Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis.

In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty.

HLA and syringomyelia.

The HLA status of 53 patients with syringomyelia was assessed. Forty had an associated Chiari anomaly. A significant increase of HLA-A9 was found. Genetic factors may influence the development of syringomyelia.

Monozygous twins discordant for multiple sclerosis. Report of one pair and discussion of possible causes of multiple sclerosis.

One pair of male monozygous twins was examined: only 1 twin had multiple sclerosis. Differences in the life histories of the twins were identified. Haematological, biochemical and microbiological studies were performed. It is possible in theory to determine which environmental factors may have been responsible for the development of multiple sclerosis in 1 twin. Several differences in life history were found in this study.

Unusual manifestations of herpes zoster. A clinical and electrophysiological study.

The literature on complicated herpes zoster is summarized in this paper. The case histories of 18 patients with herpes zoster are presented. Two patients had encephalitis, 2 had myelitis and the other 14 patients had various types of lower motor neurone disturbance. Both patients with encephalitis--one of who developed choreo-athetosis during the illness--recovered fully. Only 1 of the 2 patients with myelitis recovered fully; the other remains severely paraparetic and the reason for her incomplete recovery may be related to the presence of generalized arteriolar disease associated with seronegative rheumatoid disease. One patient developed a Guillain-Barre syndrome 3 weeks after the onset of herpes zoster. Recovery in the 15 patients with lower motor neurone involvement has been slow butcomplete--or almost complete--in all but 1, a patient with persistent facial weakness as part of the Ramsay Hunt syndrome and who also had weakness of one upper limb. Seven other patients had lower limb weakness. In 2 patients the weakness was confined to abdominal myotomes and 2 other patients had urinary retention. Electromyographic abnormalities were found in the muscles which were weak and frequently also in muscles which appeared strong. It is emphasized that neurological disturbances other than sensory abnormalities may be found in patients with herpes zoster. Motor complications of various types are not uncommon.

Neuronal anti-nuclear antibody in paraneoplastic sensory neuronopathy.

Sera from 3 patients with a paraneoplastic sensory neuronopathy and small cell carcinoma of the lung were found to contain an IgG directed against neuronal nuclei and the nuclei of cells in adrenal medulla. Plasma from one of these patients was injected into laboratory mice for 100 days but passive transfer of the syndrome could not be effected. Plasma did not affect the viability of the dorsal root ganglia cells in tissue culture but did appear to bind to their nuclei. The role of this antibody remains uncertain.

Solitary extranodal lymphoma of sciatic nerve.

A solitary extranodal malignant lymphoma (non-Hodgkin's lymphoma, centrocytic type) of the sciatic nerve is described in a 64-year-old woman. Whereas previous reports of peripheral nervous system lymphoma have described multifocal lesions and generally an association with systemic lymphomas, in this case the lymphoma was confined to a segment of a peripheral nerve and was not associated with systemic lymphoma. The clinical presentation was a progressive weakness and sensory disturbance in the right leg. Clinical and electrophysiological examination indicated a lesion in the sciatic nerve, and computerised tomography of the right thigh revealed an enlarged distal segment of the sciatic nerve. On surgical exploration, a fusiform tumour of the sciatic nerve was resected. Pathological examination, including immunohistology and electron microscopy revealed a malignant lymphoma. An unusual histological feature was the presence in the tumour and infiltrated nerve of an extracellular eosinophilic non-amyloid material, similar to that occasionally seen in nodal lymphomas. The patient showed no evidence of lymphoma at other sites at the presentation and this has been confirmed at a 9-month review.

Malignant cerebrovascular thromboembolization by phaechromocytoma.

We describe an unusual case of malignant thromboembolization within the aortic arch of a 56-year-old man who presented with a stroke. The uncommon source of this malignant embolus was an adrenal phaeochromocytoma which had permeated the inferior vena cava, metastasized into the pleural cavity and colonized the intimal surfaces of the aortic arch and carotid vessels. The relevant literature has been briefly reviewed.

Differentiating causes of headache.

Headache may be the presenting symptom of many diseases in the elderly. Some headaches are caused by significant intracranial disease, and the patient's age and general cardiologic and respiratory status may not allow investigation or neurosurgical management. Conditions that demand urgent neurosurgical attention are subarachnoid hemorrhage, pituitary apoplexy, subdural hematoma, and meningioma. Cranial arteritis, too, should be remembered as a possible medical cause of headache in the elderly.

Femoral pain of solitary neurofibromatous origin: a report of three cases.

Three patients, each with a solitary neurofibroma in the thigh, are described. The presenting complaint in each case was pain. A neurofibroma of a branch of the femoral nerve was found in two cases and an intraosseous neurofibroma of the femoral shaft was present in the third. An excellent recovery was observed in each of these three patients following surgical excision of the tumour. Attention is drawn to the unduly long interval between the onset of painful symptoms and the achievement of a clinical diagnosis leading to a surgical cure in each instance.

Brain damage in National Hunt jockeys.

Five National Hunt jockeys have been found to have post-traumatic encephalopathy- three with epilepsy and two with significant intellectual and psychological deterioration. Closer supervision is needed.