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Biomedical subjects

J Schwarz

Publications and source records attributed to J Schwarz.

At least 109 records · Page 6Linked to original sources

Validation of an automated up-timer for measurement of mobility in older adults.

OBJECTIVE: To test the reliability, validity and utility of an "up-timer", an automated device to measure time spent standing and walking. DESIGN: Repeat measurement of mobility one week apart in a convenience sample. SETTING: Hostel and nursing homes in Melbourne. PARTICIPANTS: 26 hostel and 24 nursing home residents (aged 70-99 years) participated. They were mobile, with or without the use of walking aids or personal assistance. OUTCOME MEASURES: "Up-time" (measured with the up-timer); functional activity (measured with the Barthel Index, Functional Independence Measure, Timed Up & Go, and Human Activity Profile); and disability (measured by the Rapid Disability Rating Scale). RESULTS: The test-retest reliability of the up-timer was high (Pearson's r = 0.84; P < 0.001). Pearson's correlation between the up-timer results and results of functional and disability measures ranged from r = 0.47 to r = 0.55. The functional measures correlated more highly among themselves (r = 0.79 to r = 0.92). The performance-based Timed Up & Go test had moderate levels of correlation with both the up-timer and the functional measures. Use of the device was well accepted by both participants and staff. CONCLUSIONS: The up-timer is a practical, objective and reliable means of measuring mobility. The useful information it provides is different from, but overlaps with, that obtained from subjective observation or self report. It will complement existing subjective and performance-based measures of activity and mobility.

Activities of Daily Living↗

Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C.

Members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)-box transcription factors bind an A-T-rich DNA sequence associated with muscle-specific genes. The murine MEF2C gene is expressed in heart precursor cells before formation of the linear heart tube. In mice homozygous for a null mutation of MEF2C, the heart tube did not undergo looping morphogenesis, the future right ventricle did not form, and a subset of cardiac muscle genes was not expressed. The absence of the right ventricular region of the mutant heart correlated with down-regulation of the dHAND gene, which encodes a basic helix-loop-helix transcription factor required for cardiac morphogenesis. Thus, MEF2C is an essential regulator of cardiac myogenesis and right ventricular development.

Acyltransferases↗

Heterogeneous Nucleation of Naphthalene Vapor on Water Surface

The evaporation of a water drop into a ternary gaseous mixture of air, steam, and naphthalene vapor was investigated. The experimental results were compared with a theoretical prediction based on a numerical solution of coupled boundary layer equations for heat and mass transfer from a drop moving in ternary gas. In the experiments the naphthalene vapor condensed on the water drop as a supercooled liquid even at temperatures far below the melting point of naphthalene. The condensation on drop surface is discussed in terms of classical theory of heterogeneous nucleation on smooth surfaces.

Journal Article↗

Single-fiber electromyography, nerve conduction studies, and conventional electromyography in patients with critical-illness polyneuropathy: evidence for a lesion of terminal motor axons.

Nine patients at risk for critical illness polyneuropathy (CIP) were included in a prospective study. We performed nerve conduction studies, electromyography, and a stimulation single-fiber electromyography (SFEMG). Five of 9 patients were diagnosed as CIP because they developed abnormal spontaneous activity during the follow-up period. Their SFEMG revealed a significant increase in mean jitter (25%, P < 0.005). In 4 patients without abnormal spontaneous activity there was no significant increase in the mean jitter, although 1 of the latter 4 patients showed an increased jitter, indicating that abnormal SFEMG may precede abnormal spontaneous activity. Nerve conduction studies did not show any significant changes in both patient groups. Our findings suggest that CIP is a primarily axonal motor neuropathy. The increased jitter in patients with CIP indicates that CIP is a primarily axonal neuropathy with a lesion of terminal motor axons.

Adult↗

Electromyography of the external anal sphincter in patients with Parkinson's disease and multiple system atrophy: frequency of abnormal spontaneous activity and polyphasic motor unit potentials.

Electromyographic studies of the external anal sphincter muscle have received increasing attention in the differential diagnosis of patients with parkinsonism. Based on the fact that the external anal sphincter muscle is partly innervated by fibers that originate in Onuf's nucleus in the segments S2-S4 of the spinal cord, an increased duration of the motor unit potentials (MUPs) and an increased polyphasia may reflect neuronal loss of these lower motor neurons characteristic for multiple system atrophy. We report the results of anal sphincter electromyography in 15 patients with clinically probable multiple system atrophy (MSA) and 10 patients with Parkinson's disease (PD). There was no significant difference between patients with MSA and patients with PD concerning the duration of MUPs, mean number of phases, and rate of polyphasic motor potentials. There was a tendency for a longer mean duration and increased polyphasia in patients with MSA compared to patients with PD. Spontaneous activity was recorded in 11 of 15 patients with MSA occurring especially in patients with MSA of the striatonigral type, but not in patients with PD. In this study, the duration of MUPs and the rate of polyphasia were unreliable criteria in the electrophysiological differential diagnosis of patients with parkinsonism. Abnormal spontaneous activity, although difficult to detect, is a more specific marker for neuronal degeneration of Onuf's nucleus occurring in patients with MSA.

