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Biomedical subjects

M Madsen

Publications and source records attributed to M Madsen.

At least 19 recordsLinked to original sources

Temporal decline in the prognostic impact of a recurrent acute myocardial infarction 1985 to 2002.

OBJECTIVE: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial infarction (re-AMI) during 1985-2002. DESIGN: Retrospective cohort study using nationwide administrative data from Denmark. SETTINGS: National registries on hospital admissions and causes of death were linked to identify patients with first AMI, re-AMI and subsequent prognosis. PATIENTS: Patients > or =30 years old with a discharge diagnosis of AMI during 1985-2002 were tracked for first hospital admission for re-AMI 1 year after discharge. MAIN OUTCOME MEASURES: One-year case-fatality. RESULTS: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-fatality from first AMI/re-AMI was 39% versus 43% in 1985-1989 and 25% versus 29% in 2000-2002, respectively. In 1985-89, 35 795 patients survived to discharge (71%); of these 2.5% experienced reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31-365 (late re-AMI). Re-AMI carried a poor prognosis in 1985-1989 compared to no re-AMI with age- and sex-adjusted relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to 12.4) from late re-AMI. In 2000-2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5) from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction. CONCLUSION: Prognosis after AMI has improved substantially during the latest two decades and extends to patients with re-AMI.

Adult↗

Why women want prenatal ultrasound in normal pregnancy.

OBJECTIVES: To investigate women's reasons for requesting prenatal ultrasound in the absence of clinical indications. METHODS: A postal questionnaire was completed by 370 pregnant women with no apparent obstetric risk factors, who had expressed a desire to have ultrasound scanning in their current pregnancy. The women were asked to indicate, from a list of 12 items, their three most important reasons for wanting scanning. Ninety per cent of the women were in the first trimester of pregnancy, and 10% in the second trimester. RESULTS: The items most frequently identified as important reasons for ultrasound were to check for fetal abnormalities (60% of women), to see that all was normal (55%) and for own reassurance (44%). Lower income was related to wanting to see the baby (P = 0.028) and wanting an ultrasound picture (P = 0.017); higher income was related to checking that all was normal (P = 0.003) and for own reassurance (P = 0.015). Women in their first pregnancy were more likely to want themselves and the father to see the baby (P = 0.001); women who had given birth previously were more likely to want reassurance (P = 0.002), as were women with a previous miscarriage or induced abortion. Women who believed that the presence of fetal trisomy justifies abortion or who would vote for free abortion were more likely to want to know about abnormalities (P < 0.001 and P < 0.004, respectively). Women in the second trimester were more likely to want to check for abnormalities (P = 0.041) and appropriate fetal growth (P = 0.047) than those in the first trimester. CONCLUSIONS: It would appear that women in normal pregnancy have specific reasons for wanting prenatal ultrasound that are influenced by sociodemographic, obstetric and attitudinal factors.

Adult↗

Kidney volume increases during long-term ciclosporin a treatment.

PURPOSE: Previously, we have for the first time reported enlargement of the pig kidney during long-term ciclosporin (CsA) treatment. In this paper, we summarize our findings of renal enlargement during long-term protocols with various dosages and durations of CsA administration as well as discuss possible pathogenetic mechanisms. MATERIALS AND METHODS: Twenty-two adolescent Gottingen minipigs were allocated into four groups: group A (n = 6) served as controls for 6 months; group B (n = 5) were treated with CsA (10 mg/kg per day) for 6 months, group C (n = 4), with CsA (20 mg/kg per day) for 6 months, and group D (n = 7) with CsA (10 mg/kg per day) orally for 12 months. At regular intervals, renal length and total volume were measured using magnetic resonance imaging; renal biopsies were performed for histological examination. RESULTS: A significant increase in kidney volume occurred in all CsA-treated pigs (groups B, C, and D); whereas the volume remained stable in the control animals (group A). A small but significant rise in kidney length was observed in groups A, B, and C, probably due to the normal growth of the animals. Histological examination was normal after treatment with CsA doses of 10 and 20 mg/kg per day for 6 months but showed definite interstitial fibrosis and glomerulosclerosis after treatment with 10 mg/kg per day CsA for 12 months. CONCLUSION: Long-term CsA treatment produced renal enlargement in pigs before the development of histological changes in the kidney. Thus, renal enlargement may represent an early stage of chronic CsA nephrotoxicity.

