Biomedical subjects
Publications and source records attributed to M S Salamat.
We report a case of fibrosarcoma arising in the pineal of a 36-year-old female patient. She died at the age 43 following biopsy, radiation therapy, tumor resection, chemotherapy, and stereotactic radiosurgery. Light microscopic study of all tissues obtained, including immunohistochemistry and electron microscopy of surgically resected tumor and autopsied tissue revealed a slowly progressing primary fibrosarcoma.
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BACKGROUND: Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF. METHODS: Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19. RESULTS: Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS: The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.
BACKGROUND: We describe a case of an intramedullary metastasis to the cervical spinal cord from a temporal gliosarcoma. CASE DESCRIPTION: A 48-year-old man with known temporal lobe gliosarcoma presented with a new onset of ipsilateral hemiparesis. A MRI scan revealed the presence of an intramedullary lesion in the spinal cord behind the body of C2. Despite repeated craniotomy, radiation, and chemotherapy, the patient succumbed to a rapidly progressive disease. CONCLUSION: The case illustrates the ability of gliosarcoma to metastasize to other locations in the neuroaxis. We believe this to be the first case report of an intramedullary spinal cord metastasis from a gliosarcoma. The pathological features and available literature are reviewed.
The authors report on the case of a 46-year-old man who presented with an intraparenchymal hemorrhage after the rupture of a nontraumatic aneurysm arising from the middle meningeal artery (MMA). A review of the literature revealed no published cases of intraparenchymal hemorrhage resulting from the rupture of an MMA aneurysm.
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BACKGROUND AND PURPOSE: Systemic invasive aspergillosis involves the brain through hematogenous dissemination. A retrospective review of 18 patients with aspergillosis involving the brain was performed in order to present imaging findings and thereby broaden the understanding of the distribution and imaging characteristics of brain Aspergillus infection and to facilitate its early diagnosis. METHODS: The neuroimaging studies of 17 biopsy- or autopsy-proved cases and one clinically diagnosed case were examined retrospectively by two neuroradiologists. The studies were evaluated for anatomic distribution of lesions, signal characteristics of lesions, enhancement, hemorrhage, and progression on serial studies (when performed). Medical records, biopsy reports, and autopsy findings were reviewed. RESULTS: Thirteen of 18 patients had involvement of the basal nuclei and/or thalami. Nine of the 10 patients with lesions at the corticomedullary junction also had lesions in the basal nuclei or thalami. Callosal lesions were seen in seven patients. Progression of lesion number and size was seen in all 11 patients in whom serial studies had been performed. Enhancement was minimal or absent in most cases. There was gross hemorrhage in eight of the 18, and definite ring-enhancement in three. CONCLUSION: Among our cases, lesions in perforating artery territories were more common than those at the corticomedullary junction. Ring enhancement and gross hemorrhage may be present, but are not necessary for the prospective diagnosis.
Ultrasonic aspirators are commonly used to resect brain tumours because they allow safe, rapid and accurate removal of diseased tissue. Since ultrasonic aspirators generate a spray of aerosolized irrigating fluid around the instrument tip, we questioned whether this spray might contain viable tumours cells that could contribute to intraoperative spread of tumour fragments. To test this hypothesis, we collected the spray produced during the resection of nine brain tumours with an ultrasonic aspirator and semi-quantitatively analysed it for tumour presence. The aerosolized irrigation fluid was found to contain intact tumour cells or clumps of tumour cells in all nine instances, and there was a trend of increasing tumour cell dispersion with increasing ultrasonic aspiration times. Further examination is required to determine if this intraoperative dispersion of apparently viable tumour fragments contributes to local neoplasm recurrence.
Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques offers opportunities to analyze mechanisms of CMV pathogenesis in a primate species. Four fetal rhesus monkeys were inoculated intraperitoneally with RhCMV early in the second trimester, and pregnancies were terminated by hysterotomy during the third trimester. Three fetuses had evidence of severe CMV disease, including intrauterine growth restriction, ventriculomegaly, microcephaly, lissencephaly, and extensive degenerative changes of the cerebral parenchyma. Histopathologic examination revealed polymicrogyria, gliosis, leptomeningitis, periventricular calcifications, and inclusion-bearing cells. These results demonstrate that the developing macaque brain is susceptible to infection with RhCMV early in the second trimester and that intrauterine infection results in neuropathologic outcomes similar to those observed in humans congenitally infected with CMV.
