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Biomedical subjects

A Harden

Publications and source records attributed to A Harden.

At least 19 recordsLinked to original sources
PubMed1991

Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias.

Recurring chromosomal translocations involving chromosome 11, band q23, have been observed in acute lymphoid leukemias and especially in acute myeloid leukemias. We recently showed that breakpoints in four 11q23 translocations, t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13.3), were contained within a yeast artificial chromosome clone bearing the CD3D and CD3G gene loci. We have identified within the CD3 yeast artificial chromosome a transcription unit that spans the breakpoint junctions of the 4;11, 9;11, and 11;19 translocations, and we describe two other, related transcripts that are upregulated in the RS4;11 cell line. We have named this gene MLL (myeloid/lymphoid, or mixed-lineage, leukemia.

Adult↗
PubMed1991

The clinical significance of seizures in critically ill young infants requiring intensive care.

The aetiology, severity of systemic and biochemical abnormalities, seizure duration, EEGs and CT scans have been reviewed in previously normal young infants with an acute critical illness occurring after the first week of life; none of whom had birth asphyxia. Findings were related to outcome in an attempt to evaluate the significance of seizures during the acute phase of severe illness. In three years seizures occurred in 54/251 (22%) young infants requiring ventilatory support. In these patients the acute illness was most commonly infection and encephalitis/encephalopathy. Twenty-one died, 24 had good or moderate outcome and 9 poor outcome (follow-up 6-27 months). The outcome was not directly related to diagnosis, but to systemic and biochemical changes, the most important being severe hypotension (40/54). After correction of these factors, in survivors, increasing number of days over which seizures occurred during the acute phase of illness was related to worsening outcome (tau(c) = 0.66, p less than 0.0001). In many of these patients one of three abnormal low density changes (generalized, boundary zone and focal) were seen on CT scan and were not uncommonly associated with focal/multifocal clonic seizures and characteristic type, distribution and evolution of EEG discharge. In the 45 patients with EEGs from presentation, severity of encephalopathy assessed by predominant background EEG activity was most closely related to outcome, irrespective of aetiology and seizures. There was a significant relationship between graded severity of background EEG activities and outcome both in the initial and serial recordings (tauB = 0.70, p less than 0.0001 and 0.75, p less than 0.0001 respectively). Seizures are a common occurrence in the previously well young infant with an acute critical illness necessitating intensive care. Prompt recognition and treatment may influence outcome in patients with a potentially reversible encephalopathy. However, in many patients seizures reflect severe, often multifactorial cerebral insult with variable morphological changes, EEG patterns and clinical outcome.

Anticonvulsants↗
PubMed1991

EEG features and their evolution in the acute phase of haemorrhagic shock and encephalopathy syndrome.

Serial EEGs have been carried out during the acute phase of haemorrhagic shock and encephalopathy syndrome (HS&E) in 22 infants and children aged 3 months to 14 years. Most patients presented with fits and coma and all had shock with bleeding and disseminated intravascular coagulation (DIC). The initial EEG showed prolonged runs of often rhythmic discharges which fluctuated in amount and amplitude with varying distribution and morphology ("electrical storms"). Over a period of days the "electrical storms" gradually decreased leaving only low amplitude EEG activities or evolving to electrocerebral silence (7 cases). Fifteen patients died and all five children with multifocal "electrical storms" who survived showed gross neurological handicap. The rather distinctive EEG pattern is unusual in the context of an acute encephalopathy outside the neonatal period although similar "electrical storms" may be seen in a less extreme form in infants and children with other conditions associated with DIC. This EEG pattern presumably reflects changes in the cerebral microcirculation which in HS&E are usually relentlessly progressive and associated with devastating cortical damage.

Adolescent↗
PubMed1991

Ofloxacin compared with chloramphenicol in the management of external ocular infection.

The safety and efficacy of 0.3% ofloxacin in treating bacterial ocular infections was compared with that of 0.5% chloramphenicol in a parallel-group, randomised clinical trial at five sites. Clinical and microbiological improvement rates were studied in 84 culture-positive patients. Patients with suspected bacterial ocular infections were evaluated for clinical improvement and were included in drug safety and comfort analyses. Clinical improvement did not differ significantly between drug treatments. All patients completing the study (79 assigned ofloxacin, and 74 chloramphenicol) showed clinical improvement. Clinical improvement in the culture-positive groups was 100% (41/41) after ofloxacin treatment, and 95% (41/43) after chloramphenicol treatment. Microbiological improvement rates were similar for the two drugs: 85% (33/39) improved with ofloxacin, and 88% (38/43) improved with chloramphenicol. Both drugs were well tolerated. Adverse reactions possibly due to the study medication occurred in 1% (1/89) of those who received ofloxacin, and in 4% (4/93) of those who received chloramphenicol.