Animals↗

Changes in renal dimensions evaluated by magnetic resonance imaging and ultrasonography during long-term ciclosporin-A treatment.

PURPOSE: To investigate changes in renal dimensions during long-term treatment with ciclosporin-A (CsA). MATERIAL AND METHODS: Five mini-Göttingen pigs were treated with CsA (10 mg kg(-1) day(-1)) for 6 months; 3 untreated animals served as controls. Renal length was measured by magnetic resonance imaging (MRI) and ultrasonography (US); renal volume by MRI. Examinations were performed at baseline (0 weeks) and after the start of CsA treatment at intervals of 5 weeks (5-25 weeks). RESULTS: Comparison of baseline and end-point data (0 weeks vs. 25 weeks) revealed a statistically significant increase in renal volume in CsA-treated animals (87.1 cm3 vs. 55.9 cm3, P=0.002). Renal volume remained unchanged in the control group. A significant increase in renal length was found both in the CsA-treated pigs (MRI: 96 mm vs. 84 mm, P<0.001; US: 94 mm vs. 81 mm, P<0.001) and in the control group (MRI: 97 mm vs. 85 mm, P<0.001; US: 89 mm vs. 81 mm, P=0.018). No difference was found between MRI and US measurements based on 40 paired units (MRI variance: 2.4-30.3% and US variance: -5.1-40.6%, P=0.133). CONCLUSION: During long-term CsA treatment, renal volume increases in mini-pigs, but there is no correlation between the increase in volume and the increase in length in this pig model.

Animals↗

Temporal trends in the prescription of vitamin K antagonists in patients with atrial fibrillation.

OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish National Hospital Registry was used to identify subjects with a first hospital diagnosis of AF and the Danish Register of Medical Products Statistics to determine the proportion of these patients who claimed a prescription of VKA within 3 months from discharge. RESULTS: Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who survived 3 months following discharge, 24 991 (36%) patients claimed a prescription of VKA within 3 months. In both men and women a gradual increase in the use of VKA with time was observed, the relative increase being largest amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was lower in women than in men, including patients with a prior or concurrent stroke. CONCLUSIONS: From 1995 to 2002 the proportion of AF patients receiving VKA therapy increased significantly but the use of VKA therapy amongst women was lagging behind that of men. Even in patients with AF and prior stroke, the use of VKA seems to be less than optimal.

Aged↗

Cytomegalovirus infection in renal transplant recipients.

We have retrospectively analyzed the incidence of cytomegalovirus (CMV) infection in 250 consecutive renal allograft transplants performed in 244 recipients. The mean follow-up was 35.1+/-25.4 months. Immunosuppression was cyclosporine- or tacrolimus-based triple therapy. CMV infection prophylaxis with ganciclovir for 3 months post transplant was prescribed in CMV-seronegative recipients of allografts from seropositive donors (D+R-) and in all recipients treated with OKT3. CMV antigenemia was monitored by the pp65-antigen assay. Thirteen of 57 D+R- recipients (22.8%) developed CMV antigenemia. One recipient had a breakthrough of CMV antigenemia during ganciclovir prophylaxis; 12 D+R- recipients developed CMV antigenemia 147.5+/-173.8 days after transplantation. Four of 13 (30.7%) D+R- recipients had asymptomatic CMV infection, 8 (61.6%) had CMV infection with non-specific symptoms including fever, and 1 (7.7%) developed CMV pneumonia. Six of 13 (46.1%) D+R- patients had been treated with intensified immunosuppressive therapy before CMV infection. In the low-risk CMV groups (D+R+; D-R+; D-R-), 28 recipients (14.5%) developed CMV antigenemia 42.5+/-15.2 days post transplantation. Ten of the 28 (35.7%) recipients had asymptomatic CMV infection, 17 (60.7%) developed CMV infection with non-specific symptoms, and 1 (3.6%) developed CMV pneumonia. Twenty-one of 28 (75.0%) had intensified immunosuppressive therapy before CMV infection. In conclusion, ganciclovir prophylaxis diminished and delayed the onset of CMV infection but did not totally prevent it from occurring in D+R- renal transplant recipients. Clinicians should be vigilant to the possibility of CMV infection in both seronegative and seropositive recipients, especially after anti-rejection therapy.

