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Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 37 records · Page 2Linked to original sources

PC-based system for an objective quantification of manual movement disability for clinical and scientific purposes.

In clinical management and research of movement disorders exact knowledge about the extent of motor impairment is essential. This paper presents a computer program which allows for an objective measurement of manual movement disability. The program was developed for standard hardware and can easily be used in a variety of clinical and research environments. The program runs on MS-DOS computers and uses a Microsoft computer mouse as the only input device. The temporal resolution is 100 Hz, the spatial resolution 400 dots per inch. The user may choose between standard test sets or he may design sets according to his individual needs from a pool of available protocols which includes tracking tasks, ballistic tasks, complex sequential tasks, and finger tapping. All tasks are implemented in a similar way in order to keep the test environment as consistent as possible for the patient. The patient must usually carry out movements which correspond to the movements of a target symbol on the computer screen. This entails the manipulation of a follower symbol, also visible on the computer screen, via the computer mouse. The program itself and the theoretical background of the protocols are described in the paper. Additionally, preliminary results from pilot experiments are presented.

Computer Simulation

Designing interventions in psychosocial research.

There is little guidance in the literature on how to design cost-effective interventions for preventing or treating psychosocial health care problems. Four sources of information are described for developing interventions that are based on a strong theoretical and empirical foundation: (1) an explicit theory for intervention, (2) supporting descriptive data, (3) an evaluation of possible intervention strategies that are consistent with the theory and the supporting data, and (4) focus groups to examine the feasibility and external validity of the intervention before formal testing.

Child Behavior Disorders

Evidence for early Th 2 T cell predominance in xenoreactivity.

Two distinct subsets of CD4+ Th lymphocytes have been characterized by their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells predominate in cell-mediated responses, TH2 cells support the humoral response. We have examined the mRNA cytokine profile of normal mouse lymphocytes in response to alloantigen versus xenoantigen (rat) in MLC, and present evidence to suggest that early in proliferative responses, alloreactivity is dominated primarily by TH1-type lymphocytes, while xenoreactivity is predominantly TH2. Normal mouse lymphocyte-responding cells were cultured in a one-way MLR with either allo or xeno antigen and examined for production of mRNA for cytokines characteristically produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mouse IL-2, IL-4, IL-10, and IFN-gamma mRNA. In the mouse anti-rat xeno response, mRNA for TH2 gene products were upregulated, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared with controls. In contrast, upregulation of mRNA for TH1 gene products occurred in the mouse anti-mouse allo response, with higher levels of IL-2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregulation of all 4 cytokines occurred by day 4 and peak levels of mRNA for all cytokines examined were 2-3 times that seen for the peak anti-allogeneic response. These data suggest that early xenorecognition may differ from allorecognition by differential activation of the TH2 subset. A better understanding of the balance between Th subset function and cytokine profile in allo and xeno reactivity may allow a more targeted and specific approach to control the early events in xenograft rejection.

Animals

Determination of nerve growth factor concentrations in human samples by two-site immunoenzymometric assay and bioassay.

Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues.

Animals

[Importance of antiphospholipid antibodies in cerebral ischemia].

The association between cerebrovascular complications and detection of antiphospholipid antibodies (aPA) has been under clinical and immunological investigation during the last ten years. The occurrence of aPA in coincidence with recurrent thrombosis, miscarriages and thrombocytopenia is termed "primary antiphospholipid syndrome". The most important neurological symptoms are recurrent cerebral arterial and venous ischemias. Especially in the case of young patients with a history of recurrent infarcts, migraine-like headaches and the absence of classical risk factors should lead to a determination of these antibodies. Although the pathogenetic importance of these antibodies is still unclear, patients positive for them seem to carry a higher cerebrovascular risk and should be observed more cautiously. More studies are necessary to define the origin of these antibodies and their role in thrombogenesis. To develop standards for therapeutic management a multicenter study is desirable.

Adult

[Local injection treatment with botulinum toxin A in severe arm and leg spasticity].

In patients with predominantly focal spasticity, oral antispastic drugs are relatively ineffective or cause unwanted side effects of central origin. Therefore we treated patients disabled by focal spasticity with local injections of Botulinum-Toxin A (Porton Products BOTOX). Efficacy, dosage, side-effects and injection technique were examined. 11 patients (mean age 48 years) with severe focal spasticity of the flexor muscles of the hand and arm (5 patients), the adductor muscles of the legs (5) or the plantar flexors of the foot (1) due to multiple sclerosis, cervical myelopathy or stroke-related hemi-paresis were treated with BOTOX. Rating scales, including Ashford spasticity scale, pain scale and a hygienic rating scale, were used to evaluate the efficacy. 25 to 30 ng (1000-1200 MU Porton) were injected in the flexor group of the hand or arm and 42 to 50 ng (1680-2000 MU Porton) BOTOX in the adductor group of one leg. 10 of the patients showed an improvement of at least one point on the scales for spasticity, pain and hygiene. Effects could be observed after 4-7 days and lasted for 6-13 weeks. There were no unwanted side-effects. We conclude that BOTOX is an alternative to the systemic application of antispastic drugs. Focal spasticity and pain can be successfully reduced and hygienic care is facilitated.

