Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption.

In contrast to reports of extensive hypoxia in human gliomas in situ measured by pO2 histography, non-invasive methods of assessing glioma oxygenation, including nitroimidazole binding, have yielded surprisingly contradictory results. In order to investigate the relationship of necrosis, hypoxia, nitroreductase activity and cellular respiration in human gliomas, subcutaneous models using the human glioma cell lines M059K, M006 and M010b were developed in the murine SCID host. Intracranial growth of the M006 line was achieved in nude rats. The nitroreductive capacity of glioma cell lines was assessed and found to be similar to transplanted tumours previously reported in the literature. This suggests that if substantial numbers of viable hypoxic cells were present in situ in gliomas, then nitroimidazole-binding techniques should be capable of identifying them. Inter-tumour variability in the amount of necrosis was seen. M006 xenografts growing in subcutaneous and intracranial sites revealed extensive necrotic regions histologically, some of which were surrounded by cells labelled heavily for [3H]misonidazole, while other areas were lightly labelled. Similar binding patterns were seen for subcutaneous M059K tumours, while subcutaneous M010b tumours display necroses of which almost all were surrounded by heavily labelled cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which venous pO2 concentrations are of the order of 2-5%, were two to sevenfold less than those of the same lines grown as monolayers in vitro under oxygen concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen conformers', in that their rate of oxygen consumption appears to vary with the availability of oxygen. Together with the misonidazole-binding data, the results in this glioma tumour model are consistent with coordinate inhibition or down-regulation of respiration under moderate hypoxia.

Autosomal dominant keratitis: a possible aniridia variant.

OBJECTIVE: To describe the findings in a family with hereditary keratitis. DESIGN: Case series. SETTING: Eye genetics clinic at a university-affiliated hospital in Edmonton. PATIENTS: Fifteen affected members, nine female and six male, of a four-generation family with hereditary keratitis. RESULTS: The pattern of transmission was consistent with autosomal dominant inheritance. The disorder was characterized by the presence of a circumferential band of opacification and vascularization at the level of Bowman's membrane adjacent to the limbus. Progression toward the central cornea occurred in some instances. Penetrating keratoplasty was performed in certain cases when the visual axis was involved and the acuity deteriorated. Histopathological studies confirmed the inflammatory nature and the anterior stromal localization of the keratitis. Thirteen of the affected members in whom a detailed fundus examination was possible had macular hypoplasia. Several had abnormalities of the iris, including iris stromal defects and ectropion uveae. CONCLUSIONS: The presence of macular hypoplasia in association with the iris and corneal changes suggests that autosomal dominant keratitis is likely a variant of aniridia.

Fatal rebleeding from a dural arteriovenous malformation of the posterior fossa: case report with pathological examination.

A seventy-year-old woman suffered a fatal cerebellar rehemorrhage from a large venous aneurysm associated with a dural arteriovenous malformation (AVM) of the posterior fossa. The malformation, fed by branches of the right vertebral, occipital and middle meningeal arteries, had a nidus in the transverse sinus wall with a pedunculated extension reaching the pial surface of the adjacent cerebellum, from where the malformation drained exclusively into an aneurysmal cerebellar vein. There was no associated venous sinus obstruction. Histopathological examination of the venous sinuses, arteriovenous malformation and venous drainage is described and these findings as they relate to the pathogenesis of dural AVMs are discussed. Vascular malformations of the dura mater do not appear to be a single clinical or pathological entity. The serious risk of hemorrhage from a parenchymal venous aneurysm is emphasized.

Cytology of atypical and malignant meningiomas in intraoperative crush preparations.

Six cases of atypical and malignant meningioma studied by intraoperative crush preparations are reported. Four atypical meningiomas were characterized by large cohesive and dyshesive cell clusters showing slightly pleomorphic nuclei and scant cytoplasm. The papillary meningioma yielded dyshesive groups of pleomorphic cells with variable and well-defined cytoplasm. The malignant meningioma, hemangiopericytic type, showed dyshesive cells with scant, ill-defined cytoplasm and spindle-shaped or vesicular nuclei.

Comparison of intrathecal administration of urokinase and tissue plasminogen activator on subarachnoid clot and chronic vasospasm in a primate model.

