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Biomedical subjects

A H Kaye

Publications and source records attributed to A H Kaye.

At least 73 records · Page 4Linked to original sources
PubMed1990

Selective uptake of hematoporphyrin derivative into human cerebral glioma.

The uptake of hematoporphyrin derivative (HpD) into human cerebral glioma was measured using a porphyrin extraction technique. Patients with cerebral glioma were injected with HpD at a dose of 5 mg/kg body weight 24 hours before surgery and photoradiation therapy (PRT). Biopsies of tumor, and where possible, adjacent brain and normal brain were taken for analysis of HpD uptake. HpD was selectively localized into all grades of glioma, and there was a direct correlation between the grade of glioma and HpD level in the tumor. The levels were highest in glioblastoma multiforme (mean uptake of 5.9 micrograms of HpD/g of tumor wet weight) and lower in the intermediate-grade anaplastic astrocytoma (mean uptake of 2.4 micrograms/g of tumor) and the low-grade astrocytoma (1.6 micrograms/g of tumor). Uptake into normal brain tissue taken from HpD-sensitized patients was 0.2 microgram/g. HpD was also localized into the "brain adjacent to tumor" region. The selective uptake into the low-grade glioma suggests that PRT may be of use as an adjuvant therapy in these tumors and the detection of HpD in this region indicates that PRT may control the spread of tumor infiltrating into the adjacent normal brain.

Brain Neoplasms↗
PubMed1989

Photoradiation therapy of brain tumours.

Present methods for treating cerebral glioma are inadequate and the possible benefit of using photosensitization therapy to obtain improved local control of the tumour has been studied in the laboratory and in clinical trials. The biological basis for photoradiation therapy and the laboratory studies and clinical trials using photoradiation to treat cerebral tumours are discussed. Photoradiation therapy results in selective tumour destruction in an intracerebral glioma model with an effect up to 1 cm in depth. Clinical studies using haematoporphyrin derivative and up to 260 J/cm2 of red light from laser sources indicate that the therapy is well tolerated and may be of value as an adjuvant treatment of cerebral tumours.

Animals↗
PubMed1988

Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme.

Primary brain tumors of glial origin often overexpress epidermal growth factor receptors (EGF-Rs). This may be associated with amplification of the EGF-R gene. We have examined tissue from 23 glioblastoma multiforme tumors and found amplification and rearrangement of the EGF-R gene in four of these. The cytoplasmic domain of the EGF-R gene was invariably amplified in these four tumors, while the epidermal growth factor binding domain was not uniformly amplified in three of these tumors. Western blot analysis of the EGF-R protein revealed high levels of a truncated EGF-R protein in two of the four tumors with EGF-R gene amplification.

Cytoplasm↗
PubMed1988

A quantitative assessment by flow cytometry of the preservation of the Thy-1 antigen by various fixation procedures.

A quantitative assessment of the effects of various fixatives upon the preservation of the Thy-1 surface antigen has been undertaken. A panel of 5 monoclonal antibodies (MAbs) have been reacted with mouse lymphocytes treated with various fixatives, and their binding analysed by flow cytometry using a fluorescence activated cell sorter. It was found that 2% paraformaldehyde (PFA) provided the best antigenic preservation, as detected by both the anti Thy-1.1 and anti Thy-1.2 MAbs. The effectiveness of 2% PFA fixation is further demonstrated by the immunohistochemical identification of the Thy-1 antigen in sections of mouse cerebellar cortex.

Animals↗
PubMed1988

A review of photoradiation therapy in the management of central nervous system tumours.

Photoradiation therapy depends on the selective retention of a photosensitizer within the tumour followed by activation of the sensitizer by irradiating the tumour with light of the appropriate wavelength. The present methods of treatment of cerebral glioma are inadequate and the possible benefit of utilizing photoradiation therapy to obtain improved local control of the tumour has been studied in the laboratory and in clinical trials. The biological basis for photoradiation therapy and the laboratory studies and clinical trials involving the use of photoradiation therapy to treat cerebral tumours are discussed.

Animals↗
PubMed1988

Photoradiation therapy and its potential in the management of neurological tumors.

Photoradiation therapy is a form of local treatment that depends on the selective retention of a photosensitizer, such as hematoporphyrin derivative (HpD), by the tumor followed by treatment with light of an appropriate wavelength to activate the sensitizer in the tumor. The selective uptake of HpD by cerebral tumors has been demonstrated both in laboratory animal model studies and in clinical studies, and selective destruction of intracerebral tumors has been demonstrated in animal glioma models. The biological basis for photoradiation therapy and, in particular, the mechanisms for the selective uptake of the sensitizer into the tumor and the destruction of tumor with photoradiation therapy are discussed. Current evidence suggests that singlet oxygen is the major intermediary leading to cell damage, although other radicals such as hydrogen peroxide and hydroxyl radicals may be involved. Other studies suggest that the initial damage is to the blood vessels, and the tumor subsequently undergoes ischemic changes. Sixty-four patients treated with photoradiation therapy have been reported in the literature. The initial clinical studies were disappointing in their therapeutic effect but these studies often included treatment of recurrent gliomas and low doses of light were used. Technical advances, particularly in laser technology, have enabled more effective photoradiation therapy and the clinical trials are reviewed.

