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The article presents the medical case of a 23-year-old woman with idiopathic intracranial hypertension (IIH). The patient underwent magnetic resonance venography (MRV), ventriculoperitoneal shunt insertion, and ventriculoperitoneal shunting. Moreover, venous sinus thrombosis (VST) in a patient with IIH could be due to more than a coincidence of risk factors and lateral sinuses are well recognised to taper in patient diagnosed with IHH.

Objective Differentiating idiopathic Parkinson's disease from atypical parkinsonian syndromes is challenging, especially in the early stages. We assessed whether the Revised Addenbrooke's Cognitive Examination (ACE-R) could differentiate between parkinsonian syndromes and reflect longitudinal changes in cognition in these disorders. Methods The ACE-R was administered at baseline and after approximately 18 months to 135 patients with parkinsonian disorders: 86 with idiopathic Parkinson's disease (PD), 30 with progressive supranuclear palsy (PSP), 19 with corticobasal degeneration (CBD). We assessed differences between groups for ACE-R, ACE-R subscores and Mini Mental State Examination (MMSE) scores at baseline (analyses of variance, receiver operating characteristics curves), and the interaction between diagnosis and change in ACE-R scores between visits (analyses of variance). Results The ACE-R verbal fluency subscore distinguished between PSP and PD with a high sensitivity (0.92) and specificity (0.87); total ACE-R score and the visuospatial subscore were less specific (0.87 and 0.84 respectively) and sensitive (0.70 and 0.73). Significant group level differences were found between PD and PSP for MMSE and ACE-R (total score and subscores for attention and concentration, fluency, language, and visuospatial function), and between PD and CBD for the ACE-R visuospatial subscore. Performance worsened between visits for ACE-R score in PD ( p=0.001) and CBD (p=0.001); visuospatial subscore in PD ( p=0.003), PSP (p=0.022) and CBD (p=0.0002); and MMSE in CBD (p=0.004). Conclusions We propose the ACE-R, particularly the verbal fluency subscore, as a valuable contributor to the differential diagnosis of parkinsonian syndromes in the correct clinical context. The ACE-R may reflect disease progression in PD and CBD. [ABSTRACT FROM AUTHOR]

We have analysed six South African families with osteogenesis imperfecta type I using three DNA polymorphisms associated with the pro alpha 2(I) collagen gene. In four of these families linkage of the pro alpha 2(I) gene and the osteogenesis imperfecta phenotype was suggested, whereas in the remaining two families there was a lack of linkage. No distinct correlation could be made between the phenotypic features of the families studied and linkage or lack of linkage to the pro alpha 2(I) gene. Two different haplotypes were found to be associated with the mutant pro alpha 2(I) alleles. These findings suggest that molecular heterogeneity exists within osteogenesis imperfecta type I and that in a significant proportion of cases the defect is linked to the pro alpha 2(I) gene. [ABSTRACT FROM PUBLISHER]

The human pro alpha 2(I) collagen gene was analysed for the presence of restriction fragment length polymorphisms. DNA from randomly selected unrelated persons of three Southern African populations was cleaved with one of eight different restriction enzymes, electrophoresed, blotted, and hybridised with cDNA and genomic probes specific for the pro alpha 2(I) gene. An MspI polymorphism was detected which results from the loss of a cleavage site within the 3' half of the gene. In two of the populations studied, the polymorphism occurred at significant frequencies, and should therefore prove useful as a genetic marker for the study of inherited disorders of connective tissue involving collagen structure or biosynthesis. [ABSTRACT FROM PUBLISHER]

Restriction endonuclease analysis of specific gene sequences is proving to be a valuable technique for characterisation and diagnosis of inherited disorders. This paper describes detailed protocols for isolation, restriction, and blot hybridisation of genomic DNA. Problems and alternatives in the procedure are discussed and a troubleshooting guide has been provided to help rectify faults. [ABSTRACT FROM PUBLISHER]

Introduction and Objectives We undertook a clinical trial of non-viral CFTR gene therapy assessing safety, dose and transgene expression in preparation for a Multi-dose trial (MDT) designed to assess clinical efficacy. Methods A single nebulised and/or nasal dose of plasmid CFTR (pGM169)/GL67A was delivered to patients aged =16 years with a baseline FEV1>60% predicted. Clinical and laboratory parameters were measured at intervals until day 28. A cohort of patients also underwent pre- and post-dosing (day 6 or 14) bronchoscopies for functional (airway potential difference (PD)) and molecular (QRT-PCR) evidence of vector-specific CFTR expression. Patients receiving a nasal dose underwent brushings for QRT-PCR and serial nasal PD measurements. Results 35 patients received a nebulised dose of 20 ml (n=17), 10 ml (n=10) or 5 ml (n=8). A short-lived, dose-related drop in FEV1 was observed over the next 6 h (mean [SD]: 20 ml 25.7 [10.2]%; 10 ml 17.7 [9.9]%; 5 ml 13.0 [4.4]% of baseline). Subjects also experienced a systemic inflammatory response which was similarly dose-related and generally limited to the first 24-48 h post-dosing. A cohort of 6 patients (4@10 ml; 2@5 ml) received 4 g paracetamol over an 18-h period post-dosing; none of these patients developed a fever. Intriguingly, these subjects also appeared to have reduced systemic inflammatory responses. Molecular (mRNA) evidence of gene transfer was observed in some individuals from upper or lower airway brushings. On lower airway PD measurement, the majority of patients showed an increase towards non-CF values after nebulised gene therapy. 19 patients received a 2 ml nasal dose and 11 (58%) had some response in chloride secretion on nasal PD. In the two most positive individuals, responses were within the normal (non-CF) range and persisted to days 63 and 91, respectively. Conclusions We consider the side effects after 20 ml nebulised dose excessive for repeated application. Those at 10 and 5 ml were more acceptable. Gene expression was confirmed in some patients, and restoration of CFTR function to the non-CF range has been observed out to 13 weeks following a single nasal dose. These data support progression of this agent to MDT. Funding UK CF Trust. [ABSTRACT FROM AUTHOR]