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The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactive N-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the arene ortho position. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly to ortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuable ortho-phenylenediamines, this work demonstrates the potential for utilizing noncovalent interactions to control positional selectivity in radical reactions.

Ortho-sulfonyl anilines are important building blocks for a range of applications. We report the discovery of an aromatic rearrangement reaction of O-(arenesulfonyl)hydroxylamines which leads directly to ortho-sulfonyl anilines through formation of a new C-N bond with excellent levels of regiocontrol for the ortho position(s) over all others. We establish that the rearrangement is proceeding through an intermolecular mechanism and propose that the regiocontrol observed is the result of attractive non-covalent interactions occurring during the C-N bond-forming step. Importantly, this method is complementary to classical aniline sulfonation in terms of the variously substituted regioisomers that can be obtained and it is also applicable to O-(benzylsulfonyl) hydroxylamines.

Purpose Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy. Patients and Methods We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy. Results Fifty-eight patients were assessable for second tumors. Nine (50%) of 18 patients who received radiotherapy after their OPGs developed 12 second tumors in 308 person-years of follow-up after radiotherapy. Eight (20%) of 40 patients who were not treated with radiotherapy developed nine tumors in 721 person-years of follow-up after diagnosis of their OPGs. The relative risk of second nervous system tumor after radiotherapy was 3.04 (95% CI, 1.29 to 7.15). Conclusion There is a significantly increased risk of second nervous system tumors in those NF1 patients who received radiotherapy for their OPGs, especially when treated in childhood. Thus radiotherapy should only be used if absolutely essential in children with NF1.

Editor—We have previously reported on a large clinical study of patients with neurofibromatosis 2 (NF2)1and described the usefulness of audiological screening in early detection of VS in NF2.2 Although DNA diagnosis is possible by linkage analysis and by detecting the NF2 family specific mutation, this is not possible in all cases. Only 40% of sporadic patients (new mutations) have an identifiable NF2 mutation3 and as 50% of NF2 patients have no family history,4 up to 30% of those at risk of NF2 will not be able to have a DNA presymptomatic test. While it is possible to calculate residual risks of NF2 from age at onset of symptoms curves,5 a more useful measure would be the level of risk reduction from a normal cranial MRI scan. A database recording information on affected subjects with NF2 was set up in Manchester in 1989. Patients were actively sought across the UK from paediatricians, neurosurgeons, ENT surgeons, geneticists, and dermatologists. We have used this database to determine the age at which MRI detects asymptomatic tumours in subjects with NF2 and the value of audiological screening. We have also created life curves for risk reduction in subjects at 50% risk of NF2. Patient details from hospital notes and proformas have been entered into a database at St Mary's Hospital Manchester since 1989. A total of 344 patients fulfilling our published criteria for NF2 are recorded (table 1).1 3 5 Information on all known tumours, age at presentation and diagnosis, and many different symptoms are included. We have analysed details of patients who have been detected as having VS on a screening MRI scan without any known central nervous system pathology, signs, or symptoms. It has been our practice to carry out a baseline MRI …

Background Meningiomas have been reported to occur in approximately 50% of neurofibromatosis type 2 (NF2) patients. The NF2 gene is commonly biallelically inactivated in both schwannomas and meningiomas. The spectrum of NF2 mutations consists mainly of truncating (nonsense and frameshift) mutations. A smaller number of patients have missense mutations, which are associated with a milder disease phenotype. Methods This study analysed the cumulative incidence and gender effects as well as the genotype–phenotype correlation between the position of the NF2 mutation and the occurrence of cranial meningiomas in a cohort of 411 NF2 patients with proven NF2 mutations. Results and Conclusion Patients with mutations in exon 14 or 15 were least likely to develop meningiomas. Cumulative risk of cranial meningioma to age 50 years was 70% for exons 1–3, 81% for exons 4–6, 49% for exons 7–9, 56% for exons 10–13, and 28% for exons 14–15. In the cohort of 411 patients, no overall gender bias was found for occurrence of meningioma in NF2 disease. Cumulative incidence of meningioma was close to 80% by 70 years of age for both males and females, but incidence by age 20 years was slightly increased in males (male 25%, female 18%; p=0.023). Conversely, an increased risk of meningiomas in women with mosaic NF2 disease was also found.