Safety and efficacy of the thrombolytic agent urokinase (URO) in the elimination of subarachnoid clot and prevention of chronic vasospasm was compared with tissue-type plasminogen activator (rt-PA) in a blind, randomized placebo-controlled trial. Twenty monkeys were randomly assigned to one of five groups of four. Each group underwent baseline cerebral angiography followed by bilateral craniectomy and experimental subarachnoid hemorrhage. An Ommaya reservoir was inserted on the right side with its catheter placed into the ipsilateral subarachnoid space. Twenty-four hours later, depending upon group assignment, the animals received 100,000 IU URO, 200,000 IU URO, 1 mg rt-PA, 2 mg rt-PA, or the equivalent volume of normal saline (control group). On Day 7, angiography was repeated and the animals were killed. One animal died as a result of complications during the baseline angiography, presumably due to blood loss and prolonged anesthesia, and a replacement animal was obtained. No animals demonstrated any delayed neurological deficits. The study demonstrated that a single intracisternal bolus injection of rt-PA, 2.0 mg in 2 ml sterile water, or URO, 200,000 IU in 2 ml sterile water, 24 hours after induction of experimental subarachnoid hemorrhage in primates, was equally effective in thrombolysing ipsilateral clot, but neither dosage prevented angiographic vasospasm. Vasospasm occurred bilaterally in all groups. Whereas gross subarachnoid clot was found bilaterally in all animals in the placebo group and both smaller-dose URO and rt-PA groups, right-sided subarachnoid clot was virtually absent and left-sided clot reduced in both higher-dose URO and rt-PA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative cytomorphology of pituitary adenomas and oligodendrogliomas in intraoperative crush preparations.

Minute fresh tissue fragments from 20 pituitary adenomas and 18 oligodendrogliomas were crushed between two glass slides and stained with hematoxylin and eosin for cytologic examination. These two tumor types displayed distinctive cytologic features that may permit their correct identification. Pituitary adenomas were characterized by single and clustered tumor cells with monomorphic, round or vesicular nuclei that were commonly denuded of cytoplasm. Rare well-preserved tumor cells showed well- or ill-defined, variable and granular cytoplasm. Oligodendrogliomas showed cells with monomorphic or slightly pleomorphic nuclei and scant, fibrillary, wispy cytoplasm, commonly arranged in clusters or around circular and empty spaces.

Cerebral phaeohyphomycosis caused by Xylohypha bantiana, with a review of the literature.

A 76-year-old male with chief complaints of back and right leg sciatica was hospitalized. His abdominal CT scan revealed lumber spondylitic stenosis. A laminectomy was performed. Postoperatively, he became febrile, aphasic and had grand mal seizure. A left craniotomy of the front abscess, seen in the CT scan, was performed. H and E stained smears of drainage revealed dematiaceous, septate hyphae. Cultures of the abscess drainage grew an olivaceous-grey fungus. Based on macro- and micro-morphological characters, growth at 42 degrees C, and exoantigenic analysis, the patient's fungus was identified as Xylohypha bantiana. Treatment with amphotericin B and 5-fluorocytosine was initiated. Despite surgical procedures and antifungal therapy, the patient's condition deteriorated and he died a few weeks later due to cerebral edema. The case reported here is the first microscopically, culturally, histopathologically and exoantigenically proven case of phaeohyphomycosis caused by X. bantiana in the province of Alberta and from Canada. A review of the literature on cases of X. bantiana infections has also been presented.

Etiology of cerebral vasospasm in primates.

A primate model was used to determine whether oxyhemoglobin (OxyHb), methemoglobin (MetHb), or bilirubin is likely to be responsible for cerebral vasospasm following subarachnoid hemorrhage (SAH). Forty cynomolgus monkeys were randomly assigned to one of five groups. On Day 0, each animal underwent angiography followed by right craniectomy and placement of an Ommaya reservoir with its catheter adjacent to the right middle cerebral artery (MCA). The animals received intrathecal injections twice a day for 6 days of one of the following solutions: mock cerebrospinal fluid (CSF); OxyHb; MetHb; bilirubin; or supernatant fluid from an incubated mixture of autologous blood and mock CSF. On Day 7, angiography was repeated and the animals were killed. Comparison of angiograms obtained on Day 0 and Day 7 of the experiment showed significant vasospasm of the right MCA and the right anterior cerebral and internal carotid arteries in the animal groups that had received OxyHb or supernatant fluid. There was a smaller reduction in diameter of the same vessels in the bilirubin group (not statistically significant), while no effects were observed in the groups receiving MetHb or mock CSF. Electron microscopy of the right MCA's gave results consistent with the angiographic findings. One monkey in the OxyHb group developed a delayed-onset right MCA infarction. These data suggest that OxyHb is the cause of cerebral vasospasm following SAH.

Juvenile xanthogranuloma of the corneoscleral limbus.

