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Biomedical subjects

H Coakham

Publications and source records attributed to H Coakham.

At least 19 recordsLinked to original sources
PubMed2000

Miniaturised ultrasonic aspiration handpiece for increased applicability.

OBJECTIVE: At present, ultrasonic aspiration is routinely used in several fields of surgery, especially in brain and spinal micro-surgery for tumour removal. In order to broaden the access to difficult surgical sites, it is important to design highly miniaturised but still efficient handpieces. The internal resonant system, always made of high-grade materials, must be optimally dimensioned. Normally this is done semi-empirically, by successively improving the design during many iterative test steps. This method however involves several additional difficulties when the degree of miniaturisation increases. For example, small transducer weights exacerbate heat-dissipation problems and make design optimisation important. METHODS: To resolve these problems we have produced modelling software that makes it possible to simulate and automatically tune each individual interacting section of the design before it is actually manufactured, thereby assuring optimal efficiency. RESULTS: Using a new mini-handpiece, designed via the software, two cases of dissection of acoustic neurinomas were successfully performed. CONCLUSION: Using conventional physical steps for improving ultrasonic aspiration handpieces, several problems arise when the grade of miniaturisation increases, due to increasing demands. We have designed computer software for handpiece simulation. Using this model it has been possible to manufacture a highly efficient miniaturised handpiece.

Equipment Design↗
PubMed1998

Central nervous system metastasis in Wilms' tumor: a review of three consecutive United Kingdom trials.

BACKGROUND: Central nervous system (CNS) metastasis is an uncommon event in pediatric oncology, and typically occurs at the end stage of the disease. Previous reports suggest that brain metastases in patients with Wilms' tumor might behave differently. METHODS: This study reviews the data from three consecutive United Kingdom Children's Cancer Study Group trials (UKW 1, 2, and 3) focusing on this entity. RESULTS: Seven children of 1249 (0.6%) entered into Wilms' tumor studies developed CNS metastases between 2-27 months after initial diagnosis. At last follow-up 3 patients still were alive and 4 had died; the mean follow-up from recurrence in the surviving patients was 63 months. Radiotherapy and chemotherapy were administered to all surviving patients. Those patients who died had tumors with particularly aggressive features or extensive disease. CONCLUSIONS: CNS metastasis of Wilms' tumor is not in itself a terminal event. With regard to other sites of recurrence, salvage therapy can be expected to be effective in patients without other adverse prognostic features.

Central Nervous System Neoplasms↗
PubMed1998

Chemotherapy for spinal cord astrocytoma: can natural history be modified?

Standard treatment of spinal cord astrocytomas is based upon surgery, followed by radiotherapy when resection is incomplete or when histology is of high grade. Owing to the major consequences of radiotherapy on the spine in childhood, alternative therapies must be explored. The potential role of chemotherapy in the management of spinal cord astrocytoma remains to be defined. Two patients are described. The first was a 19-month-old child with an anaplastic astrocytoma of the cervical spinal cord that progressed rapidly after initial partial resection. Chemotherapy was begun according to the UKCCSG Baby Brain Protocol, with marked clinical improvement. Reassessment by MRI at 4 months showed improvement, and at the end of treatment no evaluable disease remained. The second was a 4-year-old child with a recurrent low-grade astrocytoma. Chemotherapy according to the SIOP Protocol for Low Grade Gliomas was administered for 3 months, after which marked tumour regression was seen, with neurological recovery. These patients demonstrate the potential value and low morbidity of chemotherapy in spinal cord astrocytoma. The management of this rare tumour is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for the treatment of central nervous system malignancies.