A case of a patient with a posterior fossa meningioma extending through the hypoglossal canal to the cervical region as described in this article has not been previously described in the literature. Investigations and surgical management are outlined and pathological classifications are discussed. A literature review including recent reports of extracranial meningiomas is presented. Extracranial meningiomas are exceedingly rare and a high index of suspicion is necessary to make the diagnosis.

This was a study of the use of virtual reality modelling language (VRML) for cross-platform interactive three-dimensional (3-D) visualization of high-resolution magnetic resonance (MR) images of the inner ear in the assessment of cochlear implant candidates.A retrospective case review was made of cochlear implant candidates undergoing pre-operative high-resolution MR studies to determine their suitability for implantation. 3-D visualizations of MR scans of the inner ear structures were created using surface rendering and exported as portable VRML files.Case studies are presented to illustrate different points of interest. VRML reconstructions aided the interpretation of two-dimensional (2-D) source images in a variety of inner ear abnormalities.VRML is an internationally recognized standard for cross-platform 3-D visualization that creates a means of providing the implanting surgeon with a portable 3-D representation of the inner ear, aiding interpretation of the complex cross-sectional anatomy of these structures, and guiding selection of patients for implantation as well as implantation technique. The elucidation of the mechanisms behind inner ear malformations can also be aided by detailed imaging studies of the temporal bone, with VRML reconstructions providing an easily interpreted representation of deformities.

Thirty-three eyes of 22 patients with primary open-angle glaucoma or severe ocular hypertension had topical timolol maleate added to their maximally tolerated medical regimens. With minimal side effects, 25 eyes (76%) could be treated medically for one year, and only eight eyes (24%) required filtering surgery. Thirteen (39%) of the medically treated eyes achieved intraocular pressures of 21 mm Hg or less. After the addition of timolol, 17 of the 33 eyes (52%) completed the one-year protocol with final mean intraocular pressure decreases of 5 mm Hg or more on medical therapy.

(1944). The Venerable Anglo-Portuguese Treaty. The Social Studies: Vol. 35, No. 2, pp. 65-70.

✓ This case report describes a patient with sciatica resulting from lumbar root compression by a gas-containing cyst in the extradural space. Removal of the cyst provided prompt relief. The origin and anatomic distribution of gas collections in the spine are considered based on a review of the literature.

✓ Benign tumors of the middle fossa components of the trigeminal nerve are rare. The authors describe the case history, radiological investigation, and operative findings of a patient with a large trigeminal neurofibroma of the middle fossa. The unusual mode of presentation is discussed. Valuable information was provided by magnetic resonance imaging prior to successful removal of this tumor.

Three-dimensional (3D) computed tomographic reformations have been used successfully as an adjunct to standard axial computed tomography (CT) in the evaluation of disorders affecting areas of complex anatomy. The basic requirements for high-quality 3D reformations are an absence of patient movement and narrow-width transaxial sections. Speed of examination is an important factor in optimizing image quality. One hundred examinations were performed on an IGE CT 9800 scanner. For bone studies, 80 mAs and, for certain soft tissues, 140 or 200 mAs were employed with 120 kVp. The advantages of such a "low-dose" technique are significant reduction in patient skin dose and a faster examination. The main disadvantage is a reduction in signal-to-noise ratio. The image quality obtained in 3D presentations has nevertheless been sufficient to enable all bony abnormalities to be identified. Three-dimensional examinations are now being performed routinely using a dynamic mode and this "low-dose" technique.

• Eighteen patients with glaucoma with a mean intraocular pressure (IOP) ± SD of 28.7 ± 5.5 mm Hg who were receiving maximum-tolerated antiglaucoma therapy were given 0.5% timolol maleate or a placebo twice daily to one eye in a double-masked cross-over fashion in addition to their usual antiglaucoma drugs. After one week of timolol therapy, the mean IOP was significantly lower (23.1 ± 4.1 mm Hg) than after one week of placebo administration (26.4 ± 7.8 mm Hg; P 4 mm Hg, while six patients reached IOPs