ECT in Parkinson's disease. Changes in motor symptoms, monoamine metabolites and neuropeptides

Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.     

BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations in 17 families from Wales with two or more cases of breast cancer under age 50 and/or ovarian cancer. Eight out of 17 (47%) families had demonstrable mutations. Six out of 17 (35%) carried BRCA1 mutations and 2 out of 17 (12%) carried BRCA2 mutations. Two recurrent mutations in BRCA1 were identified, which appear to represent founder mutations in this population. These data support the existence of additional breast and ovarian cancer susceptibility genes.     

Ovarian hyperstimulation syndrome: facts and fallacies

Severe or critical ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian hyperstimulation for assisted reproduction techniques (ART). The syndrome is characterized by cystic enlargement of the ovaries and fluid shifts from the intravascular to the third space. The morbidity in OHSS is mainly determined by the hemodynamic changes caused by increased capillary permeability. The incidence of OHSS depends on definitions, risk factors, ovarian stimulation protocols, luteal support and conception. Currently, research on the pathogenesis of OHSS is focused on increased capillary permeability. Several theories are reviewed. Until the pathogenesis of OHSS becomes clear, treatment is restricted to supportive therapy. The various proposals for management of OHSS are discussed and, based on the available data, directions for the management of various grades of OHSS are summarized. However, prevention and early recognition are still the most important tools to handle OHSS. A flowchart with preventive measures for OHSS is presented derived from the available literature.     

Modeling protein stability: a theoretical analysis of the stability of T4 lysozyme mutants

Free energy calculations were conducted to determine the relative stability of the unnatural amino acid mutants of T4 lysozyme norvaline (Nvl) and O-methyl-serine (Mse) and of alanine at residue 133, which is leucine in the native sequence. These calculations were performed both to assess the validity of the methodology and to gain a better understanding of the forces which contribute to protein stability. Peptides of different length were used to model the denatured state. Restraints were employed to force sampling of the side chain chi1 dihedral of the perturbed side chain, and the effect of protein repacking in response to mutation was studied through the use of different constraint sets. In addition, the convergence behavior and hysteresis of the simulations in the folded and unfolded states were determined. The calculated results agree well with experiment, + 1.84 versus + 1.56 kcal/mol for Mse-->Nvl and -3.48 versus -2.2 to -3.6 kcal/mol for Nvl-->Ala. We find that free energy calculations can provide useful insights to protein stability when conducted carefully on a well chosen system. Our results suggest that loss of packing interactions in the native state is a major source of destabilization for mutants which decrease the amount of buried nonpolar surface area and that subtle responses of the backbone affect the magnitude of the loss of stability. We show that the conformational freedom of the chi1 dihedral has a noticeable effect on protein stability and that the solvation of amino acid side chains is strongly influenced by interactions with the peptide backbone.      

Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index

OBJECTIVE: To determine the most appropriate clinical measurements for the assessment of ankylosing spondylitis (AS) to develop the new metrology index. METHODS: One hundred and ninety-three individuals with AS were studied. The patients reflected the entire spectrum of cases of AS. Metrology was performed on 327 occasions. First the metrology (20 measurements) of 43 patients was analyzed. From this, 5 simple clinical measurements were defined which most accurately reflect axial status: cervical rotation, tragus to wall distance, lateral flexion, modified Schober's, and intermalleolar distance. These measurements were assessed for reliability, speed and both inter and intraobserver variability in another 40 patients. RESULTS: Analysis of the first group of 43 patients and a subsequent group of 54 patients, using the 5 measurements that constitute this new Bath AS Metrology Index (BASMI), demonstrated that they accurately and reliably mirror the 20 clinical measurements assessed previously (r = 0.92, p < 0.001). In a new group of 40 patients the measurements were demonstrated to be accurate and reproducible for both intraobserver variability (r = 0.99, p < 0.001) and interobserver variability (r = 0.97, p < 0.001). In a further 56 patients, admitted for inpatient therapy, an improvement in the BASMI from 3.34 (SD 2.71) to 2.16 (SD 2.42) was noted over a period of 3 weeks (regardless of disease severity) which indicates a sensitivity to change (chi 2 = 6.55, p < 0.01). The mean improvement over baseline was about 30%. CONCLUSION: Five clinical measurements provide a composite index (BASMI) and define disease status in AS. The BASMI is quick (7 min), reproducible and sensitive to change across the disease spectrum.