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Biomedical subjects

R Dom

Publications and source records attributed to R Dom.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of dilated cardiomyopathy on the diaphragm in the Syrian hamster.

This study aimed to elucidate changes in respiratory muscles and their mechanism in cardiomyopathy. The contractile properties and histology of the diaphragm, as well as serum levels of insulin-like growth factor (IGF)-1, were examined in 10 hamsters with idiopathic dilated cardiomyopathy (CM) and 10 controls. At 28 weeks, body weight in CM was reduced compared with controls (114+/-10 versus 144+/-14 g, p<0.0001). The ratio of diaphragm to body weight was significantly higher in CM than in controls (0.228+/-0.015 versus 0.182+/-0.017, p<0.0001). In vitro, maximal diaphragmatic twitch (303+/-63 versus 455+/-119 g x cm(-2)) and tetanic tensions (1,555+/-369 versus 2,204+/-506 g x cm(-2)) were significantly lower in CM than in controls (p<0.005). The half-relaxation time was significantly shorter in CM (19+/-1 ms) than in controls (24+/-3 ms, p<0.0005). Fatiguability at 25 Hz was significantly less in CM (28%) than in controls (42%, p<0.0001). Diaphragm and gastrocnemius adenosine triphosphatase staining showed type I fibre atrophy in CM, associated with an increase in the number of type I fibres in the diaphragm. Histological examination of both muscles revealed an abnormal muscular pattern. Finally, serum levels of IGF-1 were 47% lower in the CM group than in controls (p<0.0001) and were clearly related to the changes in the contractile properties and histology of the diaphragm. In conclusion, cardiomyopathy in hamsters: 1) depressed the force-generating capacity and shortened the relaxation of the hamster diaphragm; 2) induced type I fibre atrophy in combination with a myopathic pattern; and 3) was associated with a significant reduction in serum levels of insulin-like growth factor-1, related to the diaphragmatic changes. Whether these changes are primary myopathic or secondary to heart failure remains to be elucidated.

Adenosine Triphosphatases↗
PubMed1999

Treatment of Alzheimer's disease: an evaluation of the cholinergic approach.

The cholinergic hypothesis claims that a decrease of acetylcholine (ACh) in the brain of patients with Alzheimer's Disease (AD) plays an important role in the deterioration of cognitive functioning. This hypothesis has led to extensive research in possible therapeutic approaches towards improving cholinergic transmission in AD patients. The different approaches have focused on the following six strategies: ACh precursors, ACh release, M1, M3, or M4 receptor agonists, M2 receptor antagonists, nicotinic agonists, and acetylcholinesterase inhibitors (AChEI). The aim of this review is to assess the effectiveness of the cholinergic approach for the treatment of AD.

Acetylcholine↗
PubMed1999

Methodological issues in a cost-of-dementia study in Belgium: the NAtional Dementia Economic Study (NADES).

The NAtional Dementia Economic Study (NADES) is an on-going prospective, one-year cohort study developed in Belgium to assess the socio-economic consequences of dementia in a group of patients and their caregivers (n = 400). Comparison is made with a group of subjects with cognitive impairment and no dementia (n = 100) and a group of subjects without any cognitive impairment (n = 100). Recruitment of subjects is based on screening of warning signs of dementia by general practitioners, followed by a Cambridge Mental Disorders of the Elderly Examination (CAMDEX) performed at home. This paper presents an overview of the study protocol and the rationale for basic design options, such as the choice of study population, screening strategy, and methods used for the case validation. It also presents preliminary results on the prevalence of dementia in general practice, the sensitivity and specificity of the warning signs as a screening test of dementia, and the validity of a computerised case ascertainment algorithm based on DSM-III-R criteria.

Aged↗
PubMed1999

Psychological functioning before predictive testing for Huntington's disease: the role of the parental disease, risk perception, and subjective proximity of the disease.