Adult

Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations.

The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.

Adolescent

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.

Adolescent

Imprecise excision of plasmid pE194 from the chromosomes of Bacillus subtilis pE194 insertion strains.

Plasmid pE194 has been shown to be rescued by integration after cultivation of infected Bacillus subtilis recE4 cells at a restrictive high temperature. The plasmid is also spontaneously excised from the chromosome at a low frequency by precise or imprecise excision (J. Hofemeister, M. Israeli-Reches, and D. Dubnau, Mol. Gen. Genet. 189:58-68, 1983). We have investigated nine excision plasmids, carrying insert DNA 1 to 6 kbp in length, either in a complete pE194 or in a partially deleted pE194 copy. Type 1 (additive) excision plasmids have the left- and right-junction DNAs preserved as 13-bp direct repeats (5'-GGGGAGAAAACAT-3') corresponding to the region between positions 864 and 876 in pE194. In type 2 (substitutive) excision plasmids, a conserved 13-bp sequence remains only at the right junction while the left junction has been deleted during the excision process. The type 3 excision plasmid carries at each junction the tetranucleotide 5'-TCCC-3', present in pE194 between positions 1995 and 1998. Although we isolated the excision plasmids from different integration mutants, the insert DNAs of eight independently isolated plasmids showed striking sequence homology, suggesting that they originated from one distinct region of the B. subtilis chromosome. Thus, we postulate that imprecise excision of pE194 occurs most frequently after its translocation from the original insertion site into a preferred excision site within the host chromosome. The imprecise excision from this site occurs at excision breakpoints outside the pE194-chromosome junctions in a chromosomal region which remains to be investigated further.

Bacillus subtilis

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.

Adult

Increased F-wave duration in patients with spasticity.

F-wave responses of the posterior tibial nerve have been studied in 22 patients with spasticity and in 18 normal control subjects with surface EMG. Mean amplitude and mean duration of the F-waves were significantly (p less than 0.001) longer in patients with spasticity than in healthy controls. These findings could be the result of an enhanced spinal excitability in spasticity. Based on the present results F-wave recording may be used as a simple and practical technique for detection and documentation of spasticity.

Adult

Do brief bursts of spike and wave activity cause a cerebral hyper- or hypoperfusion in man?

The correlation between brain activity and cerebral blood flow velocities during brief bursts of generalized spike and wave activity was analysed by simultaneous registration of the EEG and the intracranial flow patterns. The flow patterns of the middle cerebral artery were continuously recorded by means of transcranial Doppler ultrasonography using a specially developed monitoring system. A total of 25 bursts was investigated in 3 patients with spontaneous occurrence of generalized 3 Hz spike and wave activity and normal background EEG. Characteristic changes of the flow patterns were found in all cases: 3.41 +/- 0.98 s (n = 25) after the beginning of generalized spike and wave patterns, the flow velocity decreased by 25.84 +/- 10.45% (n = 25) below the 'preictal' flow velocity level. The period of flow velocity changes lasted several times longer than the phase of spike and wave activity.

Adult

Abnormal conduction in corticospinal pathways in Wilson's disease: investigation of nine cases with magnetic brain stimulation.

Electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation were studied in nine patients with Wilson's disease (WD). Six of the nine patients had prolonged central motor latencies (CMLs), reduced amplitude, or absent responses in at least one of the examined muscles. In one patient, abnormal EMG responses normalized following treatment with penicillamine. Pathophysiologically abnormal EMG responses might result from a potentially reversible impairment of corticomotoneuronal pathways and/or a reduced excitability of motoneurons due to basal ganglia dysfunction. The possible pathophysiological mechanisms are discussed.

Adult

Is there an age-dependent continuous increase in the duration of the motor unit action potential?

The duration of the motor unit potential plays an important role in the diagnosis of neuromuscular diseases, but is also subject to physiological variations. In order to evaluate the age-related changes the mean motor unit potential duration was studied in 4 proximal and distal muscles of the upper and lower extremities in 111 healthy subjects between 20 and 80 years. Contrary to the results of previous researches no marked increase of mean duration could be found in subjects younger than 55 years. Subjects older than 55 showed a slight tendency towards increased duration of the motor unit potential. These findings are interpreted as the result of changes in fiber density and are in accordance with single fiber EMG records.

Action Potentials