Adult↗
PubMed1990

Deletions of interferon genes in acute lymphoblastic leukemia.

Structural rearrangements involving the short arm of chromosome 9, including bands 9p21 and 22, are found in the leukemia cells of 7 to 13 percent of patients with acute lymphoblastic leukemia. The interferon-alpha gene cluster and the interferon-beta 1 gene have been localized to this chromosomal region. We have previously demonstrated deletions of these genes in several cell lines established in vitro from patients with lymphoblastic leukemia. We report here homozygous or hemizygous deletions of the interferon-alpha and interferon-beta 1 genes in samples of leukemia cells from patients with lymphoblastic leukemia. Of 62 patients examined, 18 (29 percent) had such deletions. Four patients (7 percent) had homozygous deletions of the interferon-alpha gene cluster; of these, one also had a homozygous deletion and three had hemizygous deletions of the interferon-beta 1 gene. Fourteen patients (23 percent) had hemizygous deletions of both the interferon-alpha gene cluster and the interferon-beta 1 gene. In 8 of the 18 patients with deletions, the deletions of interferon genes were submicroscopic; in the 11 other patients, chromosomal rearrangements of 9p, including translocations or deletions, were visible on light microscopy. These chromosomal and molecular deletions are likely to be related to the loss of a tumor-suppressor gene (or genes) located on 9p, which may be an interferon gene or an unrelated but closely linked gene.

Adolescent↗
PubMed1990

The cerebral function analysing monitor in paediatric medical intensive care: applications and limitations.

Practical guidelines for continuous single channel EEG monitoring using the Cerebral Function Analysing Monitor (CFAM) have been outlined based on experience of 54 critically ill comatose and/or paralysed sedated children monitored for up to 9 days during the acute phase of illness. Fall in amplitude and slowing of frequency following either a cerebral insult or barbiturate administration as well as paroxysmal events were readily recognisable in the CFAM traces. Such changes could be used to (1) identify effects of cerebral insults (acute or cumulative), (2) recognise unstable patients exquisitely sensitive to aspects of standard care and (3) evaluate seizure control. Despite these useful contributions to clinical care, significant limitations were apparent. It is recommended that CFAM monitoring should be combined with serial conventional EEG recording in order to check the appropriateness of the cortical areas being monitored, the quality and type of signal being processed as well as the significance of the 1 or 2 channel CFAM findings in relation to global cerebral function.

Adolescent↗
PubMed1990

Megalencephaly with dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings.

A progressive neurological condition characterised by megalencephaly, spasticity, ataxia and seizures in two siblings of consanguineous parents is described. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response whereas brainstem auditory evoked potential findings were consistent with a white matter disorder. Computerized tomography scans revealed diffuse hypodensity of the white matter and a brain biopsy on one sibling showed features of dysmyelination without evidence of demyelination, Rosenthal fibres or the spongy changes characteristic of Canavan's disease. There was no detectable biochemical abnormality. This combination of clinical, neurophysiological and neuropathological abnormalities has not previously been described.

Biopsy↗
PubMed1989

EEG monitoring of prolonged thiopentone administration for intractable seizures and status epilepticus in infants and young children.

Thiopentone anaesthesia was used in the treatment of seizures in 19 infants and young children. Nine had a pre-existing seizure disorder without acute cerebral injury and 10 had status epilepticus secondary to an acute cerebral illness. Clinical details, drug levels and findings from serial multichannel electroencephalograms (EEG) and continuous 1 to 2 channel signal processed EEGs using a Cerebral Function Analysing Monitor (CFAM) were reviewed to evaluate the contribution of these techniques to clinical management. Initial EEGs showed discharges that were not generalised in 16/19 patients. This necessitated the use of 7 different montages for continuous monitoring. Three different CFAM patterns representing particular EEG paroxysmal findings were seen. Acute seizure control was achieved in all 19 patients. All patients with a pre-existing seizure disorder survived, although 4/10 with an acute cerebral illness died. During treatment, patterns of burst-suppression to electrocerebral silence (ECS) were eventually seen in 16/19 patients and repeat EEGs demonstrated concordant multi-channel findings in 8/8. Although increasing thiopentone levels (13 patients) correlated with deeper suppression of cortical electrical activity, there was marked inter-patient variability. Inotropic support was not required during the period of treatment even when ECS was induced. In young children a combination of multi-channel EEG and continuous 1 to 2 channel monitoring has advantages over either method used alone. In individual patients on-line monitoring can be easily incorporated in a protocol of controlled cortical suppression and drug titration for seizure control.