Adult↗

Strategies for the inclusion of an internal amplification control in conventional and real time PCR detection of Campylobacter spp. in chicken fecal samples.

To illustrate important issues in optimization of a PCR assay with an internal control four different primer combinations for conventional PCR, two non-competitive and two competitive set-ups for real time PCR were used for detection of Campylobacter spp. in chicken faecal samples. In the conventional PCR assays the internal control was genomic DNA from Yersinia ruckeri, which is not found in chicken faeces. This internal control was also used in one of the set ups in real time PCR. In the three other set-ups different DNA fragments of 109 bp length prepared from two oligos of each 66 bp by a simple extension reaction was used. All assays were optimized to avoid loss of target sensitivity due to the presence of the internal control by adjusting the amount of internal control primers in the duplex assays and the amount of internal control in all assays. Furthermore, the assays were tested against faecal inhibitors to ensure that the internal control and the target PCR had the same sensitivity towards inhibitors.

Animals↗

Chronic cyclosporine nephrotoxicity: a pig model.

Cyclosporine A (CsA) is one of the keystones in immunosuppressive treatment after solid organ transplantation, despite its major side effects such as nephrotoxicity. The chronic nephrotoxic effects of CsA seen in humans have been difficult to reproduce in small-animal models. The aim of the present study was to examine the chronic nephrotoxicity produced by therapeutic dosages of CsA in a pig model. Among 11 Gottingen minipigs included in the study, three died, yielding data from five animals given CsA (10 mg/kg/d, orally) for 6 months, and three controls. Body weight, blood pressure, glomerular filtration rate (GFR) by plasma clearance of (51)Cr-ethylenediamine-tetraacetic acid, CsA concentration, serum creatinine, and other values were measured every 5 weeks. Our results showed that the whole blood trough CsA levels were lower in pigs than in humans treated with similar CsA doses. Renal biopsies, which were obtained successfully, except one case of macroscopic hematuria, showed no histological changes in the kidney. No significant increase in serum creatinine or blood pressure was observed. Surprisingly, there was a significant increase in GFR during CsA treatment. We conclude that the pig model displays a hyperfiltration that warrants further investigation.

Animals↗

Estimating the organ donor potential in Denmark: a prospective analysis of deaths in intensive care units in northern Denmark.

To estimate the organ donor potential in Denmark we conducted a prospective registration of deaths in all intensive care units (ICUs), counting 15 ICUs and two neurosurgical ICUs in the four northern Danish counties, which cover a population of 1.64 million inhabitants or 30% of the Danish population. From September 1, 2000 till August 31, 2002, all deaths in the ICUs in 15 hospitals were recorded. Each case was evaluated locally postmortem with respect to medical suitability to organ donation. A total of 1655 deaths were recorded, corresponding to 504 deaths per million population per year (PMP). Median age was 70 years (0 to 99 years), 52% were more than 70 years, and 22% more than 80 years of age. The cause of death was cerebral lesion in 18% of the cases (neurosurgical ICUs: n = 182; ICUs: n = 110). By thorough medical record examination, the number of potential donors was estimated to be 169, corresponding to 51 PMP. The cause of death was cerebral lesion in 96% of the potential donors. Organ donation was performed in 43 cases (32 from neurosurgical ICUs and 11 from ICUs) or 13.1 PMP. Thus, 25% of the potential became organ donors. The major reason for nondonation was refusal from the relatives. Out of 127 questioned, the relatives refused in 62 cases (49%). By comparison, 74% of the general Danish population are willing to donate organs after death. The rate of nondetection of potential donors by the hospital staff could be estimated to 22%. In conclusion, the organ donor potential may allow for improvement in donation rates. An increased effort for donor hospitals is warranted. The motives for refusal by the relatives need elucidation.