Adolescent↗
PubMed1987

Nature of the tumor-localizing components of hematoporphyrin derivative.

Hematoporphyrin derivative linked by ether bonds (HE) was synthesized by unambiguous procedures in order to compare its properties to hematoporphyrin derivative (HpD). Reverse phase high performance liquid and gel filtration chromatography were used to compare the HE derivatives to HpD. The cellular uptake of HE derivatives was compared to HpD using the WEHI 3B (D+) cell line and was shown to be taken up to a degree and in a manner similar to HpD. The efficiency of HE porphyrins as photosensitizers was compared to HpD using the V79 cell line. HE porphyrins were more efficient in sensitizing the V79 cells than was HpD. The in vivo tumor localizing properties of HE porphyrins were compared to HpD in CBA mice bearing the C6 cerebral glioma, and BALB/c mice bearing the EMT6 mammary tumor. HE derivatives localized in both tumor models as effectively as HpD. We conclude that the properties of ether linked hematoporphyrin derivatives are very similar to properties of HpD.

Animals↗
PubMed1987

Dynamic CT brain scanning in the haemodynamic evaluation of cerebral arterial occlusive disease.

Dynamic cerebral CT scanning (DCT) was used to quantitatively analyse the haemodynamic effects of extracranial and intracranial arterial occlusive lesions in 17 patients with TIA's or minor cerebral infarcts. Using DCT and gamma variate curve fitting, mean transit times were determined for the terminal internal carotid arteries, middle cerebral arteries and middle cerebral-supplied Sylvian cortex at the level of the Circle of Willis. Six patients were studied sequentially, four before and after transcranial bypass surgery. No arterial or tissue delays were found in patients without haemodynamic arterial lesions or cortical infarcts. Seven of nine patients with haemodynamic, extracranial carotid lesions showed ipsilateral delays in arterial or tissue transit times. Tissue delays usually correlated with CT or clinical evidence of infarction. Improved haemodynamics in patients re-studied correlated with the effects of surgery or clinical recovery. DCT has several important limitations but has the potential to provide additional haemodynamic information about the cerebral circulation in selected patients with cerebral arterial occlusive disease.

Adult↗
PubMed1987

Analysis of dynamic computed tomography scan brain images.

Dynamic computed tomography (DCT) of the brain can be used to study the transit time of first passage of a bolus injection of intravenous contrast medium. Comparison of cerebral perfusion with corresponding sites in the left and right cerebral hemispheres is of diagnostic interest because a real difference may be indicative of differential damage. A method for estimating the mean transit time and approximating its standard error, by assuming a gamma function for the response curve and an appropriate error structure, is presented. Expressed as log-linear regression, estimation is achieved by maximum likelihood using a statistical package such as GLIM or SPSSX. Statistical comparison of the mean transit time to or between corresponding sites can be made; issues of model fit and biologic interpretation need to be considered as an integral part of statistical inference. These methods enable users of CT equipment (without specific software for estimation of mean transit time) to use any log-linear routine for diagnostic purposes. An example of the fit procedure and interpretation in the light of clinical evidence is given.

Brain↗
PubMed1987

Photoradiation therapy causing selective tumor kill in a rat glioma model.

We evaluated the effect of photoradiation therapy using the photosensitizer, hematoporphyrin derivative (HpD), and the argon-pumped rhodamine dye laser tuned to 630 nm in the rat C6 glioma model. Animal models of cerebral glioma were established by implanting 10(6) C6 glioma cells in adult Wistar rats, and craniotomies were performed on normal and tumor-bearing animals. HpD in doses of up to 80 mg/kg followed by craniotomy resulted in no damage to the normal brain, and laser light at doses of up to 1200 joules/cm2 without the prior administration of HpD produced no significant damage if the craniotomy site was irrigated with normal saline to prevent a temperature rise. Photoradiation caused no brain necrosis in non-tumor bearing animals if less than 20 mg of HpD per kg and 200 joules of red light per cm2 were used. At higher doses of HpD and light, cerebral necrosis did occur. The depth of necrosis depended on the dose of both HpD and light. Treatment with 40 mg of HpD per kg and 400 joules of light per cm2 resulted in cerebral necrosis in 50% of the treated animals. The mean depth of brain necrosis was 1.3 mm. Selective kill of a cerebral glioma with sparing of the normal brain was achieved with photoradiation therapy at doses of HpD of less than 20 mg/kg and light doses of less than 200 joules/cm2. At these doses, the mean depth of tumor kill was 4.5 mm. In 2 of 10 animals, the depth of tumor destruction was more than 6 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Pachymeningitis cervicalis hypertrophica. Case report.

The authors present the case of a 25-year-old man with idiopathic pachymeningitis hypertrophica that caused cervical radiculopathy. Decompressive surgery produced significant neurological improvement. The etiology and management of the condition are discussed and the literature is reviewed.

Adult↗
PubMed1987

Adjuvant high-dose photoradiation therapy in the treatment of cerebral glioma: a phase 1-2 study.

