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Biomedical subjects

B Conrad

Publications and source records attributed to B Conrad.

At least 109 records · Page 6Linked to original sources

Relationship between cerebral blood flow velocities and cerebral electrical activity in sleep.

The dynamics of cerebral blood flow velocity during sleep were measured in the right and left middle cerebral artery of 12 and 10 healthy male volunteers, respectively. A computer-assisted pulsed (2-MHz) Doppler ultrasonography system was modified for continuous long-term and on-line recording of cerebral hemodynamics in combination with polysomnography. Mean flow velocity (MFV) decreased steadily during deepening nonrapid eye movement (NREM) sleep and increased suddenly during rapid eye movement sleep, corresponding to changes in brain function. However, spontaneous or provoked changes in sleep stage patterns as well as awakenings from NREM sleep were not regularly accompanied by corresponding changes in MFV. Differing values for MFV in subsequent sleep cycles could be shown for several sleep stages. Furthermore, MFV values in sleep stage II at the end of an NREM-sleep period were lower than in preceding slow-wave sleep. After application of short acoustic signals the electroencephalogram frequency rose, indicating an arousal, whereas MFV rapidly decreased for several seconds and then gradually returned to the prior level. These results imply an uncoupling between cerebral electrical activity and cerebral perfusion during sleep and support a dissociation in the activity of central regulatory mechanisms. In light of the proposal that cortical energy consumption can be accounted for by cerebral electrical activity, the concept that cerebral perfusion during sleep is regulated solely by the metabolic rate must be reconsidered.

Adult↗

[The importance of 24-hour-blood pressure monitoring in hemodynamic and thromboembolism-induced cerebral infarcts].

Night and day blood pressure profiles of 45 patients with cerebral infarction of hemodynamic or thromboembolic origin were assessed to detect subsequent changes of circadian blood pressure variability. The data were also analysed for a possible relationship between variability of circadian blood pressure, site of cerebral infarction and activation of the autonomic nervous system. Patients with a stroke of hemodynamic origin, when compared to a control group, manifested significantly greater variability of circadian blood pressure (diastolic: -25.2 +/- 4.5% vs. -13.8 +/- 6.5%; p < 0.005). Patients who showed the greatest decrease in vasomotor reactivity (< 40%) developed a prolonged disturbance of the blood-brain barrier. This disturbance regressed slowly only after the pathological 24-hour blood pressure profile had normalized. By way of contrast, patients with cerebral infarctions due to thromboembolic events, when compared to normal individuals, showed a distinctly decreased circadian blood pressure variability (diastolic: -5.2 +/- 6.9%). Initially 40% of these patients presented a pathological increase of nocturnal blood pressure. Circadian blood pressure variability was positively correlated with serum concentration of norepinephrine (r = 0.79; p < 0.01). Patients with a stroke affecting the insular cortex manifested an increase of nocturnal blood pressure significantly more often (66.7% vs. 11.8%; p < 0.005), indicating increased sympathetic activation. They had higher serum levels of norepinephrine (540 +/- 110 pg/ml vs. 290 +/- 178 pg/ml) as compared to patients without damage to the insula and also a significantly higher incidence of prolonged QT intervals and cardiac arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Increased striatal glucose consumption in Sydenham's chorea.

Positron emission tomography and 18F-fluorodeoxyglucose were used to measure the regional cerebral glucose consumption in a 15-year-old choreatic girl with classical Sydenham's chorea shortly after the onset of hyperkinetic movements and 5 months later after chorea had resolved and in a 74-year-old hemichoreatic woman with long-standing hyperkinesia as a residuum of Sydenham's chorea in adolescence. Whereas cerebellar, thalamic, and cortical glucose consumption was within normal limits in both patients, lentiform and caudate glucose consumption was significantly increased in both hemispheres of the 15-year-old patient and in the hemisphere contralateral to the chorea in the 74-year-old patient. In the younger patient, striatal glucose consumption returned to normal after her hyperkinesia had disappeared with antibiotic therapy. The observation of an increase in striatal glucose consumption in Sydenham's chorea, in contrast to the decrease of this variable encountered in the vast majority of other choreatic disorders, leads to questioning the pathophysiology of chorea in humans and suggests the use of emission tomographic measurement of variables related to cerebral energy metabolism for differential diagnosis in choreatic disorders.

Adolescent↗

The value of magnetic stimulation in the diagnosis of radiculopathies.

We studied 42 patients with cervical and lumbar radiculopathies using magnetic stimulation. Prolonged latencies following magnetic stimulation of the brain, the paravertebral spinal nerve, or both, showed a highly significant correlation with muscle weakness in clinical testing (24 of 26 patients with weakness had pathological motor evoked potentials) as well as with spontaneous activity of the target muscles in needle electromyography (24 of 25 subjects). The determination of both the central and the peripheral motor conduction time was found to be essential in patients with radiculopathies, because different patterns of latency changes correlated with different morphological results in computed tomography: in patients diagnosed as having a lateral compression of the nerve root the peripheral nerve latency was delayed; whereas, in patients with more medially localized herniations, a prolonged central motor latency was the most frequent finding. This study posits that combined magnetic stimulation of the brain and nerve root is an effective and painless technique for the noninvasive evaluation of nerve root function.

Adult↗

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↗