Cadaver↗

Intrarenal blood oxygenation and renal function measured by magnetic resonance imaging during long-term cyclosporine treatment.

Treatment with cyclosporine (CsA) markedly affects the renin-angiotensin-aldosterone system in parallel with an increase in the net tubular reabsorption or a decrease in secretion. Since tubular reabsorption is closely linked to medullary oxygen consumption, the aim of the present study was to investigate the intrarenal oxygenation and renal function in response to CsA. Six mini Göttingen pigs were treated with CsA (10 mg/kg/d) for 6 months. The intrarenal oxygenation was indirectly measured as R2* obtained with a multiecho gradient-echo magnetic resonance imaging (MRI) sequence. Single-kidney renal blood flow (skRBF) was measured by a velocity-sensitive gradient-echo MRI sequence. Relative single-kidney glomerular filtration rate (rskGFR) was derived from the MRI time-activity curve in response to an intravenous bolus of Gd-DTPA (0.05 mmol/kg). The present study showed that administration of CsA increased the medullary R2* (23.1 Hz vs 19.0 Hz, P = .002), whereas R2* was slightly increased in the renal cortex (13.3 Hz vs 12.3 Hz, P = .012). In parallel, rskGFR increased significantly (47.2 mL/min vs 19.8 mL/min, P = .005) but skRBF was unchanged (197.6 mL/min vs 202.5 mL/min, P > .05). The increased R2* in the renal medulla indicated that CsA augments the tubular reabsorption of water, leading to increased oxygen consumption. The supply of oxygen to the kidney was, however, maintained during treatment with CsA as suggested by an unchanged renal blood flow. The increased tubular reabsorption was compensated for by an elevated glomerular filtration rate.

Animals↗

Does chronic low-dose treatment with cyclosporine influence the brain? A histopathological study in pigs.

Twenty percent of the patients immunosuppressed with cyclosporine A (CsA) develop neurological side effects such as tremor, paresthesias, headache, seizures, visual disorders, paresis, and coma-CsA encephalopathy. The encephalopathy resolves on CsA discharge; autopsies of recovered patients are normal. Characteristic lesions are seen on magnetic resonance imaging (MRI) during the period of encephalopathy. MRI of asymptomatic patients receiving CsA as well as most recovered patients are normal. Several theories of pathogenesis have been proposed, but none has been firmly established. The current placebo-controlled study, blinded to the investigator, was accordingly initiated to elucidate histopathological changes in the brain. Twelve adult Göttingen minipigs were randomized into two groups treated with either low-dose CsA (10 mg/kg/d) or no treatment for 6 months. Behavior, blood pressure, and blood parameters were measured throughout the study. All animals had a cerebral MRI before sacrifice. Three control pigs and one CsA-treated pig died during observation and were excluded from the study. None of the remaining eight pigs displayed behavioral signs or MRI-visible lesions characteristic of CsA encephalopathy. The brains appeared all normal on the gross pathological examination, but microscopy revealed perivascular, meningeal, and neuronal tissue infiltration with granulocytes and mononuclear cells in one CsA-treated pig, while the remaining pigs were without histopathological lesions. Pathological changes were noticed in one out of five CsA-treated animals, corresponding to the percentage of patients treated with CsA who develop CsA encephalopathy. To pursue this finding, two studies, one using CsA 20 mg/kg/d for 6 months and one using CsA 10 mg/kg/d for 12 months, have been initiated.

Animals↗

The granule exocytosis and Fas/FasLigand pathways at the time of transplantation and during borderline and acute rejection of human renal allografts.

