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Biomedical subjects

J Mogensen

Publications and source records attributed to J Mogensen.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence and clinical significance of systolic impairment in hypertrophic cardiomyopathy.

OBJECTIVES: To determine the frequency of systolic impairment (SI) and its impact on the natural history of hypertrophic cardiomyopathy (HCM). METHODS: 1080 patients (mean (SD) age 43 (15) years, 660 men) with HCM were evaluated. Initial assessment included history, examination, 48 hour Holter monitoring, cardiopulmonary exercise testing, and echocardiography; SI was defined as a fractional shortening (FS) < or = 25%. Survival data were collected at clinic visits or by direct communication with patients and their general practitioners. The results of serial echocardiography in 462 patients with normal FS at presentation are also reported. RESULTS: 26 (2.4%) patients (49 (14) years, 18 men) had SI at the initial visit. During follow up (58 (49) months), nine (34.6%) died or underwent cardiac transplantation compared with 108 (10.2%) patients with normal FS (p = 0.01). Five year survival from death (any cause) or transplantation was 90.1% (95% confidence interval (CI) 87.8 to 92.4) in patients with normal systolic function versus 52.4% (95% CI 25.2 to 79.6, p < 0.0001) in patients with SI. In patients who underwent serial echocardiography, 22 (4.8%, aged 41 (15) years) developed SI over 66 (40) months; the annual incidence of SI was 0.87% (95% CI 0.54 to 1.31). On initial evaluation patients who developed SI had a higher frequency of syncope (67 (15.2%) v 10 (45.5%) of those who did not develop SI, p = 0.001), non-sustained ventricular tachycardia (91 (20.6%) v 11 (50%), p = 0.002), and an abnormal blood pressure response on exercise (131 (29.7%) v 15 (68.2%), p = 0.001). Patients with SI had greater wall thinning (p = 0.001), left ventricular cavity enlargement (p < 0.0005), and deterioration in New York Heart Association functional class (p = 0.001) during follow up. Thirteen (59.1%) patients who progressed to SI died or underwent transplantation compared with 38 (8.6%) patients who maintained normal systolic function. CONCLUSIONS: SI is an infrequent complication of HCM but, when present, is associated with a poor prognosis.

Adolescent↗
PubMed2005

Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I.

OBJECTIVE: To examine the influence of genotype on late gadolinium enhancement (LGE) and the potential of cardiovascular magnetic resonance (CMR) to detect preclinical hypertrophic cardiomyopathy. DESIGN: Prospective, blinded cohort study of myocardial LGE in a genetically homogeneous population. PATIENTS: 30 patients with disease causing mutations in the recognised hypertrophic cardiomyopathy gene for cardiac troponin I (TNNI3): 15 with echocardiographically determined left ventricular hypertrophy (LVH+) and 15 without (LVH-). MAIN OUTCOME MEASURES: CMR measures of regional left ventricular function, wall thickness, and mass, and the extent and distribution of LGE. RESULTS: LGE was found in 12 (80%) LVH+ patients but with variable extent (mean 15%, range 3-48%). LGE was also found in two (13%) LVH- patients but the extent was limited (3.6%) and both patients were found to have an abnormal ECG and regional hypertrophy by cine CMR. The extent of LGE was positively associated with clinical markers of sudden death risk (21% with > or = 2 risk factors v 7% with < or = 1 risk factor, p = 0.02) and left ventricular mass (r = 0.56, p < 0.001) and was inversely associated with ejection fraction (r = -0.58, p < 0.001). Segmental analysis showed that as regional wall thickness increased, LGE was more prevalent (p < 0.0001) and more extensive (r = 0.98, p = 0.001). CONCLUSION: In patients with disease causing mutations in TNNI3, focal fibrosis was not detected by LGE CMR before LVH and ECG abnormalities were present. Once LVH is present, LGE is common and the extent correlates with adverse clinical parameters. This suggests that focal fibrosis is closely linked to disease development.

Adolescent↗
PubMed2000

[Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. A new therapeutic option].

We here report on the PTSMA results in four HOCM patients having severe symptoms despite medical treatment and dual chamber pacing. Between two and five ml of ethanol was injected in one or two septal branches from the left coronary artery. Six months after treatment the pressure gradient across the left ventricular outflow tract was reduced between 25-80 mmHg at rest and between 55-180 mmHg at exercise. There was an increase in functional capacity of about two NYHA-classes. Two patients developed permanent right bundle branch block, and one patient with pre-existing left bundle branch block developed persistent total atrioventricular block after the treatment. Serum creatine phosphokinase MB increased on average to 146 U/l. No other complications were seen. In conclusion, our initial PTSMA results seems promising.

