Automatic analysis of agarose gel images.

MOTIVATION: Automatic tools to speed up routine biological processes are very much sought after in bio-medical research. Much repetitive work in molecular biology, such as allele calling in genetic analysis, can be made semi-automatic or task specific automatic by using existing techniques from computer science and signal processing. Computerized analysis is reproducible and avoids various forms of human error. Semi-automatic techniques with an interactive check on the results speed up the analysis and reduce the error. RESULTS: We have successfully implemented an image processing software package to automatically analyze agarose gel images of polymorphic DNA markers. We have obtained up to 90% accuracy for the classification of alleles in good quality images and up to 70% accuracy in average quality images. These results are obtained within a few seconds. Even after subsequent interactive checking to increase the accuracy of allele classification to 100%, the overall speed with which the data can be processed is greatly increased, compared to manual allele classification. AVAILABILITY: The IDL source code of the software is available on request from jonathan.flint@well.ox.ac.uk

Persistence of photosensitivity.

PURPOSE: One hundred patients with photosensitive epilepsy were investigated as part of an ongoing follow-up study. Average duration of follow-up was 14 years; mean age at follow-up was 27 years. METHODS: All patients were EEG investigated using a standard technique of intermittent photic stimulation (IPS). The presence of a photoparoxysmal response (PPR) or a degraded PPR indicated the presence of photosensitivity. RESULTS: Seventy-seven patients became seizure free. Of the untreated patients, photosensitivity disappeared in 14 patients but was present in 32 patients. Of the patients who were treated, 31 showed evidence of PPRs or degraded PPRs, but 23 patients no longer showed evidence of photosensitivity. Thirty-two mothers had 67 children during the follow-up period. Thirteen have so far proved to be sensitive to IPS in the laboratory and four have also had photosensitive seizures induced in the outside environment. Nine of the children have been found not to be photosensitive nor have they had seizures. CONCLUSIONS: This study suggests that photosensitivity persists in at least two thirds of patients with photosensitive epilepsy and that valproate is effective in controlling this photosensitivity.

'Telephillic syndrome' in pattern and photosensitive epilepsy: report of three cases.

The incidence of 'telephillic syndrome' (impulsive attraction to television), in three photosensitive epileptic patients who were referred to our neurophysiology clinic because they were having seizures is reported. Two were females, aged fourteen and eight respectively, one was a male aged twenty-five years. All the patients had a family history of epilepsy. The age range of onset of photosensitivity was 3.5-12 years and the most common seizure inducing factor was flickering light from the television (TV) viewing. They were all 'telephillic'. The predominant seizure type found in these patients was tonic-clonic seizure. Comprehensive electroencephalographic (EEG) investigation was carried out including hyperventilation. The basic EEG showed abnormal spike and wave activity on eye opening and eye closure in all the patients. Intermittent photic stimulation (IPS) evoked occipital spikes and photoparoxysmal response (PPRs) at a photosensitivity range of 758 flashes per second (fps). Pattern sensitivity test using a Gratings pattern revealed a sensitivity range of 1.03-3.5 cycles per second (cpd). And the predominant area of brain activity was the right mid-post temporal regions. Binocular stimulation offered no protection in one patient.

Video material and epilepsy.

Nine patients who had epileptic attacks while playing computer games were studied in the laboratory. Patients had an EEG recorded as well as their response to intermittent photic stimulation (IPS) at flash rates of 1-60 fps. In addition, pattern sensitivity was assessed in all patients by a gratings pattern. Only 2 patients had no previous history of convulsions, and only 2 had a normal basic EEG. All but 1 were sensitive to IPS, and all but 1 were pattern sensitive. Most patients were male, but although this appears to conflict with previously published literature results regarding the sex ratio in photosensitivity, it was due to the male predominance of video game usage. We compared our results with those reported in the literature. Diagnosing video game epilepsy requires performing an EEG with IPS and pattern stimulation. We propose a standard method of testing.