Adult↗

Long-term changes of striatal dopamine D2 receptors in patients with Parkinson's disease: a study with positron emission tomography and [11C]raclopride.

We used [11C]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. After 3-5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at "off" had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3-4 months after therapy began and that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long-term downregulation of striatal dopamine D2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons.

Aged↗

[123]IBZM binding predicts dopaminergic responsiveness in patients with parkinsonism and previous dopaminomimetic therapy.

We investigated the cases of 55 patients with parkinsonism and prior dopaminomimetic therapy in whom the response to this treatment was questionable or reported to be negative. None of these patients had shown motor fluctuations prior to this study. We compared the results of imaging of dopamine-D2 receptors by using [123I]iodobenzamide-single-photon-emission computed tomography (IBZM-SPECT) with the improvement in motor signs following a subcutaneous injection of apomorphine and a subsequent increase in oral dopaminomimetic therapy. IBZM-SPECT accurately predicted a positive or negative response to apomorphine in 37 (84%) of 44 patients. The sensitivity/specificity was calculated as 96.3%/ 64.7%. The sensitivity/specificity of IBZM-SPECT for the response to oral treatment with levodopa (L-dopa) was calculated as 100%/75%. After a follow-up period of 2-4 years, 25 patients developed motor fluctuations. All of these patients had normal IBZM binding. Nine developed clinical signs indicating a basal ganglia disorder other than Parkinson's disease. Eight of these nine patients had reduced, and one patient had normal, IBZM binding. We conclude that normal IBZM binding is a useful predictor of a good response to dopaminergic drugs in patients with parkinsonism and a questionable response to previous dopaminomimetic therapy. Reduced IBZM binding seems to exclude a diagnosis of Parkinson's disease, because none of the latter patients clearly benefited from L-dopa and 66.7% developed clinical signs indicating another disorder of the basal ganglia.

Adult↗

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography.

IPT [N-(3-iodopropen-2-yl)- 2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane] is a new cocaine analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1-2 h post injection. In the present study [123I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40-79 years) and eight age-matched controls were studied. SPET imaging was performed 90-120 min after injection of 160-185 MBq [123I]IPT using a triple-head camera. For semiquantitative evaluation of specific [123I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [123I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [123I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [123I]IPT binding was significantly correlated with disease duration (r=-0.7, P<0.0001) but not with the age of PD patients (r=-0.10, P=0. 61). Specific [123I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [123I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [123I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.

Adult↗

D2-dopamine-receptor occupancy during treatment with haloperidol decanoate.

We investigated in an open, explanatory study a total of 24 patients meeting DSM-III-R criteria for schizophrenia. Eighteen patients were treated for at least 4 weeks with a fixed dose of orally administered haloperidol for at least 4 weeks (mean daily dosage ranging from 0.07 to 0.35 mg/kg b.w.), and 6 patients received haloperidol decanoate with a fixed dose for at least 4 months (dosage range 50-150 mg/4 weeks; calculated mean daily dosage ranging from 0.02 to 0.09 mg/kg b.w.). One week after injection of haloperidol decanoate, the single photon emission computed tomography examination was performed. Our data suggest that D2-dopamine-receptor occupancy of 50 mg/4 weeks haloperidol decanoate 1 week after injection corresponds to an oral dose of 4.5 mg/day haloperidol.

Adult↗

Surgery of the thoracic aorta using deep hypothermic total circulatory arrest. Are there neurological consequences other than frank cerebral defects?