A Phase 1-2 study of high-dose photoradiation therapy was performed in 23 patients with cerebral tumors. Twenty-two patients had high-grade gliomas (13 glioblastomas, six recurrent glioblastomas, two anaplastic astrocytomas, and one recurrent anaplastic astrocytoma) and one had a right frontal metastasis from a carcinoma of the lung. Hematoporphyrin derivative was administered to these patients in a dose of 5 mg/kg and, 24 hours later, they all underwent a craniotomy with radical excision of the tumor. The tumor bed was then irradiated with 630 nm of laser light from either an argon dye laser or a gold metal vapor laser for between 43 and 94 minutes, receiving total doses of 70 to 120 J/sq cm (six cases) or 120 to 230 J/sq cm (17 cases). The temperature of the tumor bed was kept below 37 degrees C by irrigation. Fifteen patients who developed new tumors underwent postoperative radiotherapy (45 Gy in 20 divided doses). There was no evidence of increased cerebral edema and no other toxicity from the therapy. All patients were discharged from the hospital within 18 days of surgery. Four of seven patients with gliomas have suffered a further recurrence at 12 to 16 weeks, and two of 15 patients with primarily treated gliomas experienced recurrence at 3 and 13 months following therapy. Fifteen patients have had no recurrence of their tumor and are alive and well at a median follow-up period of 7 months (range 1 to 16 months). It is concluded that photoradiation therapy using 5 mg/kg of hematoporphyrin derivative and 630 nm light at doses of up to 230 J/sq cm can be used as an adjuvant to surgery and radiotherapy with no additional complications.

Adolescent↗
PubMed1986

Development of a xenograft glioma model in mouse brain.

Xenograft intracerebral glioma models have been developed in normal mice by growing the rat C6 glioma in either adult or neonatal mouse brains. Using this tumor line it was possible to grow discrete intracerebral gliomas in either CBA or AKR adult mice or neonatal mice. The size of the tumor mass and length of survival was directly related to the number of tumor cells injected and the time after implantation. To obtain localized intracranial tumor growth cells were suspended in a 1% agarose solution before implantation. Following injection of 10(6) cells into the frontal lobe of adult CBA or AKR mice, discrete tumor masses greater than 4 mm in diameter were obtained in 90% of animals at 14 days, and the largest tumors in adult mice occurred between 21 and 28 days after implantation. The tumor size following implantation of 10(6) cells was significantly greater than with 10(5) cells at 7 days (P less than 0.05) and at 14 and 21 days (P less than 0.01). Less than 60% of mice of BALB/c, RIII, or C57 black strains developed tumors greater than 4 mm diameter at 14 days after intracerebral injection of 10(6) C6 cells. Using neonatal mice it was found that when 10(5) cells were injected intracranially tumors greater than 4 mm in diameter developed in 14 of 15 animals within 2 weeks (CBA mice). Similar results were seen in the RIII, AKR, C57 black, and BALB/c strains. Longer growth periods resulted in larger tumors, up to 8 mm in diameter (6 of 10 animals at 20 days). The tumors in the neonatal animals were not as discrete as in the adult mice, and tumor often spread to the meninges and into the lateral ventricles. The tumor harvested from the brain had a cloning efficiency of 1.2 +/- 0.4% (SD). A panel of monoclonal antibodies was raised to the C6 glioma, and this was used to define clearly the margins of the tumor within the brain. The xenograft mouse models should prove useful for the study of the therapy of gliomas.

Animals↗
PubMed1985

Uptake and retention of hematoporphyrin derivative in an in vivo/in vitro model of cerebral glioma.

Photoirradiation treatment depends on exposing tumors to a photosensitizer and light to achieve selective tumor kill. We evaluated the kinetics of uptake of a photosensitizer, hematoporphyrin derivative (HpD), in an animal model of cerebral glioma to ascertain the optimal time for photoirradiation therapy. Animal models of cerebral glioma were established by implanting cells from the rat C6 glioma cell line into rat brains or as xenografts in adult mouse brains. C6 cells (10(7] injected into the frontal lobe of adult Wistar rats produced intracranial tumors greater than 5 mm in diameter in 90% of the animals at 21 days. Tumors greater than 4 mm in diameter developed in adult mouse brains within 14 days after 10(6) cells were implanted into the frontal lobe. These two tumor models were used to investigate the localization of HpD. After HpD administration, its presence was detected in fresh, unfixed specimens by fluorescence emission after excitation with an ultraviolet lamp. Fluorescence was determined quantitatively by an image analysis method using an optical data digitometer. The fluorescence, which was highly localized selectively to the intracerebral tumor, was just detectable 5 minutes after an intravenous injection of HpD. Patchy, bright fluorescence was evident 4 hours after injection, and the tumor was uniformly fluorescent after 6 hours. A minimal dose of 0.5 mg of HpD per kg of body weight was necessary to produce detectable fluorescence, and the dose of HpD necessary to produce detectable fluorescence was 4 mg/kg of body weight. The intracarotid route of administration was unsatisfactory because seizures were induced, and intrathecal injection did not produce significant fluorescence in the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