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Biomedical subjects

A M Kerr

Publications and source records attributed to A M Kerr.

At least 19 recordsLinked to original sources
PubMed1995

Early clinical signs in the Rett disorder.

This review of the period from birth until the end of regression in classic Rett syndrome (RS) is based on personal experience of more than 600 cases over 12 years including video material on 42 cases showing behaviour before regression. A period of undoubted developmental progress followed by loss of skill is apt to persuade the physician that a fresh toxic or infective insult has afflicted a normal child but close scrutiny of classic Rett syndrome cases indicates that the cognitive and motor problems of the disorder are detectable from birth, that a developmental ceiling limits progress and that the timing and nature of the regression event and subsequent behaviour of the child indicate inherently defective central receptive processing with a highly specific profile. A model illustrates how the characteristic disturbances may express incompetent higher control. The robust mid infancy level skills of the Rett child and woman deserve careful analysis and offer potential for therapy. Metabolic and immune sequelae may occur as the developmental defect becomes manifest and such cascade events demand careful evaluation and offer further opportunities for intervention.

Adolescent↗
PubMed1995

Short fourth toes in Rett syndrome: a biological indicator.

Classic Rett syndrome is now well-known as a non-dysmorphic developmental disorder almost certainly of genetic origin. Short 4th toe (uni- or bi-lateral) is inherited as an autosomal dominant with 27% penetrance and is found also in certain dysmorphic syndromes. Having observed the anomaly in several Rett cases, we examined a cohort of classic Rett people at advisory clinics and all the residents in an adult learning disabled hospital in order to determine the significance of the association. Among the Rett clinic group 28 of 137 showed the anomaly (20%). Among the heterogeneous hospital group it was found in 19 of 526 people, 9 of 206 females (4%) and 10 of 320 males (3%). Rett syndrome was present in 7% of all the women (14 of 206 women). Four of the Rett women showed the toe anomaly (28% of the Rett cases). The anomaly was found in 4 men and 4 women with Down syndrome, representing 16% (8 of 49). Diagnoses in other men with the anomaly included foetal alcohol syndrome, toxoplasmosis, 18/2 translocation and birth injury. The only other woman with the anomaly was profoundly disabled with short limbs. The strong positive association of the anomaly with Rett syndrome and Down syndrome throws new light on the developmental processes affected by these diseases.

Brain↗
PubMed1995

Visual function in Rett syndrome.

The authors examined refractive error, pattern onset visual evoked potentials, ocular posture and they performed internal and external eye examinations in 11 subjects with Rett syndrome (aged between four and 24 years) and 18 normal controls (aged between six and 20 years). Substantial refractive errors were common in the Rett syndrome group. Spectacle correction had never previously been worn and glasses were provided where appropriate. No subjects had nystagmus or optic nerve pallor and only one was strabismic. All subjects had recognisable and reproducible pattern-onset VEPs and latencies and amplitudes did not differ significantly from those of the controls. All demonstrated VEP thresholds of at least 24'. In contrast to other populations with profound disabilities, people with Rett syndrome have good function of the afferent visual pathways and, in view of their substantial refractive errors, are likely to benefit from spectacle correction.

Adolescent↗
PubMed1994

Medical concerns in people with severe learning difficulties: report on a vision week and symposium at the Royal College of Physicians and Surgeons of Glasgow, Scotland, 8-12 March 1993.

Over the course of a week, vision clinics were conducted in the wards of Lennox Castle, one of the largest remaining mental handicap institutions in Scotland. Receptions and a seminar encouraged participation by staff and local services. A day Symposium at the Royal College of Physicians and Surgeons in Glasgow presented recent developments in medical care and facilitated discussion on methods of ensuring effective health surveillance, assessment and advisory services.

Combined Modality Therapy↗
PubMed1992

A review of the respiratory disorder in the Rett syndrome.