Automated interference refractometer: an algorithm for locating an irregular fringe pattern.

The interference refractometer is potentially a valuable instrument for the measurement of gas concentrations, but its usefulness has been limited by the necessity to locate visually a pattern of light and dark bands in order to obtain the reading. The instrument is therefore liable to human error and is unsuitable for continuous monitoring. An improved design has been patented, in which this location process is automated by the use of a microprocessor and an array of light-sensitive diodes. To implement this improvement it was necessary to design an algorithm which would reliably locate the pattern. This paper describes the approaches which were considered and the successful algorithm. Some examples are given to illustrate the power of the final algorithm to locate patterns even after severe distortion.

The prognosis of photosensitivity.

Since 1968, annual EEG recordings during photic stimulation using a standardised technique have been made on photosensitive patients and siblings. In 1983, 72 were aged greater than or equal to 20 years and 14 were aged 16-19 years. Mean duration of follow-up was 9.8 +/- 4.8 years. Seventy-five patients were treated with sodium valproate (VPA), which was withdrawn in 15 but restarted in eight because of return of photosensitivity. Eighty-two patients had seizures at some time; at follow-up 58 were receiving monotherapy with VPA, seven were receiving comedication, and three were taking other drugs. Fifty-four of them were seizure free, as were 10 of the 15 who were not being treated with drugs. Photosensitivity disappeared in 44 of 65 patients at a mean dosage of VPA at 21.5 +/- 6 mg/kg day. In 55 of 86 patients photosensitivity was no longer present at follow-up; in 18, slight abnormality was evoked by intermittent photic stimulation, and in 13, photoconvulsive responses were still present. Eighteen patients were not receiving drugs, 10 of them being no longer photosensitive at the mean age of 24.5 +/- 4.9 years. Thirty-one treated and untreated patients were still photosensitive at age 21.5 +/- 3.4 years. Photosensitivity disappeared earlier in those treated with VPA than in the untreated. Spontaneous remission in the treated cases may have occurred at 22.9 +/- 2.5 years of age. Photosensitivity appears around puberty and may disappear around 24 years of age. Photosensitive epilepsy is easily and rapidly controlled by VPA.

Regional and global myocardial function in the dog when nitrous oxide is added to halothane in the presence of critical coronary artery constriction.

The effect of substituting 66% nitrous oxide for nitrogen on global and regional myocardial function before and after critical constriction of the left anterior descending coronary artery (LAD) was studied in six open-chested dogs anesthetized with 1% halothane (inspired). Regional myocardial function was measured in the region of the LAD and in the region of the left circumflex artery using sonomicrometry, and LAD blood flow was measured. Administration of nitrous oxide produced moderate depression of global performance. Regional shortening in both myocardial segments was reduced, and dysfunction also appeared in the LAD segment. This dysfunction was observed in the presence of both normal coronary blood flow, and after critical constriction. The appearance of dysfunction when coronary blood flow was unimpaired suggests that ischemia may not be the only cause of regional myocardial dysfunction.

Complex partial seizures: EEG foci and response to carbamazepine and sodium valproate.

The EEG and clinical records were reviewed of 85 subjects who had been treated for complex partial seizures with carbamazepine alone or with a combination of carbamazepine and sodium valproate. There was a correlation between the site of the EEG abnormality and the therapeutic response to anticonvulsant therapy. Subjects who had a left sided temporal lobe EEG abnormality responded better to carbamazepine alone, while those who had an abnormality on the right responded to a combination of carbamazepine and sodium valproate.

Non-dose-related side effects of valproate.

