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Biomedical subjects

A D Mendelow

Publications and source records attributed to A D Mendelow.

At least 19 recordsLinked to original sources

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

Adolescent

A thermal clearance probe for continuous monitoring of cerebral blood flow.

Thermal clearance has been used as a measure of tissue blood flow for over 60 years. We have developed a probe which can be used to monitor cerebral cortical thermal clearance in patients suffering from acute neurosurgical disorders. Despite its limitations of size, invasiveness, small sample volume, and difficult quantification it has proved a reliable method, showing a good correlation between measured thermal clearance and the onset of clinical signs of ischaemia.

Adult

The effect of immunosuppression on the development of cerebral oedema in an experimental model of intracerebral haemorrhage: whole body and regional irradiation.

The oedema which forms around an intracerebral haemorrhage has a complex aetiology. The immune response may have a role in its formation. There is clinical and experimental evidence that circulating leucocytes and platelets may mediate oedema formation. Global depletion of circulating leucocytes and platelets by whole body irradiation in a rodent model of intracerebral haemorrhage was found to confer protection against both ischaemia and oedema formation. This was not a direct effect of irradiation of the brain. The possible mechanisms for this protection are discussed.

Animals

Closed loop blood pressure control for cerebral perfusion studies.

A method is presented which maintains mean arterial blood pressure at predetermined values during cerebrovascular occlusion studies in a rat model. The system consists of a pressure measurement apparatus, a pump capable of infusing and withdrawing fluids, and a personal computer to control the infusion and withdrawal rate. An evaluation of the system is presented, and potential advantages and difficulties are discussed.

Animals

Triphenyltetrazolium chloride (TTC) as a marker for ischaemic changes in rat brain following permanent middle cerebral artery occlusion.

Triphenyltetrazolium chloride (TTC) was used to delineate ischaemic lesions in the rat brain at various times following middle cerebral artery occlusion. A comparison was made of TTC staining by immersion and perfusion techniques and conventional light microscopy. The lesions were quantified by measuring the ischaemic area at the sections corresponding to 7 mm in front of the AO line (atlas of Konig and Klippel). In animals examined 24 h after middle cerebral artery occlusion (MCAO), the area of infarction was 17.4 +/- 1.3 mm2 on the TTC perfused slices and 17.6 +/- 1.6 mm2 on the TTC immersed slices (mean +/- SEM). By contrast, there was a marked difference between the two TTC methods when tissues were examined at shorter intervals after artery occlusion. In the TTC-perfused animals, there was no significant difference between the mean areas of infarction measured at 5-20 min, 3-4 h, or 24 h post occlusion. Immersion in TTC, however, failed to reveal any consistent ischaemic damage when applied at the earlier post-occlusion times. Conventional histopathology demonstrated minimal lesions at 5-20 min but at 4 h or more the lesions were not significantly different from those demonstrated by TTC perfusion. TTC immersion staining can, thus, only be used as a reliable marker of cerebral ischaemia damage with post-occlusion survival periods of 24 h. TTC perfusion staining gives results not significantly different from histopathology at 4 h or more post-occlusion but at earlier intervals than 24 h it differs significantly from TTC immersion staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Subarachnoid haemorrhage in Wegener's granulomatosis, with negative four vessel angiography.

Two patients with Wegener's granulomatosis and spontaneous subarachnoid haemorrhage are presented in whom four vessel angiograms were normal. The diagnosis of Wegener's granulomatosis should be considered in patients with subarachnoid haemorrhage and negative four vessel angiography. The presence of antibodies to a neutrophil cytoplasmic antigen may be of diagnostic value.

Adult

Risks of acute traumatic intracranial haematoma in children and adults: implications for managing head injuries.