Adult↗
PubMed1999

Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

Actins↗
PubMed1997

Behavioral symptoms in adult rats after postnatal L-nitro-arginine.

We addressed experimentally the suggestion by Gally et al. [Gally J. A., Read Montague P., Reeke G. N. Jr and Edelman G. M. (1990) Proc. Natl Acad. Sci. U.S.A. 87, 3547-3551] that nitric oxide may play a role in the use-dependent modification of synaptic efficacy in the developing nervous system. In a preliminary control experiment, we treated rat pups from postnatal day 8 to postnatal day 22 with a nitric oxide synthase blocker (L-nitro-arginine) and compared their growth curves and brain weights to those of saline injected control pubs. No significant differences were found after the 14 days of nitric oxide synthase inhibition. In the subsequent experiment, we inhibited nitric oxide synthesis in rat pups from postnatal day 8 to day 29 and assessed their place learning ability and open field behavior as adults. We found an increased speed of habituation of locomotion in an open field in 5-month-old rats that had been treated postnatally with a nitric oxide synthase blocker. There was no difference between treated and non-treated rats with respect to place learning in a water maze. We conclude that perturbation of nitric oxide production during early postnatal development does not preclude normal learning and memory function in the adult.

Animals↗
PubMed1996

[Characteristics of mortality among patients waiting for coronary arteriographic evaluation or heart surgery].

It was the aim to reduce deaths among future patients queuing for heart catheterization or surgery. All the patients who died, after they were referred for heart catheterization or surgery because of coronary heart and heart valve disease, were registered over a three year period (July 1, 1990 to June 30, 1993). The total number of deaths was 98. Ninety-two (94%) died of cardiac disease. Seventyfour (80%) only had symptoms of cardiac disease; ten (11%) had competitive disease and eight (9%) had received revascularizing treatment previously. The number of catheterizations increased from 968 to 1312 per year, while the number of operations remained constant at about 600 per year. The death-rate for patients referred to heart catheterization was 2.5% for patients with aortic valve disease and 1.7% for patients with coronary heart disease. For patients referred for coronary artery bypass grafting the death-rate was 2.6% and for heart valve surgery 3.9%. The survival-time for patients waiting for catheterization was 4.2 months (0.3-16) and 4 months (1-16) for patients waiting for surgery. Half of the deaths in patients queuing for cardiac catheterization occurred within one month of waiting while half of the deaths in patients waiting for heart surgery appeared within 1.3 months. In the early deaths among patients queuing for cardiac catheterization there was a tendency towards prolonged doctor's delay and a surplus of patients with aortic valve disease. Deaths among patients awaiting heart catheterization or surgery can hardly be avoided. However, in the present study the death-rates for patients referred to surgery was 1.8 to 7.7 times higher compared to the conditions in other Western countries. The waiting-time was long and cardiac deaths frequent, reflecting the low capacity for invasive procedures as well as operations during this period.

Adult↗
PubMed1995

Functional and neurochemical profile of place learning after L-nitro-arginine in the rat.

Rats in which near-total inhibition of the nitric oxide synthesizing enzyme (NOS) had been obtained by a 5-day pretreatment during which two daily injections of L-nitro-arginine (50 mg/kg per injection) had been administered were subjected to five sessions of training on a place learning task (one session per day). NOS inhibition was associated with significantly impaired task acquisition but on the fifth training session normal task proficiency was achieved. Subsequent pharmacological and behavioral challenges established that dissimilar neural substrates mediated the task in NOS-inhibited and normal animals. In NOS-inhibited rats the neural substrate of task mediation depended less than normally on cholinergic mechanisms while potentially relying more on catecholaminergic mediation. In a separate experiment rats that had acquired the place learning task to asymptotic quality of performance were subjected to a L-nitro-arginine treatment similar to the pretreatment of the first experiment. Such a NOS inhibition did not impair subsequent task performance. It is concluded that nitric oxide participates in processes subserving acquisition rather than performance of at least some forms of place learning.

Amino Acid Oxidoreductases↗
PubMed1995

L-nitroarginine reduces hippocampal mediation of place learning in the rat.