PURPOSE: To evaluate the in vivo and in vitro properties of collagen-coated acrylic microspheres and to compare them with polyvinyl alcohol (PVA) particles. METHODS: Samples of 100- to 300-microns, 300- to 500-microns, 500- to 700-microns, and 700- to 900-microns collagen-coated acrylic microspheres and 200- to 300-microns PVA particles were suspended in solutions of 50% saline and 50% contrast material. The samples were evaluated for quantitative and qualitative microscopic characteristics (shape, size, deformability); injectability via standardized microcatheters; degree of particulate penetration in the pig rete mirabile; and reaction of tissue to the particles in 48-hour- and 4-week-old specimens. RESULTS: The acrylic microspheres were spherical and deformable. The sample of 100- to 300-microns microspheres (n = 202) had a mean diameter of 210 microns (standard deviation, 43 microns). Hub accumulation, particle aggregation, and catheter occlusion were not observed with the microspheres (all sizes) but were noted with the PVA particles. The 200- to 300-microns PVA particles formed aggregates in the proximal rete. The 100- to 300-microns microspheres were found throughout the rete and beyond. Chronic transmural and perivascular inflammation was observed with the microspheres and the PVA particles. CONCLUSIONS: Particle aggregation and catheter occlusion do not complicate the transcatheter delivery of collagen-coated acrylic microspheres as they do with PVA particles. For a given particle and vessel size, acrylic microspheres penetrate to a much greater extent than the PVA particles. Tissue reaction to acrylic microspheres and PVA particles is similar.
OBJECTIVE: Although the features of neuronal migration have been known since the turn of the century, the serial features of neuronal migration as seen with magnetic resonance imaging (MRI) have not been described. Our objective was to provide a template of the normal appearance and the temporal pattern of neuronal migration in the human fetal brain early in the second trimester as seen with MR imaging and to correlate our findings with histological sections and atlases. METHODS: Twenty-eight normal fetal specimens, which ranged from 9 to 24 weeks of gestational age, were imaged with a 1.5 T clinical MRI unit by use of conventional spin echo, fast spin echo, and three-dimensional Fourier transformation spoiled gradient refocussed pulse sequences. RESULTS: The three-dimensional Fourier transformation spoiled gradient refocussed pulse sequence provided the highest resolution images of neuronal migration. At 13 weeks of gestational age, the germinal matrix was identified. A five-layer pattern of the fetal forebrain, which included layers of neuroblast formation and migration, could be identified at 16 to 18 weeks by MRI. The germinal matrix and layers of migrating neurons diminished considerably in size by 21 weeks. Histological studies and correlation with anatomic atlases confirmed the MRI findings. CONCLUSION: Images obtained by use of MRI with standard clinical pulse sequences can document the appearance and the temporal patterns of neuronal migration in postmortem fetal specimens. With the evolution of high-resolution MRI and faster scanning techniques, these findings may serve as a template for the in utero MRI appearance of neuronal migration and thereby compliment the antenatal ultrasonic investigation of congenital anomalies.
PURPOSE: To identify the sonographic appearance of normal fetal midface anatomy of in vitro fetal specimens and to correlate the appearance with that of in utero fetuses to determine which aspects of this anatomy can be evaluated clinically. MATERIALS AND METHODS: The midface structures of 12 normal fetal specimens were examined in the axial, sagittal, and coronal planes with ultrasound. The results were correlated with those of other modalities. One hundred consecutive, normal in utero fetuses were scanned in the same planes in an attempt to identify the same anatomic landmarks identified in the fetal specimens. RESULTS: In the fetal specimens, the upper lip (coronal plane), alveolar ridge, tooth sockets, point of fusion of primary and secondary palates (axial plane), and fusion line of the secondary palate (sagittal plane) were consistently observed. In the 100 in utero fetuses, the same anatomy was visualized in the coronal plane in 95 (95%), in the axial plane in 97 (97%), and in the sagittal plane in 26 (26%). The mean scanning time was 2.8 minutes. CONCLUSION: Important aspects of fetal midface anatomy that relate to facial clefts can be observed in utero at prenatal sonography in the coronal and axial planes.
OBJECTIVE: The aims of this study were to evaluate sonographically observable fetal cerebellar development by use of MR image and anatomic correlations to determine what aspects of this development can be visualized by sonography and to define the normal sonographic appearance of cerebellar development to assist in the differentiation of normal development from pathologic development during prenatal sonography. MATERIALS AND METHODS: The posterior fossae of 19 normal, whole, fixed fetal specimens of 11-21 weeks' gestational age were imaged by sonography and MR imaging. Images were correlated with anatomic atlases and anatomic sections. RESULTS: By 13-14 weeks, both sonography and MR imaging demonstrated the vermis between the hemispheres rostrally, but the caudal vermis was undeveloped. Although visualized on MR images, the caudal fourth ventricular roof was not yet appreciated on sonograms, giving the false impression of communication between the fourth ventricle and the cisterna magna. Separation of these CSF spaces was not appreciated at all levels sonographically until 16 weeks. CONCLUSIONS: The sonographic appearance of normal cerebellar development can resemble pathology early in the second trimester. Caution is warranted in making an early diagnosis of fetal cerebellar dysgenesis.
Aneurysms involving cerebral cortical vessels are distinctly unusual. An aneurysm of a frontal cortical artery was discovered when a craniotomy was performed to excise a well-differentiated astrocytoma in a 3-year-old child. The aneurysm was located at the site where a computed tomography-guided stereotactic biopsy of the tumor had been performed. Although significant complications of stereotactic procedures are rare, they are most often related to vascular injuries and can be devastating to affected patients. The complications of stereotactic procedures are reviewed, and suggestions to minimize the development of these unusual events are provided.
