A new approach to the analysis of the human sleep/wakefulness continuum

SUMMARY The conventional approach to the analysis of human sleep uses a set of pre-defined rules to allocate each 20 or 30-s epoch to one of six main sleep stages. The application of these rules is performed either manually, by visual inspection of the electroencephalogram and related signals, or, more recently, by a software implementation of these rules on a computer. This article evaluates the limitations of rule-based sleep staging and then presents a new method of sleep analysis that makes no such use of pre-defined rules and stages, tracking instead the dynamic development of sleep on a continuous scale. The extraction of meaningful features from the electroencephalogram is first considered, and for this purpose a technique called autoregressive modelling was preferred to the more commonly-used methods of band-pass filtering or the fast Fourier transform. This is followed by a qualitative investigation into the dynamics of the electroencephalogram during sleep using a technique for data visualization known as a self-organizing feature map. The insights gained using this map led to the subsequent development of a new, quantitative method of sleep analysis that utilizes the pattern recognition capabilities of an artificial neural network. The outputs from this network provide a second-by-second qualification of the sleep/wakefulness continuum with a resolution that far exceeds that of rule-based sleep staging. This is demonstrated by the neural network's ability to pinpoint micro-arousals and highlight periods of severely disturbed sleep caused by certain sleep disorders. Both these phenomena are of considerable clinical value, but neither are scored satisfactorily using rule-based sleep staging.     

LICHEN PLANUS: FAILURE TO CULTIVATE VIRUSES OR MYCOPLASMA

SUMMARY. —Eleven patients with lichen planus were studied for evidence of virus or mycoplasma as the possible causative agent. Extracts of skin biopsy specimens from 10 patients were inoculated on to HeLa, monkey kidney and human amnion cells. After incubation for up to 28 days at 33° C. there was no evidence of a virus. Cultures in fluid and on solid P.P.L.O. media, (aerobic and anaerobic) did not show any growth of mycoplasma. Serology using Mycoplasma pneumoniae C.F.T. antigen gave inconclusive results on the sera from the 11 patients.     

Immunoglobulins in the skin in dermatitis herpetiformis and their relevance in diagnosis

Eighty skin biopsies from fifty patients with dermatitis herpetiformis (DH) have been examined for immunoglobulin deposits by direct immunofluorescence. IgA was found in all fifty patients. However, in two patients no IgA was detected in their first biopsy, and it is stressed that if the clinical suspicion of DH is high and no IgA is found in a single biopsy, then the biopsy should be repeated. There are two distinct patterns of immunoglobulin deposition in DH. The most common form of deposition is seen in the dermal papillae, termed the 'papillary' pattern. This pattern was the only one present in sixty-seven of the seventy-eight biopsies. A less common pattern is that of a 'continuous' line along the dermo-epidermal junction. This was the only pattern of immunoglobulin deposition in nine of the seventy-eight biopsies. In two biopsies both the papillary and continuous patterns were present. IgA was found in all seventy-eight of the positive biopsies and was the only immunoglobulin detected in sixty-seven biopsies. In addition to IgA, IgM was present in seven biopsies, and IgG in two biopsies. In one biopsy IgM and IgG were present with the IgA. The detection of IgA in the uninvolved skin in patients with DH is a simple test to perform, and at the present time is the most reliable way of establishing the diagnosis     

The ultrastructural changes in the skin in dermatitis herpetiformis after withdrawal of dapsone

The development of skin lesions in patients with dermatitis herpetiformis after the withdrawal of their dapsone therapy was studied with the electron microscope. In control biopsies from patients prior to cessation of treatment, membrane-bound vacuoles were found beneath the basal lamina of the epidermis as previously described. After dapsone withdrawal, there was an apparent increase in the number of vacuoles and occasionally several vacuoles appeared to have coalesced forming an early blister. At this stage, the basal lamina and associated hemidesmosomes were normal although in places there were small discontinuities in the basal lamina. Where the reaction was more intense, vacuoles and cells, mainly eosinophils, were embedded in fibrin de posits. Above this, the basal lamina was usually disrupted with involvement of the basal epidermal cells. These results suggest that the vacuoles do play a part in the formation of the pathological lesion in dermatitis herpetiformis. In addition, the basal lamina is shown to be only secondarily involved. The nature of the vacuoles has still to be elucidated.     

THE ACTION OF CHEMOTHERAPEUTIC AGENTS ON PSORIATIC EPIDERMIS

SUMMARY. —Mitotic counts and histological features have been studied in 35 psoriatic patients prior to treatment, and during treatment with topically applied fluocinolone acetonide, methotrexate, dithranol and coal tar.
Prior to treatment there was considerable variation in the mitotic counts in the 35 biopsies. The granular layer was absent in 10 biopsy specimens, partially formed in small areas in 21, well formed in most areas in 2, and normal in 2. There was no correlation between the mitotic counts and state of the granular layer.
With methotrexate and dithranol treatment the granular layer showed improvement prior to a significant fall in the mitotic counts. With fluocinolone acetonide the improvement in the granular layer appeared at the same time as a significant fall in the mean mitotic count, but the granular layer had completely reformed in 7 of the 9 patients while the mitotic count was still considerably raised compared to uninvolved psoriatic skin. With coal tar the results were not uniform; some patients showed a significant fall in mitotic counts prior to improvement in the granular layer and others first showed improvement in the granular layer.
It is suggested that in clearing psoriasis these drugs have an action other than, or in addition to, inhibiting mitosis.     

EFFECT OF EETINOIC ACID IN PSORIASIS

The effect of topical retinoic acid on the clinical and histological features and mitotic counts of lesions in 12 patients with psoriasis have been studied for a 2-week period. Serial biopsies were performed on lesions treated with retinoic acid in all 12 patients; control lesions treated with unmedicated ointment base were similarly biopsied in 7. There was a significant clinical improvement in 11 of the 12 patients treated with retinoic acid, and in all these patients it was greater than that achieved in the control lesions. Reformation of the granular layer, which was previously absent or only partially formed, occurred in 6 of the 12 psoriatic lesions treated with retinoic acid, but in none of the controls. Mitotic counts for the treated group fell after the 2-week period, but not in the controls. Topical retinoic acid would seem to be of therapeutic value in the treatment of psoriasis. The possible mechanisms of action are discussed.     

Drug Associated Acute Interstitial Nephritis: Clinical and Pathological Features and the Response to High Dose Steroid Therapy

Nine episodes of drug associated acute interstitial nephritis,in seven patients, were treated between 1972 and 1980. The drugsimplicated were cotrimoxazole (three times), ampicillin, Magnapen(amplcillin and flucloxacillin), penicillin, gentamicin, paracetamoland ben-drofluazide. The time from exposure to the onset ofsymptoms ranged from one to 30 days. Presentation was with acuterenal failure, which was non-oliguric in five cases, accompaniedby rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristicinterstitial infiltrate comprising substantial numbers of lymphocytesand plasma cells, with a variable number of neutrophils, eosinophilsand histiocytes. Immunofluorescence was negative in all fourcases studied in the acute phase, and showed scattered depositsof IgG, IgM, IgA and C3 on the tubular basement membrane inone patient during recovery. Significant proteinuria and anabnormal urine deposit were present in all cases, and sevenof nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisoloneand in all there was a response with a diuresis or spontaneousfall in serum creatinine within 72 hrs, and recovery of virtuallynormal renal function. Of two cases who did not initially receivesteroids, one improved more slowly and one developed chronicrenal impairment. Present address: Department of Medicine, Charing Cross Hospital,Fulham Palace Road, London W6 8RF.