We have previously demonstrated a 33% response rate in patients with primitive neurectodermal tumours after the direct injection of 131I-monoclonal antibodies (MAbs) into the cerebrospinal fluid (CSF). Dose-limiting toxicity is myelosuppression due to the passage of the radioimmunoconjugate from the CSF to the blood compartment. This occurs at doses of 2220 MBq of 131I-MAb and above, although this is not seen in all patients studied and appears to be related to the degree of prior therapy received. Rather than attempting to improve the efficacy of this approach to the treatment of disseminated disease within the CSF compartment by dose escalation and haemopoietic rescue, we have explored the possibility of repeatedly administering the radioimmunoconjugate. Eight patients were recruited to the study, two of whom received two and six of whom received three injections of 131I-MAb. After repeated administration of 131I-MAb pharmacokinetic data revealed that, with one exception, the radioimmunoconjugate cleared from the CSF compartment with similar kinetics, while its residence time in the blood decreased with each injection. This was due to the development of an anti-mouse Ig response in the blood. Clearance of 131I-MAb from the ventricular CSF appears to be independent of the presence of an anti-mouse Ig response in this compartment. The differential clearance of the radioimmunoconjugate from the ventricular CSF and from the blood results in a marked increase in the therapeutic index that can be achieved. Up to 5920 MBq of 131I-MAb was administered as the third injection of radioimmunoconjugate and combined doses of up to 12,500 MBq were given without either haematological or neurological toxicity. These data illustrate that dose escalation and thus an increase in the dose rate delivered to tumour cells within the CSF is possible if ways are found to reduce the residence time of the radioimmunoconjugate in the blood compartment. Suggestions as to how this can best be achieved are reviewed in detail.

Adolescent↗
PubMed1995

A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates.

A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 (90Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved.

Adolescent↗
PubMed1995

Physiological identification of the auditory nerve during surgery for acoustic neuroma.

We report the design and clinical use of an electrode which can locate the acoustic nerve fibres in the normal eighth nerve and also in eighth nerves deformed by acoustic neuromas. The improvement in facial nerve preservation during acoustic neuroma surgery is partly due to the use of a facial nerve stimulator to anatomically locate the fibres. Our new acoustic nerve detector has the capability of anatomical location of cochlear fibres which may help to improve hearing preservation in selected cases of acoustic neuroma. The device functions by detecting the compound action potential evoked by no frequency auditory simulation at 500 Hz. The 500 Hz compound action potential is detected with a bipolar probe and then amplified and filtered. This results in a 500 Hz tone when the probe contacts the auditory nerve. Detection is virtually instantaneous. The acoustic nerve detector (AND) is demonstrated in a normal eighth nerve complex and its use is then described in the total removal of an acoustic neuroma with a 1 cm extracanalicular extension in which useful hearing was saved post-operatively. The present prototype may not be sensitive enough to detect the very low signals that may result when cochlear fibres are widely distorted around a large tumour or in cases where slight contusion of the nerve occurs during dissection. In all other cases the real time anatomical information is extremely helpful in guiding acoustic nerve dissection and also in monitoring the effects of petrous bone drilling.

Amplifiers, Electronic↗
PubMed1994

Cervical lymph nodes metastases from a pituitary carcinoma.

The authors report a case of a pituitary carcinoma which was locally invasive and which metastasized to cervical lymph nodes more than 9 years after the initial presentation. Cells from the tumour and metastasis immunostained with antibodies to prolactin and growth hormone, even though there was no clinical or biochemical evidence that the tumour was secreting prolactin or growth hormone. In addition, ultrastructural studies showed a monomorphic tumour with secretory granules much smaller than those normally associated with prolactin and growth hormone secretion. The clinical and pathological features suggest that the tumour is probably an acidophil stem cell adenoma, which although known to be aggressive in its clinical behaviour has not been previously reported to metastasize.

Adenoma, Chromophobe↗
PubMed1994

Facial and acoustic nerve preservation during excision of extracanalicular acoustic neuromas using the suboccipital approach.

The results are presented from a consecutive operative series of 62 acoustic neuromas in 60 patients following the introduction of improved neurophysiological monitoring techniques. Twenty-two patients had usable preoperative hearing. Thirty tumours were less than 2.5 cm diameter and 32 greater in size. Operation was via a 3-4-cm diameter retromastoid craniectomy. The internal auditory meatus was opened by an ENT surgeon (RM) using a drill and the facial nerve identified by stimulation. The tumour was then centrally evacuated by a neurosurgeon (MT/HC) using an ultrasonic aspirator, and the thin exterior part of the tumour carefully dissected off the nerves in or around the capsule with constant stimulation and monitoring of facial EMG, BSAEP and electrocochleography. A new type of stimulation probe has been designed and coupled to a stimulator/integrator/tone burst generator (SB) so that continuous immediate direct feedback to the surgeon is possible. A variable amplitude discriminator rejects baseline EMG (> 50 microV) and a gating circuit prevents stimulus artefact (during monopolar stimulation) from causing interference. By these means the VII nerve could be identified even when translucent and undefinable as a nerve bundle. Anatomical preservation was possible in 98% of VII nerves. Full facial function was present in 20 cases immediately postoperatively. Full delayed recovery occurred in 23 cases giving an eventual total in House Grade I of 69%. Seven other cases recovered to House Grade II. There was therefore 81% satisfactory facial nerve function. This percentage is exactly the same for larger and for smaller tumours. Anatomical preservation of the VIII nerve was achieved in 24/62 (39%) of the whole series and 11/16 (69%) of those with a hearing loss of < 50 dB. Functional preservation of hearing described as usable by the patient (< 65 dB) was achieved in 7/22 cases (32%), 3/13 (23%) in tumours < 2.5 cm and 4/9 (44%) in those > 2.5 cm diameter. Hearing preservation of < 50 dB in patients with preoperative hearing threshold < 50 dB and tumours of < 2.5 cm was 3/11 (27%). Monitoring by BSAEP and ECochG was technically unsatisfactory because the responses were affected by drilling and stimulation. Acoustic nerve preservation should be attempted in all cases with measurable hearing, regardless of tumour size.