Cytotoxic lymphocytes induce target cell death by the granule exocytosis mechanism in which perforin and granzyme B induce target cell lysis, and ligation of the Fas-FasLigand, which results in apoptosis. The purpose was to detect the level of activation of cytolytic pathways at the time of renal transplantation and during acute rejection. We investigated 119 biopsies obtained at transplantation from 100 deceased donor allografts and 19 living donor allografts as well as 45 allograft biopsy specimens collected from recipients because of a clinical suspicion of an acute rejection episode. Total RNA was isolated and transcribed to cDNA. To measure mRNA encoding perforin, granzyme B, and FasLigand by real-time quantitative, polymerase chain reaction we used oligonucleotide primers in a LightCycler equipment with cyclophilin B as the housekeeping gene. At the time of transplantation, the transcript expression levels of perforin and granzyme B were the same in the biopsies from deceased and living donors. During acute rejection episodes (n = 10), perforin (P < .01), and granzyme B levels (P < .05) were significantly up-regulated. In cases of suspected rejection (n = 12), both the clinical picture and the effector gene responses were heterogeneous. The FasLigand expression was up-regulated during acute rejection episodes (n = 8) compared with the time of transplantation, but the change was not significant. In conclusion, brain death did not seem to influence the granule exocytosis pathway in the kidney. The cytolytic effector pathways are up-regulated in renal allograft tissue in acute rejection episodes.

Acute Disease↗

Attitudes, knowledge, and proficiency in relation to organ donation: a questionnaire-based analysis in donor hospitals in northern Denmark.

The aim of this study was to assess knowledge, attitudes, and proficiency in relation to organ donation among staff members of intensive care units (ICUs) in donor hospitals, and possibly identify areas for improvement. The investigation was carried out as a collaboration between the transplant center and appointed key persons in all 17 ICUs in 15 hospitals in northern Denmark. A total of 1168 structured questionnaires were distributed to the health care professionals in the ICUs in the region; 689 were returned, giving a response rate of 59%. In general, there is a positive attitude among health care professionals toward organ donation. However, a considerable fraction of 11% declares to be against organ donation. Only 49% of the ICU health care professionals are willing to donate their own organs after death. By comparison, 74% of the general Danish population are willing to donate organs after death. Doctors are more positive toward organ donation than the nursing staff. Thus, 95% of the doctors are positive to organ donation compared to 81% of the nurses; 70% of the doctors will donate own organs after death compared to 45% of the nurses. Further, the survey demonstrates as expected a significant lack of experience in organ donation. Our data show a considerable need for more education and training, especially on how to inform and support the donor relatives and how to identify potential donors. The survey also discloses a substantial need for information regarding the results of transplantation.

Attitude of Health Personnel↗

Selected activities in Scandiatransplant.

Scandiatransplant is the Nordic organ exchange organization. It has existed for 35 years and it is owned by all organ transplantation hospital departments in the five Nordic countries--Denmark, Finland, Iceland, Norway, and Sweden. The use of living organ donors for kidney transplantation has become a more common procedure not only in Norway but also in Sweden and Denmark. For the first time, in 2003, one transplant center performed relatively more living donor kidney transplantations than with deceased donors. The overall organ transplant activity reveals a remarkably stable situation in the area covered by Scandiatransplant. Scandiatransplant as an organ exchange organization has changed from a solely kidney exchange organization to an organization in which the more immediate vital organs as liver and heart are exchanged more commonly than kidneys.

Humans↗

Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in human skeletal muscle: influence of gender and exercise.

AIM: To investigate gender-related differences in the responses of oxidative enzymes and eukaryotic elongation factor-2 (eEF2) to exercise. METHODS: The influence of exercise (90 min, 60%VO(2peak)) on citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HAD) activity and mRNA content, together with eEF2 expression and phosphorylation at rest, were assessed in skeletal muscle of untrained (UT) and endurance trained (ET) females and males. RESULTS: Citrate synthase and HAD mRNA were higher in females than in males (27% and 48%, respectively, P < 0.05) whereas CS and HAD activity did not differ between females and males (NS). In females only, CS activity was enhanced (P < 0.05) by 90 min exercise. Resting CS mRNA content did not differ between UT and ET but, nevertheless, CS activity was 56% higher in ET than in UT volunteers (P < 0.001). HAD mRNA and activity were not influenced by training status (NS). In UT, CS mRNA was enhanced 37% (P < 0.05) by exercise whereas exercise did not change CS mRNA in ET (NS). eEF2 expression was 31% higher (P < 0.05) and eEF2 Thr56 phosphorylation (which leads to translation inhibition) was 24% lower (P < 0.05) in females than in males. eEF2 expression and phosphorylation were unaffected by training status (NS). CONCLUSION: Basal transcriptional, translational, and/or post-translational control of CS and HAD seems to be gender-dependent. Also, gender differences in translation and/or post-translational protein modification of CS occur during exercise. Accordingly, the potential for peptide-chain elongation, based on eEF2 expression and phosphorylation, appears to be higher in females than in males.

