The effect of sleep on the dyskinetic movements of Parkinson's disease, Gilles de la Tourette syndrome, Huntington's disease, and torsion dystonia.

The effect of sleep on the involuntary movements or dyskinesias in Parkinson's disease, Huntington's disease, primary and secondary torsion dystonia, and Gilles de la Tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry. Movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies, and in each condition reappeared under similar circumstances. The movements were most likely to occur after awakenings or lightenings of sleep, or in stage one sleep. The movements were very rare during the deeper phases of sleep. Those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and, rarely, by sleep spindles or slow waves. The control group showed normal "semipurposeful" movements under the same conditions during sleep. The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.

Botulinum toxin treatment in spasmodic torticollis.

Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received toxin in a total of 117 treatment periods. The mean follow up period was 8.4 months. In 39 patients with pain there was benefit in 77% of treatment periods. Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks. Side effects were frequent with dysphagia being the most common (28% of treatment periods). Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units).

Ophthalmological complications of cryptococcal meningitis.

Two patients with cryptococcal meningitis associated with ophthalmological complications are described. One patient developed a cryptococcal fundal lesion which disappeared during chemotherapy. Chronically raised intracranial pressure was associated with a visual field defect. This resolved with repeated lumbar punctures. The second patient developed visual deficits secondary to papilloedema and responded to optic nerve decompression. In both cases CT scanning demonstrated swelling of the optic nerves. In the second patient this regressed after decompression. A review of the variety of the ophthalmological complications of cryptococcal meningitis and their prevalence is presented. The risk of developing severe visual disability is assessed.

A new method for the quantitative analysis of sleep spindles during continuous overnight EEG recordings.

Sleep spindles are one of the most characteristic EEG transients of sleep. Quantitative analysis of sleep spindles may be of value in the study of involuntary movement disorders, depression, and sleep disorders, but this is difficult to perform manually. Phase-locked loop based devices have previously been used to analyse preselected periods of artefact-free non-REM sleep. We have developed a device of this type that provides reliable quantitative analysis of sleep spindles during continuous overnight EEG recordings. The number of sleep spindles detected by the device during overnight recordings correlated well with the mean of two independent human observers and measurements of the amplitude and duration of individual sleep spindles were similar to those obtained by visual analysis. The general applicability of the device was demonstrated by studying 61 patients with a range of neurological disorders.

Real-time monitoring and control of glucose and lactate concentrations in a mammalian cell perfusion reactor.

On-line monitoring and control of cell culture fermentation is important for optimal and consistent production of biologicals. In this work, glucose and lactate concentrations are monitored on-line using a commercially available analyzer (Model 2700, Yellow Springs Instruments, Yellow Springs, OH) during batch and perfusion hybridoma cell fermentation. Cell free samples from the reactor are obtained using a 0.45 mum hollow fiber filtering system placed in a circulation loop. The samples were analyzed at specified times and the data are collected on a computer. A process control strategy was developed to control the concentrations of glucose and lactate in a perfusion reactor where the feed rate is adjusted to maintain their concentrations at desired set points. Hybridoma cells (A10G10) were cultivated in a high density perfusion culture where cell density increased from 2 to 14 million cells/mL. During this period the control algorithm successfully adjusted the perfusion rate while maintaining constant glucose and lactate concentrations. Glucose consumption and lactate accumulation rates as well as net lactate yield on glucose were monitored continuously during perfusion culture. These metabolic rates were observed to be independent of cell concentration and were used for the estimation of viable cell density in the reactor. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 372-378, 1997.

Real-time monitoring of protein secretion in mammalian cell fermentation: measurement of monoclonal antibodies using a computer-controlled HPLC system (BioCad/RPM).

On-line, "real-time" monitoring of product concentration is important for mammalian cell culture fermentation. The continuous measurement of monoclonal antibodies allows for instantaneous determination of cell productivity and effective manipulation of the fermentor operating conditions for optimal production. This article will present the evaluation and application of a BioCad/RPM system (Per Septive Biosystems) for rapid analysis of lgG concentration for hybridoma cell cultivation. Several commercial crossflow filtration devices are tested for low protein retention and fouling properties. A protein G column is used successfully for analyzing about 400 samples of lgG(1), without significant loss in separation efficiency. The Immuno Detection system is integrated into a computer-controlled 15-L fermentor. This fermentor could be operated in batch and perfusion modes with cell densities up to 20 million cells/mL. A continuous cell-free sample stream obtained by a hollow fiber filter system is introduced to the BioCad/RPM for analysis. The speed of this system allows for real-time monitoring even at high densities with fast dynamics. A murine hybridoma cell (A10G10) is cultivated in batch and continuous reactors and antibody concentration is measured continuously with complete sterility. The results are compared to offline measurements with good agreement.

Acute myopathy in status asthmaticus.

An acute myopathy complicating life-threatening asthma has been reported with increasing frequency. We present a further 3 patients with this complication. Each patient had nerve conduction studies, electromyography and muscle biopsy performed. The records of a cohort of 12 patients, ventilated in an intensive care unit over a 16 month period, were reviewed. Eleven out of the 12 patients developed an elevated creatine kinase level (median 1311 U/L, range 185-9973 U/L) and 4 developed symptomatic weakness. The myopathy of status asthmaticus is not a homogeneous clinicopathological entity. Although myopathy is the predominant feature, there is a neuropathic component in some patients. Full recovery is usual. The combination of corticosteroids and neuromuscular blocking agents has been proposed as the possible cause of the complication.

The natural history of late-onset epilepsy secondary to vascular disease.

Twenty-nine patients with late-onset epilepsy were followed prospectively for a mean period of 4.9 years; 14 had CT evidence of occult cerebral infarction and 15 had normal scans. The prognosis was similar in the 2 groups; 57% and 53% respectively became seizure-free. One patient in each group had a myocardial infarction and one patient with occult cerebrovascular disease had a stroke. A separate study was made of the prognosis of 24 patients with epilepsy following stroke (mean follow-up 5.9 years). Twelve of 12 patients with seizure onset within 2 weeks of the stroke became seizure-free, compared with 7/12 with more delayed onset. Late-onset epilepsy has a favourable prognosis, and excellent control should be expected if seizures commence within 2 weeks of stroke.

Evaluation and applications of optical cell density probes in mammalian cell bioreactors.

On-line optical cell density probes were implemented to continuously monitor the cell densities in mammalian cell bioreactor and to achieve advanced bioreactor controls. We tested cell density probes from six manufacturers in high cell density bioreactors. When externally calibrated, Aquasant and Ingold backscattering probes produced the most linear probe responses (PR) versus cell density (CD), followed by the ASR and Cerex laser probes. Monitek and Wedgewood transmission probes had lower resolutions. All probes were tested in two murine hybridoma fermentations. Cell densities varied between 1 x 10(6) cells/mL to 20 x 10(6) cells/mL and the bioreactors were operated for 5 to 7 weeks. For our bioreactors, Aquasant, Ingold, ASR, Wedgewood, and Monitek probes gave satisfactory responses. Little fouling was observed with any probe at the end of 2 weeks. Fouling was a possibility after 3 weeks in one bioreactor but its effect can be easily corrected. Cell density control and specific perfusion control of bioreactors based on the Aquasant probe were achieved. Implementation of cell density probe based perfusion control, instead of "step perfusion adjustments" based on manual hemacytometer control, will result in smoother operation, healthier cultures, increased medium delivery efficiency, and reduced operational excursions.