Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains

Summary: Bovine immunoglobulins are made from genes belonging to a small family of closely related Vh, genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen Independent. Diversity seems to be generated by hypermutation, although other mechanistns cannot be discomited at this time. Contrary to humans and mice, which have several Vh gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.     

Estimation of nitrogen balance based on a six-hour urine collection in infants

The accuracy of a 6-hr vs a 24-hr urine collection for the determination of urinary urea nitrogen was studied in 15 infants. Patient's age ranged from 2 weeks to 3 yr, encompassing a wide variety of diagnoses. All patients had normal renal function at the time of the study. Participants had indwelling foley catheters throughout the study. Urine specimens were collected over a continuous 24-hr period. Aliquots obtained from urine collected over 0 to 6 hr and the total urine collection were analyzed utilizing the urease enzymatic method in the Astra. Statistical analysis was performed comparing the actual 24-hr determination to the estimation based on the 6-hr collection, utilizing linear regression. The analysis of data produced a highly significant correlation (r = 0.904, p less than 0.0001). When a 24-hr urine collection is not possible, a 6-hr collection is a useful alternative for the calculation of nitrogen balance in infants.     

Application of ECCLS guidelines to the analysis of Toxoplasma IgG and Rubella IgG using laboratory kits based on the Meia method.

The Meia method is an enzymo-immunoassay involving fluorometric detection, which is used in the Abbott IMx automatic analyzer. The purpose of this report was to analyse the Meia Toxoplasma gondii IgG antibody and Rubella IgG antibody assays, following ECCLS guidelines for the analysis of laboratory kits. The results showed that between-run imprecision for Rubella IgG was close to 15%; for Toxoplasma IgG the percentage was 13%. The mean recovery for Rubella IgG was 104% and 94% for Toxoplasma IgG. The carry-over for Rubella IgG was 0.64% and 0.26% for Toxoplasma IgG which, in both cases, was less than the analytical variability. Both Meia and Elisa showed a linear relationship in the analytical range of the method. Comparing Meia with the Elisa method, constant and proportional differences were found for IgG Rubella and proportional differences for IgG Toxoplasma. The Meia method has many positive analytical features to recommend and it can easily be used in a multidisciplinary laboratory, needing only a small number of serum samples.     

Pathophysiology of HPA axis abnormalities in patients with major depression: an update

Four hypotheses have been proposed to explain why nonsuppression on the dexamethasone suppression test occurs in patients with major depression. These include 1) increased metabolism of dexamethasone, 2) decreased sensitivity of pituitary glucocorticoid receptors to dexamethasone, 3) hyperresponsivity of the adrenal gland to ACTH stimulation, and 4) increased central drive of the pituitary from hypothalamic/limbic structures that overrides the action of the dexamethasone. A critical review of the literature suggests that the last hypothesis is most closely supported by the data. Despite this conclusion, factors other than depression may be involved in hypothalamic-pituitary-adrenal axis dysfunction.     

Deletion of the Major Proteolytic Site of the Helicobacter pylori Cytotoxin Does Not Influence Toxin Activity but Favors Assembly of the Toxin into Hexameric Structures

The Helicobacter pylori cytotoxin is proteolytically cleaved at a flexible hydrophilic loop into two subunits. Deletion of the loop sequences had no effect on biological activity of the toxin in the HeLa cell vacuolation assay but favored the organization of the protein into hexameric rather than heptameric structures.     

A comparision of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS patients

Twenty patients with AIDS who had intracranial lesions underwent both brain biopsy and cerebro-spinal fluid (CSF) examination to compare histological diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of infectious agents. CSF-PCR was performed for herpes simplex virus, varicella zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV), Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven) cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis (the former also had PML) and positive for M. tuberculosis DNA in one case of tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one definite, four presumptive) were T. gondii DNA positive. There was close correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL. Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR methods. Received: 8 November 1995 Received in revised form: 9 July 1996 Accepted: 19 July 1996