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  • Author or Editor: F. Curtis Dohan Jr x
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W. Craig Clark, James D. Acker, F. Curtis Dohan Jr. and Jon H. Robertson

✓ Five cases of sarcoid presenting as an intracranial tumor are reported. In one instance, the lesion presented as a tumor in the cerebellopontine angle, a site not previously reported for the initial presentation of sarcoid isolated to the central nervous system. The role of computerized tomography, surgery, and steroid therapy is discussed. In the absence of pulmonary involvement, serum angiotensin-converting enzyme levels do not appear to be helpful in predicting steroid response.

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Erich W. Wolf, Amit Banerjee, Jill Soble-Smith, F. Curtis Dohan Jr., Richard P. White and James T. Robertson

Object. Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH).

Methods. The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 µmol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 µmol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 µmol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-µmol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8.

The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 µmol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen.

Conclusions. This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

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James T. Robertson, Albert L. Meric, F. Curtis Dohan Jr., John B. Schweitzer, Jerome R. Wujek and Shafik Ahmad

✓ Spinal peridural fibrosis following total laminectomy in New Zealand White rabbits was significantly decreased by the intraoperative application of GT1587, a semi-synthetic carbohydrate polymer. The application of a similar polymer, GT1043, or phosphate-buffered saline (PBS) was not as effective. Laminectomies were performed at L-2 and L-4 in 25 rabbits. Absorbable gelatin sponge soaked with GT1043, GT1587, or PBS was applied in a blinded fashion to the operative sites, with untreated (sham) laminectomy sites serving as controls. Animals were sacrificed after 2 or 4 weeks. The extent of peridural fibrosis was evaluated by gross microdissection and histological analysis. Dense scar formation and dural adhesions were evident at both time intervals in the sham- and PBS-treated laminectomy sites. The sites treated with GT1587 showed significantly decreased peridural scar formation and dural adhesions, whereas GT1043 treatment caused modest reduction of scar formation at only the 2-week examination. The healing of skin and lumbosacral fascia was not affected by treatment of the laminectomy site with GT1587. These results suggest that GT1587 may prove beneficial in preventing postlaminectomy dural adhesions and peridural fibrosis in humans.

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W. Craig Clark, F. Curtis Dohan Jr., Timothy Moss and John B. Schweitzer

✓ Neoplastic angioendotheliomatosis is a rare disorder usually characterized by primarily cutaneous or neurological symptoms. Approximately 40 cases of malignant angioendotheliomatosis with primary central nervous system (CNS) symptoms have been reported. Some investigators have postulated a hematopoietic origin for this neoplasm. Most of the literature, however, has perpetuated the idea that the often bizarre symptoms seen with this entity result from neoplastic endothelial cell proliferation within the small vessels of affected organs, including the brain and spinal cord. This report describes the immunohistochemical examination and confirmation of the cell of origin of this neoplasm based on five previously unpublished cases of malignant angioendotheliomatosis with primarily CNS symptoms. It includes the first documentation of a T-cell lymphoma presenting as malignant angioendotheliomatosis.

All cases include autopsy findings, and in four cases the diagnosis was made postmortem. One case was proven by stereotactic biopsy, but the patient succumbed as a result of severe intracranial bleeding that occurred at the time of biopsy. Tissues were studied with avidin-biotin peroxidase immunohistochemical techniques using a panel of monoclonal antibodies directed against the leukocyte common antigen, LN-1, LN-2, and anti-Factor VIII, and also using Ulex europaeus agglutinin 1.

Based on the results obtained, the authors conclude that the proliferative cells seen within the vessel lumina are of lymphocytic origin and agree that the condition should more properly be designated intravascular lymphomatosis. The therapeutic implications of this conclusion point to the possible administration of chemotherapy and radiotherapy in an effort to achieve remissions in an otherwise relentlessly progressive neurological disorder.