The clinical and histological findings in 88 patients in whom hepatotoxicity with valproate has been reported were reviewed. The characteristic lesion is microvesicular steatosis. Hepatotoxicity appears to be an idiosyncratic reaction and is most likely to appear within 6 months from the start of therapy, especially in young patients on comedication. The condition may be reversible if the drug is immediately withdrawn in patients who show acute gastrointestinal symptoms, drowsiness or lethargy, jaundice, or change in seizure pattern. Clinical monitoring is more important than laboratory monitoring. The outcome of pregnancies in 344 women who received valproate in the first trimester was reviewed. There were 225 normal babies and 68 abnormal babies. The role of valproate in the aetiology of neural tube defects remains uncertain, but mothers treated with valproate should receive prenatal counselling.

Aura in temporal lobe epilepsy: clinical and electroencephalographic correlation.

Patients with temporal lobe epilepsy were evaluated for their aura and the site of EEG abnormality. Autonomic and psychic auras were more frequently associated with right-sided temporal lobe lesions in 290 patients.

Sodium valproate: monotherapy and polytherapy.

Of the 605 patients seen since 1973, 336 patients have been treated with sodium valproate (VPA) alone or in combination with drugs other than carbamazepine (CBZ). Of these 336, 240 have been on monotherapy, of whom 200 are seizure-free. Follow up has been longer than 3 years in 78%. Complete control of seizures has been achieved in more than 80% of patients with absence, myoclonic, and primary tonic-clonic seizures, in 72% of those with photosensitive epilepsy including eyelid myoclonia, and in 47% of partial epilepsies, for which carbamazepine was the initial drug of choice. Only 21% of those with myoclonic astatic epilepsy have become free from seizures. At first VPA was given twice daily, but in recent years it was given once daily, as this was more effective. Reasons for failure of VPA therapy are given. Side effects in 436 patients (100 more patients were added for this assessment only) were uncommon, though where they did occur, weight increase was the most frequent. Platelets were reduced without clinical problems. There were no severe hepatic disorders. Serum levels were assessed in seizure-free patients, and the optimum level was between 60 and 120 mg/L (most patients received between 20 and 30 mg/kg). VPA was given during 30 pregnancies, and there was no evidence of teratogenicity on monotherapy. VPA is most effective in primary generalized epilepsy, especially if given as the sole antiepileptic drug. If the daily dose does not exceed 40 mg/kg or 2.5 g, it is singularly free from serious side effects.

Once-daily sodium valproate in the treatment of epilepsy.

Using monotherapy with enteric-coated sodium valproate, seizures have been completely controlled in 35 patients with administration of the drug once daily, usually at night. The mean serum levels in seven patients were the same whether the drug was taken once or twice daily. The mean serum level was 65.4 mg/l on a mean daily dose of 19.4 mg/kg. Drowsiness in the morning occurred in four patients, but only one had to return to twice-daily administration. Compliance improves with once-daily administration.

Television epilepsy--the role of pattern.

Patients with photosensitive epilepsy were asked to view normally functioning 625-line televisions while the EEG was monitored. In the first of two studies paroxysmal EEG activity was reliably induced by television at a viewing distance related to a patient's sensitivity to intermittent photic stimulation (IPS); patients who were sensitive to diffuse IPS at 50 Hz were sensitive to the television at greater viewing distances than those who were not. No such relationship was obtained with patterned IPS. On the other hand, patterned IPS was generally more epileptogenic than diffuse IPS with the same luminance. In the second study, where the angular subtense of the television screen and the subtense of its lines were manipulated independently, the convulsive response was found to be a function of both factors, the relative contribution of each depending on the viewing distance at which the patient was sensitive. For patients sensitive at normal viewing distances, where 50 Hz diffuse flicker appeared to be responsible for the induction of paroxysmal activity, the probability with which paroxysmal activity was induced was closely related to the subtense of the screen. For patients sensitive only at closer viewing distances the probability was influenced not by the subtense of the screen but by the subtense of its lines, suggesting that the paroxysmal activity was induced by the 25 Hz pattern alternation produced by the scan. A television with a small screen was considerably less epileptogenic than one with a large screen for all patients, presumably due to the reduced contribution of both diffuse flicker and pattern alternation.