Ear Neoplasms↗
PubMed1994

A mutation in the neurofibromatosis type 2 tumor-suppressor gene, giving rise to widely different clinical phenotypes in two unrelated individuals.

We have sought mutations in the recently identified neurofibromatosis type 2 (NF2) tumor-suppressor gene in a large panel of NF2 patients, using PCR-based SSCP and heteroduplex analysis, followed by cloning and sequencing of appropriate PCR products. Two unrelated NF2 patients were found to have identical nonsense mutations caused by a C-to-T transition in a CpG dinucleotide that is a potential mutational hot spot in the NF2 tumor-suppressor gene. Unexpectedly, the two individuals had widely different clinical phenotypes, representing the severe Wishart and mild Gardner clinical subtypes. Analysis of DNA samples from different tissues of the mildly affected patient suggests that he is a somatic mosaic for the mutation.

Adolescent↗
PubMed1993

Cerebellopontine angle epithelial cyst. A case report.

A case of epithelial cyst in the cerebellopontine angle is reported. The cyst wall showed glandular epithelium with areas of non-keratinized stratified epithelium and flattened cuboidal cells. The glandular areas stained positively with antibodies to cytokeratin. In addition, the cyst wall contained areas of arachnoid tissue. This, and the unusual position of the cyst, suggest that the epithelial elements in the cyst wall may be metaplastic in origin. Similar previously described cysts were considered to be endodermal in origin.

Adult↗
PubMed1992

Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma homing into the brain.

We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one secondary) were stained with monoclonal antibodies to LFA-1 alpha chain (CD11a), beta chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat monoclonal antibodies to the human and mouse high endothelial venule antigens HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was also studied in mice with severe combined immunodeficiency (SCID) mice, bearing intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed LFA-1 alpha (one strongly, one intermediate, nine weakly). Nine of the tumors weakly expressed LFA-1 beta.. Nine of twelve tumors weakly expressed ICAM-1. In six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain from two patients and non-tumor cerebral blood vessels showed no staining with CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1 antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains showed no staining with either HECA 452 or MECA 79.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A pilot study of monoclonal antibody targeted radiotherapy in the treatment of central nervous system leukaemia in children.

A pilot study was performed to investigate the toxicity, pharmacokinetics and therapeutic effect of intrathecally administered radiolabelled monoclonal antibody (MAb) in patients with meningeal acute lymphoblastic leukaemia (ALL). Six children aged 3-16, in second or subsequent central nervous system (CNS) relapse of ALL, received between 629 and 1480 MBq of 131Iodine conjugated to either MAb HD37 (CD19, n = 2) or WCMH15.14 (CD10, n = 4). Conjugate was administered as a single injection either via an Ommaya reservoir (n = 4) or by lumbar puncture (n = 2). Acute toxicity was manifest by headache (n = 4), nausea and vomiting (n = 4) and pyrexia (n = 2). All acute symptoms resolved within 72 h. Transient myelosuppression occurred in three patients. Pharmacokinetic studies included investigation of whole body, blood and CSF clearance of isotope. 131I was seen to clear from the CSF by biexponential kinetics. Five patients responded to therapy. In four, the CSF became clear of blast cells at both 2 and 4 weeks following antibody injection, but evidence of relapse was seen at 6 weeks. The fifth patient, with blast cells present on a cytospin preparation, responded to therapy over an 8-week period but relapsed at 12 weeks. This study demonstrates the potential of targeted radiotherapy in CNS ALL, but further studies are necessary to increase the length of remission.

Adolescent↗