The characteristics and physiological accompaniments of the respiratory disorder in the Rett syndrome are reviewed and placed in the context of other clinical studies. Events are indicated which may play a part in the occurrence of vacant spells. A scheme is proposed to explain the various manifestations of the Rett syndrome disorder throughout life. The Rett syndrome is viewed as a developmental disorder in which the evolving clinical signs are due to the effects of maturation and aging on an abnormal brain rather than to primary degenerative disease. Thus development elicits preexisting defects which subsequently become clinically manifest. The clinical evidence is suggestive of a genetically determined early defect in central receptive processing which leads to failure of central motor planning with release of extrapyramidal rhythms.

Child↗
PubMed1991

Rett syndrome.

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Carbon Dioxide↗
PubMed1990

Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome.

The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome. Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles. The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons. Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations. In contrast cervical motor root stimulation resulted in responses of normal latency and duration. The phasic stretch reflex had a low threshold, short latency and prolonged duration. It is concluded that in Rett syndrome the corticospinal pathway is intact. The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways.

Adolescent↗
PubMed1990

Rett's syndrome.

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Adolescent↗
PubMed1988

A low-cost method for simultaneous video-recording of ambulant subject and electroencephalograph: the Quarrier's system.

A system is described by means of which the ambulant subject may be video-filmed over several hours with the electroencephalograph superimposed on the same tape, allowing correlations to be observed in the active state. Our first subjects have been girls with Rett syndrome. Requirements are: one portable video camera/recorder, a conventional e.e.g. machine, the 'Medilog 9000' system for prolonged ambulatory recording (Oxford Medical), a specialized video mixer (videogram ForA FVG600, commercially available) a video timer, a conventional video cassette recorder and a television monitor. The cost is small for a department already equipped to carry out ordinary ambulatory e.e.g. monitoring. The method is safe, well tolerated, simple to use and adaptable. To the best of the authors' knowledge, they are the first to use this system and they believe that it should find wider application when it is desirable to correlate the behaviour of a subject with physiological parameters, on a restricted budget.

Ambulatory Care↗
PubMed1988

Hyperventilation in the awake state: potentially treatable component of Rett syndrome.

Hyperventilation, which occurs in some patients with severe mental handicap, is a prominent feature in the histories of most girls with Rett syndrome but its mechanism and effects have not been established. Respiratory function was therefore studied in 18 patients with Rett syndrome and 23 healthy controls. Ten of the patients (56%), but none of the controls, hyperventilated only when awake, and began doing so after a period of normal breathing without hypoxaemia. After hyperventilation was established it was interspersed with prolonged periods of apnoea (over 19 seconds) accompanied by Valsalva manoeuvres. Hypoxaemia (less than 90%) occurred in 47% of these periods of apnoea and five (50%) of the patients had oxygen saturation values of under 50%. During hyperventilation severe hypocapnia developed in every patient, and recorded arterial pH measurements ranged from 7.47 to 7.60. A further four patients (22%) did not hyperventilate, but had clear histories of hyperventilation when younger. All had frequent apnoeic pauses accompanied by Valsalva manoeuvres. The remaining four girls (22%) neither hyperventilated nor gave a clear history of doing so. Three had occasional apnoeic pauses associated with the Valsalva manoeuvres. All but one of the 18 patients had increased quantities of periodic apnoea compared with the control subjects. The hypocapnic alkalaemia and hypoxaemia resulting from hyperventilation may contribute to the cerebral impairment in Rett syndrome. Since the hyperventilation is 'primary', and not secondary to preceding apnoea, it is potentially treatable. Further studies will determine if treatment is practical and of benefit.

Adolescent↗
PubMed1987

The hands, and the mind, pre- and post-regression, in Rett syndrome.

Forty girls with Rett syndrome were included in a study of behaviour, with particular regard to the hands, before, during and after regression. Data was taken from examination of each girl, and in some cases from detailed developmental histories given by parents, and films taken before, during and after regression. The important findings are shown in two tables and described. Pre-regression abnormalities included hypotonia, jerky incoordination, an excess of patting or waving activity and involuntary movements which included alternate opening and closing of the fingers and twisting of wrists or arms. Hand use did not progress beyond the ten- to twelve-month stage. Language did not develop beyond the stage of one word utterances. When well-developed, the stereotyped hand movements were simple and clumsy, consisting of tapping, rubbing and clasping, with the hand moved as a unit. Before regression hands were usually separate, during regression usually together and thereafter with increasing age inclined to separate again. Voluntary hand use was observed when girls were relaxed and strongly motivated, particularly during musical interactions. The characteristic abnormalities of behaviour in pre-regression Rett syndrome, and hand behaviour in later childhood should allow earlier and more accurate diagnosis.

