Pilocytic astrocytoma of the adult--clinical features, radiological features and management.

Pilocytic astrocytoma is a histological subtype of astrocytoma classically located in the cerebellum of children and young adults. Cases occurring over the age of 30 years are rare and have not been classified in terms of their clinical features and management. Suitable cases were identified using diagnostic coding and by reviewing a neuropathology database. Casenotes and neuroradiology were reviewed retrospectively. Ten cases were identified over a 6 year period with an incidence of 0.49 cases per million population per year. Tumours were equally distributed between the supra- and infra-tentorial spaces. The most common symptom was headache occurring in 90%. No patient suffered seizures. Total macroscopic treatment remains the treatment of choice. Pilocytic astrocytoma of the adult is a rare tumour with a favourable prognosis.

Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors.

Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.

Neurocytoma of the thoracic spinal cord.

Central neurocytoma is an unusual tumour that arises in the supratentorial ventricular system of young adults. Similar lesions, termed simply neurocytoma, have been described at a variety of locations outside the ventricular system. Here, we report the case of a 50-year-old man who presented with pain and a rapidly progressive myelopathy due to a neurocytoma of the upper thoracic spinal cord. The literature on spinal neurocytoma and its relation to central neurocytoma are discussed.

The discovery of anthranilic acid-based MMP inhibitors. Part 3: incorporation of basic amines.

Anthranilic acid derivatives bearing basic amines were prepared and evaluated in vitro and in vivo as inhibitors of MMP-1, MMP-9, MMP-13, and TACE. Piperazine 4u has been identified as a potent, selective, orally active inhibitor of MMP-9 and MMP-13.

The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5-position and P1(1) groups.

A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, MMP-13, and TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE were identified, including the potent, orally active MMP-13 inhibitor 4p.

Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases.

Heteroaryl and cycloalkyl sulfonamide-hydroxamic acid MMP inhibitors were investigated. Of these, the pyridyl analogue 2 is the most potent and selective inhibitor of MMP-9 and MMP-13 in vitro.

The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3-position.

A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, and MMP-13 was prepared and evaluated both in vitro and in vivo. The most potent compound, 6e, has in vivo activity in a rat sponge-wrapped cartilage model.

Unusual radiological appearance of a skull osteoma.

A 24-year-old woman presented with a 7-week history of headache and left frontal scalp swelling. A plain radiograph and CT demonstrated a 2-cm lytic lesion in the frontal bone which was excised via craniotomy. Histology showed this to be an osteoma. Osteomas very rarely, if ever, appear as lytic lesions. The differential and radiological diagnoses are discussed.

Cotton gauze foreign body granuloma following microvascular decompression.

We describe a case of a cotton gauze foreign-body granuloma developing 2 months after microvascular decompression for trigeminal neuralgia and hemifacial spasm. This complication has not been previously described. Moreover, the patient's initial clinical and radiological findings were suggestive of an acoustic neuroma or meningioma at the time.

An unusual cause of acute labyrinthine failure.

We report a case of a 40-year-old man presenting with acute vertigo and deafness. Computed tomography (CT) scanning at initial presentation was normal. However, one year later he developed numbness on the right side of his face and examination revealed fifth, seventh and eighth cranial nerve palsies as well as cerebellar dysfunction. Magnetic resonance imaging (MRI) demonstrated a cerebellopontine angle lesion. He underwent near total excision followed by neuro-axis irradiation. The main mass of the tumour projected into the cerebellopontine angle. Histology showed this to be a medulloblastoma. All features of this case are unusual; hence we discuss the pathogenesis and management of this very rare tumour.

Spinal meningiomas: a 20-year review.

The long-term outcome of 78 patients with spinal meningiomas operated on over 20 years at a single neurosurgical unit was analysed. Age, sex and tumour location were similar to those reported by others. Overall, 95% of our patents were independently mobile postoperatively, despite 25% of the group being unable to walk before operation, including four paraplegic patients. Only two tumours were entirely extradural, and a further two were both intra- and extradural. In all cases, tumour exposure was by posterior laminectomy, without recourse to more complex approaches. Complete tumour resection was achieved in 77 (98%) of cases. The dural attachment was excised in 20 cases and diathermy was applied in 58. There was one recurrence, 14 years after the original surgery. Complex and technically challenging surgical approaches are unnecessary to obtain complete removal even for anteriorly placed tumours. Excision of the dural base would seem unnecessary to attain a low recurrence rate.

