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Biomedical subjects

J Carlsen

Publications and source records attributed to J Carlsen.

At least 19 recordsLinked to original sources

Randomized controlled trial of yoga and exercise in multiple sclerosis.

OBJECTIVE: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). METHODS: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. RESULTS: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. CONCLUSION: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

Adult↗

A 60-kDa protein abundant in adipocyte caveolae.

To search for caveolar proteins, mice were immunised with rat adipocyte membranes. Hybridoma supernatants were screened for antibodies to proteins on the cytosolic face of caveolae by indirect immunoelectron microscopy of immunogold-labelled adipocyte plasma membrane sheets adsorbed on electron-microscope (EM) grids. One of the hybridoma supernatants (2F11) produced a specific labelling of caveolae which was much more intense than that obtained with caveolin-1 antibodies. In Western blots of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) separated proteins in crude membrane fractions from different rat tissues, 2F11 labelled a band corresponding to 60 kDa. The intensity of 2F11 labelling was high in adipose tissue and in other tissues varied in parallel to caveolin- labelling. In blots of plasma membrane (PM) and light-microsomal (LM) fractions from a homogenate of adipocytes, prior insulin stimulation of the adipocytes translocated GLUT-4 from the LM to the PM fraction, but was without effect on the distribution of the 60-kDa protein labelled by 2F11. Digestion with endoproteinase lys-C produced the same pattern of immunoreactive fragments of the protein in the vesicular PM and LM fractions, indicating similar membrane topology of the 2F11-reactive, 60-kDa protein in vesicles of PM and LM fractions.

Adipocytes↗

Facial reanimation surgery utilizing the Mitek anchor system: A case report.

A flaccid hemi-face is frequently the most noticeable and cosmetically unacceptable consequence of facial nerve palsy, whether due to trauma, Bell's palsy or other etiologies. A variety of face-lift and reanimation techniques have been utilized in the past, but with time, these frequently require further surgery. We describe the use of Mitek (Norwood, MA) suture anchors for cheek resuspension in a patient with facial palsy. This system is composed of a drill guide, drill, inserter, and anchor. Although the titanium alloy anchors come in multiple sizes, the Mini GII Anchor is typically most appropriate for use in facial procedures. The actual size of the Mini GII Anchor is 1.8 mm in diameter and 5.4 mm in length. Two small arched prongs extend from the body of the anchor, and an eyelet at the superior surface is used for suture placement. When placed into a pre-drilled hole with the insertion tool, the prongs extend, effectively fixing the anchor in place. The drill guide protects adjacent soft tissues during the drilling process and allows drilling to a predetermined fixed depth. Sutures attached to the anchor may then be used for soft tissue fixation to bone.

Journal Article↗

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Adult↗

Myocardial perfusion scintigraphy as a screening method for significant coronary artery stenosis in cardiac transplant recipients.

BACKGROUND: Several studies have explored the feasibility of using myocardial perfusion imaging to detect allograft vasculopathy after heart transplantation. We undertook the present prospective consecutive study to comparatively evaluate the role of serial myocardial perfusion single-photon emission computed tomography (SPECT) scanning and coronary arteriography (CAG) in detecting coronary artery stenosis suitable for coronary angioplasty in heart transplant recipients. METHODS: Within a 2-week interval during a follow-up period of 5.6 (95% confidence limits 2.1 to 12) years, 255 serial CAGs and myocardial perfusion scintigraphies were performed in 67 patients. Arteriography and scintigraphy were performed once yearly after heart transplantation. We retrospectively analyzed the data. RESULTS: Myocardial scintigraphy showed pathologic reversible defects in 9 out of 67 patients. Four of these patients had significant (>50% and also >70%) focal segmental stenosis in the middle and proximal parts of the coronary arteries (Type A lesions), 1 had diffuse and circumferential narrowing in the distal parts (Type B lesions), whereas CAG showed no lesions in the remaining 4 patients. The patients with significant Type A lesions were revascularized with percutaneous coronary angioplasty. Coronary arteriography showed that 1 patient had extensive Type A and Type B lesions, whereas myocardial perfusion scans detected no. The predictive value of a negative (normal) SPECT was 98% (95% confidence limits 94% to 100%) for the detection of lesions suited for revascularization. CONCLUSIONS: Annual myocardial SPECT seems well suited to screen for significant coronary artery stenosis. A SPECT study without reversible defects virtually excludes lesions suitable for coronary artery revascularization.

Adolescent↗

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

Adult↗

Involvement of PI 3-kinase and activated ERK in facilitating insulin-stimulated triacylglycerol synthesis in hepatocytes.