OBJECTIVE: To determine the factors influencing the risk of an acute traumatic intracranial haematoma in children and adults with a recent head injury. DESIGN: Prospective study of incidence of risk factors in samples of patients attending accident and emergency departments and in all patients having an acute traumatic intracranial haematoma evacuated in one regional neurosurgical unit during 11 years. SETTING: Accident and emergency departments in Scotland or Teesside and regional neurosurgical centre in Glasgow. PATIENTS: 8406 Adults and children (less than or equal to 14 years) who attended accident and emergency departments and 1007 consecutive patients who had an operation for an acute traumatic intracranial haematoma. Data were complete in 8366 and 960 patients respectively. RESULTS: Overall, children were less at risk than adults (one in 2100 v one in 348 respectively). In both age groups the presence of a skull fracture and changes in conscious level permitted identification of subgroups of patients with widely differing degrees of risk. In children the absolute risk ranged from one in almost 13,000 without a fracture or altered conscious level to one in 12 for a child in a coma and with a fracture; the pattern was similar in adults, the risks in corresponding groups ranging from one in almost 7900 to one in four. CONCLUSIONS: Although children attending hospital after a head injury have a lower overall risk of a traumatic haematoma, the main indicators of risk, a skull fracture and conscious level, are the same as in adults, and the pattern of their combined effect is similar. Guidelines for managing adults with recent head injury may therefore be applied safely to children; with the increasing provision of facilities for computed tomography they should be revised to ensure early scanning of more patients with head injury.

Acute Disease

The effect of nimodipine on outcome after head injury: a prospective randomised control trial. The British/Finnish Co-operative Head Injury Trial Group.

To study the effect of nimodipine on the outcome of head injury, three hundred and fifty-two patients who were not obeying commands were randomised to placebo or nimodipine (2 mg per hour intravenously for 7 days). The 2 groups were well matched for important prognostic features. Six months after injury, more of the patients who were given nimodipine had a favourable outcome (moderate/good recovery) than in the control group, but the increase in favourable outcome (8%) was not significant statistically.

Craniocerebral Trauma

The effect of immunosuppression with whole body and regional irradiation on the development of cerebral oedema in a rat model of intracerebral haemorrhage.

A lesion simulating intracerebral haemorrhage was produced in the right caudate nucleus of rats immunosuppressed with whole body or regional irradiation. Whole body irradiation produced significant leucopaenia and thrombocytopaenia and conferred protection against cerebral ischaemia and oedema when compared to nonirradiated control animals. Local radiation to the head or torso did not confer protection.

Animals

Acoustic neuroma and the contralateral ear: recovery of auditory brainstem response abnormalities after surgery.

Auditory brainstem responses are an established technique in the diagnosis of acoustic neuroma. In several reports abnormalities are shown to occur in the contralateral ear. That these abnormalities recover has been demonstrated, but only in terms of changes in inter-peak latency. In only one case has the waveform trace showing this been published. We present a case in which a highly abnormal wave form was obtained from the ear contralateral to a large acoustic neuroma. Following excision of the lesion, the waveform reverted to a normal pattern. The literature on the subject is reviewed.

Audiometry, Pure-Tone

A clinical evaluation of the Camino subdural screw and ventricular monitoring kits.

The aim of this study was to compare readings of intracranial pressure from a ventricular catheter with those obtained from a Camino catheter-tipped transducer. The Camino transducer was evaluated in two ways: firstly, when it was inserted by a subdural screw, and secondly, when it was inserted into a ventricular catheter using a ventricular monitoring kit. Data were recorded for 376 hours for the subdural screw method and for 486 hours for the ventricular monitoring kit. Average pressure readings were calculated every 5 minutes (10 half-minute values), and regression analysis was performed. For the subdural screw method, the correlation coefficient was 0.945 (gradient, 1.04; intercept, -5.51. The results from the ventricular monitoring kit showed that the correlation coefficient was 0.901 (gradient, 0.93; intercept, -0.92. The correlation between recordings of ventricular fluid pressure and the Camino recordings obtained from both subdural screw insertions and ventricular monitoring kits was good, with the subdural screw method proving more accurate and reliable in clinical use.

Brain Injuries