BACKGROUND: Psychometric testing of participants in predictive DNA testing for Huntington's disease (HD) has shown that 15% of the subjects at risk for HD had at least mild depression or a high score for general anxiety or both in the pre-test period. The main aim of the study was the delineation of variables associated with pre-test distress of applicants for predictive testing for HD. Based on theoretical considerations, four specific hypotheses were tested regarding the role of (1) the test participant's age at the (perceived) parental onset of HD, (2) the affected parent's sex, (3) the perception of the risk for HD, and (4) the subjective proximity of the disease. Secondly, these four variables were used in multiple regression analyses to select the best predictors of pre- and post-test psychological functioning (one year after the test). Increasing the understanding of pre- and post-test distress is important for developing better counselling and support strategies for test applicants. METHODS: Data were collected by means of clinical interviews and psychometric questionnaires during the pre- and post-test (one year after the test) counselling sessions for predictive testing for HD. RESULTS: We found significant associations of the participant's age at the parental onset, the subjective proximity of the disease onset, and the perceived risk with pre-test psychometric measures of psychological functioning. Multiple regression analyses showed that the best predictors of pre-test functioning were the perceived proximity of the disease onset and its interaction with risk perception. Regarding post-test functioning, none of the proposed variables had a unique contribution beyond that accounted for by pre-test psychological functioning. CONCLUSIONS: Test participants who are close to the perceived age of onset of HD and who have a pessimistic risk perception should be given special attention during pre-test counselling because of their possible negative affective condition at that time. Pre-test psychological measures were the best predictors of post-test distress, irrespective of the test result. Suggestions for future longitudinal research are formulated. This kind of research should enable clinical geneticists and mental health professionals to refine the pre- and post-test counselling strategies for predictive DNA testing, not only for HD, but also for other incurable late onset disorders.

Adult↗
PubMed1998

Neuropathological findings in Moebius syndrome.

Pathological findings in two patients with Moebius syndrome and lethal fetal akinesia sequence are described. In both patients a congenital brain stem malformation with neuronal loss in the cranial nerve nuclei and tegmental microcalcifications was observed. In one patient, the association with splenogonadal fusion was observed, whilst in the second patient, the association with tetraperomelia was present. As the association of peromelia and splenogonadal fusion is a well-known association, the different combination of splenogonadal fusion, peromelia and Moebius syndrome due to congenital brain stem anomalies with necrosis might be the result of a disruptive phenomenon during a prolonged vulnerable critical period in the 5th and 6th week of embryonic life. The finding of olivary dysplasia in one case, reminiscent of olivary dysplasia in Zellweger syndrome and in Miller Dieker syndrome, might suggest a primary malformation underlying Moebius syndrome due to brain stem defects.

Abnormalities, Multiple↗
PubMed1998

Systolic ventricular dysfunction causes selective diaphragm atrophy in rats.

In order to examine the relative impairment of the diaphragm and other skeletal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined alterations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I expression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size averaged 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynamic measurements revealed a decrease in left ventricular peak systolic pressure of 19% (p < 0. 05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaphragm contractile properties was present in VD animals. For all animals combined, the reduction in diaphragm weight was related to infarct size (r = -0.74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alterations. IGF-I expression was increased by 55% in the diaphragm of rats with VD (p < 0.05). IGF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensatory mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude that systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not associated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.

Adenosine Triphosphatases↗
PubMed1998

A frequency and correlation analysis of motor deficits in Parkinson patients.

PURPOSE: The present study explored the frequency and pattern of functional motor problems of a group of Parkinson patients, as a first step towards developing a rational approach to rehabilitation intervention addressing the primary symptoms of the disease. METHOD: Sixty patients, consisting of 40% women and 60% men with a mean age of 63.5 years and of which 88% were taking L-dopa, underwent a number of standardized clinical tests including part III of the UPDRS. They were also interviewed about the frequency of motor problems occurring at home. RESULTS: Loss of trunk rotation as expressed in rolling in supine and reduced arm swing were the most frequently registered motor disorders (73%, 75%). Freezing at the start of, or during, walking was not observed during clinical testing but was frequently claimed to occur at home (48%, 23%). A broad spectrum of deficits regarding gait, posture, transfers and distal motor problems formed a cluster, which was strongly correlated with bradykinesia (p < 0.001). Principal component analysis identified four distinct problem areas: (1) axial motor performance; (2) akinetic gait problems; (3) rigidity; and (4) tremor. CONCLUSIONS: Parkinson patients, particularly in the later stages of the disease, presented with significant levels of functional disability which was mainly linked with the underlying impairment of bradykinesia.

Adult↗
PubMed1997

Interlimb coordination deficits in patients with Parkinson's disease during the production of two-joint oscillations in the sagittal plane.

Two-limb coordination patterns involving cyclical flexion-extension movements, performed in the same or in different directions, were studied in patients with Parkinson's disease and a group of elderly subjects. The three patterns referred to the homologous (both arms or legs), homolateral (right or left arm and leg), and heterolateral (right arm and left leg or vice versa) limb segment combinations that were performed in the sagittal plane from a seated position. Findings revealed that interlimb coordination deficits were evident in patients with Parkinson's disease. Moreover, mean cycle duration and its variability were increased, particularly during the production of nonhomologous limb movements in different directions. These temporal findings suggest that movement slowness was not a primary consequence of an intrinsic inability to move the limb segments at the required speed but rather reflected an intentional strategy to cope with the complexity of the coordination pattern. Finally, movement amplitude was substantially smaller and more variable in patients with Parkinson's disease, suggestive of hypometria during the production of these cyclical tasks.