OBJECTIVE: Deep hypothermic total circulatory arrest has reduced primary morbidity and mortality in thoracic aortic surgery. Although frank neurological deficits have been proven to be a rare complication of this technique, the rate of subtle but irreversible neuropsychological disorders remains unknown. METHODS: A total of 23 patients (15 male, 8 female) who had undergone surgery for dissection or aneurysm of the thoracic aorta using deep hypothermic total circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively. The mean follow-up was 17 months. The following psychometric tests were conducted: a computer-based test battery to assess tonic alertness and sustained attention, the trail making test (TMT part A and B), the Münchner Gedächtnistest and a verbal learning test. In addition, a cerebral dopamine D2 receptor scintigraphy (using the SPECT technique) was performed. For comparison, 10 healthy subjects were studied. RESULTS: With regard to tonic alertness, 69.6 and 30.4% were below the 50th and 10th centiles, respectively, according to age- and education-corrected standard values. The impairment in sustained attention correlated significantly with the duration of the circulatory arrest. On the tests assessing short-term memory, the patients scored 30% below their age- and education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the patients were below one and two standard deviations, respectively. Concerning speed of information processing whilst 78.3% of the patients were below the 50th and 21.7% below the 10th centile. Indicative of some persistent and functional brain alteration, the dopamine D2 receptor binding was significantly reduced when compared with healthy subjects. CONCLUSIONS: These data prove a substantial and chronic reduction of higher cognitive function in some of the patients who underwent cardiac surgery using deep hypothermic total circulatory arrest; this was accompanied by a depression of the cerebral dopamine D2 receptor binding.

Adult↗

Cardiovascular and renin responses to head-up tilt tests in parkinsonism.

OBJECTIVES: We investigated cardiovascular and renin responses to head-up tilt tests in patients with Parkinson's disease (PD), multiple system atrophy (MSA), and in controls to determine variables for the assignment of parkinsonism to the potential underlying neurologic condition. PATIENTS AND METHODS: Sequential changes in sympathetic-mediated circulatory variables such as heart rate, blood pressure, and plasma renin concentration during head-up tilt tests were studied in 14 patients with PD and 11 patients with MSA. Twelve subjects with normal autonomic functions were studied as controls. RESULTS: Head-up tilt resulted in significant differences in blood pressure and heart rate responses between PD, MSA, and controls. The baseline plasma renin concentration was significantly lower in MSA than in controls. Twenty min head-up tilt revealed significant differences in plasma renin concentration between PD, MSA, and controls. CONCLUSION: We conclude that investigating sequential changes in mean arterial blood pressure, heart rate, and plasma renin concentration during head-up tilt test can potentially support differential diagnosis of PD and MSA.

Adult↗

Improvement of motor fluctuations in patients with Parkinson's disease following treatment with high doses of pergolide and cessation of levodopa.

The combination of levodopa and a dopamine agonist in the treatment of patients with Parkinson's disease often reduces the severity of motor fluctuations. In patients with very severe motor fluctuations, monotherapy with continuous subcutaneous infusions of the dopamine agonist apomorphine may result in a marked reduction of hyperkinesia and on-off phenomena. We report 3 patients with Parkinson's disease and motor fluctuations who received high doses of pergolide without levodopa resulting in a reduction of motor fluctuations. All patients received doses of pergolide exceeding the maximum recommended dose. One patient also required additional therapy with amantadine. These data show that in some patients oral treatment with high doses of a dopamine agonist may improve the severity of motor fluctuations and achieve a good control of parkinsonian signs without concomitant levodopa treatment.

Aged↗

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human primates is antagonized by pretreatment with nimodipine at the nigral, but not at the striatal level.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Hypotheses concerning the mechanism of action of MPTP have been related to the pathogenesis of nigral cell death in Parkinson's disease. For instance, alterations of calcium influxes have been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease. Recently, we reported that nimodipine, a blocker of L-type calcium channels, prevents dopaminergic MPTP-induced neurotoxicity in C57B1/6 black mice. The present study extended these rodent findings to the non-human primate model of Parkinson's disease and assessed the effects of nimodipine, continuously applied by pellet for 18 days, on behavioural, biochemical and histological parameters, following systemic application of MPTP in common marmosets (Callithrix jacchus). The experimental design involved five groups of common marmosets and a total of 24 animals. Monkeys assigned to group I (n = 4) received subcutaneously implanted vehicle pellets 7 days prior to subcutaneous saline injections (control). Monkeys of group II (n = 4) were treated with nimodipine pellets (80 mg) and saline injections. Marmosets in group III (n = 8) were treated with vehicle pellets and received 4 times MPTP (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 h for a total of 4 days). Monkeys in group IV (n = 4) and V (n = 4) were treated as group-III animals except for the implantation of nimodipine pellets (80 mg and 120 mg, respectively) 7 days prior to toxin exposure. In common marmosets MPTP induced severe parkinsonian symptoms, a pronounced dopamine depletion in the caudate-putamen (more than 99% of control) and a loss of tyrosine hydroxylase immunoreactive cells in the substantia nigra (50% percent of control) 7 days after MPTP-administration. Pretreatment with nimodipine (120 mg pellets) did neither attenuate the behavioural impairments in MPTP-treated animals nor antagonize the striatal neurotoxin-induced dopamine depletion, but almost completely prevented (in a dose-dependent manner) the MPTP-induced decrease of nigral tyrosine hydroxylase immunoreactive cells. These data suggest that application of nimodipine, during the observation period of 7 days, protects against MPTP-induced neurotoxicity in common marmosets at the cellular nigral level, but not at the synaptic striatal level, implicating differential mechanisms of actions of MPTP-induced neurotoxicity at the nigral versus the striatal level.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Computational analysis of open loop handwriting movements in Parkinson's disease: a rapid method to detect dopamimetic effects.