Child, Preschool↗
PubMed1989

Rett syndrome: an EEG study in 52 girls.

EEG studies have been carried out on 52 girls with Rett syndrome, the majority of records being taken between two and 7 years of age. Discharges were a common feature, occurring in 43 patients, and did not appear to be related to the onset of seizures. The discharges, consisting of sharp waves or spikes, were characteristically most prominent around the middle third of the head, often occurring asymmetrically and could be infrequent or almost continuous. They were usually enhanced by light sleep and were seen only during sleep in 15 EEGs taken in 13 patients, most of whom were under four years of age. These EEG features when present may help confirm the diagnosis of Rett syndrome in the appropriate clinical setting and in particular are quite distinct from the usual EEG patterns seen in Angelman (Happy Puppet) syndrome.

Adolescent↗
PubMed1989

The electroretinogram.

The electroretinogram, findings, in response to a flash stimulus, was recorded from a skin electrode placed on the bridge of the nose in 4465 infants and children seen over a 10 year period. The electroretinogram was combined with a flash visual evoked potential. From this total, the electroretinographic findings in 240 patients, aged 1 day to 17 years, without suspected retinal pathology and with a normal visual evoked potential, were used as controls and normal electroretinographic parameters of different age groups defined. There were 332 patients who showed an absent or very reduced amplitude electroretinogram. They were divided into primarily ocular disorders (n = 195), neurodegenerative disorders (n = 94), and various syndromes (n = 43). Fundus examination did not always show any obvious abnormalities. The use of this simple and reliable technique for recording the electroretinogram made it possible to include this investigation as a routine procedure without the need for sedation in infants and uncooperative children. Electroretinographic studies, especially when combined with visual evoked potentials, and in some cases electroencephalography, may aid diagnosis in a wide variety of paediatric conditions, many of which have genetic implications.

Adolescent↗
PubMed1988

The EEG in early diagnosis of the Angelman (happy puppet) syndrome.

An EEG study has been carried out on 19 children (including siblings in 3 families) with clinical features of Angelman syndrome. The age at time of the first EEG ranged from 11 months to 11 years with the majority under 5 years. Six children had no history of seizures at the time of the first EEG. One or more of the following EEG abnormalities were seen in all patients: 1. Persistent rhythmic 4-6/s activities reaching more than 200 microV not associated with drowsiness. 2. Prolonged runs of rhythmic 2-3/s activity (200-500 microV) often more prominent anteriorly, sometimes associated with discharges (ill-defined spike/wave complexes). 3. Spikes mixed with 3-4/s components usually more than 200 microV mainly posteriorly and facilitated by, or only seen with, eye closure. Two and sometimes three of these EEG features could be present in the same record particularly at a young age. The appearance of discharges mixed with slow components on eye closure was the commonest finding seen at some stage in 17 patients (aged from 11 months to over 12 years). The EEG features of Angelman syndrome appear to be sufficiently characteristic to help identify patients at an early age before the clinical features become obvious and at a time when genetic counselling may be particularly important.

Adolescent↗
PubMed1988

Monitoring in non-traumatic coma. Part II: Electroencephalography.

Forty eight comatose children had electroencephalograms (EEG) recorded during the acute phase of their illnesses. These were classified according to a simple grading system and the findings correlated with the presence of seizures, deep coma, minimum cerebral perfusion pressure, and eventual neurological outcome. Serial EEGs proved important, particularly when slow activity was seen initially. None of the 20 patients who showed low amplitude EEG activity or electrocerebral silence at any stage of the acute illness did well. Discharges were seen in only 13 of the 29 patients with seizures and their presence did not correlate with outcome except in five patients with a distinctive pattern of discharges, none of whom had a good outcome. EEG findings associated with poor outcome did not always correlate with the clinical assessment of deep coma, emphasising the difficulties of neurological evaluation in these patients. Five of the patients with cerebral perfusion pressures greater than 42 mm Hg had a poor outcome that was predicted by serial EEGs. In nine patients with a minimum cerebral perfusion pressure in the borderline range 38-42 mm Hg the EEG was useful as an indication of the outcome. The EEG reflects changes in cerebral function which may be due to multifactorial or repeated insults. An EEG is therefore important in both the initial assessment and as an indicator of the neurological outcome, particularly in those patients in whom the cerebral perfusion pressure has apparently been adequate or within the borderline range.