Aged↗
PubMed1997

Interlimb coordination in patients with Parkinson's disease: motor learning deficits and the importance of augmented information feedback.

The basal ganglia have traditionally been associated with motor control functions and this view has prevailed since the late nineteenth century. Recent experimental studies suggest that this neuroanatomical system is also critically involved in motor learning. In the present study, motor learning/transfer capabilities were compared between patients with Parkinson's disease and a group of normal elderly people. Subjects practiced a bimanual coordination task that required continuous flexion-extension movements in the transverse plane with a 90 degrees phase offset between the forearms. During acquisition, augmented visual feedback of the relative motions was provided in real time. The findings revealed improvements in the bimanual coordination pattern across practice in both groups when the augmented concurrent feedback was present. However, when transferred to performance conditions in which the augmented information was withheld, performance deteriorated (relative to the augmented condition) and this effect was more prevalent in the Parkinson patients. More specifically, no improvement in interlimb coordination was observed under nonaugmented feedback conditions across practice. Instead, a drift toward the preferred in-phase and antiphase coordination patterns was evident. The present findings suggest that Parkinson patients can improve their performance on a new motor task, but they remain strongly dependent on augmented visual information to guide these newly acquired movements. The apparent adoption of a closed-loop control mode is accompanied with decreases in movement speed in order to use the feedback to ensure accuracy. When the augmented feedback is withheld and the movement pattern is to be controlled by means of intrinsic information feedback sources, performance is severely hampered. The findings are hypothesized to indicate that learning/transfer is affected in Parkinson patients who apparently prefer some constancy in the environmental contingencies under which practice takes place. The present findings are consistent with the notion that the basal ganglia form a critical neuroanatomical substrate for motor learning.

Aged↗
PubMed1997

Fetal akinesia sequence caused by nemaline myopathy.

Nine patients with the characteristic signs of fetal akinesia sequence (polyhydramnion, multiple joint contractures and lung hypoplasia) are described. In 8 of the 9 patients nemaline myopathy could be demonstrated with histology. The ninth patient presented the same phenotype as his 4 affected siblings in whom the nemaline myopathy could be histologically proven. Seven of the patients belonged to 2 families; the other 2 patients were isolated cases. In one fetal case nemaline myopathy was documented at week 22 of gestation. These observations demonstrate that nemaline myopathy can cause the fetal akinesia sequence, with onset of first symptoms as early as the beginning of the second trimester of pregnancy.

Abnormalities, Multiple↗
PubMed1997

Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats.

Thirty male and 18 female adult rats received weekly an intramuscular injection of either saline (control; C), 1.5 mg/kg (low-dose; LD) nandrolone decanoate or 7.5 mg/kg (high-dose; HD) nandrolone decanoate during 5 wk. Compared with respective C, growth rate was stunted in male HD rats from 2 wk of treatment on, whereas it was enhanced in female LD and HD rats after 1 wk. Mass of all muscles studied varied proportionally to body weight, except for the gastrocnemius (males: 0.49 +/- 0.04 vs. C: 0.52 +/- 0.03%, not significant; females: 0.17 +/- 0.01 vs. C: 0.15 +/- 0.01%, P < 0.05). In vitro contractile and fatigue properties of the diaphragm remained unchanged, except for a decrease in twitch kinetics (time to peak tension: C, 21 +/- 2; LD, 19 +/- 1; HD, 19 +/- 2 ms, P < 0.05; half-relaxation time: C, 26 +/- 5, LD, 25 +/- 5, HD, 23 +/- 3 ms, P < 0.01). Histochemistry of the diaphragm and the gastrocnemius revealed a significant increase in type IIx/b dimensions. In the gastrocnemius, type I fiber dimensions also increased. A pair-fed study, including another 24 female rats, showed that the changes in oral food intake only partly accounted for the observed anabolic effects.

Anabolic Agents↗
PubMed1997

Intermittent inspiratory muscle training induces fiber hypertrophy in rat diaphragm.