3-Hydroxyacyl CoA Dehydrogenases↗

Genotyping of Campylobacter jejuni strains from Danish broiler chickens by restriction fragment length polymorphism of the LPS gene cluster.

AIMS: To apply and evaluate LG (LPS genes) genotyping, which is a genotyping method based on a cluster of genes involved in the synthesis of surface lipopolysaccharides (LPS) in Campylobacter species, for typing of Campylobacter jejuni isolates obtained from Danish broiler chickens. Furthermore, the LG genotyping method was used to study the genetic stability of four C. jejuni strains after gastrointestinal passage through experimentally infected chickens. METHODS AND RESULTS: In the present study, the LG genotyping method was modified with respect to the restriction enzymes used. To validate the method, 63 Penner serotype reference strains and 107 C. jejuni chicken isolates, representing the most common Penner serotypes of C. jejuni in Danish poultry, were selected for typing. The method was successfully used for typing all isolates and the LG genotype profiles were reproducible. There were no changes in the LG genotype of the C. jejuni strains obtained after experimental passage through chickens. CONCLUSIONS: All C. jejuni strains obtained from broiler chickens were typeable by the LG genotyping method. Application of the RsaI restriction enzyme improved the method in terms of ease and consistency of analyses and increase of discriminatory power. SIGNIFICANCE AND IMPACT OF THE STUDY: The LG genotyping method is a valuable tool for typing C. jejuni isolates obtained from poultry. However, the association between Penner serotyping based on passive haemagglutination of heat-stable antigens and LG genotyping was low when applied to poultry isolates. This is in contrast to previous studies on isolates of human origin that reported a high correlation between results obtained by the two typing methods (Shi et al. 2002).

Animals↗

Analysis by pulsed-field gel electrophoresis of the genetic diversity among Clostridium perfringens isolates from chickens.

The aim of this study was to analyse the genetic diversity among Clostridium perfringens isolates from Danish broiler chickens since both sick and presumably healthy animals were investigated. Isolates (n=279) collected from chickens from 25 farms were analysed by pulsed-field gel electrophoresis (PFGE) with the restriction enzyme SmaI. A high genetic diversity was found. Isolates with different PFGE types were toxin typed by PCR and all were found to be of type A. The results showed that healthy broiler chickens carried several different C. perfringens clones both within a flock and even within individual birds, whereas flocks suffering from necrotic enteritis (NE) or cholangio-hepatitis carried only one or two clones.

Animals↗

A one-year study of campylobacter carriage by individual Danish broiler chickens as the basis for selection of Campylobacter spp. strains for a chicken infection model.

From February 1999 to February 2000, 1,250 individual broiler chickens representing 125 broiler flocks originating from 62 broiler farms in Denmark were screened for campylobacter carriage. Every month, 10 flocks were tested for campylobacter carriage. The swabs were tested individually and as a pooled sample representing the flocks. Campylobacter spp. carriage was detected from 512 (40.9%) broiler chickens originating from 63 (50.4%) positive flocks. Campylobacter carriage by both individual chickens and flocks showed seasonal variation. Campylobacter jejuni was the dominant species (95.5%). Campylobacter isolates were typed using Penner heat-stable serotyping and flaA-typing methods. Data of campylobacter carriage by individual chickens and data generated by the use of different typing methods contributed to a better understanding of the dynamics of campylobacter infection within the broiler flocks. C. jejuni Penner heat-stable serotype HS2, flaA-type 1 was the most common type found in Danish broiler chickens.

Animals↗