PURPOSE: To improve the prediction of individual survival in patients with intracranial astrocytomas through the analysis of volumetric tumor doubling time (VDt) and DNA ploidy. METHODS: A pilot study was retrospectively conducted on a group of 25 patients with intracranial astrocytomas in whom recurrent and/or progressive disease was observed on serial contrast-enhanced CT or MR examinations. VDt was computed using two or more data points from a semilogarithmic plot of tumor volume versus time. Size-adjusted survival was calculated using a method based on VDt and initial tumor volume to decrease the lead time bias attributable to differing tumor sizes at presentation. RESULTS: Slower VDt was associated with significantly longer survival and size-adjusted survival as determined by a univariate Cox proportional hazard analysis. Aneuploidy was a significant indicator of poor survival. Aneuploid and multiclonal astrocytomas had poor size-adjusted survivals compared with diploid astrocytomas. Grade IV astrocytomas had significantly poorer survival and size-adjusted survival compared with lower grades (I to III), which individually were not significantly correlated. However, grade IV histology was not a significant independent predictor of size-adjusted survival in a multivariate Cox model, whereas VDt and DNA ploidy remained significant. VDt also had a significant direct linear correlation to survival and size-adjusted survival. CONCLUSIONS: VDt and DNA ploidy were more sensitive than histologic grading as indicators of individual survival. Initial tumor size needs to be considered when staging and assessing survival in patients with intracranial astrocytomas.
The role of the corpus callosum in diaschisis was examined through the acute effects of stereotactic corpus callosum section on cerebral blood flow and somatosensory or auditory evoked potentials bilaterally during unilateral brain retraction ischemia, using a previously reported swine model. Cerebral blood flow and evoked potential amplitude contralateral to retraction increased during retraction with the corpus callosum intact, compared with post-callosal section values. With retraction following callosal section, there was no increase in cerebral blood flow or evoked potential amplitude contralateral to retraction. Diaschisis during the early stages of a focal, unilateral injury takes the form of a contralateral disinhibition (as measured by cerebral blood flow and evoked potentials), an effect which is lost following callosal section.
A linear hyperechoic structure in the cisterna magna, previously described as the straight sinus, was investigated during routine obstetric ultrasound (US) examination. One hundred three fetal US examinations were performed to determine the prevalence and appearance of this finding. Also, US water-bath examination of 18 fixed postmortem specimens and fetuses was performed, and results were correlated with those of gross and microscopic examination of the fetal brain. The structure was identified in 95 (92%) prenatal examinations between 15 and 38 menstrual weeks. It was located posteriorly between the cerebellar hemispheres in the cisterna magna. In those 95 cases in which it was identified, it appeared as a single echogenic line in 31 cases (33%), as two echogenic lines in 47 (49%), or as three or more lines in 17 (18%). When two echogenic lines were identified, they appeared "cystlike" in 17 (18%) of the 95 examinations. Correlation of the gross and histologic findings demonstrated these lines to represent normal subarachnoid septa rather than the straight sinus.
Systemic fibrinolytic therapy for acute stroke is no longer recommended because of resulting systemic fibrinolysis and the risk of intracerebral hemorrhage. Human tissue-type plasminogen activator (TPA) is a native enzyme that converts plasminogen to plasmin with subsequent clot lysis. The affinity for plasminogen is increased several-fold when the substrate is bound to fibrin. At appropriate dosage, "clot-specific" thrombolysis may be achieved at the surface of the thrombus without creating systemic fibrinolysis. The authors designed a study to evaluate the effect of intravenous TPA administered 2 hours after acute thromboembolic stroke in rats. This time course was chosen to simulate an analogous clinical situation. Middle cerebral artery embolic stroke was caused by intracarotid injection of 0.025 cc of human blood clot in 16 rats. Regional cerebral blood flow, measured by the hydrogen clearance technique, and electroencephalographic (EEG) recordings were obtained every 30 minutes for 5 hours after thromboembolism. Eight rats received a 1-hour infusion of intravenous TPA (1.5 mg/kg) 2 hours after injection of emboli. Ipsilateral blood flow increased significantly within 30 minutes after intravenous TPA and reached preembolic levels within 60 minutes. Blood flow did not improve in the eight control rats throughout the experiment. Power spectral analysis of the EEG recordings showed improvement in the treated group compared to the control group. Postmortem angiography revealed proximal middle cerebral artery occlusion in control animals and patent middle cerebral arteries in TPA-treated animals. Serum fibrinogen and fibrin split products were unchanged in both groups, indicating the absence of systemic fibrinolysis. There were no intracerebral hemorrhages. It is concluded that, in this rat model, TPA increases blood flow with subsequent improvement in the EEG recording after thromboembolic stroke without evidence of systemic fibrinolysis. Intravenous TPA may be useful in the treatment of acute stroke in man.