Juvenile xanthogranuloma presenting as an isolated corneoscleral lesion is rare. We report such a case in a 5-year-old boy who required lamellar sclerokeratectomy to the level of Descemet's membrane. Ten months after treatment by total excision and lamellar corneoscleral grafting with donor tissue there was no evidence of recurrence. We discuss the clinical and histologic features of this disorder, the differential diagnosis and treatment options.

Primate brain tolerance to temporary focal cerebral ischemia during isoflurane- or sodium nitroprusside-induced hypotension.

Isoflurane has properties that suggest it may provide cerebral protection from ischemia. This study compared, in primates, neurologic outcome after a 45-min period of temporary focal ischemia during hypotension induced with either isoflurane or sodium nitroprusside (SNP). Fourteen macaque monkeys were studied. Seven animals received halothane and seven isoflurane anesthesia during surgical preparation. After transorbital exposure of the middle cerebral artery (MCA), in the halothane group, the inspired halothane was reduced to 0.75% and the mean blood pressure (BP) reduced to 50 mmHg by the infusion of SNP. In the isoflurane group, the isoflurane was titrated to reduce mean BP to 50 mmHg. Stable hypotension was maintained for 90 min, which included a 45-min period of MCA occlusion. Monitoring included intraarterial blood pressure, arterial blood gases, EEG, somatosensory evoked potentials (SEP), and temperature. After the procedure the animals were allowed to awaken and were assessed neurologically every 8 h. On the third postoperative day, they were reanesthetized and underwent magnetic resonance imaging (MRI) and SEP recording. Thereafter, they were killed with iv KCl and the brains fixed for neuropathology. All animals survived the surgical procedure, but two animals receiving halothane and none receiving isoflurane died prematurely (P less than 0.2). The SEP disappeared in all animals within 10 min of MCA occlusion and then returned partially or completely. There was no difference between groups in neurologic scores, in the size of the lesion as assessed by MRI (isoflurane 15.7 +/- 6%, halothane/SNP 10.5 +/- 4%), or in the extent or severity of the neuropathologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

New long-wavelength Nd:YAG laser at 1.44 micron: effect on brain.

A wavelength-shifted Nd:YAG laser, tuned to coincide with the infrared absorption peak of water at 1.44 microns, was used to make lesions in normal rabbit brain. A total of 48 lesions were made with power up to 20 W, with energy up to 40 joules, and with two different spot sizes. These lesions were compared to lesions made with 1.06 microns radiation from an Nd:YAG laser under identical operating conditions. Measurements of blood-brain barrier damage and width, depth, and volume of tissue affected were obtained 30 minutes after placement of the lesions. It was found that 1.44-microns lesions produced photoevaporative tissue loss at the highest intensities used. The layer of coagulated tissue remaining after photovaporization had a mean thickness of 0.6 mm irrespective of the volume of tissue removed. There was no photovaporization in the 1.06-microns lesions. In addition, the amount of peripheral edema per unit volume of tissue coagulated was approximately half at the 1.44-microns wavelength. These findings suggest that the 1.44-microns Nd:YAG laser may be a useful surgical instrument since it combines the photoevaporative effect of the CO2 laser while maintaining the advantages of the conventional Nd:YAG laser (quartz fiber delivery and effective hemostasis).

Cytology of neuroectodermal tumors of the brain in crush preparations. A review of 56 cases of deep-seated tumors sampled by CT-guided stereotactic needle biopsy.

Fifty-six brain tumors of neuroectodermal origin were sampled by computed tomographic stereotactic needle biopsy. Crush preparations prepared from tiny tissue fragments displayed distinctive cytologic characteristics of different tumor types in 77% of the cases. The adjunctival value of crush preparations to frozen section diagnosis is discussed, and the cytologic features of different types of neuroectodermal brain tumors in crush preparations are illustrated.

Cytology of meningiomas and neurilemomas in crush preparations. A useful adjunct to frozen section diagnosis.

Twenty-three meningiomas and 14 neurilemomas were studied by frozen section and crush-preparations techniques. These two types of tumors displayed distinctive cytologic pictures, permitting a correct identification in all cases. Six cases of deeply seated and unusually located meningioma and neurilemoma with equivocal or erroneous frozen section diagnoses were correctly diagnosed cytologically in the crush preparations.

Chondroid chordoma of the skull base diagnosed by squash-smear technique.

Squash-smears of tissue from a chondroid chordoma arising from the skull base of a 26-year-old white man showed numerous single and clustered physaliferous cells with multiple intracytoplasmic vacuoles, and atypical cartilaginous cells in an amorphous myxoid background.

Effects of photoradiation therapy on normal rat brain.

Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.