Triacylglycerol synthesis was studied in hepatocytes isolated from fasted/refed rats by EDTA perfusion. Insulin induced a 1.5-fold increase in glucose incorporation into triacylglycerol. Insulin-stimulated triacylglycerol synthesis and insulin-stimulated protein kinase B/Akt activity were inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY 294002, and the mitogen-activated protein kinase kinase inhibitor PD 98059. Inhibition of p70 ribosomal protein-S6 kinase with rapamycin was without effect. Insulin-stimulated pyruvate dehydrogenase activity was abolished by phosphatidylinositol 3-kinase inhibitors. No effect of insulin on acetyl CoA carboxylase activity was observed.

Acetyl-CoA Carboxylase↗

Pulmonary function in chronic heart failure. Changes after heart transplantation.

To investigate the impact of chronic heart failure on pulmonary function in heart transplant recipients, pulmonary function was evaluated in 41 consecutive patients (mean age 43 years, range 15-57 years) before and 6 months after successful heart transplantation. The pulmonary function tests included measurements of forced vital capacity [FVC], forced expiratory volume in 1.s [FEV1], FEV1/FVC ratio, total lung capacity [TLC], and diffusion capacity for carbon monoxide [TLCO] and KCO [TLCO per l alveolar volume]. Compared to pretransplant values, spirometry after transplantation revealed modest improvements in FVC (from 77 +/- 16 to 88 +/- 21% of predicted [%pred]; p < 0.001) and FEV1 (from 75 +/- 16 to 85 +/- 22%pred; p < 0.001), whereas the FEV1/FVC ratio was unchanged (81% +/- 11 and 80% +/- 10; p = NS). A slight but statistically significant increase in TLC (from 78 +/- 15 to 86 +/- 18%pred, p < 0.001) was also observed. Prior to transplantation the mean TLCO was 76 +/- 17%pred; 7 of the patients had a TLCO below 60%pred (mean 51% pred). In 33 of the 41 patients a reduction in TLCO was observed after transplantation; for all 41 patients the mean fall in TLCO was 14% of the predicted value (SD 12%pred) (p < 0.0001). Likewise, a significant reduction in KCO was noted (p < 0.0001). Multiple regression analysis revealed that high pretransplant TLCO %pred (p = 0.02) and FVC %pred (p = 0.04) were associated with a less favorable outcome concerning posttransplant TLCO %pred. Although normalization of FEV1, FVC and TLC can be anticipated after correction of severe chronic left ventricular failure by heart transplantation, the pronounced concomitant decline in diffusion capacity observed in this study may be explained by underlying pulmonary disease caused by factors other than long-standing heart failure. Our findings support the notion that pulmonary function abnormalities attributable to chronic heart failure should not preclude consideration for heart transplantation.

Adolescent↗

Long-term prognosis after acute myocardial infarction in patients with a history of arterial hypertension. TRACE study group.

AIMS: The objective of the study was to investigate the influence of a history of arterial hypertension on long-term prognosis after an acute myocardial infarction in a representative population, and secondly to assess the impact on prognosis of left ventricular systolic function in hypertensives after acute myocardial infarction. METHODS: A retrospective analysis of survival data on 6676 patients with acute myocardial infarction screened for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Follow-up time was 4-6 years. RESULTS: One thousand five hundred and seven (23%) of the patients had a history of arterial hypertension. During the time of observation 763 (50.6%) hypertensives and 2253 (43.7%) normotensives died, corresponding to a risk ratio for death in hypertensives of 1.23 (1.13-1.33, P < 0.0001). In a multivariate analysis considering 12 other major risk factors after myocardial infarction, the risk ratio for death in hypertensives was 1.14 (1.04-1.24). There was a significant interaction between hypertension and age. Thus, hypertension only increased risk in patients aged 65 years or less (P < 0.001). No interaction with left ventricular systolic function was found. CONCLUSION: A history of arterial hypertension is a moderate risk factor for mortality after an acute myocardial infarction in patients aged 65 years or less. This excess risk is present at all levels of left ventricular systolic function.

Age Distribution↗

Insulin stimulated glycogen synthesis in isolated rat hepatocytes: effect of protein kinase inhibitors.

Glycogen synthesis was studied in rat hepatocytes isolated by EDTA perfusion. Insulin induced a one and a half to twofold increase in glucose incorporation into glycogen. Insulin stimulated glycogen synthesis was inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin (IC50 approximately 40 nM) and LY 294002 (IC50 approximately 20 microM) and the mitogen-activated protein kinase kinase inhibitor PD 98059 (IC50 approximately 40 microM). Wortmannin was without appreciable effect on non-insulin stimulated glycogen synthesis, while LY 294002 and PD 98059 also inhibited the non-insulin stimulated glycogen synthesis. Rapamycin, an inhibitor of p70 ribosomal protein-S6 kinase, was without effect on glycogen synthesis regardless of insulin stimulation.

