohistochemistry, and to evaluate the use of serum aminoterminal propeptide of type III procollagen (PIIINP) as a marker of marrow fibrogenesis and disease activity in MM. 34 consecutive patients with newly diagnosed MM were included prospectively, and followed for 12-30 months. Compared with the findings in 15 normal individuals we found increased interstitial deposits of collagen III in 48% of MM patients, whereas deposits of collagen I were not increased. Interstitial fibrosis appeared to be restricted to areas of severe plasma cell infiltration, but it could also have a more dispersed presentation in the severely infiltrated marrow. There was a high co-distribution of collagen III fibrils and reticulin fibres. Serum PIIINP levels were elevated in most patients, and in the follow-up study serum PIIINP showed a good correlation with the response to treatment. Patients with resistant or progressive disease had continually elevated levels of PIIINP. In most patients with responsive disease serum PIIINP normalized, and we observed no relapses in patients who had normal serum PIIINP levels. Other patients who responded to treatment by reduced M-component level, but had persistently elevated serum levels of PIIINP, had either early relapses or developed progression of osteolytic lesions in spite of unchanged M-component levels. Therefore an elevated serum PIIINP during treatment might indicate an active malignant clone. Serum PIIINP does not simply follow the M-component, but gives further information of potential therapeutic value.

Adult↗

Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP). Nordic Myeloma Study Group (NMSG).

This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (> 5.0 micrograms/l) in most patients (median 6.6 micrograms/l range 1.4-29.4 micrograms/l). Serum PIIINP was elevated (> 4.2 micrograms/l) in 46% (median 4.0 micrograms/l, range 1.4-20.1 micrograms/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum beta 2-microglobulin (beta 2m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP (P = 0.026) and serum osteocalcin (P = 0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum beta 2m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum beta 2m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.

Adult↗

Abnormal bone turnover in monoclonal gammopathy of undetermined significance: analyses of type I collagen telopeptide, osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens.

The main difference between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is the presence of lytic bone destructions in the latter. About 20% of MGUS patients develop MM, and histomorphometric studies have shown disturbed bone turnover rates in some of these patients. This study was performed in order to evaluate whether serum analyses of the C-terminal telopeptide of type I collagen (ICTP), as a reflector of bone degradation, and of osteocalcin, bone-specific alkaline phosphatase (bAP) and the C-terminal propeptide of type I procollagen (PICP), as markers of bone formation, might give information on disturbances of bone metabolism in MGUS. Furthermore, serum N-terminal propeptide of procollagen III (PIIINP) might give information on disturbances in collagen III metabolism in the bone marrow. In the 35 patients examined, serum ICTP was elevated in 12 patients (34%), serum PIIINP elevated in 6 patients (17%), serum osteocalcin elevated in 11 patients (31%), serum bAP elevated in 6 patients (17%), and serum PICP elevated in 4 patients (11%). Serum ICTP correlated significantly with PIIINP (r = 0.72, p < 0.001), and with serum osteocalcin (r = 0.57, p < 0.001) and serum bAP (r = 0.51, p = 0.002). These findings indicate disturbances of bone turnover and affected collagen metabolism in some MGUS patients. Follow-up observation may reveal any prognostic value of these findings.

Aged↗

Increased levels of type I and III collagen and hyaluronan in scleroderma skin.

The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma from scleroderma patients levels of PIIINP and HA were 38% and 127% higher, respectively, than in plasma of healthy volunteers. The plasma PICP level was not significantly higher in scleroderma patients. Finally, PICP, PIIINP and HA levels were several times higher in suction blister fluid than in plasma. The data indicate that a fibrogenetic process takes place in the transition zone of scleroderma. The method may be used to monitor the progression of scleroderma skin lesions in vivo.

Adult↗

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload.

Long-term follow-up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration. It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Adolescent↗

Insulin-like growth factor axis, bone and collagen turnover in children with atopic dermatitis treated with topical glucocorticosteroids.

BACKGROUND: Topical glucocorticosteroids are widely used in the treatment of children with atopic dermatitis. Due to percutaneous absorption, these agents may become systemically available and cause inhibition of growth in children. However, the mechanisms responsible for the growth-suppressive effective are not fully understood. OBJECTIVE: To evaluate whether treatment with topical budesonide has any adverse effects on growth-hormone-dependent serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), and on the serum markers of bone and collagen turnover osteocalcin, the carboxy-terminal propeptide of type I collagen (PICP), the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of type III procollagen (PIIINP). METHODS: 13 children (mean age 9.5 years) with atopic dermatitis were studied in an open longitudinal trial with run-in and budesonide treatment periods of 2 weeks' duration. During the run-in, only emollient was used. During the treatment period, budesonide cream 0.025% followed by emollient were applied twice daily all over the body except on the face. At day 14 of each period, blood samples were taken and eczema was scored according to a severity index based on extent and activity of the disease. RESULTS: Compared to the run-in, budesonide treatment was associated with a statistically significant reduction in mean severity index (p = 0.002). No statistically significant effects on serum levels of IGF-I, IGFBP-3, osteocalcin or ICTP were observed. The serum concentrations of PICP and PIIINP were reduced with (mean +/- 1 SD) 43 +/- 64 milligrams (95% confidence interval 3.5-80 milligrams, p = 0.03, t = 2.4, d.f. = 12) and 1.2 +/- 1.5 milligrams (95% confidence interval 0.3-2.1 milligrams, p = 0.01, t = 3.0, d.f. = 12), respectively. CONCLUSION: Type I and III collagen turnover may be suppressed during short-term treatment with topical budesonide in children with atopic eczema. clinical implications need further study.

Administration, Topical↗

Methotrexate-induced liver cirrhosis. Clinical, histological and serological studies--a further 10-year follow-up.

BACKGROUND: Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of an aggressive nature. OBJECTIVE: The aim of this study was to evaluate the present status of surviving patients 10 years later, together with the latest clinical and histological data on patients who had died. METHODS: The investigations were carried out on 186 liver biopsies and 5 autopsies. All biopsies were studied by the same pathologist. Eleven surviving patients were also studied by analysis of serum aminoterminal propeptide of type III procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially suitable for follow-up of fibrotic liver disease. RESULTS: Thirteen patients had died; 1 of these died of liver failure. Another patient died form an overdose due to misunderstanding of the prescribed dosage given elsewhere. The remaining deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis. On the other hand, 13 patients had no histologically verified liver cirrhosis in their latest biopsy, and PIIINP was within the normal range in all 11 patients investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg (mean 7,171 mg). CONCLUSIONS: This study confirmed that in most patients MTX-induced liver cirrhosis is not aggressive. However, continued low-dose MTX led, in spite of normal liver tests, 8 years after the last biopsy to liver failure and death in 1 of our patients. Our data support the continued use of liver biopsies in the surveillance of MTX-treated psoriatics.

Adult↗