Malonyl alpha-mercaptoketones and alpha-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors.

A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal alpha-mercaptoketone or alpha-mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).

The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases.

A series of succinyl based mercaptoketones and diastereomeric mercaptoalcohols were prepared and evaluated in vitro as inhibitors of the matrix metalloproteinases collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).

The synthesis and biological activity of a novel series of diazepine MMP inhibitors.

A novel series of diazepine-based hydroxamic acid inhibitors of MMP-1, MMP-9, and MMP-13 were prepared and evaluated both in vitro and in vivo.

Spontaneous spinal extradural hematoma during pregnancy.

BACKGROUND: Spontaneous spinal hematomas are rare in pregnancy, and only two cases have previously been described. This report reviews other similar cases and discusses the aetiology and management of this condition in relation to pregnancy. CASE: A 26-year-old primigravida presented at 35 weeks of gestation with a history of sudden onset of back pain and weakness with loss of sensation of her legs. On examination there was tenderness over the seventh thoracic vertebra with loss of sensation below the level of the T7 dermatome and reduced power in both lower limbs. Magnetic resonance imaging demonstrated an anterior extradural lesion in the mid-thoracic region of the spinal cord. An elective cesarean section was performed followed by a costotransversectomy and removal of an extradural hematoma. The patient's neurological function subsequently improved. CONCLUSION: Acute spontaneous spinal extradural hematoma occurring during pregnancy can be associated with successful outcome following prompt diagnosis and surgical treatment.

Spontaneous cervical epidural haematoma.

Spontaneous spinal epidural haematoma can occur in the elderly and is a reversible cause of neurological deficit if treated promptly. The diagnosis can be made from a careful history and a simple neurological examination, but it can be confused with myocardial infarct, musculoskeletal pain, vasculitis and acute dissection of an aortic aneurysm. For a favourable outcome, early decompressive laminectomy and evacuation of the haematoma are necessary. We report an unusual case of acute quadriplegia in which prompt diagnosis and early intervention led to almost complete functional recovery with minimal disability.

Therapeutic blood levels of sirolimus (rapamycin) in the allografted rat.

A study was conducted to determine the relationship among oral dose, trough whole blood levels, graft survival, and side effects in sirolimus-treated allografted rats. The heterotopic heart allograft model using Brown Norway donors and Lewis rat recipients was used. Rats were dosed daily with sirolimus or vehicle until graft failure or up to a maximum of 28 days. Upon graft failure, rats were bled for measurement of trough blood levels of drug and tissues sent for histopathologic analysis. Sirolimus blood concentration correlated positively with dose and graft survival. Significant graft survival occurred at whole blood trough levels of 0.5 ng/ml achieved at the 0.3 mg/kg/day dose. Analysis of the concentration-effect data using a sigmoidal Emax model calculated a whole blood EC50 of 2.0 ng/ml for graft survival. With mean trough concentrations of 7 ng/ml and higher, grafts survived after cessation of drug treatment. At the 0.8 mg/kg/day dose, there was a significant decrease in body weight gain in the rats. Histopathologic examination of sirolimus-treated animals detected thymic and lymphoid atrophy, both considered pharmacologic extensions of sirolimus's immunosuppressive activity and focal myocardial degeneration, an exacerbation of a spontaneous occurring lesion. These results demonstrate that sirolimus prolongs graft survival in rat in a concentration dependent manner with therapeutic whole blood levels of about 10 ng/ml.

Perils of a 'true' posterior communicating artery aneurysm.

Successful 'clipping' of the apparent neck of a posterior communicating artery aneurysm was carried out, but 2 days later the patient had a further haemorrhage and died. Postmortem examination revealed that the aneurysm was that of a rare fusiform 'true' posterior communicating artery aneurysm.