Based on previous results it was hypothesized that the neural substrate of the acquisition of place learning during inhibition of the nitric oxide synthesizing enzyme (NOS) by L-nitroarginine (L-N-ARG) differs from the neural substrate of normal task acquisition by a reduced or abolished participation of the hippocampus. This hypothesis was tested in two independent experiments. In Experiment 1 the behavioral consequences of bilateral transection of the fimbria-fornix--a lesion that abolishes normal hippocampal function--were investigated in animals that had acquired the task after either a vehicle control pretreatment or a 5-day pretreatment period during which near-total inhibition of NOS had been accomplished by L-N-ARG injections. While fimbria-fornix transections significantly impaired task performance in normal animals the rats which had acquired the task during NOS inhibition did not reveal a lesion-associated impairment. In Experiment 2 four groups of rats were studied: two groups initially received bilateral transection of the fimbria-fornix, while the two others were subjected to sham surgery. Subsequently, one of the fimbria-fornix-transected and one of the sham-operated groups received a 10-day period of L-N-ARG injections, while the two remaining groups received saline control injections. During the final 5 days of injections the four groups were subjected to training on the place-learning task. While NOS inhibition clearly impaired task acquisition in the sham-operated animals, L-N-ARG administration in fimbria-fornix-transected animals failed to impair place-learning acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Afferents to different layers of the dorsolateral isocortex in rats.

Fluorescent somatopetal tracers were used to infiltrate, by diffusion rather than injections, the dorsolateral cortex of one hemisphere in rats. In different animals the tracers penetrated into the cortex to different depths. We found several interesting features of the commissural system: first, there were no areas without commissural neurons. At least a few labelled cell bodies were present in a single-cell layer also in "acallosal" cortical areas. Secondly, there is a considerable variety of laminar distribution patterns of labelled perikarya in different areas. Thirdly, some cortical fields, which cytoarchitecturally appear uniform, can be subdivided according to different distributions of cell bodies with commissural projections. Fourthly, when only supragranular layers were infiltrated, labelled cell bodies were present mainly in the supragranular layers of the contralateral cortex. Infiltration of the first layer alone did not label any neurons in the contralateral cortex but did label neurons in layer VIb ipsilaterally. In the subcortex, the labelled perikarya were found in the structures already known to project directly to the cortex. In rats with the tracer restricted mainly to the supragranular layers, a conspicuously reduced labelling was found in the basal forebrain and the thalamus. In the thalami of those animals, labelled neurons were found only in paralamellar nuclei. The high sensitivity of the tracer used, together with infiltration of the entire dorsolateral cortex, allows us to conclude that probably all sources of innervation of the isocortex in rats have been seen.

Afferent Pathways↗
PubMed1995

Prefrontal cortical mediation of rats' place learning in a modified water maze.

The acquisition of a place learning task in a water maze modified from the "standard" set-up by restriction of distal cues and addition of "proximal" cues (ping-pong balls in fixed positions on the surface of the water) was tested in three groups of rats: (I) animals subjected to bilateral ablation of the anteromedial prefrontal cortex, (II) rats in which the parietal "association" cortex had been removed bilaterally, and (III) a sham operated control group. The task acquisition of the prefrontally ablated group was significantly impaired, whereas the animals in which the parietal cortex had been removed acquired the task as quickly as the control group. Upon reaching criterion level performance all animals were tested on "challenge" sessions on which the cues were manipulated. Such "challenges" demonstrated that the animals of all three groups discriminated between the distal cues and utilized such a discrimination for navigational purposes.

Animals↗
PubMed1995

Place learning by fimbria-fornix transected rats in a modified water maze.

The acquisition of a place learning task in a water maze modified from the "standard" setup by restriction of distal cues was tested in two groups of rats: (1) animals subjected to bilateral transection of the fimbria-fornix--a manipulation that renders the hippocampus dysfunctional--and (2) a sham operated control group. The fimbria-fornix transected animals acquired the task as quickly and to the same level of proficiency as the control group. Upon reaching criterion level performance all animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that both groups relied upon the distal cues for navigational purposes. Finally, the performance of all animals was "challenged" on two sessions by administration of d-amphetamine and scopolamine, respectively. The outcome of the pharmacological challenges demonstrated that the normal proficiency of place learning by the fimbria-fornix transected rats had been accomplished due to compensatory processes mediated at least partly by the catecholaminergic systems.

Animals↗