Showing papers by "British Hospital published in 2009"

CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5.

Abstract: Thirty-four different loci for hereditary spastic paraplegias have been mapped, and 16 responsible genes have been identified. Autosomal recessive forms of spastic paraplegias usually have clinically complex phenotypes but the SPG5, SPG24 and SPG28 loci are considered to be associated with 'pure' forms of the disease. Very recently, five mutations in the CYP7B1 gene, encoding a cytochrome P450 oxysterol 7-alpha hydroxylase and expressed in brain and liver, have been found in SPG5 families. We analysed the coding region and exon-intron boundaries of the CYP7B1 gene by direct sequencing in a series of 82 unrelated autosomal recessive hereditary spastic paraplegia index patients, manifesting either a pure (n = 52) or a complex form (n = 30) of the disease, and in 90 unrelated index patients with sporadic pure hereditary spastic paraplegia. We identified eight, including six novel, mutations in CYP7B1 segregating in nine families. Three of these mutations were nonsense (p.R63X, p.R112X, p.Y275X) and five were missense mutations (p.T297A, p.R417H, p.R417C, p.F470I, p.R486C), the last four clustering in exon 6 at the C-terminal end of the protein. Residue R417 appeared as a mutational hot-spot. The mean age at onset in 16 patients was 16.4 +/- 12.1 years (range 4-47 years). After a mean disease duration of 28.3 +/- 13.4 years (10-58), spasticity and functional handicap were moderate to severe in all cases. Interestingly, hereditary spastic paraplegia was pure in seven SPG5 families but complex in two. In addition, white matter hyperintensities were observed on brain magnetic resonance imaging in three patients issued from two of the seven pure families. Lastly, the index case of one family had a chronic autoimmune hepatitis while his eldest brother died from cirrhosis and liver failure. Whether this association is fortuitous remains unsolved, however. The frequency of CYP7B1 mutations were 7.3% (n = 6/82) in our series of autosomal recessive hereditary spastic paraplegia families and 3.3% (n = 3/90) in our series of sporadic pure spastic paraplegia. The recent identification of CYP7B1 as the gene responsible for SPG5 highlights a novel molecular mechanism involved in hereditary spastic paraplegia determinism.

Lung cancer as a second primary malignancy: increasing prevalence and its influence on survival.

Abstract: The purpose of this study was to review the experience with lung cancer as a second primary malignancy (LCSPM) and to determine whether a history of previous malignancy was an independent prognostic factor in resected non small cell lung cancer (NSCLC). We included 414 patients undergoing pulmonary resection with a curative intention between January 1986 and January 2007. The criteria for classifying a lesion as a lung cancer as a second primary malignancy (LCSPM) were a different histological type or a tumor of identical histological type occurring more than 3 years after treatment of the primary tumor, or separated from the initial primary tumor by more than 2 cm of clinically normal epithelium. Thirty-four patients (8.2%) had a history of a previous malignancy. LCSPM were more frequent during the last decade (11.4% vs. 3.91%, P = .0009). Breast, uroepithelial, and lung cancer were the most prevalent initial primary tumors. In 64.7% of patients the time interval between the last malignancy and the current lung cancer was 2 years or shorter. Patients with NSCLC and a previous malignancy did not have a significantly different survival rate than patients with the current NSCLC as the first malignancy (5-year survival 65.3% vs. 58.6%, log-rank P = .416). The effectiveness of the surgical resection and the subsequent survival of these patients appear to be well demonstrated, and operative mortality and complications are no higher than for other lung cancer patients.

Postural control and sensory perception in patients with Parkinson's disease.

Abstract: Conclusions. This study suggests that patients with Parkinson's disease (PD), even in the early stages, have decreased body limits of stability (LOS) and changes in the visual input impair their postural control. Objective. To assess the LOS and the postural responses after changes in visual input in a group of PD patients in stage 1 of the Hoehn and Yahr classification. Subjects and methods. Twenty PD patients in stage 1 and a group of 24 normal subjects as control were assessed in two tests: (1) the LOS and (2) measurement of the body center of pressure area (COP) 10 s before and after sudden change in visual flow velocity. We also investigated labeling of the COP trajectory in these two periods. The stimulation paradigm was a horizontal optokinetic stimulation (60°/s and suddenly stopped) using a virtual reality system. Results. LOS showed significant decrease in PD patients as compared with the control group (p<0.001, Kruskal-Wallis and Wilcoxon ranked test). The COP values increased significantly (p<...

Anatomical landmarks for positioning the head in preparation for the transsphenoidal approach: the spheno-sellar point.

Abstract: The transnasal approach is the most utilized approach to the sellar region. This study was conducted to identify an anatomical landmark on the lateral surface of the head that corresponds to the midpoint of the sellar floor at the level of sphenoidal rostrum. This point, lined up with the nostril, simulates the surgical path and facilitates the transnasal access to the sella turcica. Four adult, formalin-fixed and silicon-injected cadaveric heads, and ten dried skulls were used for laboratory dissection. The heads and skulls were sectioned along the midline; and the spheno-sellar point, corresponding to the midpoint of the sellar floor at the level of sphenoid rostrum, was determined. The spheno-sellar point was plotted on the lateral surface of the skull, and its position measured relative to the external acoustic meatus. Linking the spheno-sellar point with the nostril created the spheno-nostril line. This line represents the surgical path to be taken for direct access to the sphenoid rostrum, and was used to align the cadaveric heads as in surgery. The endonasal transsphenoidal approach was then utilized in one hundred and two adult patients with sellar lesions, using the spheno-sellar point and the spheno-nostril line as the superficial landmarks to guide the approach. The results of this clinical experience are summarized. The spheno-sellar point was found to be located an average of 40.1 mm (SD+/-2.9 mm) anterior and 23.3 mm (SD+/-3.2 mm) superior to the external acoustic meatus. The spheno-nostril line represents the straight surgical path to the sphenoidal rostrum. This landmark was used in 102 correlative transnasal surgeries for sellar lesions of adult patients, and has allowed an easy and straightforward access to the sella. In only 3 cases with poor pneumatisation of the sphenoid sinus (presellar type), the actual location of the surgical instruments had to be confirmed by fluoroscopy. The application of the spheno-sellar point and the spheno-nostril line is a fast, reliable and very simple way to facilitate transsphenoidal surgery, and their use may avoid complications associated with misdirection of this approach. Its use may be limited in cases of poor pneumatisation of the sphenoid sinus, where fluoroscopic guidance could be necessary as a rule.

Patterns of pulmonary function in smoking and nonsmoking patients with progressive systemic sclerosis

Abstract: Pulmonary involvement is a prominent feature in systemic sclerosis and a significant cause of morbidity and mortality. A restrictive ventilatory defect is typical and static lung volumes are usually reduced in patients with ILDs. The possibility of obstruction of small airways in progressive systemic sclerosis (SSc) has been suggested by widespread bronchiolectasis and peribronchial fibrosis noted at necropsy. A total of 46 patients with a diagnosis of SSc were retrospectively included in this study. Patients were classified according to their smoking status (never smokers, n = 34 and ex or current smokers, n = 12). Patients were also compared on the basis of the presence or not of an obstructive pattern on spirometry. The purpose of this study was to establish if SSc patients who are smokers have a different pattern of pulmonary function involvement. Our hypothesis was that smoking habit was not the only cause of air trapping and that the existence of small airway involvement secondary to SSc itself cannot be excluded.