We used a computational analysis of open loop handwriting movements and a clinical rating scale for monitoring the effect of apomorphine in 16 patients with early untreated parkinsonism [subsequently L-DOPA responsive, probable Parkinson's disease (PD)], six patients with long-standing PD with L-DOPA associated motor fluctuations, and seven patients with known L-DOPA unresponsive parkinsonism. Subjects were instructed to write fluently concentric circles of approximately 12 mm in diameter. Movements were recorded for two periods of 3 s each, using a digitizing tablet. Mean peak velocity (Vmax) and mean peak acceleration (Amax) were determined. In addition, two sensitive indices describing the degree of automation of handwriting were derived: (a) NCV, calculated as the mean Number of Changes in direction of Velocity per half circle, and (b) NCA, the mean Number of Changes in the direction of Acceleration. Clinical rating was performed according to the Unified Parkinson's Disease Rating Scale part III (UPDRS III). After apomorphine injection, the patients with early untreated probable PD showed significant improvement of Vmax, Amax, NCV, NCA, and UPDRS III scores. Likewise, the patients with long-standing PD improved significantly in all kinematic parameters and UPDRS III scores. Patients with L-DOPA unresponsive parkinsonism failed to change significantly in any of the parameters tested. These observations suggest that the computer-assisted analysis of automated handwriting movements can be used as an objective quick method for quantifying dopamimetic effects on the kinematics of handwriting movements in parkinsonian patients.

Adult↗

[Endoscopic hernia surgery (TAPP)--gold standard in management of recurrent hernias?].

From April 1993 to December 1995 210 TAPP procedures were performed because of recurrent hernia. With the TAPP method there is no difference between primary and recurrent repair. All procedures in this study were done with general anaesthesia by senior surgeons. The learning curve shows a reduction of operation time (60 to 55 min) with increasing experience and a reduction in complications as well (total 4.3%). Recurrence was observed in two cases. The reasons for these recurrences were technical failures during the previous repair. In both cases a second TAPP repair was carried out successfully. The main advantage of TAPP in recurrent hernia is that this method gives possibilities to avoid anterior scar tissue. Secondly tension-free repair can be combined with the benefit of the minimal access technique. For this reason, the TAPP procedure must be considered the method of choice in recurrent hernia repair.

Adult↗

Acute MPTP treatment produces no changes in mitochondrial complex activities and indices of oxidative damage in the common marmoset ex vivo one week after exposure to the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause a Parkinsonian syndrome in man and non-human primates. Hypotheses concerning the pathogenetic mechanisms of MPTP toxicity on nigro-striatal dopaminergic neurons relate to impairment of mitochondrial function and oxidative stress. However, surprisingly few primate studies addressed these issues ex vivo. Thus, the present study assessed the enzyme activities of the respiratory chain, GSH/GSSG and ubiquinol/ubiquinone content in the MPTP primate model (common marmoset, Callithrix jacchus; 2 mg MPTP-hydrochloride/kg body wt were injected subcutaneously (s.c.) on four consecutive days; animals were sacrificed 7 days after last MPTP exposure). Activities of respiratory chain enzymes were measured in crude homogenates of the caudate nucleus, because the probable toxic metabolite of MPTP, MPP+, is transported into dopaminergic neurons via the dopamine uptake system in striatal synapses and mitochondria are concentrated in axonal terminals. Since MPP+ can damage membranes of axonal terminals of nigro-striatal neurons we measured GSH/GSSG contents in the putamen and ubiquinol/ubiquinone concentrations in the substantia nigra and putamen as indices of oxidative damage. At the time of sacrifice MPTP-induced deficits comprised severe behavioural Parkinsonian symptoms, profound depletion of striatal dopamine and its major metabolites as well as pronounced loss of nigro-striatal neurons. Despite these severe lesions, acute MPTP treatment had no effect on any of the enzymes of the respiratory chain in the caudate nucleus and indices of oxidative damage in both the substantia nigra and putamen. These results suggest that factors other than mitochondrial impairment and/or oxidative stress may be involved in MPTP neurotoxicity in primates. Alternatively, early compensatory mechanisms and/or transient effects could account for the reported results and will be discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