The effects of 8 wk of moderate load intermittent inspiratory resistive loading on diaphragm contractility, and histochemistry of the diaphragm, scalenes, and gastrocnemius were studied in rats. A resistance was placed in the inspiratory port of a Hans-Rudolph valve, through which each animal breathed during 30 min/d, 5 times/wk (loaded group, n = 10). These rats were compared with animals breathing through the same device without inspiratory resistance (control group, n = 10). During loading, animals generated mean inspiratory pressures of -3.2 +/- 1.7 cm H2O with a TI/Ttot of 0.69 +/- 0.06, resulting in a tension-time index of 0.050. At the end of training, the diaphragm mass increased in loaded animals (0.17 +/- 0.01% body mass) compared with control animals (0.15 +/- 0.01%, p < 0.01), while scalene and gastrocnemius mass remained unchanged. Diaphragmatic force as well as fatigue resistance were similar in both groups, whereas time to peak tension was significantly (p < 0.01) shorter in loaded rats (18.8 +/- 1.7 ms) compared with control rats (21.2 +/- 1.8 ms), half-relaxation time remaining unchanged. Finally, hypertrophy of diaphragmatic type IIa (+19%, p < 0.01) and IIx/b (+12%, p < 0.05) was present in the loaded group. Histochemistry of the scalenes remained unchanged, whereas type IIx/b hypertrophy (+12%, p < 0.001) was observed in the gastrocnemius internus. We speculate that the latter was due to multiple escape maneuvers. We conclude that intermittent inspiratory muscle training: (1) caused fast twitch fiber hypertrophy in the diaphragm; (2) did not produce any effect in the scalenes.

Adaptation, Physiological↗
PubMed1996

Clinical and molecular genetic features of congenital spinal muscular atrophy.

A neonate presented with the fetal hypokinesia sequence and signs of spinal muscular atrophy (SMA). Severe pathological changes including ballooned neurons and neuronophagia were found not only in the motor nerve nuclei but also in the thalamic, cerebellar, and brainstem nuclei as well as in the dorsal root ganglia. Direct DNA analysis showed the presence of a chimeric SMN gene, with a rearrangement occurring between exon 7 of the centromeric SMN gene and exon 8 of the telomeric SMN gene. Circumstantial evidence suggests that only a single copy of this gene is present, with transcriptional characteristics of a centromeric SMN gene. In addition, a homozygous deletion in the NAIP genes was demonstrated. This observation demonstrates that at least some cases with fetal hypokinesia and SMA may represent the severe end of a spectrum of disorders caused by deletions in the SMA locus on chromosome 5q13. In addition, these findings are compatible with a modifying role for the centromeric SMN genes and the NAIP genes in the severity of the SMA phenotype.

Autoantigens↗
PubMed1996

Lymphocytic infundibulohypophysitis presenting in the postpartum period: case report.

BACKGROUND: Lymphocytic adenohypophysitis is a well-known autoimmune disorder affecting the anterior pituitary gland. Posterior pituitary gland function can be impaired by a similar autoimmune disorder called lymphocytic infundibulohypophysitis. Only very few cases have been reported. CLINICAL PRESENTATION: We present a patient with central diabetes insipidus in the postpartum period. On radiologic and endocrine evidence lymphocytic involvement of the pituitary stalk and infundibulum was suspected. INTERVENTION: A diagnostic pterional craniotomy was performed. The diagnosis of lymphocytic infundibulohypophysitis was confirmed by biopsy. CONCLUSION: We present a case of lymphocytic infundibulohypophysitis. In view of its autoimmune pathophysiology the occurrence of this disorder in the postpartum period is not surprising, even though it has not been reported before. This rare disorder should be distinguished from the more common lymphocytic adenohypophysitis.

Adult↗
PubMed1996

Production of tumor necrosis factor in spinal cord following traumatic injury in rats.

Production of tumor necrosis factor (TNF) in the spinal cord following traumatic injury has been studied. In these experiments, the level of TNF was examined in the homogenate of the spinal cord, cerebrospinal fluid (CSF) and serum (n = 56). TNF could be detected in the injured spinal cord but not in the normal spinal cord. The TNF level increased in the spinal cord after the injury. At the lesion site, a maximal TNF concentration was observed 1 h after the injury, and the TNF concentration remained at this level until 8 h after the injury. Thereafter, it decreased gradually. However, TNF still could be detected 72 h after the injury. No TNF could be detected in the CSF and serum, collected from rats both with and without spinal cord injury (SCI). This study thus suggests that TNF is produced locally in the spinal cord following traumatic injury, and this TNF production is caused by the injury. The present results also demonstrate that TNF production is an acute and rapid reaction in the spinal cord following traumatic injury.

Animals↗