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Biomedical subjects

M A Mikhael

Publications and source records attributed to M A Mikhael.

At least 19 recordsLinked to original sources
PubMed1991

Quantitative measurements of capillary transport in human brain tumors by computed tomography.

The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (Am) and arterial plasma (Cp) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and Vp, tissue plasma vascular volume. Images of K1, k2, and Vp were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0 mu 1 gm-1 min-1 in a thalamic astrocytoma to 33.9 mu 1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and Vp varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9 mu 1 gm-1 min-1; k2 was 0.058 min-1; and Vp was 2.1 ml 100 gm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A method to quantitatively measure transcapillary transport of iodinated compounds in canine brain tumors with computed tomography.

We present a quantitative method for determining a blood-to-tissue influx constant (K1), a tissue-to-blood efflux constant (k2), and tissue plasma vascular space (Vp) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5-5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K1, k2, and Vp were calculated for each voxel of the 320 x 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus-induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K1 of meglumine iothalamate was 2.4 +/- 1.7 microliter g-1 min-1 (mean +/- SD) and Vp was 3.4 +/- 0.5 ml 100 g-1. Mean whole-brain tumor K1 values ranged from 3.3 to 97.9 microliters g-1 min-1; k2 ranged from 0.032 to 0.27 min-1; and Vp ranged from 1.1 to 11.4 ml 100 g-1. These values were reproducible in serial experiments in single animals. Independent verification of K1 values was obtained with quantitative autoradiographic measurements of alpha-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of transcapillary transport in brain tumors and may be of value in the study of human brain tumors.

Aminoisobutyric Acids↗
PubMed1990

Effect of hyperosmotic blood-brain barrier disruption on transcapillary transport in canine brain tumors.

Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t], and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t]. The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.

Animals↗
PubMed1988

Cerebral vasospasm and eclampsia.

We describe a patient who experienced focal cerebral and brainstem ischemia in the setting of postpartum eclampsia. Cerebral angiography showed spasm of large- and medium-caliber arteries. This case provides rare documentation that vasospasm may account for cerebral ischemia in eclamptic women with focal signs. This observation suggests that in such patients cerebral angiography may be informative and useful.

Adult↗
PubMed1987

Hodgkin's disease of spine: computed tomography and magnetic resonance imaging.

Early recognition of spinal block in a young man by magnetic resonance imaging and immediate surgical decompression of the spinal cord by removing the epidural mass, which proved to be Hodgkin's disease, was a determining factor in the complete neurologic recovery of the patient. Postoperative and postchemotherapy repeat magnetic resonance imaging showed complete resolution of the compressing mass. We believe that magnetic resonance imaging has a prominent role in the diagnosis and follow-up studies of spinal lesions without the inherent risks of other neurologic diagnostic procedures.

Adult↗
PubMed1987

Current concepts in neuroradiological diagnosis of acoustic neuromas.

Two hundred twenty-one cases with clinical suspicion of a cerebellopontine angle (CPA) and/or internal auditory canal (IAC) lesions were evaluated in our hospital in the last 21/2 years by various radiological modalities. Fifty-two tumors were diagnosed and surgically removed; 48 were acoustic neuromas (33 large tumors and 15 intracanalicular small tumors) and 4 meningiomas. Polytomography detected 10 lesions out of 15 (66.7%) with 5 false-negative (33.3%) and 4 false-positive (26.7%) studies. Routine CT scan visualized large and enhancing lesions (37 out of 52), but missed the small intracanalicular tumors (15 tumors) which were only visualized by CT scan combined with cisternography or magnetic resonance imaging (MRI). MRI diagnosed 23 lesions out of 23 (100%) with no false-positive or negative studies, including 8 intracanalicular small tumors missed on the routine CT scans. MRI is far more reliable in the radiological diagnosis of CPA and IAC lesions.

Cerebellar Neoplasms↗
PubMed1986

Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation.

In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

Adult↗
PubMed1985

Vascular malformations of the thalamus with normal angiograms.

We describe two patients with fatal vascular malformations of the thalamus whom we thought had gliomas. They had progressive neurological impairment with subacute onset as adults. Computed tomography showed lesions of increased density with slight post-contrast enhancement; cerebral angiography was normal. Without biopsy, they received radiation therapy without benefit. Two other patients with similar radiological studies have done well with conservative treatment. We believe that these lesions have a distinctive appearance on CT, that vascular malformations can be diagnosed, even with normal cerebral angiograms, and distinguished with reasonable certainty from gliomas.

Adult↗
PubMed1985

Lumbar spinal-lateral recess stenosis.

The syndrome of a lumbar spinal and lateral recess stenosis is characterized by pain and a variety of paresthetic symptoms occurring principally when the patient stands or walks. Sitting or lying down alleviate the symptoms promptly. The neurologic examination is characterized by a negative straight leg-raising test and a paucity of abnormal neurologic findings. The diagnosis is confirmed by a high-resolution CT scan. If conservative treatment fails, a myelogram is in order to establish a definitive diagnosis and assess the severity of neural compression prior to placing the indication for a surgical decompression of the stenotic spinal canal. The surgical procedure consists of a laminectomy and a partial facetectomy of the hypertrophied portion of the facet joint that compresses the adjacent lumbar nerve root from a dorsal direction. It is important to recognize all associated pathologic processes that must be dealt with accordingly at the same time in order to assure success of the operative procedure. The results of a surgical decompression for a lumbar spinal and lateral recess stenosis are excellent.

Cauda Equina↗
PubMed1981

Detection of pneumoencephaly secondary to mechanical ventilation in neonates.

Two newborn infants with respiratory distress syndrome developed massive systemic air embolisms and pneumoencephaly. These complications occurred during positive-pressure ventilation therapy. Intracranial gas was probably due to the rupture of cerebral vessels secondary to systemic gas embolism. The diagnostic features of plain radiographs, computed tomography, and ultrasonography in the evaluation of this unusual entity are described. The importance of early CT scans of the head is emphasized.

Embolism, Air↗
PubMed1981

Computed tomography of virally induced canine brain tumors: a preliminary report.

Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Computed tomography accurately detected all tumors over 5 mm in diameter and predicted the size of the tumors within 3 mm. The intensity of contrast enhancement was directly related to the dose of Conray-60. The area of enhancement on the CT scan correlated precisely with tumor permeability as determined histologically with horseradish peroxidase (HRP). Edema seen in CT scans correlated well with edema present in histological sections. Peritumoral edema was impermeable to both Conray-60 and HRP. The ASV-induced canine brain tumor model appears well suited for future CT studies.

Animals↗
PubMed1981

Neuroradiological evaluation of lateral recess syndrome.

Fifty asymptomatic patients and 35 with surgically proved lateral recess syndrome (LRS) were studied retrospectively to determine the depth of the normal and abnormal lateral recess. Plain radiography, polytomography, CT, and myelography of the lumbosacral area were performed. The normal and abnormal ranges are presented and the role of the various radiographic procedures in the diagnosis of LRS is discussed.

Humans↗