Acute Disease↗
PubMed1987

Diagnostic difficulties in infantile neuroaxonal dystrophy. A clinicopathological study of eight cases.

The clinical features of eight children with infantile neuroaxonal dystrophy are presented. Diagnosis was established by brain biopsy (4 cases), conjunctival biopsy (1 case), and the family history (2 cases), while in one case a presumptive diagnosis was made on the combination of clinical and neurophysiological findings without histopathological confirmation. The pleomorphic clinical picture and variable neurophysiological findings make a firm diagnosis difficult without histopathological confirmation. However, in the appropriate clinical context, serial neurophysiological investigations (ERG, VEP, EEG, ENMG) may suggest the diagnosis after the age of 2 years. Conjunctival biopsy is not invariably helpful, and neuroaxonal spheroïds are not always demonstrated in brain biopsies by conventional techniques. However, they were consistently identified using a non-specific esterase stain and by electron microscopy. This technique is described, and the significance of ultrastructural and neuropathological findings in infantile neuroaxonal dystrophy is discussed.

Axons↗
PubMed1986

Progressive neuronal degeneration of childhood with liver disease ("Alpers' disease"): characteristic neurophysiological features.

A clinico-pathological entity of progressive neuronal degeneration of childhood with liver disease has now been recognised. Onset is in early childhood with intractable fits and progressive dementia. EEG/ERG/VEP studies have been carried out in 12 children with this condition. In most patients the EEG showed strikingly similar and unusual abnormal patterns (high amplitude slow activity together with smaller polyspikes). The flash VEP was usually abnormal and often asymmetrical. In the appropriate clinical setting the neurophysiological features are sufficiently characteristic to aid the clinician in early diagnosis of this autosomal recessive disorder.

Atrophy↗
PubMed1978

Menkes' disease: neurophysiological aspects.

The evolution of neurophysiological features including the electroencephalogram (EEG), electroretinogram (ERG), and visual evoked potentials (VEP) is reported in eight cases of Menkes' "kinky hair" disease. All EEGs were severely abnormal, with some characteristic features seen from 3-5 months of age, after the onset of clinical symptomatology. From the age of 5 months, the EEGs resembled hypsarrhythmic patterns. The ERG was not affected in any patient, but the VEP was either of low amplitude or completely absent in all but one of the six patients tested. All eight patients received copper injections without substantial effect on either the clinical course of the disease or the EEG features.

Brain Diseases, Metabolic↗
PubMed1977

So-called neuronal ceroid lipofuscinosis. Neurophysiological studies in 60 children.

EEG, ERG, and VEP studies were carried out in 60 children with verified neuronal storage of ceroid/lipofuscin-like material. Comparing and contrasting the EEG/ERG/VER features of each child during the symptomatic phase of the disease, three distinct main groups could be recognised: (1) Progressive diminution in amplitude of the EEG and VEP beginning about the age of 2 years was seen in seven children, and all phasic cerebral activity was unrecordable at 3-4 years of age; the clinical onset with regression in skills began at 1-2 years of age; (2) Large amplitude irregular slow activity and polyphasic spikes appeared in 27 children in whom characteristic discharges were elicited at low rates of photic stimulation (grossly enlarged VEP); the clinical onset was around 3 years of age with an occasional seizure and some clumsiness; (3) Runs of slow wave and spike complexes were seen in the EEG of 10 children with a small or absent VEP; the clinical onset with visual failure began around 5-7 years of age. In the remaining 16 children, the EEG and the clinical features fell into much smaller groups, possibly of rarer type. The ERG became unrecordable at an early symptomatic phase in all 60 children. The present findings suggest that such umbrella terms as neuronal ceroid lipofuscinosis or Batten's disease, which imply a single disease entity, are misleading. Neurophysiological investigations can help in early identification of these separate conditions. When the biochemical basis of these disorders becomes fully understood a more rational nomenclature will be possible.

Child↗