Adolescent↗
PubMed1987

In vitro chemosensitivity testing using the multicellular tumor spheroid model.

Using growth delay and clonogenic cell survival as end points, we have shown that the 3-dimensional structure of human lung tumour spheroids confers a degree of resistance to the anthracyclines doxorubicin and 4'-deoxydoxorubicin, relative to cells grown as monolayer. 4'-deoxydoxorubicin induces a longer growth delay and greater clonogenic cell kill than doxorubicin in spheroids, although it is no more cytotoxic in monolayer. Using fluorescent microscopy we have demonstrated, qualitatively, that lipophilic anthracycline analogues partition into the spheroid more rapidly and to a greater degree than doxorubicin. It is apparent that penetration is an important aspect of anthracycline drug resistance in spheroids, and the spheroid model may represent a better in vitro system for testing lipophilic analogues of cytotoxic drugs.

Antibiotics, Antineoplastic↗
PubMed1986

Comparative intracellular uptake of adriamycin and 4'-deoxydoxorubicin by non-small cell lung tumor cells in culture and its relationship to cell survival.

4'-Deoxydoxorubicin (4'-deoxy) is a new adriamycin analogue with a similar spectrum of antitumour activity but is significantly more lipophilic than the parent compound. We report the kinetics and uptake of the two drugs by human non-small cell lung tumour cells in monolayer culture and the relationship between intracellular drug levels and cytotoxicity. The rate and degree of cell uptake of 4'-deoxy (Vmax = 30 ng/10(5) cells/min) was greater than that of adriamycin (Vmax = 0.15 ng/10(5) cells/min). Although for a given intracellular drug concentration adriamycin was more lethal, on the basis of extracellular drug concentration, cell kill was virtually identical. The log cell survival vs intracellular drug concentration plot was linear for adriamycin but biphasic for 4'-deoxy. Intracellular distribution of the two drugs was followed by fluorescent microscopy and it was apparent that adriamycin was localized mainly within the nucleus whereas 4'-deoxy accumulated within the cytoplasm. Our results suggest that the relationship between intracellular distribution of the two drugs could reflect different modes of action for the drugs with respect to binding sites or could be a non-specific phenomenon, unrelated to lethal effects.

Carcinoma, Squamous Cell↗
PubMed1986

A study of the natural history of Rett syndrome in 23 girls.

We have studied 23 patients with Rett syndrome with particular reference to the character and natural history of the clinical disorder. We found a prevalence of 0.8 per 10,000 girls 0-14 years in the region from which cases came. We consider that the disorder of tone, posture and movement is extrapyramidal in nature and suggest that the gradual emergence of its fully developed pattern leads to the familiar regression in skills on presentation. We have not found proof of dementia at this stage but rather of severe mental handicap.

Adolescent↗
PubMed1986

The effect of adriamycin and 4'-deoxydoxorubicin on cell survival of human lung tumour cells grown in monolayer and as spheroids.

Using growth delay and clonogenic cell survival as end points, we have shown that the 3-dimensional structure of human lung tumour spheroids confers a degree of resistance to the anthracyclines adriamycin and 4'-deoxydoxorubicin, relative to cells grown as monolayer. 4'-deoxydoxorubicin induces a longer growth delay and greater clonogenic cell kill than adriamycin in spheroids, although it is no more cytotoxic in monolayer (exponential and plateau phase). There is a log linear relationship between clonogenic cell survival and duration of adriamycin exposure in monolayers, and biphasic curve with a lesser degree of cell kill for disaggregated spheroid cells. Using fluorescent microscopy we have demonstrated, qualitatively, that the more lipophilic analogue partitions into the spheroid more rapidly and to a greater degree than adriamycin. It is possible that adriamycin penetration is a relatively important aspect of spheroid drug resistance, which may be related to intraspheroidal pH gradients, and that we have partially overcome this by using a lipophilic analogue.

Cell Survival↗