Androstadienes↗

The effect of metformin on blood pressure and metabolism in nondiabetic hypertensive patients.

OBJECTIVES: To study the effect of metformin on blood pressure and metabolism in nondiabetic hypertensives. DESIGN: A six-week single-blind placebo wash-out, followed by a double-blind placebo-controlled parallel group design with skew randomization (2:2:1) to metformin 850 mg b.i.d. (n = 10), metformin 500 mg b.i.d. (n = 10), or placebo b.i.d. (n = 5) for 12 weeks. Office blood pressure (oBP), ambulatory blood pressure (aBP), lipoproteins, and oral glucose tolerance (OGTT) were measured/performed before and during treatment. SUBJECTS: Sixteen male and nine female nondiabetic (OGTT) patients (median age 57 (39-74) years) with verified hypertension (White-coat excluded) for 4 (0-20) years. RESULTS: The possible effect of metformin treatment and dosage was tested with a two-factor analysis of variance. Treatment induced a significant decline in diastolic oBP, P < 0.05. This decline was, however, not significantly different comparing metformin and placebo. Systolic oBP, diastolic aBP, and systolic aBP showed no significant change by treatment. The decline in diastolic oBP was 5 mmHg in the pooled group of metformin-treated patients, P < 0.005. Different gender and the presence of obesity had no impact on the decline in diastolic oBP within this group. Changes in fasting C-peptide and fasting insulin during treatment were unrelated to blood pressure changes. High fasting insulin (> 60 pmol L[-1]) or high fasting C-peptide (> 1000 pmol L[-1]) at baseline did not favour an effect of metformin on diastolic oBP. Glucose metabolism and lipoproteins were unchanged in all groups. CONCLUSIONS: Although metformin treatment induced a decline in diastolic office blood pressure in nondiabetic hypertensives, the decline was not different from that during placebo treatment. Metformin had no significant effect on ambulatory blood pressure. Thus, metformin has, if any, only a minor clinically insignificant effect on blood pressure in nondiabetic hypertensives. The study does not support the hypothesis that circulating insulin is a major regulator of blood pressure in hypertension.

Adult↗

Treatment of massive haemoptysis with microcoil embolization after en bloc double-lung transplantation with bronchial artery revascularization.

Successful treatment of a severe haemoptysis with microcoil embolization in an en block double-lung transplanted patient is described. A 53 year old woman with advanced bronchiolitis obliterans syndrome experienced severe haemoptysis 26 months after an en bloc double-lung transplantation with direct bronchial artery revascularization using the left internal mammary artery. Bronchoscopy showed that the haemoptysis originated from the lingula. Only two months after the transplant, left internal mammary arteriograms revealed proliferation and enlargement of the bronchial arteries in the lingula. The early occurrence of the vascular malformation indicated a pre-existing bronchiectasis in the donor lung, possibly due to tobacco smoking. After uncomplicated microcoil embolization of the left internal mammary artery, the patient experienced no further episodes of haemoptysis. Microcoil embolization can be used successfully to treat massive haemoptysis related to proliferated and enlarged bronchial arteries in transplanted lungs with bronchial artery revascularization.

Bronchial Arteries↗

Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study.

To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.

Aged↗

The subcellular localization of newly synthesized cytochrome b5.

The fate of newly synthesized cytochrome b5 was studied in rat hepatocytes. Using an antibody specific for microsomal cytochrome b5, we found newly synthesized microsomal cytochrome b5 in both mitochondria and a mitochondria associated membrane fraction as well as in microsomes. Newly synthesized cytochrome b5 was quickly removed from the site of synthesis on free ribosomes and inserted into membranes at random. No migration of newly synthesized cytochrome b5 between cellular compartments was observed and therefore the assembly of the apoprotein with the heme moiety is apparently not taking place in any particular cellular compartment.

Animals↗

Insertion of functional intact insulin receptors into hepatocytes.

Isolated insulin receptors were inserted into hepatocytes by fusion with receptor-lysophospholipid micelles. The number of receptors was increased approximately two times as monitored by insulin binding experiments. Addition of exogenous receptors resulted in increased receptor autophosphorylation. The exogenous added receptors could be coupled to the intracellular effector system as shown by increased phosphorylation of the insulin receptor substrate 1, IRS-1, and by increased glycogen synthesis. The co-incorporated lysophospholipid was partly metabolized to phospholipid. This method for introducing insulin receptors into cells represents a novel system to study the pathway of insulin signalling and may provide information as to the role of variation of receptor number in insulin action in cellular metabolism of specific cells.

Animals↗